A multidisciplinary approach that includes surgery, medical oncology, and radiation oncology is required for optimal treatment of patients with rectal cancer
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.
A multidisciplinary approach that includes surgery, medical oncology, and radiation oncology is required for optimal treatment of patients with rectal cancer
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.
Carcinoma rectum the complete aproach to how to investigate and treat a case ...nikhilameerchetty
this is a complete guide to the understanding of the anatomy clinical features and the latest investigation to the most modern methods of treating the case of carcinoma rectum , all the latest journal published and the ongoing trials hav been searched and incorporated
Surgery of Rectal Cancer : Potentials and Limitations - Dimitris P. KorkolisDimitris P. Korkolis
EPIDEMOLOGY
2015 Estimates
New cases: 96,830 (colon); 40,000 (rectal)
Deaths: 50,310 (colon and rectal combined)
Death rate over last 20 years declining
Screening and improvements in treatment
In Depth review of the Surgical management of esophageal carcinoma including management overview, endoscopic management, Type of surgeries, Open, and minimally invasive, Extent of lymphadenectomy. Literature review of evidence for type of surgery and complications
GB cancer is the 5th most common GIT malignancy(worldwide).200 years later it is still considered to be a highly malignant disease with a poor survival rate
.Here is a brief description regarding
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!
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
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
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.
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.
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.
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
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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3. Transrectal ultrasound –EUS
use for clinical staging.
80-95% accurate in tumor staging
70-75% accurate in mesorectal lymph
node staging
Very good at demonstrating layers of
rectal wall
Use is limited to lesion < 14 cm from
anus, not applicable for upper rectum,
for stenosing tumor
Very useful in determining extension of
disease into anal canal (clinical
important for planning sphincter
preserving surgery)
Figure. Endorectal
ultrasound of a T3 tumor of
the rectum, extension
through the muscularis
propria, and into perirectal
fat.
4. CT scan
Part of routine workup of patients
Useful in identifying enlarged pelvic lymph-nodes and
metastasis outside the pelvis than the extent or stage of
primary tumor
Limited utility in small primary cancer
Sensitivity 50-80%
Specificity 30-80%
Ability to detect pelvic and para-aortic lymph nodes is
higher than peri-rectal lymph nodes.
5. Figure: Mucinous adenocarcinoma of the
rectum. CT scan shows a large
heterogeneous mass (M) with areas of
cystic components. Note marked luminal
narrowing of the rectum (arrow).
Figure: Rectal cancer with uterine
invasion. CT scan shows a large
heterogeneous rectal mass (M) with
compression and direct invasion into the
posterior wall of the uterus (U).
6. Magnetic Resonance Imaging (MRI)
Greater accuracy in defining extent of rectal cancer
extension and also location & stage of tumor
Also helpful in lateral extension of disease, critical in
predicting circumferential margin for surgical excision.
Different approaches (body coils, endorectal MRI)
11. Stage and Prognosis
Stage 5-year Survival (%)
0,1 Tis,T1;No;Mo > 90
I T2;No;Mo 80-85
II T3-4;No;Mo 70-75
III T2;N1-3;Mo 60-70
III T3;N1-3;Mo 50-65
III T4;N1-2;Mo 25-45
IV M1 <10
12. Prognostic factors
Good prognostic
factors
Old age
Gender(F>M)
Asymptomatic pts
Polypoidal lesions
Diploid
Poor prognostic
factors
Obstruction
Perforation
Ulcerative lesion
Adjacent structures
involvement
Positive margins
LVSI
PNI
Signet cell carcinoma
High CEA
Tethered and fixed
cancer
13. PRINCIPLES OF PATHOLOGIC
REVIEW
The following parameters should be reported:
Grade of the cancer
Depth of penetration (T), the T stage, is based on
viable tumor.
Acellular mucin pools are not considered to be
residual tumor in those cases treated with
neoadjuvant therapy.
Number of lymph nodes evaluated and number
positive (N).
14. Acellular mucin pools are not considered to be
residual tumor in those cases treated with
neoadjuvant therapy
Status of proximal, distal, and circumferential
(radial) margins.
A positive circumferential resection margin (CRM)
has been defined as ≤1 mm
Neoadjuvant treatment effect
Lymphovascular invasion
Perineural invasion
Extranodal tumor deposits
17. Surgery
Surgery remains the mainstay of curative
treatment for carcinoma of the rectum
Surgical management depends on the stage
and location of a tumor within the rectum.
18. GOAL
The general principles of a surgical approach
remain the removal of all gross and microscopic
disease with negative proximal, distal, and
circumferential margins
reserve intestinal continuity and the sphincter
mechanism whenever possible while still
maximizing tumor control
19. Early cancers can be managed with limited
surgery
majority of tumors tend to present as more
advanced disease
require either a low anterior resection (LAR) or
abdominoperineal resection (APR).
20. Local Excision
Polypectomy
Transanal excision
Transanal endoscopic microsurgery (TEM)
patients need to be carefully selected for these
procedures
21. Transanal Excision
selected T1, N0 early-stage cancers.
Small (<3 cm)
well to moderately differentiated tumors
within 8 cm of the anal verge
limited to less than 30% of the rectal
circumference
no evidence of nodal involvement
22. transanal excision and TEM involve a full-
thickness excision performed perpendicularly
through the bowel wall into the perirectal fat.
Negative (>3 mm) deep and mucosal margins are
required, and tumor fragmentation should be
avoided.
The excised specimen should be oriented and
pinned before fixation
brought to the pathologist by the surgeon to
facilitate an oriented histopathologic evaluation of
23. Advantages of a local procedure include minimal
morbidity (eg, a sphincter-sparing procedure) and
mortality
rapid postoperative recovery.
If pathologic examination reveals adverse
features
positive margins, LVI, poor differentiation, or
invasion into the lower third of the submucosa
a more radical resection is recommended
24. Limitations of a transanal excision include the
absence of pathologic staging of nodal
involvement
lymph node micrometastases are both common in
early rectal lesions and unlikely to be identified by
endorectal ultrasonogram or MRI
A recent retrospective study of 282 patients
undergoing either transanal excision or radical
resection for T1 rectal cancer from 1985 to 2004
showed respective local recurrence rates of
13.2% and 2.7% for these 2 groups
25. Transabdominal Resection
Abdominoperineal Resection
APR has been considered the gold standard for
surgical resection of distal rectal cancer located within
6 cm of the anal verge.
This procedure requires a tranabdominal as well as a
transperineal approach with removal of the entire
rectum and sphincter complex.
A permanent end colostomy is created and the
perineal wound either closed primarily or left to
granulate in after closure of the musculature
26. APR is associated with a slightly higher morbidity and
mortality than LAR
a worse quality of life related to changes in body
image and depression due to the presence of a
colostomy
There is also a higher risk of positive margins with
APR as the mesorectum is very thin in the distal
segment of the rectum
lateral margins are restricted by the close presence of
the prostate in the male and vagina in females
The bony confines of the lower pelvis also restrict
surgical access especially in males.
27. Low Anterior Resection
The availability of circular stapling devices has
expanded the role of sphincter preservation
surgical options in rectal cancers
LARs are now being performed not just for
cancers of the upper third of the rectum but also
for middle and lower third cancers
Preserving adequate anorectal function becomes
a bigger problem the more distal the level of
anorectal anastomosis
28. Patients should have good anal sphincter
continence prior to considering sphincter-
preserving options
A 2-cm distal margin of preserved normal rectum
is considered optimal for preservation of good
bowel function.
In carefully selected patients a functional coloanal
anastomosis can be achieved with significantly
reduced margins for more distal cancers
especially after neoadjuvant therapy.
29. Advances in stapling instruments have been very
important as aids in reconstruction.
Narrow, low-profile staplers allow the surgeon to
place a staple line across the rectum at the level
of the anorectal ring or below.
This, combined with the circular stapler, allows
the surgeon to construct a quick and reliable
“double-stapled” anastomosis even at the level of
the anal canal.
30.
31. Total Mesorectal Resection
In the rectum the mesorectum is the structure that
contains the blood supply and lymphatics for the
upper, middle, and lower rectum.
Most involved lymph nodes for rectal cancers are
found within the mesorectum
T1 lesions associated with positive lymph nodes
in 5-7%
T2 -20%
T3 -65%
T4-78%
32. Bill Heald from
Basingstoke,
England, 1982, first
began to write about
his technique of TME
He recognized that
most local
recurrences seen
after rectal cancer
resection were a
result of inadequate
resections performed
using imprecise, blunt
33. He recognized that by using meticulous, sharp
dissection, under direct vision
staying between the visceral and parietal pelvic
fascia down to the level of the levators, or upper
aspect of the anal canal
the rectum and its mesentery could be removed
as an intact unit
34. A TME involves an en bloc removal of the
mesorectum, including associated vascular and
lymphatic structures, fatty tissue, and mesorectal
fascia as a “tumor package”
through sharp dissection and is designed to spare the
autonomic nerves
After a TME the specimen is typically shiny and
bilobed in contrast to the irregular and rough surface
after a blunt dissection where much of the mesorectal
fat is left behind.
TME attempts not only to clear involved lymph nodes
35. Distal mucosal margins of 1 cm or greater are
adequate for local control
however, the margin on the mesorectum should
extend beyond the distal mucosal margin in order
to ensure a successful surgical outcome.
positive CRM as tumor within 1 mm from the
transected margin
36.
37. 786 patients from August 1993 to July 2002. Of these,
622 patients (395 men and 227 women; median age, 67
years) underwent anterior resection.
mid and distal rectal cancer were treated with TME
The local recurrence rate was 9.7% and the cancer-
specific survival was 74.5%.
38. Laparoscopic Resection
The phase III COLOR II trial, powered for
noninferiority
randomized patients with localized rectal cancer to
laparoscopic or open surgery.
patients in the laparoscopic arm lost less blood, had
shorter hospital stays, and had a quicker return of
bowel function,
had longer operation times.
No differences were seen in completeness of
resection, percentage of patients with positive CRM,
39. Role of Combined Modality
Therapy
Older studies demonstrate local failure rates of up
to 50% in patients with T3-4 or N+ disease
Local failure is related not just to the stage of the
disease
but also the location of the tumor in the rectum
experience and ability of the surgeon.
40. initial studies reported local-regional failure rates
of less than 5% after TME without the use of any
adjuvant therapy
there was concern that these excellent results
could not be replicated in larger population-based
studies
As most of surgeries done even now are not
proper TME
42. Adjuvant Therapy
The problem of unacceptably high local
recurrence after surgery has led to many studies
exploring the potential benefit of postoperative
adjuvant therapy
Advantages of postoperative radiation
ability to selectively treat patients at high risk of
local failure on the basis of pathologic stage
43. Disadvantages
potentially hypoxic postsurgical bed, making
radiation less effective
higher complications due to increased small
bowel in the radiation field
a larger treatment volume, especially if the patient
undergoes an APR and the perineal scar needs
to be covered
44. There have been several large trials of
postoperative radiation with or without
chemotherapy.
In general, surgery alone has resulted in a 25%
local failure rate and 40% to 50% overall survival
for T3 or T4 or node-positive patients
while radiation with the addition of chemotherapy
has yielded a lower local failure rate of 10% to
15% and higher overall survival rate of 50% to
60%.
45. Earlier studies
NSABP R-01study (randomized 555 patients
into three arms after surgery: (a) observation, (b)
postoperative chemotherapy of eight cycles of
MOF (5FU, CCNU [semustine], and vincristine),
and (c) postoperative radiation treatment alone of
46 to 47 Gy
Postoperative chemotherapy improved disease-
free survival but not overall survival.
Postoperative radiation treatment trended toward
improved local control but not overall survival
46. NSABP R-02 study
enrolled 694 stage B and C patients
asked two questions in its study design
(a) Does the addition of radiation to
chemotherapy improve outcome?
(b) Is MOF superior to 5-FU/LV
The radiation dose was 50.4 Gy.
47. At 5 years, the LRF was 13% for the
chemotherapy VS 8% with the addition of
radiation and chemotherapy.
5-FU/LV showed better relapse-free survival and
disease-free survival but not overall survival as
compared to MOF
Conclusion of 2 NSABP trials- while postoperative
radiation treatment did not appear to improve
overall survival
48. Gastrointestinal Tumor Study Group (GITSG)
North Central Cancer Treatment Group (NCCTG)
studies
show an improvement in survival
49. GITSG study
four-arm trial of 227 patients with stage B2 and C
rectal cancer who were randomized to either
(a) surgery alone
(b) postoperative chemotherapy of bolus 5-FU (500
mg/m2 in weeks 1 and 5 and methyl-CCNU
(semustine given day 1)
(c) postoperative radiation treatment of 40 to 48 Gy
split course
(d) postoperative chemotherapy and radiation therapy
50. In a 9-year update
Post op CRT improved the overall survival to 54%
versus 27% with observation after surgery.
There was a prolonged time to recurrence and a
decreased recurrence rate of 33% versus 55%.
Local failure rate was decreased to 10% versus
25% with surgery alone
51. Mayo-NCCTG
Compared postoperative radiation therapy against
postoperative radiation therapy and chemotherapy
The 5-year local regional failure was higher in the
radiation only arm of 25% versus 15%
5-year overall survival rate was 40% versus 55%.
reduced local recurrence by 46% and distant
metastases by 37%.
Cancer deaths were reduced by 36%, and overall
deaths were reduced by 29%.
53. Intergroup 0114 study
(a) bolus 5-FU alone
(b) 5-FU and leucovorin
(c) 5FU plus levamisole
(d) 5-FU and leucovorin plus levamisole.
The radiation treatment dose was 45 Gy with a
5.4- to 9-Gy boost to a total of 50.4 to 54 Gy.
54. With a median follow-up of 7.4 years
there was no difference in overall survival or
disease-free survival among the four groups.
The three-drug regimen had a greater toxicity.
Levamisole and leucovorin did not appear to add
any benefit to the 5-FU.
55. NEO ADJUVANT THERAPY
Due to potential disadvantages of post op RT
potentially hypoxic postsurgical bed, making
radiation less effective
higher complications due to increased small
bowel in the radiation field
a larger treatment volume, especially if the patient
undergoes an APR and the perineal scar needs
to be covered
56. Although both pre- and postoperative adjuvant
therapy can be effective
there has been a significant recent trend toward
greater use of neoadjuvant treatment
Tumor down staging, improved resectability, and
potential for expanded sphincter preservation
options in the distal rectum also encourages
57. Studies from Europe have demonstrated that
appropriate neoadjuvant preoperative radiation
results in improvement of both local control and
survival
these results have had a significant impact on the
current management of this disease
59. Main flaw of study is that the surgery alone arm
did not utilize TME
which may have resulted in an unacceptably high
local failure rate of 27%
Late effects suggested more bowel movement
frequency, incontinence, urgency, and soiling in
the preoperative radiation treatment arm,
although overall quality of life was rated good
60. the dose of 5 Gy times five fractions may induce
significant acute and late toxicity
the short interval between radiation and surgery
may not have allowed sufficient time for tumor
regression (downstaging) for improved sphincter
preservation.
61. TME alone is required?
A Dutch (CKVO 95-04) multicenter, phase III
study
1,861 patients was undertaken to evaluate the
role of short course preoperative radiation with
TME.
TME alone versus 25 Gy in five fractions followed
by TME surgery
No fixed tumors were included in the study, and
half of the patients had T1 or T2 disease
62. RESULTS
The OS was same (82% at 2 years).
However the local recurrence at 2 years was
8.2% in the TME-only arm as compared to 2.4%
in the preoperative arm
This study highlighted the value of radiation
treatment, even with TME
The sphincter preservation rate was the same in
both arms
and there was no clear evidence of any
63. The perineal complication rate was slightly higher
in the preoperative radiation arm of 26% versus
18%.
A more recent update indicates a higher
incidence of sexual dysfunction and slower
recovery of bowel function
More fecal incontinence and generally poorer
quality of life with short-course preoperative
radiation
64. META ANALYSIS
Two meta-analyses of approximately 6,000
patients each were done to explore the benefit of
preoperative radiation treatment
They noted a significant reduction in the risk of
local recurrence and death from rectal cancer
with preoperative radiotherapy
65. Neoadjuvant Chemoradiation
The improvement in outcomes with combined
chemoradiation and postoperative adjuvant
therapy has led to similar recent approaches in
the neoadjuvant therapy of this disease
66. French study FFCD 9203
Patients with resectable T3 and T4 tumors were
randomized to 45 Gy of radiation alone
versus radiation with concurrent bolus 5-FU (350
mg/m2) plus leucovorin on days 1 to 5 during
weeks 1 to 5
After surgery, four cycles of adjuvant
chemotherapy were given.
With a median follow-up of 69 months, there was
an equivalent rate (51%) of sphincter-sparing
67. Combined treatment led to improved PCR rate of
11.4% versus 3.6%
improved 5-year local failure rate of 8% versus
16.5%.
There was, however, no difference in overall
survival
68.
69. SHORT COURSE VS LONG
COURSE RT
Polish rectal cancer group
(5 Gy for five fractions) VS 50.4 Gy using 1.8 to
2 Gy fractions with concomitant bolus 5-FU and
leucovorin given during weeks 1 and 5
higher PCR was seen with chemoradiation (16%
vs. 1%), fewer positive radial margins (4% vs.
13%), and considerably reduced size of the tumor
by approximately 1.9 cm
no difference in the rate of sphincter preservation,
local control or survival was seen.
70. Preoperative Versus
Postoperative
The definitive phase III study in favor of
preoperative radiation therapy was the
CAO/ARO/AIO-94 study performed by the
German Rectal Cancer group
72. RESULTS
The 5-year results revealed a pelvic recurrence
ratio of 6% versus 13% (p = 0.02) in favor of the
preoperative arm.
No differences in DFS ,OS, or distant failures
There was significant tumor downstaging with an
8%PCR.
Nodal positivity was 25% VS 40%
73. sphincter-preserving low anterior resection 39%
versus 19% had a (p = 0.004)
There were fewer acute (27% vs. 40%) and late
toxicities (14% vs. 24%) in preoperative-treatment
group
WITH THIS EVIDENCE PRE OP CHEMO
RADIATION HAS BECOME THE STANDARD OF
CARE FOR OPERABLE T3/T4/N+ RECTAL
CANCERS
74. Locally Advanced Rectal Cancer
Clinical T4 tumors may not be resected
completely due to tumor fixation.
Preoperative radiation treatment is recommended
to facilitate curative resections
M.D. Anderson investigators demonstrated that
preoperative chemotherapy and radiation therapy
increased overall survival (80% vs. 60%), local
control (95% vs. 66%), and the number of
sphincter preserving procedures (35% vs. 7%) as
compared to radiation alone
75. IORT
Preoperative continuous infusion 5-FU plus 50.4
to 54 Gy of radiation was given followed by a 4-
to 6-week break and surgery.
IORT-Ten to 12.5 Gy were given for complete
resection
12.5 to 15 Gy for microscopic residual
17.5 to 20 Gy for gross residual disease.
76. No IORT was given if metastases were present at
surgical exploration
if there were adequate margins >1 cm
if there was less than T4 disease.
IORT improves local control, especially with a
gross total resection, but not survival for locally
advanced rectal cancer
77. Adjuvant Chemotherapy
Adjuvant chemotherapy is recommended for all
patients with stage II/III rectal cancer
following neoadjuvant chemoRT/surgery
regardless of the surgical pathology results
A recent systematic review and meta-analysis of
9785 patients with nonmetastatic rectal cancer
from 21 randomized controlled trials from 1975
until March 2011
concluded that OS and DFS are improved with
the addition of postoperative 5-FU–based therapy
78. Most of the support for use of FOLFOX or
capecitabine as adjuvant chemotherapy in rectal
cancer is an extrapolation from the data from
colon cancer
The use of a shorter course of adjuvant FOLFOX
in rectal cancer (ie, 4 months) is justified when
preoperative chemoRT is administered.
79.
80.
81. Management of Metastatic Disease
Approximately 50% to 60% of patients diagnosed
with colorectal cancer will develop metastases
synchronous metastatic colorectal liver disease is
associated with a more disseminated disease
state and a worse prognosis
than metastatic colorectal liver disease that
develops metachronously.
82. Factors associated with a poor prognosis in
patients with colorectal cancer
the presence of extrahepatic metastases
the presence of more than 3 tumors
a disease-free interval of fewer than 12 months
retrospective analyses and meta-analyses have
shown that patients with solitary liver metastases
have a 5-year OS rate as high as 71% following
resection.
83. CRITERIA FOR RESECTABILITY OF METASTASES
AND LOCOREGIONAL THERAPIES WITHIN
SURGERY
Hepatic resection is the treatment of choice for
resectable liver metastases from colorectal cancer.
Complete resection must be feasible based on
anatomic grounds and the extent of disease;
maintenance of adequate hepatic function is required
The primary tumor must have been resected for cure
(R0).
There should be no unresectable extrahepatic sites of
disease.Plan for a debulking resection (R1/R2
resection) is not recommended.
84. Patients with resectable metastatic disease and
primary tumor in place should have both sites
resected with curative intent.
These can be resected in one operation or as a
staged approach
91. TARGET VOLUME
External-beam treatment portals for rectal carcinoma
should always encompass the sites at greatest risk:
The presacral space
the primary tumor site, and the perineum (for post-
APR cases)
The mesorectal and lateral lymph nodes and internal
illiac are included in all patients
The external iliac nodes should be covered for T4
lesions.
92. The inguinal lymph nodes may be included
if tumour invades the lower third of the vagina
if there is major tumour extension into the internal
and external anal sphincter
93. RADIATION TECHNIQUES
Patients may be treated supine or prone
though placing the patient prone with a belly
board may help move small bowel out of the
pelvis.
A rectal marker or rectal contrast can help
delineate the location of the tumor
wire perineal scar if present
small bowel contrast
97. Conventional Field borders
Whole pelvic field:
A : Posterior-anterior
Superior border: L5-S1 junction
Distal border: 3 cm below the primary tumor or at the
inferior aspect of the obturator foramina, whichever is the
most inferior
Lateral borders: 1.5 cm lateral to the widest bony margin
of the true pelvic side walls.
98. B : Laterals
Anterior border:
T3 disease: Posterior margin of the symphysis pubis
(to treat only the internal iliac nodes).
T4 disease: Anterior margin of the symphysis pubis (to
include the external iliac nodes
Posterior border: 1 to 1.5 cm behind the anterior bony
sacral margin
99. After an abdominoperineal resection:
A :Wire the perineal scar and create a 1.5-cm
margin beyond the wire in all fields.
Boost field:
A : Treat the primary tumor bed plus a 3-cm
margin (not the nodes).
100. Fig B: For a T4N1M0 rectal
cancer 8 cm from the anal
verge. Since the tumor was a
T4, the anterior field is at the
anterior margin of the
symphysis pubis (to include
the external iliac nodes).
Fig A: Treatment fields after a low anterior
resection for a T3N1M0 rectal cancer 8 cm
from the anal verge. The distal border is at
the bottom of the obturator foramen and the
perineum is blocked. Since the tumor was a
T3, the anterior field is at the posterior
margin of the symphysis pubis (to treat only
the internal iliac nodes).
Fig C: Treatment fields following an
abdominoperineal resection for a T4N1M0
rectal cancer 2 cm from the anal verge,
because the tumor was a T4, the anterior
field is at the anterior margin of the
symphysis pubis (to include the external
iliac nodes). Since the distal border is
being extended only to include the scar
and external iliac nodes, the remaining
normal tissues can be blocked
104. CT based treatment planning is preferred to
ensure adequate coverage of the tumor and
regional nodes and improve dose homogeneity
Planning CT should be taken from the level of mid
abdomen (L1) to level of mid thigh with 5mm cut
Iv, rectal and bowel contrast will clearly defining
target as well as critical structures
Fusion of the treatment planning CT with other
imaging modalities MRI or PET may also help
identify the tumor location
105. The GTV includes all gross tumour seen on the
planning CT scan with reference to information
from diagnostic endoscopy, MRI and DRE
Any involved lymph nodes, extrarectal extension,
or extranodal deposits seen on MRI should be
included
CTV should include peri-rectal, pre-sacral,
internal iliac regions
106. RTOG GUIDELINES
The caudad extent of this elective target volume
should be a minimum of 2 cm caudad to gross
disease, including coverage of the entire
mesorectum to the pelvic floor
The posterior and lateral margins of CTV should
extend to lateral pelvic sidewall musculature or,
where absent, the bone
Anteriorly, the group recommended extending 1
cm into the posterior bladder, to account for day-
to-day variation in bladder position.
107. The recommended superior extent of the peri-
rectal component
the rectosigmoid junction or 2 cm proximal to the
superior extent of macroscopic disease in the
rectum/peri-rectal nodes.
To include illiac vessels it should be kept at L5/S1
JUNCTION
108. Margin around blood vessels:
The group recommended a 7-8 mm margin in
soft tissue around the external iliac vessels
but one should consider a larger 10+ mm
margin anterolaterally IF nodes are identified
in this area
109. BOOST VOLUME
The group did recommend that any boost clinical
target volumes extend to entire mesorectum and
presacral region at involved levels
including ~2 cm cephalad and caudad in the
mesorectum and ~2 cm on gross tumor within the
anorectum.
PTV margin should be ~0.7 to 1.0 cm, except at
skin
110.
111.
112.
113.
114. Techniques to Decrease Radiation
Toxicity in Small Bowel
High-energy (>6 MV) linear accelerators.
Treatment 5 days per week and all fields each
day.
Port films once per week or more often if clinically
indicated
Pelvic field: multiple-field technique (posterior-
anterior plus laterals or posterior-anterior-anterior-
posterior plus laterals) is recommended.
115. Boost field: opposed laterals.
Computerized dosimetry optimizing between
minimizing the lateral hot spots and small bowel
dose and increasing the homogeneity within the
target volume
In thin patients, a combination of 6 MV for the
posterior fields and higher-energy photons for the
lateral fields may result in more homogeneous
dosimetry.
Shaped blocks and, if needed, wedges on the
lateral fields.
Small bowel contrast. Shield as much small bowel
116. Rectal contrast. Barium sulfate is injected with a Foley
catheter. A wire is placed on the catheter to indentify
the anal verge
Prone position.
Full bladder, only if it does not make the patient so
uncomfortable as to cause movement.
The entire perineum can be blocked after a low
anterior resection
Immobilization molds (belly boards) and abdominal
wall compression may be helpful
117. Intensity-Modulated Radiation
Therapy
may offer the potential to reduce toxicity
but there are no set standards regarding its use
Different IMRT volume–based dose constraints
have been proposed for bowel and bladder, but
there is no set consensus.
IMRT-based sparing of the iliac crests may also
reduce bone marrow toxicity
118. Currently, IMRT is not recommended for routine
use.
IMRT can be used in re irradiation for recurrence
119.
120. endocavitary radiation therapy.
T1 or T2 tumors less than 3 cm
not poorly differentiated
with no evidence of nodal involvement.
Patients are treated with a special low energy x-
ray machine (50 kVp) that is attached to a rigid
endoscopic-type device that can be placed in the
rectum directly over the tumor.
As the opening of the applicator is 3 cm, it is
difficult to treat tumors larger than this.
121. Patients typically receive four treatments of 2,500 to 3,000
cGy each with 2 to 3 weeks between treatments to allow
for tumor regression.
Although the total dose is extremely high, the minimal
penetration of the radiation beam protects the underlying
normal tissue.
Local control results with this approach have been very
good in properly selected patients
but specialized equipment is required (which is not
generally available)
less pathological information is obtained than after a local
excision.
This approach is rarely used at the present time
122. Dose
Preoperative radiotherapy
Short course: 25 Gy in 5 daily fractions of 5 Gy given in 1
week.
Long course
Phase 1
45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.
Phase 2
5.4 in 3 daily fractions of 1.8 Gy
Postoperative radiotherapy
Phase 1
45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.
Phase 2
5.4–9 Gy in 3–5 daily fractions of 1.8 Gy.
123. Adverse effects
Acute complications
diarrhea and increased bowel frequency (small
bowel)
acute proctitis (large bowel)
thrombocytopenia, leukopenia, and dysuria are
common during treatment.
These conditions are usually transient and
resolve within a few weeks following the
completion of radiation.
124. In the small bowel, loss of the mucosal cells
results in malabsorption of various substances,
including fat, carbohydrate, protein, and bile salts.
The bowel mucosa usually recovers completely in
1 to 3 months following radiation.
Management usually involves the use of
antispasmodic and anticholinergic medications.
125. Delayed complications
occur less frequently, but are more serious.
The initial symptoms commonly occur 6 to 18 months
following completion of radiation.
persistent diarrhea and increased bowel frequency
proctitis, small bowel obstruction (SBO) not requiring
surgery,
perineal and scrotal tenderness,