This document discusses radiation therapy guidelines for prostate cancer treatment based on risk stratification. For low-risk prostate cancer, active surveillance is recommended. For intermediate-risk disease, radiation therapy alone or surgery are equally effective with comparable long-term tumor control. For high-risk or locally advanced prostate cancer, long-term androgen deprivation therapy combined with radiation therapy improves survival outcomes. The document also reviews evidence on dose escalation, which has demonstrated improved biochemical control and reduced metastases and disease-specific mortality compared to lower radiation doses.
advancements in the diagnostics help detect states like oligometastasis ,which can lead to selection of patients for local and MDT and prolong the time to adjuvant therapy, at present There is no consensus on the treatment of oligometastatic cancer and clinical trials can help in evidence formation.
Induction chemotherapy followed by concurrent ct rt versus ct-rt in advanced ...Santam Chakraborty
Small Presentation where the benefit of addition of induction / neoadjuvant chemotherapy to concurrent chemoradiation in head neck cancers is explored.
Locally advanced Ca prostate
Courtesy : NCCN , Perez, Gunderson and Tepper
Brief outline on management
ADT, Radiotherapy, Surgery indications and Standard of care
Large patient cohort prospective study with more than 500 patients and more than 5
years follow up have shown that CyberKnife is equally effective as long coures RT
SBRT/ CyberKnife is now standard of care treatment for localized prostate cancer
Large patient cohort prospective study with more than 500 patients and more than 5
years follow up have shown that CyberKnife is equally effective as long coures RT
SBRT/ CyberKnife is now standard of care treatment for localized prostate cancer
Outcome of CyberKnife treatment is similar to long course RT
Side-effect after Cyberknife is less than 1% in prostate cancer
CyberKnife is safe, out patient, short course
Radiotherapy in Uterine & Cervical Cancer.pptxAtulGupta369
Radiotherapy
uterine carcinoma
cervix carcinoma
brachytherapy in uterine carcinoma
brachytherapy in cervical carcinoma
detailed decription
explanation about recent recommendations
explanations about landmark trials
one shot whole ppt for learning about EBRT and brachytherapy in cervical and uterine carcinoma
advancements in the diagnostics help detect states like oligometastasis ,which can lead to selection of patients for local and MDT and prolong the time to adjuvant therapy, at present There is no consensus on the treatment of oligometastatic cancer and clinical trials can help in evidence formation.
Induction chemotherapy followed by concurrent ct rt versus ct-rt in advanced ...Santam Chakraborty
Small Presentation where the benefit of addition of induction / neoadjuvant chemotherapy to concurrent chemoradiation in head neck cancers is explored.
Locally advanced Ca prostate
Courtesy : NCCN , Perez, Gunderson and Tepper
Brief outline on management
ADT, Radiotherapy, Surgery indications and Standard of care
Large patient cohort prospective study with more than 500 patients and more than 5
years follow up have shown that CyberKnife is equally effective as long coures RT
SBRT/ CyberKnife is now standard of care treatment for localized prostate cancer
Large patient cohort prospective study with more than 500 patients and more than 5
years follow up have shown that CyberKnife is equally effective as long coures RT
SBRT/ CyberKnife is now standard of care treatment for localized prostate cancer
Outcome of CyberKnife treatment is similar to long course RT
Side-effect after Cyberknife is less than 1% in prostate cancer
CyberKnife is safe, out patient, short course
Radiotherapy in Uterine & Cervical Cancer.pptxAtulGupta369
Radiotherapy
uterine carcinoma
cervix carcinoma
brachytherapy in uterine carcinoma
brachytherapy in cervical carcinoma
detailed decription
explanation about recent recommendations
explanations about landmark trials
one shot whole ppt for learning about EBRT and brachytherapy in cervical and uterine carcinoma
- 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
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
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.
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.
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
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
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.
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
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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1. Radiation Therapy in Prostate Cancer
Dr Atul Gupta
DM Resident
Radiotherapy & Oncology
AIIMS Jodhpur
2. Management Guidelines (Brief Overview)
Radiation Therapy in Low Risk Disease
RT in intermediate risk disease
RT in high/very high risk disease
Role of SBRT
Role of Brachytherapy
Radiation Technique & Specifications
Topics to be discussed-
6. Radiation Therapy in low risk disease -
Management
Options
Active
Surveillance
Radical RT
Radical
Prostatectomy
Focal Therapy
Management
Options
Active
Surveillance
Radical RT
Radical
Prostatectomy
Focal Therapy
*PSA < 10 ng/mL
GS < 7 (ISUP grade 1)
and cT1-2a*
7. In Low Risk Prostate Cancer –
3 Large RCTs done- PIVOT, SPCG-4 & ProtecT
They reported cancer specific survival rate of 98-99% at 10 yrs for men on Active Surveillance
Active Surveillance is safe in appropriately selected individuals who follow a specified surveillance protocol.
Active Surveillance Watchful waiting
Treatment intent Curative Palliative
Follow-up Pre-defined schedule Patient-specific
Assessment/markers used DRE, PSA, MRI at recruitment, re-
biopsy
Not pre-defined, but dependent on
development of symptoms of
progression
Life expectancy > 10 years < 10 years
Aim Minimize treatment-related toxicity
without compromising survival
Minimize treatment-related toxicity
Eligible patients Mostly low-risk patients Can apply to patients with all stages
8. Radiation Therapy in intermediate risk disease -
Management options in
Favorable Intermediate Risk
Observation
(If life expectancy
<10yrs)
AS RT alone Surgery
Management options in
Unfavorable Intermediate Risk
RT + Short Term ADT RP +/- Adj RT +/- ADT
PSA 10–20 ng/mL
or GS 7 (ISUP grade
2/3)
Or cT2b
9. In Intermediate Risk Disease –
Use of RT vs Surgery should not be driven by efficacy (Level 1 evidence of similar long term tumor control with
either therapy)¹
If RT is used, it is recommended to be given as monotherapy in general (not to be used in combination with
Brachy)¹
RTOG 0232 trial –
Randomized patients to receive wither LDR brachy monotherapy or with supplemental EBRT
Concluded that there was no difference in biochemical control between both arms
Higher toxicities with addition of both EBRT & Brachy
1. Devita 12th edition
10. Nodal Radiotherapy in Intermediate Risk Group-
The use of nodal radiotherapy is allowed per national cancer consensus guidelines and is directed more
specifically to UIR patients.
However, there remains no evidence in intermediate-risk prostate cancer that nodal EBRT improves outcomes
NRG/RTOG 0924 has completed accrual and primarily enrolled intermediate-risk patients, and the control arm
(i.e., standard of care) is the use of prostate-only radiotherapy. Thus, the experimental arm is the addition of
nodal EBRT given that there is no randomized evidence of benefit. ------- Results awaited
11. Radiation Therapy in High risk disease -
Current Treatment Options-
1. RT + long term ADT +/- Abiraterone/Prednisone
2. Radical Prostatectomy +/- Adj RT +/- ADT
PSA > 20 ng/mL
or GS > 7 (ISUP grade
4/5)
Or cT2c
any PSA
any GS (any ISUP grade)
cT3-4* or cN+**
(Locally Advanced)
12. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more
than 40 g/L or PSA of 20 to 40 g/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to
ADTRT
At a median follow-up time of 8 years, Overall survival was significantly improved in the patients allocated to ADTRT
(hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P .001).
Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P
.001).
This study firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.
14. RTOG 9910 RT Prolonged neoadjuvant ADT does not improve outcomes
ICORG 97-01 RT Prolonged neoadjuvant ADT does not improve outcomes
RTOG 9202 RT 28 months superior to 4 months of ADT
EORTC 22961 RT 36 months superior to 6 months of ADT
DART/GICOR RT 28 months superior to 4 months of ADT with dose-
escalated RT
TROG RADAR RT 18 months superior to 6 months of ADT
PCSIV RT 36 months not superior to 18 months of ADT
Trial Name Radical Therapy Outcome
15. The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77-
0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78-0·91], p<0·0001), but neoadjuvant ADT
extension did not (0·95 [0·83-1·09], p=0·50).
Long-term ADT significantly improved OS (HR, 0.85; 95% CI, 0.78 to 0.94) with a 12-year absolute benefit of 6.3% (2.3% to
10.4%) over short-term ADT.
Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group.
Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved
metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the
magnitude of the benefit could vary and shared decision making with patients is recommended.
*Prolongation of total ADT duration in the adjuvant setting from 4–6 months to 18–36
months
In UIR – short term ADT (4-6 months) recommended
In High Risk/Locally advanced- long term ADT (1.5-3 yrs)
recommended
17. Non-metastatic patients randomized to receive radiotherapy + ADT versus radiotherapy + ADT + abiraterone or
abiraterone plus enzalutamide.
Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher
rates of metastasis-free survival compared with ADT alone.
2 years of abiraterone and prednisolone added to ADT and, if indicated, radiotherapy should be considered a new
standard treatment for non-metastatic prostate cancer with high-risk features.
Thus , abiraterone is commonly reserved for patients with multiple high-
risk features and a significantly elevated PSA. (cT3-T4, GG>4, PSA>40)
19. Multiple trials have evaluated the benefit of docetaxel chemotherapy in addition to radiotherapy and ADT. In general,
most of these trials were negative for benefit from the addition of docetaxel, especially with long-term follow-up.
D’Amico et al (JCO 2021)-
A randomized trial of 350 men who were treated with radiotherapy, 6 months of ADT, and neoadjuvant and
concurrent docetaxel.
After a median follow-up of 10.2 years, there were no significant differences in OS between arms (HR, 0.99; 95% CI,
0.65 to 1.51; P = 0.98)
NRG/RTOG 0521-
A total of 563 men were randomized to radiotherapy plus 2 years of ADT +/– six cycles of docetaxel.
After a median follow-up of 10.4 years, the 10-year OS rates were 64% and 69% for the control and experimental
arms, respectively (HR, 0.89; 90% CI, 0.7 to 1.13; 1-sided P = 0.22).
Thus, Docetaxel chemotherapy should at this time not be recommended for patients with
high-risk localized prostate cancer.
21. This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy
for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%.
Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to
prostate, 50 Gy/25# to pelvic nodes, including common iliac).
All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen
deprivation therapy.
Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as
compared with PORT, but OS did not appear to differ.
Nodal radiotherapy is commonly recommended in men with high-risk disease.
This is based primarily on the fact that most high-risk trials mandated the use of nodal
radiotherapy rather than a clear demonstrable benefit from nodal radiotherapy
27. Local control is a critical issue for the outcome of RT of PCa.
It has been shown that local failure due to insufficient total dose is prognostic for death from PCa
as a second wave of metastases is seen 5 to 10 years later on.
Several RCTs have shown that dose escalation (range 74–80 Gy) has a significant impact on 10-
year biochemical relapse as well as metastases and disease-specific mortality.
28. Trial n Inclusion Criteria Radiotherapy
Dose
Follow-up
(median
Outcome Results
MD Anderson
study 2011
301 T1-T3, N0, M0, PSA < 10
ng/mL PSA 10-20 ng/mL
PSA > 20 ng/mL
70 vs.78 Gy 15 yr. DM, DSM, FFF All patients: 18.9% FFF at 70 Gy 12% FFF
at 78 Gy (p = 0.042)
3.4% DM at 70 Gy 1.1% DM at 78 Gy (p =
0.018)
6.2% DSM at 70 Gy 3.2% DSM at 78 Gy (p
= 0.043)
No difference in OS (p > 0.05)
Dutch randomized
phase III trial 2014
664 T1b-T4
143 pts. with (neo)
adjuvant HT
68 vs. 78 Gy 110 mo Freedom
biochemical
and/or clinical
failure at 10 yr
43% FFF at 68 Gy
49% FFF at 78 Gy (p = 0.045)
RTOG 0126 2018 1532 T1b-T2b ISUP grade 1 + PSA
10-20 ng/mL or ISUP grade
2/3 + PSA < 15 ng/mL
70.2 vs. 79.2 Gy 100 mo OS, DM, BCF
(ASTRO)
75% OS at 70.2 Gy
76% OS at 79.2 Gy
6% DM at 70.2 Gy
4% DM at 79.2 Gy (p = 0.05)
47% BCF at 70.2 Gy
31% BCF at 79.2 Gy (p < 0.001; Phoenix, p
< 0.001)
FLAME Trial 571 EAU risk classification:
Intermediate risk (15%)
High risk (84%)
77 Gy (35 fx. 2.2 Gy)
vs. 77 Gy (35 Fx.) +
focal boost (up to 18
Gy) ADT (65% both
arms – duration
unknown)
72 mo. BFS (5 yr.)
DSM (5 yr.)
BFS: 92% at 77 Gy + boost
85% at 77 Gy (p < 0.001, HR: 0.45) DSM: p
= 0.49
Focal boost in favour of: Local control (HR:
0.33) Distant MFS (HR: 0.58)
30. The study was based on five-year biochemical results from 14 168 patients treated with external beam
radiotherapy.
Treatment data from 11330 patients treated with conventional fractionation have been corrected for overall
treatment time and fitted with a logit equation.
The results have been used to determine the optimum α/β values that minimise differences in predictions
from 2838 patients treated with hypo-fractionated schedules.
The results indicate that the high fractionation sensitivity is an intrinsic property of prostate carcinomas and
they support the use of hypofractionation to increase the therapeutic gain for these tumours.
31. Study/
Author
n Risk, ISUP grade, or
NCCN
ADT RT Regimen BED,
Gy
Median
FU, mo
Outcome
Lee, et al.
2016
550
542
LOW RISK NONE 70 Gy/28 fx
73.8 Gy/41 fx
80
69.6
70 5 yr. DFS 86.3% (n.s.)
5 yr. DFS 85.3%
Dearnaley, et
al. CHHiP
2016
1,077/19
fx
1,074/20
fx
1,065/37
fx
15% low
73% intermediate
12% high
3-6 mo. before
and during
EBRT
57 Gy/19 fx
60 Gy/20 fx
74 Gy/37 fx
73.3
77.1
74
62 5 yr. BCDF( biochemical or
clinical disease failure)
85.9% (19 fx)
90.6% (20 fx)
88.3% (37 fx)
De Vries, et
al., 2020
HYPRO
403
392
30% ISUP grade 1
45% ISUP grade 2-3,
25% ISUP grade 4-5
NONE 64.6 Gy/19 fx
78 Gy/39 fx
90.4
78
89 8-yr. OS 80.8% vs. 77.6% (p
= 0.17)
8 yr. TF 24.4% vs. 26.3%
Catton, et al.
2017
608
598
intermediate risk
9% ISUP grade 1 63%
ISUP grade 2 28%
ISUP grade 3
NONE 60 Gy/20 fx
78 Gy/39 fx
77.1
78
72 5 yr. BCDF both arms 85%
HR: 0.96 (n.s)
32. To assess the effects of hypo-fractionated external beam radiation therapy compared to conventionally
fractionated external beam radiation therapy for men with clinically localized prostate cancer.
The findings suggest that moderate hypofractionation (up to a fraction size of 3.4 Gy) results in similar
oncologic outcomes in terms of disease-specific, metastasis-free and overall survival.
There appears to be little to no increase in both acute and late toxicity.
34. Ultra-HFX has been defined as RT with > 3.4 Gy per fraction.
It requires IGRT and (ideally) stereotactic body RT (SBRT).
They included 38 studies with 6,116 patients who received RT with < 10 fractions and > 5 Gy per fraction.
Five and 7-year biochemical recurrence-free survival (BRFS) rates were 95.3% and 93.7%, respectively, and estimated
late grade > 3 GU and GI toxicity rates were 2.0% and 1.1%, respectively.
The authors conclude that there is sufficient evidence to support SBRT as a standard treatment option for localised Pca.
35. Fourteen trials with a total of 2,038 patients were included.
Median follow-up was 37 months (range 6-55 months).
Most patients had cT1-T2a, Gleason ≤7 disease with median pre-treatment PSAs of 5-10; 1,042 (51%) were
low-risk, 744 (37%) were intermediate-risk, 158 (8%) were high-risk, and the remainder were unreported.
Doses ranged from 33.5-50.0 Gy, most typically in 5 fractions.
The pooled rate of FFBF was 98% [95% confidence interval, 97-98%]. The pooled rate of late grade ≥3
gastrointestinal and genitourinary toxicities were 1% [0-5%] and 2% [1-3%], respectively.
Despite the lack of long-term follow-up and heterogeneity of the available evidence, prostate SBRT affords
appropriate biochemical control with few high-grade toxicities. These data have implications for ongoing
worldwide utilization of prostate SBRT as well as ongoing prospective investigations.
37. Difference between LDR & HDR Brachytherapy
LDR Brachytherapy
• Permanent seeds implanted
• Uses Iodine-125 (I-125) (most common), Palladium-103
(103Pd-) or Cesium-131 isotopes
• Radiation dose delivered over weeks and months
• Acute side effects resolve over months
• Radiation protection issues for patient and carers
HDR Brachytherapy • Temporary implantation
• Iridium-192 (IR-192) isotope introduced through
implanted needles or catheters
• Radiation dose delivered in minutes
• Acute side effects resolve over weeks
• No radiation protection issues for patient or carers
38. Role of LDR Brachytherapy-
Low-dose rate (LDR) brachytherapy uses radioactive seeds permanently implanted into the prostate.
LDR Brachytherapy in Low/Favorable Intermediate Risk Group-
In patients declining or unsuitable for AS, LDR monotherapy can be offered to those with low-risk or NCCN
favorable intermediate-risk and good urinary function defined as an International Prostatic Symptom Score (IPSS) <
12 and maximum flow rate > 15 mL/min on urinary flow tests .
In addition, with due attention to dose distribution, patients having had a previous TURP can undergo
brachytherapy without an increase in risk of urinary toxicity. A minimal channel TURP is recommended, leaving at
least 1 cm rim of prostate tissue around the post-TURP urethral defect at the postero-lateral sides of the prostate
and there should be at least a 3-month interval between TURP and brachytherapy to allow for adequate healing.¹
1. Sylvester, J.E., et al. Fifteen-year biochemical relapse-free survival, cause-specific survival, and overall survival following I(125) prostate
brachytherapy in clinically localized prostate cancer: Seattle experience. Int J Radiat Oncol Biol Phys, 2011. 81: 376
39. LDR Brachytherapy in Unfavorable Intermediate/High Risk Disease-
ASCEND-RT trial-
External beam RT (total dose of 78 Gy) has been compared with EBRT (total dose 46 Gy) followed by LDR
brachytherapy boost (prescribed dose 115 Gy) in intermediate-risk and high-risk patients with 12 months of ADT
in both arms.
The LDR boost resulted in 5- and 7-year PSA PFS increase (89% and 86%, respectively, compared to 84% and 75%).
This improvement was achieved at a cost of increased late grade 3+ GU toxicity (18% compared to 8%).
Toxicity resulted mainly in the development of urethral strictures and incontinence and great care should be taken
during treatment planning.
40. Role of HDR Brachytherapy-
High-dose rate (HDR) brachytherapy uses a radioactive source temporarily introduced into the prostate to deliver
radiation.
Fractionated HDR brachytherapy as monotherapy can be offered to patients with low- and intermediate-risk PCa, who
should be informed that results are only available from limited series in very experienced centers. Five-year PSA control
rates of 97.5% and 93.5% for low- and intermediate-risk PCa, respectively, are reported, with late grade 3+ GU toxicity
rates < 5% and no, or very minimal, grade 3+ GI toxicity rates .
Single fraction HDR monotherapy should not be used as it has inferior biochemical control rates compared to
fractionated HDR monotherapy.
42. Radiotherapy for the treatment of prostate cancer has evolved immensely over the past 40 years.
2D 3D-CRT IMRT IGRT
High Surface dose,
Low Conformality,
Large Field size
High Dose to normal tissues
Rectal bleeding >30%
More accurately defining
the prostate and target
volumes
Smaller field sizes, Improved
conformality
Lower doses to normal
tissues
Enabled dose escalation to
the prostate
Rectal Bleeding 5-10%
Inverse treatment
planning
Ideal dose to prostate
and normal tissues
Vast improvement in
conformality
Rectal Bleeding 2%
CBCT scanning
Continuous real-time tracking
using orthogonal imaging
Rectal Bleeding 1%
43. CT Simulation Technique-
Prior to simulation, three fiducial markers can optionally be placed transperineally
A hydrogel rectal spacer can also be inserted transperineally at time of fiducial marker placement, in order to provide
temporary barrier to rectum. The spacer is reabsorbed within 6 months of placement, can significantly reduce rectal
dose from EBRT.
Patient Preparation-
Maintaining a comfortably full bladder and empty rectum can reduce dose to normal OARs .
Excessive rectal distension may be a/w worse outcomes due to geographic miss.
Enema , Suppository and/or rectal tube to relieve gas distension may be considered.
Immobilization-
A body mould such as vaccum-locking immobilization bag (vac-loc) should be considered.
44. Simulation-
CT scan from mid-abdomen to mid-femur
CT should include L4-5 intervertebral disc level superiorly to below lesser trochanters inferiorly
Contrast-
i/v contrast- typically not required (but may be considered in selected cases where nodal anatomy may need more
precise definition).
46. Acute Side Effects during RT –
Inflammation related events – urethritis , cystitis, proctitis---- should be managed conservatively
For patients with baseline obstructive symptoms/enlarged prostate
It is possible to develop acute urinary obstruction requiring catheterization
More common with Brachy due to acute severe reactions
Patients with IPSS Score >15, should be medically optimized with alpha-blockers,
potential cytoreduction with ADT , should be considered for HoLeP (Holmium Laser Enucleation of prostate)
Late Urinary Toxicities-
Chronic Urethritis , urethral strictures (Rare)
Haemorragic cystitis (Rare) -----managed with intra-vesicle formalin selective embolization of hypogastric arteries
for refractory cases- Hyperbaric Oxygen Therapy
47. Late Rectal Toxicities-
Typically manifests within first 3 yrs after RT (rare after 5 yrs)
Rectal bleeding , mucous discharge, incontinence of stool
<1% patients- ulcer and fistula development
Radiation induced proctitis management- Steroid Suppositories
Sitz Bath
Increased Dietary fibre
Refractory Argon Beam Plasma Laser
Coagulation
Hyperbaric Oxygen Therapy
Secondary Cancers After RT-
Rare Occurrence
Estimated to be <0.1% per decade
Colonoscopy is indicated every 5-10 yearly
Careful evaluation of patients presenting with hematuria to r/o possibility of secondary cancer
48. Erectile Dysfunction Rates after RT-
For first 10 yrs after treatment, RT results in 10-20% more men who preserve erectile function than nerve sparing
prostatectomy
Other S/E- reduced/loss volume of ejaculate
Short Term ADT------ most men recover testosterone within 6-12 months after completing ADT
Long Term ADT------ more prolonged testosterone suppression and impact on libido and erectile function
50. Radiation Therapy – an integral part of management of prostate cancer irrespective of risk stratification
Should be delievered with more conformal technique (preferably IGRT)
In Intermediate Risk disease--- should be offered along with short term ADT (4-6 months)
In High Risk Disease---should be offered along with long term ADT (18-36 months)
Radiation Dose--- preferably hypo-fractionated RT (more convenient to patient without compromise in outcome)
Ultra-hypo-fractionated RT(SBRT) also show good promise in management of ca prostate
Brachytherapy---- can be offered as monotherapy in low grade/favorable intermediate risk group
can be offered along with EBRT in unfavorable/high risk disease
After Radical Prostatectomy---- Salvage RT is an acceptable option without compromise in long term outcome
Prophylactic nodal irradiation---- indicated in high risk & intermediate risk disease
Docetaxel-----negative results in non-metastatic prostate cancer
Adverse effects with RT------ short term as cystitis, proctitis while long term as ED, urethral strictures but low
incidence in era of more conformal RT and manageable