This document discusses hypofractionation in the treatment of head and neck cancers. It begins by outlining outcomes for different stages of disease, then discusses how fraction size, total dose, and treatment time impact treatment. Hypofractionation can counter tumor repopulation and improve local control. Studies show hypofractionation is effective for early disease, palliative cases, and can be safely delivered using simultaneous integrated boost with IMRT. Severe toxicity is low while disease control remains high. Extreme hypofractionation with SBRT also provides good local control with acceptable toxicity.
the role of brachytherapy in oral cavity carcinoma.
physics of brachytherapy
radiobiology of brachytherapy
clinical application in tongue, buccal mucosa cancer
Dose to the Dysphagia/Aspiration-Related Structures (DARS) is critical to ensure proper swallowing functions to the patients after IMRT to the head and neck region
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
Management of cacrinoma cervix: Techniques of radiotherapy (2D conventional, 3D Conformal radiotherapy (3DCRT) and IMRT with a review of various contouring guidelines.
the role of brachytherapy in oral cavity carcinoma.
physics of brachytherapy
radiobiology of brachytherapy
clinical application in tongue, buccal mucosa cancer
Dose to the Dysphagia/Aspiration-Related Structures (DARS) is critical to ensure proper swallowing functions to the patients after IMRT to the head and neck region
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
Management of cacrinoma cervix: Techniques of radiotherapy (2D conventional, 3D Conformal radiotherapy (3DCRT) and IMRT with a review of various contouring guidelines.
Radiotherapy and Cetuximab in head and neck cancer.pptxNamrata Das
Radiotherapy and Cetuximab in head and neck cancer
Bonner trial
RTOG 0522
TREMPLIN
RTOG 1016
De-Escalate trial
TROG
HN.6
PembroRAD
Nimotuzumab
Panitimumab
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 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
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
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
- 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
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.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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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
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
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Hypofractionation in hnc
1. HYPOFRACTIONATION IN HEAD AND
CANCERS: AN OVERVIEW
Dr. Ashutosh Mukherji
Additional Professor
Department of Radiotherapy,
Regional Cancer Centre, JIPMER
2. Outcomes
• Stages I and II
– 1/3 of patients
– Curative results: 60% to 80%
– SPTs: greater risk than recurrence
• Stages III and IV
– 2/3 of patients
– Multimodal treatment
– 40% to 80% local recurrence
– 10% to 30% distant disease
3. Treatment of head and neck cancers is influenced by
– fraction size,
– total dose
– overall treatment time
• The total radiation dose has demonstrated a direct
impact to the tumor response as well as to the acute
or late adverse events.
• For H&N cancer, most Authors suggest that
repopulation begins only after a Tk of about 3–5
weeks after the start of radiotherapy
3
4. Why Hypofractionation: Accelerated
repopulation
• Occurs after 3-4 weeks for squamous carcinomas
• Up to 0.6 Gy of each daily dose would be “wasted”
due to increased tumor cell load
• Withers et al. report that, a dose increment of
approximately 0.6–0.7 Gy per day is required to
counterbalance tumor repopulation and keep tumor
control rates unchanged for OTTs times up to 55 days
• For each extra day, local control would decrease by
1% due to accelerated repopulation
4
6. HYPOFRACTIONATION: RENEWED INTEREST
• 1) In tissues with α/β similar to late responding tissues e.g. prostate
• 2) Acceleration is better achieved by hypofractionation than
hyperfractionation since late normal tissue repair is a limiting factor
• 3) IMRT, tomotherapy & proton therapy result in improved dose
distributions with minimal normal tissue receiving high dose
• 4) Carbon ion beams – better dose distribution/high LET
• Economical
• Late normal tissue damage
7. LINEAR QUaDRATIC MODEL
• A lethal event is supposed to be
caused by one hit due to one
particle track (the linear
component αD)
or
• Two particle tracks (the quadratic
component βD2)
• Dual radiation action
• First component - cell killing is
proportional to dose
• Second component - cell killing is
proportional to dose squared
8. • Carcinomas of
the head and
neck and lung,
it is higher
• Melanomas,
sarcomas,
prostate cancers
etc it’s low
10. Why Hypofractionation: Intrinsic
radiosensitivity
• Tumors can have variable degrees of radiosensitivity.
• Range from highly radioresistant (melanoma, renal
cell carcinoma) to Highly radiosensitive (lymphomas)
• Based on the extent of sub-lethal damage repair
10
11. Hypofractionation
• Total dose delivered in a few high dose fractions with
longer intervals between fractions
• Higher exposure increases tumour response
• Acute normal tissue reactions not increased
• Late normal tissue reactions increased
12. EUD
Standard dose
constraints assume that
the whole organ is
being uniformly
irradiated at 1.8-2Gy/#.
In IMRT, aside from use
of higher dose/# (in
SIB), most OARs are
only partially irradiated.
There is also a steep
dose gradient within a
given OAR.
Equivalent Uniform
Dose (EUD) is that dose,
which had the organ
been wholly and
uniformly irradiated,
would have produced
the same biological
effect.
Complex voxel-based
calculation.
13. • Fowler’s formula used to calculate equivalent doses from
various hypofractionated regimens
• RE = (1 + d /a/β) where n is the fraction number; d the
fraction dose and α and β coefficients describe the
contribution to cell killing from linear and quadratic
components, respectively
13
14. HYPOFRACTIONATION IN HNC: WHAT DO WE DISCUSS
• Hypo# in Palliative setting
• Hypo# in Definitive setting: accelerated
regimes
• Hypo# in Definitive setting: SIB regimes
• Hypo# in Definitive setting: SBRT
14
15. Hypofractionation in Palliative setting
• phase II prospective study of 3.7 Gy BID times 4 over 2 days
(the “Quad Shot”) by Corry et al.
• This Quad Shot was then repeated at monthly intervals times
3, if patients did not progress or decline clinically.
• Median survival was 5.7 months. No grade 3 or more toxicity
noted.
• The tumor RR was 53% and 44% of patients had QOL
improvements.
15
16. Outcomes of response adapted therapy
Radiotherapy and oncology, 2004
Overall the RR for
those receiving
palliative radiation
was 37% with 47-
59% palliation of
symptoms.
17. • Study by Das et al, CMC Vellore
• All patients had advanced head
and neck cancers (27% IVA, 61%
IVB, 9% IVC, TNM stage and 3%
recurrent disease).
• Grade 3 mucositis and
dermatitis and pain was 18%,
3%, and 24%, respectively.
• Reduction of pain was observed
in 88% patients and 60%
patients had improvement of
performance status.
• Median overall survival of the
cohort was 7 months.
17
19. Bledsoe et al: SCAHRT in HNC for the Elderly or Infirm
ANTICANCER RESEARCH 36: 933-940 (2016)
• Patients received two courses of 30 Gy/10 fractions separated by
3-5 weeks to allow for toxicity recovery.
• 58 out of 65 patients (89%) completed both courses of treatment.
• Patients without metastatic or recurrent disease were evaluated
for treatment response and survival (n=39).
• Among this group, total tumor response was 91%, and median
locoregional failure-free survival and overall survival were 25.7
and 8.9 months, respectively.
• Study concluded that high risk patients unable to tolerate
continuous-course definitive (chemo)radiation can safely be
treated by SCAHRT to achieve durable locoregional disease
19
20. Group I Group II Group III
50Gy/ 15fr/
3wks
(3.3Gy/fr)
60-62.5Gy/24-
25fr/5wks
(2.5Gy/fr)
50-60Gy / 25-30Fr/
5-6wks
(2-2.5Gy/fr)
• Acceptable local control
• Acceptable late complication
• No difference in either groups
Early Glottic Ca : Stage I / II
Dinshaw et al IJRO BP 48(3) 723-35, 2000
(1975-89)
Less protracted schedules can be used
21. Hypofractionation
for early glottic cancers
Yamazaki et al (2006)
• N=180
• T1N0M0
• 5-year LCR 77% (conv) vs
• 92% (hypo) (p=0.004)
• No significant difference in
survival
• No significant difference in
acute/ late toxicities.
Int. J. Radiation Oncology Biol. Phys.,
Vol. 64, No. 1, pp. 77–82, 2006
• KROG-0201 (2013)
• N=156; T1-T2N0M0
• 5-year LFPS 77.8%(conv) vs
• 88.5%(hypo) (p=NS)
• 5-year LFPS for T1a 76.7%
(conv) vs 93% (hypo) (p=0.056)
• No significant difference in
survival
• No significant difference in
acute/ late toxicity
Moon et al. Radiotherapy & Oncology,
2013 (ahead of print) 21
22. 22
The local control curve for all patients.
The local control rate was 91.9% at 3
years and 89.8% at 5 years
The overall survival rate (OAS)
curve. The OAS was 96.8% at 3
years and 90.8% at 5 years.
Radiotherapy for Glottic T1N0
Carcinoma with Slight
Hypofractionation and Standard
Overall Treatment Time:
Importance of Overall Treatment
Time
Jpn J Clin Oncol 2011;41(1)103–109
25. Accelerated Hypofractionation
Retrospective study from Birmingham UK
• N=81; Stage II-IV SCCHN
• EBRT 55Gy/20#/4 weeks with concurrent
chemotherapy (MTX/ Carboplatin)
• Impressive disease outcomes:
– 2yr LCR=75.4%; DFS rate=68.6%; OS rate=71.6%
• Acute toxicities were tolerable. No unexpected late
toxicities at 24-month FU
Sanghera et al. Int J Radiat Oncol Biol Phys 2007 67;5:1342-51
25
27. • RTOG H-0022 trial for oropharyngeal carcinomas SIB-
IMRT in head and neck cancer, the use of 2.0, 2.11 or
2.2 Gy per session is highly effective and safe with
respect to tumor response and tolerance.
• The overall radiation therapy treatment time plays an
important role, since every single one day
prolongation of treatment beyond 30 days leads to
loss of tumor control
27
28. SIB-IMRT/SMART vs sequential
IMRT
• Dosimetric advantage: Superior PTV conformality & superior
parotid gland sparing. Dogan et al (2003)
• Logistical advantage : lesser number of treatment days
required.
• Radiobiogical advantage: Due to higher dose/# (to the target)
and lesser duration of treatment, the NTD (Normalised Total
Dose=EQD2) is actually higher than the Nominal Dose.
29. SIB vs SEQ-B• Retrospective matched cohort
analysis on patients with LAHNC
treated with definitive
chemoradiotherapy to 69.3 Gy in 33
fractions. Treatment was delivered
via sequential boost (n = 68) or SIB
(n = 141)
• At 4 years, the OS was 69.3% in the
sequential boost cohort and 76.8%
in the SIB cohort (p = 0.13). Disease-
free survival was 63 and 69%
respectively (p = 0.27).
• Rates of acute grade 3 or 4
dysphagia (82% vs 55%) and
dermatitis (78% vs 58%) were
significantly higher in the SIB group
(p < 0.001 and p = 0.012
respectively).
29
Vlacich et al. Radiation Oncology (2017) 12:13
31. SIB-IMRT vs Concomitant Boost RT (CBRT)
(MSKCC, 2006)
Study period Sep 1998- Jun 2004
N=293
All were patients of Ca oropharynx (112 were stage
III/IV).
41 received SIB-IMRT with concurrent chemotherapy
71 received conventional 2DRT with late concomitant
boost (CBRT) along with concurrent chemotherapy
RT dose was 70 Gy. Parotid dose constraint for IMRT was
mean dose <=26 Gy.
Significant advantage in terms of PEG-dependancy &
severe xerostomia at 2 years, in favour of IMRT.
Nancy Lee, et
al
42. RTOG 00-22 (2010)
N=69 (14 institutions)
All patients of Ca oropharynx, stage T1-T2,N0-N1,M0
No chemo was permitted
RT dose was 66Gy/30# to PTV(gross disease) and 54-
60Gy/30# to PTV (subclinical)
Median FU=2.8 years
2-yr LRF was only 9%.
Very low rate of severe (>grade 2) late toxicities: skin
(12%), mucosa(24%). Xerostomia (grade 2) was seen in 55%
patients at 6 months but reduced to 16% at 2 years
Moderately hypofractionated IMRT without chemotherapy
in early oropharyngeal carcinomas, is safe & well-tolerated.
43. • SIB-IMRT with conc chemotherapy is well-
tolerated and effective for all common head-
neck sites.
• Trials included mostly locally advanced cases.
• Locoregional failure rates are around 5-20%.
• Overall survival rates are around 60-85%.
• 2-yr severe xerostomia rates are around 0-
30%.
45. EXTREME HYPOFRACTIONATION: SBRT
• Fractionated SBRT allows for delivery of highly
conformal treatment of targets that are in close
proximity to critical structures.
45
46. • Radiobiologically, the higher dose per fraction with SBRT- based
treatments has been shown to provide improved local control
over standard fractionation.
• According to QUANTEC guidelines, spinal SBRT partial cord
irradiation max dose constraint is reported at 13 Gy for single
fraction treatment and 20 Gy for three fractions treatment is
thought to be associated with <1% risk for myelopathy.
• Typical re-irradiation dose constraints derived from the Pittsburgh
and Georgetown series prescribe spinal max point ≤8Gy in one
fraction and ≤ 12Gy in two fractions but these are based on re-
irradiation SBRT.
• SBRT is effective for recurrent head and neck patients previously
irradiated, but for patients with tumors encompassing the carotid
artery, SBRT hypofractionation should be considered cautiously.
IMRT or VMAT may be better options.
46
48. University of Pittsburgh Medical Center (UPMC) conducted a Phase I
dose escalation study to determine the maximum tolerated dose
(MTD) for SBRT in recurrent, unresectable SCCHN.
Doses of 15 – 44 Gy (median dose of 35 Gy) were delivered with
fraction sizes of 4-18 Gy. The median follow up for all patients was six
months (1.3 – 39 months).
1 and 2-year local control rates were 51.2% and 30.7%, respectively;
and 1 and 2-year overall survival rates were 48.5% and 16.1 %,
respectively.
Those patients who received SBRT < 35 Gy had significantly lower
local control than those with ≥35 Gy at 6 months median follow-up
time.
48
51. • Hypofractionation has emerged as a viable
alternative in breast, prostate & lung cancers
• It may be better tolerated & even more effective
• Aside from tumor DNA damage, the extra
effectiveness of hypofractionation may be due to its
anti-angiogenic effect on microenvironment
vasculature
51
52. • IMRT allows parotid gland sparing and less
xerostomia ? Better QoL
• IGRT allows margin reduction less normal tissue
irradiation? Better QoL
• Advanced imaging techniques and delineation
protocols also mean more accurate targeting
• With these advances SIB-IMRT can improve upon
treatment responses and OTT.
• SBRT can help especially in reirradiation or even
primary irradiation of very small volumes.
52