The document discusses several trials evaluating preoperative chemoradiotherapy versus postoperative chemoradiotherapy or radiotherapy alone for rectal cancer. Some key trials found that preoperative therapy improved local recurrence rates and survival compared to postoperative or no adjuvant therapy. Longer intervals between preoperative radiotherapy and surgery were associated with higher rates of tumor downstaging. Adding oxaliplatin or chemotherapy without radiation improved survival outcomes in some trials. Ongoing studies are exploring chemotherapy alone and targeted agents in rectal cancer.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
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.
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.
Management of renal cell carcinoma - presented at Asian Oncology Summit 2013Siewhong Ho
Dr Ho lectured at the Asian Oncology Summit 2013 in Bangkok on the surgical opinion on management of renal cell carcinoma. He presented to a varied audience of medical oncologist, radiation oncologist, urologists, researchers, para clinical staff and nurses. The most interesting aspect of the lecture was on the role of urologists in management of Stage 4 kidney cancer in the era of 'targeted therapy'. The role of cytoreductive nephrectomy was reviewed potential future developments in this area was discussed
Laparoscopic resections in colorectal malignancies by Dr Harsh Shah (www.gast...Dr Harsh Shah
This presentation explores the role of laparoscopy in comparison to open surgery with respect to oncological & other outcomes in colon & rectal cancer surgeries.
Cette présentation faite le 27 Avril 2017 à l'Hôpital Saint Joseph organisée par le Dr Vincent de Parades fait le point sur les nouvelles approches multidisciplinaires dans la prise en charge des cancers colorectaux en insistant sur la prise en charge de la maladie métastatique hépatique et de la carcinome péritonéale pour terminer sur les nouvelles approches par immunothérapie. Cette EPU a connu un large succès d'audience avec plus de 60 participants. Merci à toutes et tous.
A concise presentation on etiopathogenesis of head and neck cancer, oral potentially malignant disorders and role of epigenetics in head and neck cancer.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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.
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.
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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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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
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.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
- 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
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Rectal cancer chemo and radiotherapy trials
1. PROF.S.SUBBIAH et al
CHEMO AND RADIOTHERAPY
TRIALS IN RECTAL CANCER
Department of Surgical Oncology
Centre for Oncology
GRH,Royapettah
2. PROF.S.SUBBIAH et al
Objectives
• Whether trimodality therapy improves survival
• If CRT should be given pre operatively or post operatively
• Precisely which patients should be irradiated
• Duration of adjuvant therapy
• When to operate
4. PROF.S.SUBBIAH et al
• 7.5 years consecutive series
• 115 pts
• At an average of 4·2 years
postoperatively, three pelvic
recurrences have developed but there
have been no staple-line recurrences in
patients who had "curative" surgery.
5. PROF.S.SUBBIAH et al
Recommendations
• Tendency to "cone" the dissection plane towards the rectal wall
posteriorly and laterally has been condemned by Toddl
• Most rectal carcinomas can be treated without destruction of the
anal sphincters, provided that the mesorectum is completely
excised.
6. PROF.S.SUBBIAH et al
• 1168 patients from 70 hospitals throughout Sweden who were randomly assigned to
treatment groups, 908 (78 percent; 454 in each group) were treated with curative intent
• one week of preoperative irradiation, followed by surgery within the next week
(radiotherapy-plus-surgery group), or to surgery with no additional radiotherapy
(surgery alone group)
8. PROF.S.SUBBIAH et al
• At 5 years follow up, Local recurrence rate was 11% in preop RT group and
27% in surgery only group.
• Translated to both improved OS and cancer specific survival in all Duke’s
stages
9. PROF.S.SUBBIAH et al
• 1805 pts
• SCRT followed by TME versus TME alone
• LRR at 2 years- 2.4% vs 8.2%
• But OS was 82% vs 81.8%
10. PROF.S.SUBBIAH et al
• preoperative short-term
radiotherapy reduced 10-year local
recurrence by more than 50%
relative to surgery alone
• The effect of radiotherapy became
stronger as the distance from the
anal verge increased
11. PROF.S.SUBBIAH et al
• Improved 10-year survival in patients with a negative circumferential
margin and TNM stage III
• For patients with a negative resection margin, the effect of radiotherapy
led to an improved cancer specific survival, which was nullified by an
increase in other causes of death, resulting in similar overall survival
rates
13. PROF.S.SUBBIAH et al
• T3/T4-N+
• 50.4 Gy- 1.8Gy/# plus 5FU –
1000mg/sq.m as 120 hrs continuous
infusion on first and fifth week of RT
• Surgery after six weeks
• Post operatively four five day cycles of
5FU – 500mg/sq.m
• Post op CRT was similar with a 5Gy
boost
14. PROF.S.SUBBIAH et al
• 421 patients were randomly assigned to receive preoperative chemoradiotherapy and
402 patients to receive postoperative chemoradiotherapy.
• The overall five-year survival rates were 76 percent and 74 percent, respectively
(P=0.80).
• The five-year cumulative incidence of local relapse was 6 percent for patients
assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-
treatment group (P=0.006).
• Grade 3 and 4 toxicity with radiotherapy in post op setting
15. PROF.S.SUBBIAH et al
• arm 1, preop RT 45 Gy in 5 weeks
• arm 2, preop RT plus two 5-day CT courses
(fluorouracil 350 mg/m2 /d and leucovorin
20 mg/m2 /d) in the first and fifth week of
RT
• arm 3, preop RT plus four postoperative
CT courses
• arm 4, preop RT and CT plus
postoperative CT
16. PROF.S.SUBBIAH et al
• 1011 patients were entered onto the trial
• 505 received preop RT (arms 1 and 3), and 506 received preop RT-CT (arms
2 and 4).
• Median interval to surgery was 5.4 weeks.
17. PROF.S.SUBBIAH et al
• After preop RT-CT, tumors
were smaller
• Less advanced pT and pN
stages
• Had small numbers of
examined nodes
• Less frequent LVN invasions
• Mucinous tumors increased
after preop RT-CT
18. PROF.S.SUBBIAH et al
• 80 centres in four countries.
• 1350 patients with operable adenocarcinoma of the rectum were randomly assigned
• Short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or
• Initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions
with concurrent 5-fl uorouracil) restricted to patients with involvement of the
circumferential resection margin (n=676).
• The primary outcome measure was local recurrence
19. PROF.S.SUBBIAH et al
• Median follow-up of surviving patients was 4 years.
• 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72
selective postoperative chemoradiotherapy).
• Reduction of 61% in the relative risk of local recurrence for patients receiving
preoperative radiotherapy
• Relative improvement in disease-free survival of 24% for patients receiving
preoperative radiotherapy
• Overall survival did not differ between the groups
20. PROF.S.SUBBIAH et al
• cT3–4 or any node-positive disease randomized to two groups
• A control group receiving standard fluorouracil-based combined modality
treatment, consisting of preoperative radiotherapy of 50·4 Gy in 28 fractions
plus infusional fluorouracil (1000 mg/m² on days 1–5 and 29–33), followed
by surgery and four cycles of bolus fluorouracil (500 mg/m² on days 1–5
and 29);
21. PROF.S.SUBBIAH et al
• Investigational group receiving preoperative radiotherapy of 50·4 Gy in 28
fractions plus infusional fluorouracil (250 mg/m² on days 1–14 and 22–35)
and oxaliplatin (50 mg/m² on days 1, 8, 22, and 29), followed by surgery and
eight cycles of oxaliplatin (100 mg/m² on days 1 and 15), leucovorin (400
mg/m² on days 1 and 15), and infusional fl uorouracil (2400 mg/m² on days
1–2 and 15–16).
22. PROF.S.SUBBIAH et al
• Adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and
adjuvant chemotherapy (at the doses and intensities used in this trial)
significantly improved disease-free survival of patients with clinically staged
cT3–4 or cN1–2 rectal cancer compared with former fluorouracil-based
combined modality regimen (based on CAO/ARO/AIO-94).
24. PROF.S.SUBBIAH et al
• Clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in
25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily
fractions) were randomly assigned to one of the following chemotherapy regimens
• Continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m2 , 5 days per
week), with or without intravenous oxaliplatin (50 mg/m2 once per week for 5
weeks) or
• Oral capecitabine (825 mg/m2 twice per day, 5 days per week), with or without
oxaliplatin (50 mg/m2 once per week for 5 weeks)
25. PROF.S.SUBBIAH et al
• Administering capecitabine with preoperative RT achieved similar rates of
pCR, sphincter-sparing surgery, and surgical downstaging compared with
CVI FU.
• Adding oxaliplatin did not improve surgical outcomes but added significant
toxicity
26. PROF.S.SUBBIAH et al
In conclusion of three trials, STAR -01, NSABP – R04 and ACCORD 12
• No difference in pathological response, sphincter saving or surgical
downstaging
• More grade 3 and 4 adverse events
27. PROF.S.SUBBIAH et al
Lyon R90-01 - Influence of the Interval Between Preoperative Radiation
Therapy and Surgery on Downstaging and on the Rate of Sphincter-Sparing
Surgery for Rectal Cancer
28. PROF.S.SUBBIAH et al
• Population (n = 210) – Carcinoma rectum stage T2-3, NX, M0, were randomized before
radiotherapy
• Intervention (n = 99) – Short interval (SI) surgery (2 weeks)
• Comparator (n = 102) – Long interval (LI) surgery (6-8 weeks)
• Both arms received- total dose 39 Gy/ 3 Gy/fraction in 13 fractions deliveredover 17 days
29. PROF.S.SUBBIAH et al
• Outcomes – Median FU -33 months
• long interval between preoperativeradiotherapyand surgery was associated with a
significantly better clinical tumor response (53.1% in the SI group v 71.7% in the LI
group, P = .007) and pathologicdownstaging (10.3% in the SI group v 26% in the LI
group, P = .005).
• No differences in morbidity, local relapse, and short-term survival between the two
groups.
• No difference in Sphincter sparing surgeries
31. PROF.S.SUBBIAH et al
• The median follow-up was 17.2 years. The 5-, 10-, 15-and 17-year overall survival
rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and,
respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group.
• There were no significant differences between groups in terms of survival or local
recurrences
• The radiation-induced sterilization rate of the preoperative cancer specimen was a
marker of good prognosis. The interval duration (the treatment being the same)
although it is modifying the sterilization rate has no impact on survival
32. PROF.S.SUBBIAH et al
Stockholm III- Optimal fractionation of preoperative radiotherapy and
timing to surgery for rectal cancer ( non inferiority trial)
• Population: Resectable rectal cancer
• Intervention and Comparator:
• 3 arm randomization (n=840) (included grp 1 (n=129), grp 2 (n=128) and grp 3 (n=128))
• 2 arm randomization (n=455) (included grp 1 (n=228) & grp 2 (n=227))
• RT 5x5 Gy + surgery within 1 week (SRT)
• RT 5x5 Gy + surgery after 4-8 weeks (SRT- D)
• RT 25x2 Gy + surgery after 4-8 weeks (LRT-D)
34. PROF.S.SUBBIAH et al
Stockholm III
• Outcomes: 5 year survival
• Median time to recurrence – grp 1 – 33.4 months, grp 2 – 19.3 months, grp 3 – 33.4 months.
• No OS or DFS benefit noted
• Postoperativecomplicationswas similar between all arms when the three-arm randomization was analyzed.
• However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative
complications was significantly lower after short-course radiotherapy with delay than after short-
course radiotherapy (53% vs 41%)
• Short-course radiotherapy with delay to surgery is a useful alternative to conventionalshort-course
radiotherapy with immediate surgery.
35. PROF.S.SUBBIAH et al
Habr-Gamaet al. - Watch and Wait Approach Following Extended
Neoadjuvant Chemoradiation for Distal Rectal Cancer
• Population (n=72): T2-4, N0-2, M0 distal rectal cancer who completed Neoadjuvant
chemoradiotherapy (54 Gy and 5-fluorouracil/ leucovorin delivered in 6 cycles every 21
days). Patients were assessed for tumor response at 10 weeks from radiation completion
• Intervention: Patients with complete clinical response were not immediately operated on
and were monitored
• Comparator: Patients with incomplete clinical response were referred to immediate
surgery.
37. PROF.S.SUBBIAH et al
Habr-Gamma et al.
• Outcomes: MedianFU- 56 months.
• Forty-seven (68%) patients had initial complete clinical response (i.e after 10 weeks). Of these, 8
developedlocal regrowth within the first 12 months of follow-up (17%).
• 39 (57%) sustained complete clinicalresponse (i.e after 12 months).
• An additional 4 patients (10%) developedlate local recurrences (>12 months of follow-up).
• Overall, 35 patients neverunderwent surgery (51%).
38. PROF.S.SUBBIAH et al
The rectal cancer and preoperative induction therapy
followed by dedicated operation (RAPIDO) trail
39. PROF.S.SUBBIAH et al
• It is a multicenter trial (54 centers)
• phase 3 randomized trail
• 920 patients
• Median follow up of 4.6yrs
• Standard vs experimental ( SCRT – Chemo – surgery )
40. PROF.S.SUBBIAH et al
• Primary end point – disease related treatment failure
• At 3yrs - 30.4 % vs 23.7%
• P = 0.019
• Distant metastasis at 3 yrs 26.8% vs 20%
• Over all survival 88.8% vs 89.1%
• pCR is 14.3% vs 28.4%
• Ro resection rates are similar
41. PROF.S.SUBBIAH et al
• Surgical complications are similar ( anastomotic
leaks more in experimental arm but not statistically
significant)
• Quality of life is similar
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PRODIGE 23 – A French trail
• Phase 3 RCT
• N= 461
• Standard vs experimental mFOLFIRINOX – CRT - surgery –
Adjuvant chemo
• Median follow up of 46months
43. PROF.S.SUBBIAH et al
• Primary end point – 3yr
DFS
• 68.5 vs 75.7%
• P=0.019
• pCR – 11.7 vs 27.5%
• 3 yr Metastasis free survival
71.7 vs 78.8%
• 3 yr OS 87.8 vs 90.8%
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Chemotherapy without radiation
• OPRA trial – initiating treatment with chemoRT may improve colostomy
free survival
• FORWARC trial– neoadjuvant FOLFOX without RT had lower rates of
pCR
• PROSPECT trial – ongoing. Chemotherapy alone in stage II or III high
rectal cancer in patients with atleast 20% tumor regression following
neoadjuvant treatment
45. PROF.S.SUBBIAH et al
Targeted agents
• EXPERT-C trial – additition of cetuximab to capecitabine based chemoRT.
Improvement in OS in KRAS exon2/3 wild type tumors
• SAKK41/07 trial – panitumumab in pre operative setting. pCR 53% vs 32%.
More grade 3 toxicity
• RaP/STAR -03 study – pCR not met
46. PROF.S.SUBBIAH et al
cT1-2 N0
• pT1-2,N0 – no further treatment
• pT3,N0
• Observation – less than 2 mm invasion of mesorectum , well or moderately differentiated,
no LVSI, upper rectal
• FOLFOX/CAPEOX – margin neg proximal tumors
• Capecitabine +RT followed by FOLFOX
• pT4/N+- sandwich regimen – chemotherapy + concurrent chemoRT + addn
chemotherapy
• Total duration – 6 months
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• T3, N any with clear CRM and T1-2,N1-2
• chemoRT/ short course RT – transabdominal resection – adjuvant chemotherapy
• long course RT – restaging
• short course RT – within 1 week or > 6 to 8 weeks
Wait and watch
Total neoadjuvant therapy
FOLFOXIRI not recommended
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• cT3, N any + threatened CRM and T4, N any
chemoRT – restaging at 6 weeks
• bulky residue – 12 to 16 weeks chemo restaging and transabdominal
resection and addn chemotherapy
• clear CRM – surgery and adj chemo