IORT uses a high single-fraction radiation dose (10-30 Gy) is delivered during surgery to a surgically-exposed tumour bed, immediately after a chunk of the tumour has been surgically excised. This slide includes topics like APBI, IOERT, IOHDR.
EBCTCG METAANALYSIS
INDICATION OF POST OP RADIOTHERAPY
Immobilization devices
Conventional planning
Alignment of the Tangential Beam with the Chest Wall Contour
Doses To Heart & Lung By Tangential Fields
IORT uses a high single-fraction radiation dose (10-30 Gy) is delivered during surgery to a surgically-exposed tumour bed, immediately after a chunk of the tumour has been surgically excised. This slide includes topics like APBI, IOERT, IOHDR.
EBCTCG METAANALYSIS
INDICATION OF POST OP RADIOTHERAPY
Immobilization devices
Conventional planning
Alignment of the Tangential Beam with the Chest Wall Contour
Doses To Heart & Lung By Tangential Fields
Management of cacrinoma cervix: Techniques of radiotherapy (2D conventional, 3D Conformal radiotherapy (3DCRT) and IMRT with a review of various contouring guidelines.
TBI is the radiotherapy technique to irradiate whole body before doing stem cell transplant. The main purpose of doing TBIB is to condition the immune system of body so that there will be maximum chance of transplant acceptance.
Management of cacrinoma cervix: Techniques of radiotherapy (2D conventional, 3D Conformal radiotherapy (3DCRT) and IMRT with a review of various contouring guidelines.
TBI is the radiotherapy technique to irradiate whole body before doing stem cell transplant. The main purpose of doing TBIB is to condition the immune system of body so that there will be maximum chance of transplant acceptance.
The Event Industry’s Evangelist of Open SourceMichelle Bruno
Visual summary of the EventTechBrief.com article, "The Event Industry’s Evangelist of Open Source." Read the full article or subscribe to the e-newsletter at EventTechBrief.com.
Why Can't All Of Our Data Silos Just Get Along?Michelle Bruno
The technology landscape in the event industry is fragmented. There are lots of platforms that do lots of different things. The problem is that many don't share data and functionality, i.e. they don't work well together. Integration would be immensely helpful to change the situation, but there is still pushback and a layer of complexity that many event professionals aren't equipped to address. Read about what's going on and what needs to happen to change the situation.
Cancer screening may discover many dormant, regressing, or slowly progressing tumors that would not have affected the screened individuals. Such findings with there therapies are obviously harmful. This lecture is highly based on the book "over diagnosed" by H. Gilbert Welch and was presented in 2013 to KFSH-Dammam physicians
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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.
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
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.
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.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
1. Radiation Therapy
in the Management of
Breast Cancer
St. Mary’s 14th Annual Oncology Symposium
Julia Oh, M.D.
Assistant Professor
M.D. Anderson Cancer Center
November 8, 2008
2. 2007 Estimated Cancer Cases
Women
678,060 26% Breast 178,480 invasive cases
15% Lung & bronchus
62,030 in situ cases
11% Colon & rectum
2,030 male cases (1%)
6% Uterine corpus
4% Non-Hodgkin
lymphoma
4% Melanoma of skin
4% Thyroid
3% Ovary
3% Kidney
3% Leukemia
21% All Other Sites
Source: American Cancer Society, 2007
3. Trends in Breast Cancer
Incidence Rates, 1975-2003
250
200
1980s: ↑↑use of
mammography
Rate per 100,000
150
100
2000s: ↓↓use of
HRT
50
0
1975 1978 1981 1984 1987 1990 1993 1996 1999 2002
Sources:ACS, SEER
4. 2007 Estimated Cancer Deaths
Women
270,100 26% Lung & bronchus
15% Breast
10% Colon & rectum
6% Pancreas
6% Ovary
4% Leukemia
3% Non-Hodgkin
lymphoma
3% Uterine corpus
2% Brain/ONS
2% Liver & bile duct
23% All other sites
Source: American Cancer Society, 2007
5. Breast Cancer Death Facts
40,460 deaths in 2007
1990-2004: Death rates decreased by
2.2% annually
More screening
Better treatments
Largest decline in women <50
Race disparities are INCREASING
6. Strong Risk Factors
AGE:
30-39: 1 in 229
50-59: 1 in 37
80-89: 1 in 8
Personal history of breast cancer
Personal history of ADH or LCIS
1st degree family history of breast cancer
Chest irradiation as a child or young adult
Genetic mutations
7. Genetic Mutations
BRCA-1 (chromosome 17)
65% lifetime risk of breast cancer
40% lifetime risk of ovarian cancer
Frequently ER-
BRCA-2 (chromosome 13)
45% lifetime risk of breast cancer
10% lifetime risk of ovarian cancer
Frequently ER+
Li-Fraumeni syndrome (p53 mutation)
Cowden syndrome (PTEN mutation)
Peutz-Jeghers syndrome (STK11 mutation)
Sources: NCI; Antoniou, Am J Hum Genet 2003
8. ACS Screening
Recommendations
Yearly mammograms starting at age 40
15-20% relative risk reduction in breast cancer
death
1% absolute reduction in all-cause mortality
Clinical breast exam every 3 years for
women in their 20s and 30s, and every year
for women age 40 and older
9. BSE is No Longer Recommended:
Shanghai BSE Trial
266,064 women, ages 33-66
Randomized to control arm or BSE
No difference in breast cancer deaths
No difference in diagnosis of invasive cancer
More biopsies of benign breast lesions in
BSE group (i.e., more harm than good)
Conclusion: BSE should not be advocated;
“breast self awareness” is sufficient
Thomas, JNCI 2002
11. DCIS: Mastectomy versus
Breast Conserving Therapy
No randomized comparisons available
1%-2% local recurrence after mastectomy
compares favorably to BCT
1%-2% breast cancer mortality regardless
of treatment approach
BCT is preferable to mastectomy unless
extent of disease prevents complete
excision with acceptable cosmesis
12. DCIS: Randomized RT Trials
Four randomized controlled trials, aggregate N>4000
NSABP B-17 (Fisher, Semin Oncol 1998)
EORTC 10853 (Bijker, JCO 2006)
SweDCIS (Emdin, Acta Oncol 2006)
UK/ANZ (UKCCCR working party, Lancet 2003)
“no tumor at inked margins” on 3 of the 4 trials
20% positive/unknown margins on SweDCIS
Tamoxifen allowed on 1/4 trials
UK/ANZ – complicated multi-arm schema
RT dose 50 Gy to whole breast
No boost on any of the trials
14. Do All DCIS BCS Pts Need RT?
In 4 randomized trials, no subset has been
identified that does not benefit from RT
However, risk of recurrence may vary based on:
Tumor grade (EORTC)
Tumor size (B-24)
Margin status (B-17, EORTC, SweDCIS)
Comedonecrosis (B-17, B-24)
Multifocality (B-24)
Symptomatically detected lesions (EORTC)
Age ≤ 40 (EORTC)
15. BCS +/-RT for Favorable DCIS:
RTOG 98-04
MMG age R
detected S
A
T RT: 42.5-50 Gy,
grade N
Grade 1-2 R no boost
A tumor size D
≤2.5 cm O
T
margin size M
I Observation
Inked I
F tamoxifen
margins Z
≥3 mm Y use
E
Closed in 2006 due to poor accrual (<1/2 of target enrollment)
Analysis pending but results will be limited
16. Modified Van Nuys
Prognostic Index
Score 1 2 3
Size (cm) <1.5 1.6 - 4.0 > 4.1
“Group” - necrosis + necrosis G3
Margins (mm) >10 1-9 <1
Age >60 40-60 <40
Total Score
4-6 lumpectomy alone
7-9 lumpectomy + XRT
10 - 12 mastectomy
Problems
Not validated on external datasets
Model revisions have likely resulted in over-fitting on the training dataset
Only a small minority of all DCIS patients fall at either extreme
Silverstein, Breast 2003
17. Non-Randomized DCIS Trials:
Harvard Observational Study
Wide excision alone for “favorable” DCIS
Mammographic size ≤2.5 cm
Margins ≥1 cm
Predominantly nuclear G1 or G2
6% of cases contained G3 disease
Comedonecrosis allowed (present in 39%)
Tamoxifen not permitted
Wong, JCO 2006
18. Non-Randomized DCIS Trials:
Harvard Observational Study
Closed early when local recurrence rate
met predetermined stopping rules
158 patients accrued
Median follow-up 40 months
Local recurrence rate: 2.4% per patient-year
Projected 5-year recurrence rate: 12%
Wong, JCO 2006
19. Non-Randomized DCIS Trials:
ECOG 5194 Observational Study
Wide excision alone for “favorable” DCIS
Grade 1-2, size <2.5 cm
Grade 3, size <1 cm
Margins ≥3 mm
Negative postoperative mammogram
Tamoxifen allowed
Hughes, SABCS 2006
20. Non-Randomized DCIS Trials:
ECOG 5194 Observational Study
Grade 1-2 Grade 3
580 patients 102 patients
Median tumor size 6mm Median tumor size 7mm
Median margin 5-10mm Median margin 5-10mm
31% declared intention to 30% declared intention to
take tamoxifen take tamoxifen
5-yr local failure rate 5-yr local failure rate
6.8% 13.7%
Hughes, SABCS 2006
21. Benefit Seen in Elderly Patients
SEER-Medicare analysis of 3409 women age ≥66
Stratified by presence of any high-risk features:
Tumor >2.5 cm, high grade, comedo histology, age 66-69
Low Risk High Risk
5-yr Breast Recurrence 5-yr Breast Recurrence
No RT RT p-value No RT RT p-value
8.2% 1.0% <.001 13.6% 3.8% <.001
Recurrence rates without RT are comparable to ECOG 5194
Proportional benefit of RT is comparable to NSABP B-17
Smith, JNCI 2006
22. Tamoxifen for DCIS:
NSABP B-24
n=1804
Stratified by age and +Margins OK
method of detection
(MMG or PE) Extensive calcs OK
Lumpectomy
Lumpectomy
+ RT (50 Gy, no boost)
+ RT (50 Gy, no boost)
+ Tamoxifen x5 yrs
5-year Results
All breast events reduced from 13.4% to 8.2%
Benefit in both ipsilateral and contralateral events
Benefit greatest for women <50 (38% RRR vs 22% RRR)
Toxicities greater in women >50 (TE events, GYN cancer)
Fisher, Lancet, 1999
23. Summary of DCIS Management
Mastectomy or breast conserving therapy
Give RT after BCS for most patients
Reduces local event risk by about one-half
Standard dose is 50 Gy
No evidence for boost, but reasonable for high risk (large, G3)
Consider observation after BCS for select patients
<1 cm size, pure G1-2, with 5-10 mm negative margins, age>60
Consider Tam for all patients, especially
ER+
Age <50 years old
25. Mastectomy vs BCT:
Randomized Trials
Seven randomized trials
In aggregate 4100 patients with 3.3-20 years
follow up
Equivalent disease-specific and OS
Local-regional control
Was not an endpoint for most trials
In-breast recurrences frequently censored
26. Local Control for Mastectomy vs
BCT: Meta-Analysis
Indirect 10-year comparisons suggest that BCT
is equivalent to mastectomy for early stage
disease:
Node Negative
Mastectomy 8.0%
BCS+RT 10.0%
EBCTCG, Lancet 2005
27. BCS vs BCS+RT:
Randomized Trials
BCS BCS+RT
Trial n Yrs IBTR IBTR IBTR N CT/
(%) (%) event stage HT
NSABP B06 1137 20 39.2 14.3 1st N0-1 CT
Britain 400 20 49.8 28.6 any N0-1 both
Ontario 837 10 40 18 1st N0 none
Milan III 579 10 23.5 5.8 any N0-1 both
Uppsala 381 10 24 8.5 any N0 none
NSABP B21 673 8 16.5 2.8 1st N0 HT
Scotland 585 5.7 24.5 5.8 any N0-1 both
28. Local Control with BCS vs
BCS+RT: Meta-Analysis
Node Negative Patients Node Positive Patients
Isolated local recurrence, %
Isolated local recurrence, %
10 yr difference:
10 yr difference:
33% absolute
19% absolute 72% relative
66% relative
Time (years) Time (years)
EBCTCG, Lancet 2005
29. Breast Cancer Survival with BCS
vs BCS+RT: Meta-Analysis
Node Negative Patients Node Positive Patients
Breast cancer mortality, %
15 yr difference:
Breast cancer mortality, %
15 yr difference:
5.1% absolute
16.3% relative 5.1% absolute
16.3% relative
15 yr difference:
7.1% absolute
12.9% relative
Time (years) Time (years)
EBCTCG, Lancet 2005
30. Radiation after BCS Summary
Improves local control by 20-30%
Two-thirds relative risk reduction
Improves breast cancer survival by 5-7%
15% relative risk reduction
Local control gains lead to survival gains!
31. Omission of RT for Widely
Negative Margins: Milan III
Tumor ≤2.5 cm
Quadrantectomy + ALND
Quadrantectomy + ALND
+RT (50 Gy + 10Gy boost)
10-year Results
IBTR 23.5% without RT, versus 5.8% with RT (p<.001)
Veronesi, Annals Oncol 2001
32. Systemic Therapy vs RT for
Favorable Disease: NSABP B-21
Tumor ≤1cm
Node negative
BCS+ALND
Tamoxifen RT
RT + Tam
x 5 years (50 Gy +/-boost)
Primary endpoint: ipsilateral breast tumor recurrence
(IBTR)
Fisher, JCO 2002
33. Systemic Therapy vs RT for
Favorable Disease: NSABP B-21
8-yr IBTRs:
Tam: 16.5%
RT: 9.3%
p<.01
RT+Tam: 2.8%
RT benefited
all age groups
Fisher, JCO 2002
34. PBI Rationale
20-40% of patients do not receive RT after
breast-conserving surgery
proximity of RT facility
duration of standard therapy
>70% of in-breast recurrences are at/near the
tumor bed (Veronesi, NEJM 2002; Liljegren JCO 1999)
Partial breast irradiation has the potential to
Control the tumor
Increase treatment compliance
Minimize side effects
35. PBI versus WBI: RTOG 04-13
DCIS or invasive cancer
Tumor ≤3cm
0-3 positive nodes
Dec 2006: closed to
Breast-conserving surgery low risk patients
(ER+, node-, age>50)
Whole breast irradiation Partial breast irradiation
(45-50Gy in 1.8-2.0Gy fx, (physician chooses 1° endpoint: Local control
+/-boost) technique)
2° endpoints: DF, OS,
cosmesis, side effects
Multi-catheter 3D conformal
MammoSite
brachytherapy external beam RT
(34Gy in 3.4Gy fx BID)
(34Gy in 3.4Gy fx BID) (38.5Gy in 3.85Gy fx BID)
40. Most Data Still Short-Term
Multicatheter brachytherapy:
Long-term Phase I/II data
MammoSite:
Short-term registry data
Short-term Phase II data for DCIS
3D-conformal EBRT:
Short-term Phase I/II data
41. Long-term Data on PBI:
Multicatheter Brachytherapy
William Beaumont Hospital
Phase I/II trial
N=199
Tumor ≤3 cm, N0-1 (82% T1 N0)
Generous volume treated (tumor bed +2cm)
10-yr actuarial breast recurrence rate 3.8%
10-yr actuarial regional nodal failure rate 1.6%
Vicini, IJROBP 2007
42. PBI Summary
PBI may prove to be an important advance in the
treatment of early breast cancer
However, it is still unproven against a highly
effective and minimally toxic gold standard (whole
breast irradiation)
Therefore, it is best administered in the context of a
rigorous clinical trial
Physician support of RTOG 04-13 is crucial to
generate high-quality evidence on PBI
43. PBI Off Protocol
Follow the American Brachytherapy
Society’s eligibility guidelines!
Age ≥50
Infiltrating ductal carcinoma histology
Tumor ≤3 cm, unicentric and unifocal
No EIC
Pathologically node negative
ABS Breast Brachytherapy Task Group, 2007
44. Accelerated Whole Breast RT
Canadian Trial UK Start-B Trial
Whelan, SABCS 2007 Dewar, ASCO 2007
T1-T2 N0 T1-T3 N0-N1
Mostly T1 and age >50 Tumor size, age NA
50 Gy/25 fractions versus 50 Gy/25 fractions versus
42.5 Gy/16 fractions 40 Gy/15 fractions
No boost given Stratified by +/-boost
12-yr results: 5-yr results:
Identical local control Identical local control
Identical overall survival Better cosmesis with
Identical cosmesis 40 Gy/15 fractions
Conclusions:
42.5 Gy/16 fractions is safe & effective for T1 N0 and age >50
Decision to boost is independent of whole breast fx schedule
45. Timing Comparisons
Standard 5 weeks of daily XRT (+/-boost)
Canadian fractionation 4240 cGy in 3 wks
>50yo with T1N0
RTOG Partial Breast Irradiation in 1 week
47. Omission of RT for Elderly
Patients: CALGB C9343
Age ≥70
Tumor ≤2cm
Clinically node negative
ER+ or unknown
BCS, no ALND
Tam + RT
Tamoxifen
(breast and low axilla,
x 5 years
45Gy + 14Gy boost)
Endpoints: LRR, mastectomy, DM, survival
Hughes, NEJM 2004
48. Omission of RT for Elderly
Patients: CALGB C9343
5yr 8yr
LRR LRR
Tam+RT 1% 1%
Tam 4% 7%
p<.001
Trend toward increased mastectomies with Tam only (p=.07)
No difference in DM, breast cancer-specific survival, or OS
Hughes, NEJM 2004; SABCS 2006
49. Omission of RT in Elderly
Patients: SEER-Medicare
8724 women age ≥70 5yr 8yr
IBTR IBTR
CALGB C9343 eligible
No RT 5.1% 8.0%
IBTR rates similar to CALGB
RT 1.1% 2.3%
However:
Higher risk of subsequent mastectomy
without RT (p<.001)
RT most beneficial for women 70-79 with
minimal comorbidity (8 yr IBTR 16% vs 3%)
Smith, JNCI 2006
50. Life Expectancy for the Elderly
Life Expected
Current Expectancy Age at Healthy elderly
Age (years) Death
women are likely
60 23.53 84
70 15.72 86
to live long
75 12.29 87 enough to risk
80 9.22 89 increased
83 7.59 90 relapse of breast
84 6.88 91
85 6.42 91
cancer
Source: Social Security Administration
51. Summary: Management of Elderly
Patients with Early Breast Cancer
Discuss RT with all patients after BCS
Consider omitting RT for
≥70 with T1 N0, ER+ tumors
Fit for and willing to take endocrine therapy x5 years
Omission of RT is probably best reserved for
women age 70-79 with multiple comorbidities
women age >80 (LE <8 years)
For some women, RT may be preferable to HT
53. Main Difference is Nodal Risk
Axillary involvement of 1-3 LNs predicts for:
Involvement of other regional nodes
IIncreasing risk of distant failure and death
Tumor size and location may increase the
regional nodal risk in node-negative
patients
Lymph nodes at risk include axillary, SCV,
ICF, IMN
54. Nodal RT For Intermediate Dz
SCV RT IMN RT
NCCN and ASCO: NCCN:
Category 2B Category 3
recommendation for recommendation for
1-3 +nodes high-risk patients
Insufficient evidence to ASCO:
make any Insufficient evidence to
recommendation in make any
T3 N0 patients recommendation for
any patients
55. Nodal RT for Intermediate
Disease: EORTC 22922
Axillary node+
or central/medial tumor
BCS or mastectomy
RT to RT to breast/CW
breast/CW only + SCV + IM
1° endpoint: Overall Survival
Closed to accrual; results pending
56. Nodal RT for Intermediate
Disease: NCIC MA-20
R RT to
S # of nodes breast
BCS only T removed A
N
N+ or R # of nodes +
D 1° endpoint: Overall Survival
T3 N0 or A Closed to accrual;
chemotherapy O results pending
T2 N0 and T
high risk M
I hormonal
(ER-, Gr3, therapy I RT to
LVSI) F breast+
Z
institution axilla+
Y E SCV+IM
57. Target Delineation: SCV Nodes
SCV Target Depth Conventional prescriptions
Correlates to BMI using 6 MV photons miss
the target in 80% of obese
SCV Depth, cm
patients
For all BMI classes, CT-
delineated targets and
individually optimized
treatment planning
BMI
achieves the best coverage
Liengsawangwong, IJROBP 2007
61. Oxford Overview: Adjuvant CTX
LRR Breast Ca Deaths
LN- Disease
1428 women treated
with mastectomy, AC
8% vs. 3% 28% vs. 31%
chemotherapy +/- RT
Local Recurrence
• 2/3 reduction w/ RT
LN+ Disease
Breast Ca Survival
• none in LN- pts
29% vs. 8% 60%vs. 55% • 5% for LN+ pts
62. Historical Guidelines for XRT
Upfront surgery provided pathology
Pathology was the gold standard
ECOG, MDACC, NSABP
– tumor size over 5 cm (T3)
– 4 or more lymph nodes (N2)
63. Defining LRR Risk after
NCT + Mastectomy
150 patients, 1974-1998 at MDACC
treated on prospective clinical trials
neoadjuvant chemotherapy
modified radical mastectomy
no radiation therapy
Buchholz et al., JCO, 2002
64. Factors Associated with LRR
Clinical Factors Treatment Factors
• clinical stage •tamoxifen use
• T stage
• N stage
Residual Cancer Burden (RCB)
• number of +LN
• primary tumor size
65. Multivariate Analysis
Factors p value hazard ratio
• clinical IIIB/C <0.001 4.5
• 4 or more + LN (ypN2) 0.008 2.7
• no tamoxifen use 0.027 3.9
66. LRR According to Response
5-yr LRR by Path Response
• path CR (n=18) 19%
• residual disease (n=132) 28%
p=0.413
4/18 failures - Stages: T3N0, T2N2, T4N2, T4Nx
67. Recurrences in Clinical Stage I/II
n=67 (LRR 2%)
n=46
(LRR 11%)
n=19
(LRR 29%)
P=0.0057
Garg et al., Int J Radiat Oncol Biol Phys, 2004
69. NSABP B-18
B-18 Study
1230 women with operable breast cancer were
randomized to preop vs postop ACx4
• mastectomy patients did not receive radiation
• 87% of pts in the trial had T1, T2 tumors
• total population of NCT + mastectomy – 239 pts
Mamounas, SABCS, 2003
70. LRR According to Response
10-yr LRR by Path Response (B-18)
• breast CR w/ LN- or LN+ (n=13) 0%
• residual breast disease w/ LN- 10.5%
• residual breast disease w/ LN+ 20.3%
Not much different between 1-3+LN or >4 +LN
71. Is PMRT Necessary after a
Favorable Response to
Neoadjuvant Chemotherapy?
73. Caveats
• Radiation use was not randomized
• Selection of who received radiation
• Excluded recurrences < 2 months of Rx
– 11% of no XRT group excluded
– 3% of XRT group excluded
74. Treatment
Chemotherapy Phase II and III Trials
• All treated with doxorubicin
• Mastectomy: median LN = 15 removed
• Radiation to chest wall and LNs
– median dose 50 Gy
– boost to 60Gy
75. Comparisons Between Groups
Irradiated patients had significantly worse disease:
85
Clinical T3-4 56
44
Clinical N2-3 20 P < .01
Minimal response 24 for all factors
11
39
4 or more pos. nodes 22 RT
12
Close/pos. margins 3 No RT
0 20 40 60 80 100
Percentage of Patients
76. Local-Regional Recurrence
1.0
.8
P < .0001
Rate of LRR
.6
.4
No RT
22%
.2
PMRT
0.0 12%
0 5 10 15
Years
86. CT Simulation For
Breast Radiotherapy
Optimizes target delineation
Tumor bed
Regional nodes
Facilitates patient tailored 3D-conformality
Better coverage of target volumes
Reduces cardiac and pulmonary exposure
Reduces acute effects
May improve cosmetic outcome
87. Traditional Physical Wedges
Wedge acts as a
tissue compensator
for smaller separation
at nipple region,
thereby reducing
anterior hot spots
88. Intensity Modulated
Breast Radiation
Usually involves standard tangent beam
arrangement
Forward or inverse planned MLC segments
Less contralateral breast dose than physical
wedging
Better dose homogeneity than dynamic wedging
Reduces acute effects, which should improve
QOL and cosmesis
89. IMRT Field in Field
Treatment Technique
Forward-planned intensity modulation
Open tangents + 2-8 static MLC-reduced
fields
All fields share same beam orientation
MLC-reduced fields block regions with >100%
of dose
90. Field in Field:
1st MLC Reduction
Highest dose hot Relative weighting of
spot is blocked blocked field is increased
on medial field until hot spot disappears
91. Field in Field:
2nd MLC Reduction
Next highest Relative weighting of
dose hot spot blocked field is increased
is blocked on until hot spot disappears
lateral field
92. Field in Field Technique
Process is repeated
until an optimally
homogenous treatment
plan is generated
No extra work for
physicians (no organ
contouring)
Labor-intensive for
dosimetrists/physicists
93. Inverse Planned IMRT
Standard tangents or multi-
beam
Breast and normal structures
are contoured
Cost functions applied to
critical structures
Reduces dose to heart
if multiple beams are used, low
dose is spread to more normal
tissues
Labor intensive for physicians
Chiu, Med Phys 2002; Krueger, Semin Rad Oncol 2002
94. IMRT versus Wedging:
Canadian Phase III Trial
Breast-only RT
Stratified by breast size
and use of boost
IMRT 50 Gy Wedging 50 Gy
+/-16 Gy boost +/-16 Gy boost
1° Endpoints: Grade 3-4 acute skin reactions
Grade 2-4 moist desquamation
Pignol, ASTRO 2006
95. IMRT versus Wedging:
Canadian Phase III Trial
IMRT arm:
Tangent beams with segment modulation
Most (78%) inverse planned
Wedge compensation arm:
Most treated with dynamic wedging
Skin toxicity assessed by a blinded researcher
Weekly during treatment
Until 6 weeks post-treatment
Pignol, ASTRO 2006
96. Phase III Trial of IMRT vs
Wedging: Results
IMRT reduced moist desquamation:
Moist
WC IMRT p-value
desquamation
Inframammary fold 43% 26% .0012
All quadrants 48% 31% .0019
IMRT reduced any acute skin reaction in the
inframammary fold (OR .262)
Pignol, ASTRO 2006
101. Respiratory Gating for Cardiac
Protection in Breast Radiotherapy
Best technique is deep inspiration breath hold
Displaces heart from tangent field edge
Useful in select left breast cancer patients
Varian RPM system used at MDACC is well
tolerated by patients and only modestly increases
simulation and daily treatment time
105. DIBH and Cardiac Protection
Among early stage left breast cancer patients
receiving tangential breast RT:
Heart V50 Left ventricle V50
(mean) (mean)
FB 3.9% 12.7-14.6%
DIBH 0.7% 1.5-2.7%
p-value <.001 <.001
Krauss, IJROBP 2005
106. DIBH and Cardiac Protection
Among advanced stage left breast cancer patients
receiving comprehensive RT via a 3-field technique
(deep tangents + AP SCV field):
Heart V50 LAD V50 NTCP: cardiac
(median) (median) mortality
FB 19.2% 88.9% 4.8%
DIBH 1.9% 3.6% 0.1%
Korreman SS et al, Radiother Oncol 2005; IJROBP 2006
107. Summary
RT confers LC benefit in node- disease
and a survival benefit in node+ disease
After neoadjuvant chemotherapy, PMRT
for Stage II should consider RCB
108. Summary
Patients with Stage III require PMRT even
after achieving a pCR
Modern technology and imaging permit safe
delivery with minimal toxicity