En que vamos con el tratamiento neoadyuvante y adyuvante en cáncer de recto?Mauricio Lema
Simposio de coloproctología, 26.05.2018. Hotel Intercontinental Medellín (Basado en presentación realizada en el Simposio ACHO Gastrointestinal, 2017).
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
En que vamos con el tratamiento neoadyuvante y adyuvante en cáncer de recto?Mauricio Lema
Simposio de coloproctología, 26.05.2018. Hotel Intercontinental Medellín (Basado en presentación realizada en el Simposio ACHO Gastrointestinal, 2017).
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
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.
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.
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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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
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.
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.
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
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Marc Bollet : Role of radiation oncologist in neoadjuvant breast cancer treatment
1. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radiotherapy
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014
2. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radiotherapy
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014
3. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radia9on
oncologist
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014
4. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?
8. Contra-‐indica9on
for
breast
conserving
treatment?
Previous
RT
(Hodgkin
Lymphoma)?
Haberer, et al. Bollet, IJROBP 2012
72 women with history of HL 32 BCS (44%) 17 Breast RT with ILD
9. Contra-‐indica9on
for
breast
conserving
treatment?
Precluding
heart
or
lung
co-‐morbidi9es?
Deep Inspiration Breath-Hold
Irradiated
lung & heart↓
CTV to PTV
margin ↓
Synchronization
Saliou et al., Cancer Radiother 2005
10. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?
11. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
HT?
Bollet et al. Radiotherapy&Oncology 2006
40% T4b and/or ≥ 70mm
Med age 71 years
5-OS 85%, 5-RFS 84%, 5-LC 97%
12. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?
13. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?
. H&N SCC +4% in 5-OS
Pignon et al. Lancet 2000
. NSCLC +4% in 2-OS
Schaake-Koning et al. NEJM 1992
. Cervix +6% in 5-OS
Vale et al. JCO 2008
. Anal canal +18% 5-LRC
Bartelink et al. JCO 1997
Radiochemotherapy
Models with proven efficacy
Spatial and temporal collaboration
. Rectum +10% 4-OS
O’Connel et al. NEJM 1994
. Esophagus SCC +25% in 5-OS
Cooper et al. JAMA 1999
14. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?
N
F-‐U
Surg
CT
OS
LRC
Arcangeli
206
5
TCA
CMFx6
NS
NS
IJROBP
2006
Rouësse
638
5
T/M-‐CA
FEC60x4
Seq
NS
NS
IJROBP
2006
FNCx4
Conco
S
for
BCS
Toledano
695
5
TCA
FNCx6
NS
NS
JCO
2006
S
for
pN1
3 randomized studies on concomitant vs sequential radiochemotherapy
in the adjuvant setting for BC
15. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?
LRC
Breast-conserving surgery, pN+
99200A
5-LRC 97% vs 91% p=0.01
Rouesse, de la Lande et al. IJROBP 2006 Toledano, Azria et al. JCO 2007
At the cost of increased acute and late toxicities
ARCOSEIN
5-LRC 97% vs 91% p=0.02
16. No. Stage ChT RT* pCR Epid. Grade 3
%
Formenti et al 35 T3-4 5FU-ci 50 Gy 20 26
IJROBP 1997 Preop 200mg/m2
%
Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?
17. RCC
preop
Ins9tut
Curie
S14
Phase
II,
2001-‐2003,
Unifocal
breast
cancers,
59
women
T2-‐3,
N0-‐1,
M0.
not
ini9ally
amenable
to
breast-‐conserving
surgery
Bollet, Sigal-Zafrani et al. Eur J Cancer, 2006
Age (ans)! Median 49 (31-65)!
Menopausal! pre! 59%!
cT! T2! 73%!
cN! N0! 54%!
Ellis-Elston! Grade 1-2! 75%!
18. FUN 1
FUN 2
FUN 3
FUN 4
RT
Inclusion workup
Preop. workup
MCA TCA RT
Pathological response and HR
No pCR 4 FEC100
HR+ TAM x 5 years
5FU pc 500 mg/m2 D1-D5
Vinorelbine IV 25 mg/m2 D1;D5
Breast, IMC, supra/infra-
clav
50 Gy / 25 f
Normal acute toxicity
Normal compliance
No perop complication
I.Curie S14
19. • Median
9me-‐lapse
before
surgery
– Since
end
of
RT
43
days
(13-‐73)
– Since
biopsy
123
days
(106-‐162)
• 69%
(41
pa9ents)
:
breast-‐conserving
• 31%
(18
pa9ents)
:
mastectomy
• +
axillary
lymph
node
dissec9on
in
all
cases
Abcess in 8% (required surgery in 3%)
Bollet, Sigal-Zafrani et al. Eur J Cancer, 2006
pathological Complete Response = 27%
RCC
neoadjuvant
Ins9tut
Curie
S14
20. RCC
neoadjuvant
Ins9tut
Curie
S14
How
to
evaluate
the
response?
=
MRI,
best
method
RECIST
≥
50%
YES>
50%
chance
of
pCR
NO
<
10%
chance
of
pCR
Bollet, Thibault et al, Int J Radiation Onc Biol Phys 2007
21. RCC
neoadjuvant
Ins9tut
Curie
S14
Long-‐term
Results
Bollet, Belin et al, Radiother Oncol 2012
@ 5 years :
• OS 88% [95% CI 80–97]
• LRC 90% [95% CI 82–98]
• LC 97% [95% CI 92–100]
Toxicity
• 8% with ≥ 1 grade 3 (telangiectasia, fibrosis)
• 31% with ≥ 1 grade 2 (telangiectasia, fibrosis, lymphoedema and dyspnea)
Cosmetic
• 46% without (11%) or only minor modification (34%)
• 11% deformed breast
22. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?
23. S14 Phase II Trial
A histological grade 3 was the only clinicopathological
factor independently associated with pCR (p = 0.004)
Tumors which did not express FGFR1 protein on pretreatment biopsies were more
resistant to chemoradiotherapy than those with FGFR1 expression
The FGFR1 tumoral expression was independent from the proliferative markers (histological grade and
mitotic index), meaning that this gives us an additional information on the tumoral phenotype.
Massabeau, Sigal-Zafrani et al BCRT 2012
RCC
neoadjuvant
Ins9tut
Curie
S14
predic9ve
factors
of
tumour
response
24. RT
in
the
preopera9ve
secng
predic9ve
factors
of
late
toxicity?
Rodningen R&O 2008
TGFβ
Polymorphism
(SNP)
Kelsey IJROBP 2012
Radiation Induced
CD8 Lymphocyte Apoptosis
RILA
Azria Lancet Oncol 2012
25. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?
27. Alle Ding sind Gift und nichts ohn‘ Gift; allein
die Dosis macht, das ein Ding kein Gift ist.
Everything is poison and nothing is poison; only
the dose makes the poison
Paracelsus said
Maybe it is time to bring down some dogma.
Duenas González JCO 2011
Low dose Gemcitabine CDDP
Concomitantly with RT for cervical SCC
Op9misa9on
of
concomitant
CT
28. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?
30. Could
RT
replace
surgery
ader
NA
CT
for
early
breast
cancers?
Neoadjuvant therapy, compared with adjuvant therapy, was associated
with a statistically significant increased risk of loco- regional
recurrence when radiotherapy without surgery was adopted
Mauri et al. JNCI 2005
31. Year of diagnosis
RT
Surgery
165 pts with cCR after 4 cycles of NA CT: 100 RT, 65 surgery (12 mastectomies)
Larger tumours treated with RT
Trend towards younger with RT
Ring et al JCO 2003
5-LR in the no surgery CR/US: only 8%.
32. Rousseau et al JCO 2006
FDG PET capability to predict pCR of NA CT was, after 2 courses, associated with a
sensitivity, specificity, and negative predictive value of 89%, 95%, and 85%
What about now, with MRI, 18 FDG PET-scan?
34. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?
35. Conclusions
. Is there a real contra-indication to a breast RT?
. Could pre-operative RT be called for?
Meeting early with the radiation oncologist could be of value in some cases
Different CT regimen are tested concurrently to RT to ameliorate
therapeutic ratio (Taxanes, Vinorelbine…)
Interesting Neoadjuvant results, and non randomised data in rescue
Optimisation of radiotherapy techniques, and prediction of response
to chemoradiotherapy are warranted
Chemoradiotherapy is an option for Inoperable breast Cancers under
Neoadjuvant chemotherapy (≈2%), and Inflammatory breast cancers (> 5%)
Patients should be refered for surgery whenever possible in a M0 setting
36. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radiotherapy
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014
Merci ! תודה
39. Pourquoi associer RT et CT ?
1. Pas de retard entre initiation de la RT et de la CT
2. Potentialisation de la RT et augmentation du CLR
3. Diminution du temps de traitement global
NSABP : RT-CT conco = 0,5% RLR/an CT puis RT >1% RLR/an
Pourquoi ne pas associer RT et CT ?
1. RT = risque d’impacter le capital médullaire et la dose intensité de la CT
2. Les CT (ex anthracycline) ne sont pas toutes compatibles de façon
concomitante avec la RT
3. Augmentation des toxicités
Bénéfices
et
Risques
théoriques
Kurtz Ann Oncol 1999
40. • Retrospective study, 535 patients
• 109 RT-CT, 276 CT + RT, 106 RT + CT, 44 RT- CT « sandwich »
• Facteurs pronostiques + péjoratifs dans le groupe conco
• Control Local : Conco 92% vs Séquentiel 83% p<0,001
42. RCC
neoadjuvant
Ins9tut
Curie
S14
Acute
Toxicity
% Grade 3 % Grade 4
Epidermite 14 -
Hématologique 24 22
Digestive 12 2
Cardiovasculaire 5* -
* Les 3 patientes l’ont eu pendant leur premier cycle de ChT,
avant le début de la radiothérapie
Bollet, Sigal-Zafrani et al. Eur J Cancer, 2006
43. • No
per-‐op.
or
immediately
post-‐op.
complica9on
• Median
hospital
stay
7
days
(3-‐12)
• 5
abcesses
– 2
with
drainage
• 2
hematomas
• 34%
lymphocele
aspira9on
RCC
neoadjuvant
Ins9tut
Curie
S14
Post-‐op.
Toxicity
44. RCC
neoadjuvant
Ins9tut
Curie
S14
compliance
• Chemotherapy
weekly
dose-‐intensity
median
(%
theorical
dose)
– 5
Fluorouracil
98
61-‐112
– Vinorelbine
98
50-‐105
• Radiotherapy
– Median
breast
Dose
(Gy)
50
46-‐52
– Treatment
interrup9on
>
7
d
8%
Median
2
days
2-‐15
46. « We believe that the only realistic benefit that one can expect using concurrent
chemotherapy with radiotherapy is improvement in local control rates… »
« we must consider late toxicity after BCT as an
important end- point in breast cancer clinical trials »
47. Adjuvant breast cancer treatment : The longer is not the better !
Toledano et al. Cancer Radiother 2008
Reflexion on treatment duration : The shroter seems
to be better for patients, but …
48. . The ARCOSEIN « late toxicities and Cosmesis »
evaluated population
. 120 reassessed for depression
. 8,1 years Follow Up
. 6.7% with probable depression,
and 12.5% with possible depression.
49. . Adjuvant Chemoradiotherpy :
. Rational
. 3 Phase III randomized trials
. Late toxicities and cosmetic effects
. Neoadjuvant Chemoradiotherapy :
. Breast Conservative treatment
. Preoperative rescue
. Biological selection of patients candidats
PLAN
. Novel chemotherapies regimen (phase II trials)
50. « We believe that the only realistic benefit that one can expect using concurrent
chemotherapy with radiotherapy is improvement in local control rates… »
« we must consider late toxicity after BCT as an
important end- point in breast cancer clinical trials »
51. Adjuvant breast cancer treatment : The longer is not the better !
Toledano et al. Cancer Radiother 2008
Reflexion on treatment duration : The shroter seems
to be better for patients, but …
52. . The ARCOSEIN « late toxicities and Cosmesis »
evaluated population
. 120 reassessed for depression
. 8,1 years Follow Up
. 6.7% with probable depression,
and 12.5% with possible depression.
53. . Adjuvant Chemoradiotherpy :
. Rational
. 3 Phase III randomized trials
. Late toxicities and cosmetic effects
. Neoadjuvant Chemoradiotherapy :
. Breast Conservative treatment
. Preoperative rescue
. Biological selection of patients candidats
PLAN
. Novel chemotherapies regimen (phase II trials)
54. No. Stage ChT RT* pCR Epid. Grade 3
%
Formenti et al 35 T3-4 5FU-ci 50 Gy 20 26
IJROBP 1997 Preop 200mg/m2
Formenti et al. 44 IIB-III Paclitaxel 45 Gy 16 7
JCO 2003 Preop
Kao et al. 16 IIIB-C VLB + P 60 Gy 46 50
IJROBP 2004 Preop or P
* Breast + Lymph nodes
%
Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
other
regimens
of
CT?
Bollet et al. 59 IIB-III FU-N 50 Gy 27 17
EJC 2006 Preop
55. Bellon et al. IJROBP 2000
A
retrospec9ve
study
of
concurrent
RT
and
taxanes
(pacli
or
doce)
in
high
risk
BC
57. CT (4 AC60)
RT-CT (12 Paclitaxel weekly 60 mg/m2)
RT-CT (4 Paclitaxel 135-175 mg/m2/ 3 weeks)
Surgery
Skin Toxicity (no G3-4)
Lung Toxicity (P hebdo)
RT interruption 25%
Burstein et al., IJROBP 2006
phase II trial
40 patients breast cancer stage II-III
RT (1.8 Gy/#) DT 39,6Gy (breast) 45Gy (chest wall)
Concurrent treatment with weekly paclitaxel and
radiation therapy is not feasible (…) Concurrent
treatment using a less frequent paclitaxel dosing
schedule may be possible, but caution is
warranted in light of the apparent possibility of
pulmonary injury
A
phase
II
trial
of
adjuvant
concurrent
RT
and
paclitaxel
58. CT (4 AC60)Surgery RT-CT (4Taxol 175 mg/m2/ 3 weeks)
Chen et al., IJROBP 2012
44 patients
39.6 Gy / 22# + 14 Gy / 7#
Median F-U > 6y
The 5-DFS 88%, 5-OS 93%, 5-LC 100%
No cases of radiation pneumonitis
No significant change in the diffusing capacity for carbon monoxide either
immediately after RT or with extended F-U.
Acute Grade 3 skin toxicity in 2 pts. Late cosmesis was not adversely affected.
Conclusions: excellent LC & well tolerated.
A
phase
II
trial
of
concurrent
RT
and
paclitaxel
ader
BCS
in
pN+
BC
59. CT (3 FEC100) RT-CT (9Docetaxel 35mg/m2/week)
Chow et al., Acta Oncol 2014
32 patients
45 Gy / 25# + (5.4Gy/3# or 9Gy/5#)
A
phase
II
trial
of
concurrent
RT
and
weekly
docetaxel
Early close due to high rate of symptomatic radiation pneumonitis
17 (55%) symptomatic radiation pneumonitis (RP).
8 (25%) grade 3 pneumonitis
1 (3%) grade 5, died of acute respiratory distress syndrome associated with RP
60. Ismaili et al., BMC Res Notes 2010
6 cycles of (AC60, FAC50; FEC75) or CMF
After mastectomy or BCT, the adjuvant
treatment based on RT and concurrent
anthracycline CHT (vs CMF) reduced
breast cancer relapse rate, and
significantly improved LRFS, EFS and OS
in the patients receiving more than 1 cycle
of concurrent CT. There were more
hematologic and non hematologic toxicities
in the anthracycline group
61. Concomitant adjuvant chemo-radiation therapy with anthracycline-based
regimens in breast cancer: a single centre experience
Livi L, Meattini I, Scotti V, Saieva C, Simontacchi G, Marrazzo L, Franzese C, Cassani S, Paiar
F, Di Cataldo V, Nori J, Jose Sanchez L, Bianchi S, Cataliotti L, Biti G.
PURPOSE:
This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline
(AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the
impact of treatment interruptions and the feasibility of this uncommon therapeutic approach
.MATERIALS AND METHODS:
From September 2002 to December 2007, 60 patients were treated at our Centre.
The mean age at presentation was 48.5 (range 38-64) years. All patients underwent conservative
surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46-52 Gy). AC-based
regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of
epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil
(CMF).
RESULTS:
Concomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4
toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed
an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value.
Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients.
CONCLUSIONS:
In our experience, concomitant chemotherapy did not emerge as a significant factor in
radiotherapy interruption. Moreover, no severe cardiac events were recorded.
63. 5FU pc 500 mg/m2 J1 à J5
Vinorelbine IV 25 mg/m2 J1 et J5
RT – CT (4 FUN) à Surgery à 4 FEC 100
Phase II, 2001-2003
Unifocal breast cancers, T2-3, N0-1, M0.
Conservative surgery impossible
60 patients assessed, 59 evaluables
BCS was performed in 69% (n=41) patients !
64. « Progression of inoperable breast cancer under NACT is a rare event (less than 2%) for which
XUN/FUN-based chemo-radiotherapy could be proposed as locoregional ‘‘rescue’’ therapy »
65.
66.
67. A feasibility study of neo-adjuvant low-dose fractionated radiotherapy with two different
concurrent anthracycline-docetaxel schedules in stage IIA/B-IIIA breast cancer.
Nardone L et al.
Tumori. 2012 Jan-Feb;98(1):79-85.
AIMS AND BACKGROUND:
The aim of the study was to evaluate the feasibility of neoadjuvant low-dose fractionated radiotherapy, in combination
with two anthracycline-docetaxel regimens, in breast cancer treatment.
MATERIALS AND METHODS:
Women with stage IIA/B-IIIA breast cancer were assigned to receive the treatment of low-dose fractionated radiotherapy
(0.4 Gy/per fraction, 2 fractions per day, for 2 days, every 21 days for 8-6 cycles) with concomitant neoadjuvant
chemotherapy with non-pegylated liposomal doxorubicin and docetaxel. Two chemotherapy schedules were planned to
be combined with low-dose fractionated radiotherapy. The first schedule consisted of four cycles of non-pegylated
liposomal doxorubicin sequentially followed by four cycles of docetaxel, and the second schedule consisted of six
cycles of non-pegylated liposomal doxorubicin plus concomitant docetaxel. Acute toxicity was evaluated according to
the Radiation Therapy Oncology Group score system. Pathological response was evaluated by the Mandard score and
expressed as tumor regression grade.
RESULTS:
Between March 2008 and February 2009, 10 patients underwent low-dose fractionated radiotherapy and concomitant
chemotherapy. No grade 3-4 breast toxicity was observed. Five patients had a clinical complete response. Seven
patients underwent conservative surgery. Overall, tumor regression grade 1 (absence of residual cancer) was achieved
in one patient (10%) and grade 2 (residual isolated cells scattered through the fibrosis) in 4 patients (40%). The
pathologic major response rate (tumor regression grade 1 + 2) was 20% in patients receiving low-dose fractionated
radiotherapy and sequential non-pegylated liposomal doxorubicin and docetaxel and 80% in the group receiving low-
dose fractionated radiotherapy and concurrent non-pegylated liposomal doxorubicin and docetaxel treatment.
CONCLUSIONS:
Concomitant low-dose fractionated radiotherapy combined with anthracycline and docetaxel is feasible. The toxicity
profile of radio-chemotherapy was similar to that of chemotherapy alone: there was no acute skin or cardiac toxicity.
The concurrent application of liposomal doxorubicin and docetaxel with low-dose fractionated radiation led to higher
histological response rates compared to the sequential application of the same two drugs.