This document presents a case of a 60-year-old male patient with locally advanced oral cavity squamous cell carcinoma. It discusses the patient's history, investigations including imaging and biopsy results, staging, and initial treatment involving radiation therapy. It then provides introductions to oral cavity cancer epidemiology, clinical manifestations, diagnostic workup, staging, treatment considerations including surgery, radiation, and chemotherapy, as well as factors affecting treatment choices and outcomes from studies on post-operative radiation and chemoradiation.
Metastasis of Neck Node with Unknown Primary Himanshu Soni
carcinoma of unknown Primary accounts for 5%-10% of all tumours. 3–5% of head and neck cancers presented as cervical squamous cell carcinomas of unknown primary
This is a Central presentation, presented at National Institute of Cancer Research & Hospital(NICRH), Mohakhali, Dhaka, Bangladesh on Metastatic neck node of unknown primary.
Metastasis of Neck Node with Unknown Primary Himanshu Soni
carcinoma of unknown Primary accounts for 5%-10% of all tumours. 3–5% of head and neck cancers presented as cervical squamous cell carcinomas of unknown primary
This is a Central presentation, presented at National Institute of Cancer Research & Hospital(NICRH), Mohakhali, Dhaka, Bangladesh on Metastatic neck node of unknown primary.
Concurrent Chemoradiation in Postoperative Setting In LAHNC. A comparision of...Santam Chakraborty
A journal club presentation comparing and contrasting the EORTC and RTOG trials of concurrent chemoradiation in Head Neck Cancers in the post operative setting.
CARCINOMA OF THE ORAL CAVITY. Diagnosis and management.tDr. RIFFAT KHATTAK
The Oral Cavity, with it's seven subsites,is a host of multiple epithelial, mesenchymal & glandular structures. Thus, if exposed to multiple risk factors, either in isolation or in combination, could undergo drastic histological changes leading to malgnancies. A thorough clinical examination, diagnosis and timely intervention followed by rehabilitation of the patient, via a multi disciplinary approach is the mainstay of treatment.
Concurrent Chemoradiation in Postoperative Setting In LAHNC. A comparision of...Santam Chakraborty
A journal club presentation comparing and contrasting the EORTC and RTOG trials of concurrent chemoradiation in Head Neck Cancers in the post operative setting.
CARCINOMA OF THE ORAL CAVITY. Diagnosis and management.tDr. RIFFAT KHATTAK
The Oral Cavity, with it's seven subsites,is a host of multiple epithelial, mesenchymal & glandular structures. Thus, if exposed to multiple risk factors, either in isolation or in combination, could undergo drastic histological changes leading to malgnancies. A thorough clinical examination, diagnosis and timely intervention followed by rehabilitation of the patient, via a multi disciplinary approach is the mainstay of treatment.
Melanoma of the Palate: A Case Report and Literature Reviewasclepiuspdfs
Mucous melanoma accounts for 1% of melanomas. The palate and the labial mucosa are the most affected. It is a dark prognostic tumor, the treatment associated with surgery and radiotherapy in the localized stages. We report the case of a palate melanoma in a 47-year-old patient without distant metastases.
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.
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.
Follow us on: Pinterest
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
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.
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
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Oral cavity cancer
1. Locally advanced oral cavity SCC
Presenter Dr. Zerubbabel. A ( R2)
Moderator: Dr. Edom.S (consultant
Oncologist)
2. Contents of the Presentation
Case presentation
Introduction
Clinical manifestations
Diagnostic and staging workup
Staging
Management
Follow-up/ surveillance
Case critics
References
3. The case
A 60 year old male patient presented with a complaint of left buccal mucosa
swelling of 02 years duration which subsequently got ulcerated.
He is also a known RVI patient on HAART for the past 9 years with recent CD4
count of 700 before 04 months
He is a know hypertensive patient for the past 05 years on antihypertensive and
diagnosed to have type 2 DM before a year and now he is on insulin.
He has history of smoking 03 pack years, along with alcohol use and Kchat
chewing for many years
4. Investigations
Head and neck CT scan:
Left buccal mucosa enhancing mass measuring 2.4 *1.6 cm
Centrally necrotic left level IB LAP measuring 2.1 * 2 cm,
Left level IIA LAP measuring 2.4 * 2.1 cm
After re-evaluation it was known that it has Left mandibular involvement and
staged as cT4N2M0 ( stage IV A)
CXR ====normal
Abdominal U/s ===== normal
Biopsy = keratinizing squamous cell carcinoma
5.
6.
7.
8.
9. The case
He completed phase I RT (44 Gy, 22#), before 5 days
Opposed lateral fields with a filed size of 14.1 cm * 10.7 cm
Lower cervical AP field with a filed size of 20 cm * 11.4 cm
SSD ==========80 cm
Position ====== supine
No beam weighting done
No concurrent chemotherapy given
15. Introduction…..
Oral cavity cancer accounts for about 30 % of all H & N cancers, 3 - 4 % of all cancers
worldwide
In the year 2018 an estimated 320,000 new cases and about 150,000 deaths were
reported worldwide, attributable to oral cavity cancer
90% of oral cavity cancer are well to moderately differentiated squamous cell
carcinoma
Males have a higher incidence than females, with a ratio of 3:2.
Has a strong causal relationship with tobacco and alcohol use
In South Asia, it is highly prevalent and accounts for 17% of all malignancies in India
compared to less than 5% in Western countries.
The chewing of betel nut leaves mixed with tobacco is thought to be a leading cause
of oral cavity cancers in South Asian countries
16.
17. Clinical manifestation
The natural history and clinical presentation of primary carcinomas located in each
subsite of the oral cavity vary significantly
The clinical presentation also varies significantly with histologic type, and stage of
the tumor
Many patients with oral cavity tumors present with advanced-stage disease as
initial symptoms may be vague and painless.
The area has a rich lymphatic supply, and initial regional node dissemination is to
nodal groups at levels I to III.
Tumors at or reaching to the midline drains bilaterally
Rate of skip metastasis is common with oral tongue tumors
Regional node involvement at presentation is evident in about 30 – 40 % of
patients, but the risk varies according to subsite.
18. Tumor subsite Overt metastasis Occult nodal disease
Lip 5 – 10 % 5 – 10 %
Oral tongue 35 – 40 % 32 %
FOM 30 % 26 %
Buccal mucosa 9 – 31 % 16 %
Upper gingiva 16 % 18 %
Lower gingiva 21 %
RMT 39 % 25 %
Rate of overt and occult LN involvement in patients with
locally advanced oral cavity cancers by sub site ( for T3/T4
diseases)
deep mucosal invasion, higher T-stage, perineural invasion, infiltrative type , and poorly
differentiated tumors have been correlated with a higher incidence of lymph nodal
involvement
19.
20. Patterns of lymph node involvement from squamous cell
carcinoma of the buccal mucosa.
21. Approach to the patient
Comprehensive history and physical examination.
The history of present illness should address the following issues:
- tobacco and alcohol use;
- dysphagia; odynophagia
- trismus and pain
- difficulties with speech; hoarseness
- loose teeth; ill-fitting dentures
- hypoesthesia of the face, lips, or mandible
- weight loss; and malnutrition.
22. Cont’d
Detailed visual and digital examinations are particularly important
Palpation of the oral cavity can help assess bony involvement, tongue fixation,
and depth of involvement.
Deviation or fixation of the tongue suggests involvement of extrinsic muscles of
the tongue.
Bimanual palpation can help assess the depth of tumor invasion into
musculature of the tongue and floor of the mouth.
A thorough palpation of the neck is important to assess regional nodal disease.
A multidisciplinary approach of evaluation should be implemented.
A biopsy of the primary lesion and FNA from the neck nodes
23. Imaging
CT Scan determine the local extent of the disease
- extent of soft tissue invasion
- asses bony involvement and
- occult disease in the neck nodes
MRI more accurately predicts
- soft tissue invasion
- depth of invasion
- perineural spread in oral tongue cancers
MRI can be used safely in
- patients who has significant dental artifact that obscures
visualization of the primary tumor on CT
- contrast allergic patients
- lesion that is not well visualized on CT.
24. Imaging
Panoramic X ray
A chest x-ray should be performed to exclude lung metastases or a second
primary cancer
Ultrasound may be used to screen for enlarged lymph nodes that are not
clinically detectable.
In experienced hands, the accuracy of ultrasound when combined with
fine-needle aspiration may be superior to CT or MRI for staging the neck
28. Treatment
The aim of treatment
- Optimal rates of cure
- Where cure is not feasible every attempt
should be made to provide loco-regional
disease control.
- Preservation or restoration of form and function.
29. MDT Evaluation
Head and neck surgical oncology
Radiation and medical oncology
Nursing and dietary
Speech – language/
swallowing therapist
Dentistry and Plastic
surgery
Social worker
Multidisciplinary team involvement is particularly important for Oral cavity ca ,
because critical physiologic functions may be affected such as mastication,
deglutition, and articulation of speech.
30. Pre-treatment dental evaluation
A complete dental examination should be performed on all patients, whether
dentate or edentulous, before irradiating any portion of the mandible or
maxilla
ORN: Teeth with high-risk dental factors specifically, those teeth that will
reside within the high-dose radiation volume which demonstrate significant
periodontal disease or advanced caries, or are otherwise in a state of disrepair
should be extracted before initiation of RT
Once RT is initiated high risk teeth should be removed before the patient
receives doses of more than 55 Gy
A healing time of 14 to 21 days is recommended after extraction, before
initiating radiation therapy
31. Treatment
Effective management lies on successful management of primary tumor as
well as regional lymphatic
Combined modality treatment is the current standard of care for patients
with locally advanced SCC as single modality therapy has inferior outcome
Surgical Resection
Radiation
CCRT
The specific treatment is dictated by the TN stage and, if cN0 at diagnosis, by
the risk of nodal involvement
32. Factors affecting Rx choices
Tumor factors
Site and laterality
Size /stage of the tumor
Depth of invasion
Tumor grade
Patient factors
Performance status
Age
Previous treatment
Presence of comorbidity
34. Surgical Resection
Surgery is generally recommended as the initial therapy for locally advanced
oral cavity cancers.
Trans-oral approach
Trans-cervical approach
Mandibulectomy
The primary objectives are
- complete resection of the primary tumor with negative margins
- staging and treatment of the regional lymphatics
35. Cont’d
In most cases, simultaneous resection and reconstruction is feasible with
acceptable functional outcomes.
Every attempt should be made to ensure negative resection margins
Positive margins are associated with a worse prognosis, so whenever
feasible, re-resection of any positive margin is preferred
Margin status is one of the most important variables associated with
survival.
- locoregional control is significantly improved with margins of
5mm or greater, relative to margins of < 5mm
Close margins, typically defined as less than 5 mm, may also portend a
worse prognosis
36.
37. Treatment of the neck
Dictated by the extent and the site of the tumor at initial tumor staging
Depth of mucosal invasion Vs laterality /extent of the primary tumor
The depth of tumor invasion has been reported to be the best predictor for regional
metastasis in the cN0 neck.
END should be done based on at least a 20% probability of occult nodal disease being
present for tumors that are cN0
A meta-analysis identified a depth of invasion of 4 mm from the mucosal surface in oral
tongue cancers as the cutoff most frequently cited as an indication for END, based on a
NPV of 95.5%.
Tumor on the FOM may need END with a 1.5 depth of mucosal invasion.
The current recommendation is , with a depth of invasion > 4 mm, END should be strongly
considered if RT is not already planned.
38. Treatment of the neck
Therapeutic neck dissection ( TND)
- Clinically node positive neck ( cN+ve)
Elective neck dissection ( END)
- Clinically node negative neck (cN0 disease)
- Elective dissections are generally selective, preserving all major structures, unless
operative findings dictate otherwise
Whether END or TND, it should be done at the same time as part of treatment of
the primary tumor
SLNB
Observation followed by TND
RT
- Therapeutic neck radiation (TNR)
- Elective node irradiation (ENR)
ENI and END are equally effective in the management of the cN0 neck, with
control rates exceeding 90%
39.
40. Types of neck dissection
Radical neck dissection (comprehensive neck dissection)
- removes may structures in the neck/ extensive dissection
MRND/modified comprehensive neck dissection/ or functional neck dissection
- preserve structures not involved with cancer
- remove only structures involved by the tumor, fat, fascia, and lymph nodes.
There are three types of MRND:
- type I = cranial nerve (CN) XI is spared
- type II = CN XI and the internal jugular vein are spared
- type III (functional) = CN XI, the internal jugular vein, and the
sternocleidomastoid muscle are spared.
41. Selective Node Dissection
A more limited form of procedure with removal of LN levels that are at
greatest risk for nodal metastatic spread.
Supported with data demonstrating that regional control and survival
rates do not decrease, particularly when adjuvant therapies are used to
manage microscopic residual disease in high-risk patients
SND is denoted by the lymph node levels removed (e.g., SND II to IV).
Recommended for
- the cN0 neck,
- for selected clinically positive necks (mobile, 1- 3 cm lymph nodes)
- for removing residual disease after RT/CCRT when there has been
excellent regression of N2 or N3 disease
42. Therapeutic Node Dissection
Done for involved cervical LNs
- about 75 % pathologically positive
- up to 15.8% skip metastasis to level III or IV
For patients with a cN-positive neck, a SND at levels I to IV or I to V is
recommended.
The use of MRND is typically reserved for patients with
- advanced nodal disease (N3),
- disease extending into level V LNs
- invading critical structures in the neck.
43. Surgery with RT Vs RT alone
Robertson et al. conducted a phase III study in the UK of 35 patients with T2–
T4/N0–N2 oral cavity or oropharyngeal cancers comparing surgery and
postoperative radiation versus radiation alone.
The study was closed early (of the anticipated 350 patients only 35 patients
were enrolled ) because a difference in survival was identified
An interim analysis done after accrual of 30 patients revealed a highly
significant survival advantage for patients in the combination arm (12 deaths
out of 15 patients in the RT alone arm versus 2 deaths out of 15 patients in
the combination arm (P = 0.0006), stratifying for performance status).
After 23 months, LRC, OS, and CSS, were all improved in the surgery plus
radiation arm. ( P value for OS = 0.001)
44. Peters LJ. et al …………….( MDACC)
A phase III prospective, randomized trial designed to determine the optimal dose of
conventionally fractionated PORT for advanced head and neck cancer in relation to
clinical and pathologic risk factors
Patients ( N = 264) who underwent primary surgery for AJCC stage III or IV SCC of
the oral cavity, oropharynx, hypopharynx, or larynx and who required PORT were
eligible.
Dose-response relationship for PORT and pathologic risk groups in head and neck
cancer
The sites in the high-risk group --------- 63 Gy or 68.4 Gy
low risk sites ----------------57.6 Gy or 63 % Gy, all at 1.8 Gy per fraction.
The concept of “treatment package time”/ TPT was introduced to define the interval
from surgery to the completion of PORT
45. Cont’d
With daily # of 1.8 Gy, a minimum dose of 57.6 Gy should be given to the operative
bed ……..and up to 63 Gy be given to sites of increased risk, especially regions of the
neck with ENE
Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the
therapeutic ratio
Margin status and ENE were the only independent tumor-related risk factors
predicting LRC and OS
TPT cutoff of 85 days was also identified as predictor of LRC, CSS, and OS which
showed its highest impact at the lowest dose level (< 60 Gy)
46. RT Vs CCRT, Postoperatively
A combined analysis of data from two randomized landmark studies RTOG
9501 and EORTC 22931 demonstrated improved LRC and DFS rates with
chemoradiation ( cisplatin 100 mg m2 on days 1, 22, and 43) compared to
PORT alone.
The two trials had differing eligibility criteria, but a comparative analysis
by Bernier et al. showed that all patients with positive margins and/or
extranodal extension derived the greatest benefit from postoperative
chemoradiation
RTOG 9501 --------------- > LRC, DFS
EORTC 22931------------ > LRC, DFS and OS
47. EORT 22931( Bernier et al.)
Compared RT alone Vs CCRT in the post operative setting
334 patients with oral cavity, oropharynx, hypopharynx & larynx, ( pT3/T4 with
any N except T3N0), who underwent surgery with curative intent were
randomized into two arms ( 1:1 ratio)
Only 26 % were patients with oral cavity cancer
1st group taking RT alone ( 66 Gy , 30 #)
2nd group taking the same dose of RT with concurrent cisplatin
In both arms the low risk neck recived 54 Gy of RT
Primary end point: progression free survival/ PFS
48. EORTC 22931
After a median follow-up of 60 months
The 5 year cumulative incidence of distant metastasis was 25% vs 21% ( p = 0.61)
The cumulative incidence of 5 yr second primary tumors were 13 % vs 12 % ( p = 0.83)
The CCRT group showed high rate of acute toxicities but there was no significant difference
in the rate of late complications
EORTC 22931 RT ( n= 167) CCRT ( n= 167) P value
Median PFS 23 months 55 months 0.04
3 yr DFS 41 % 59 % 0.009
5 yr PFS 36 % 47 % 0.04
3 yr OS 49 % 65 % 0.02
5 yr OS 40 % 53 % 0.04
5 yr LRC 69 % 82 % 0.007
5 yr LRR 31 % 18 % 0.07
49.
50. RTOG 9501
After undergoing total resection of all visible and palpable disease, 459 patients were enrolled
into two groups:
- 231 patients were assigned to receive RT alone ( 60 – 66 Gy)
- 228 patients received same dose of RT with concurrent cisplatin
Only 27 % were patients with oral cavity cancer
Primary end point = Loco-regional control, secondary end points were DFS & OS
After a median follow-up of 45.9 months
overall survival didn’t show any significant difference among the treatment groups
RTOG 95_01 RT (n = 231) CCRT (n = 228) P value
2 year DFS 43 % 54 % 0.04
2 year LRC 72 % 82 % 0.01
LRF 30 % 19 % 0.01
OS 57 % 63 % 0.19
G 3&4 toxocity 34 % 77 %
51.
52. RTOG 9501
10 year update
Unplanned analysis of subset of those patients with positive surgical margin and/or
ENE the revealed a different result
In the analysis of all randomized eligible patients there was no significant difference in
all the tumor outcomes assessed.
With long time of follow-up the differences initially observed were narrowed
Subgroup analysis of those who had either microscopically involved margins and /or
ENE showed improved LRC and DFS with CCRT
PSM/ENE RT alone CCRT p value
LRF 33.1 % 21 % 0.01
DFS 12.3 % 18.4 % 0.05
OS 19.6 % 27.1 % 0.07
RTOG 9501 RT CCRT p value
LRF 28.8 % 22.3 % 0.1
DFS 19.1 % 20.1 % 0.25
OS 27 % 29.1 % 0.31
53.
54. Indications for Chemoradiotherapy
The impact of chemoradiotherapy appears to be most pronounced in patients with
Extranodal extension
Positive surgical margins
Indications for postoperative radiotherapy ( PORT)
Close/ uncertain resection margins
Perinueural invasion
Lypmphovascular space invasion
Multiple positive LNs
Unknown LN status
Preferred interval between resection and postoperative RT is ≤6 weeks
55. Treatment Delay ( TPT)
It is well appreciated that head and neck tumors are rapidly proliferating.
A multi-institutional prospective study by Ang et al. demonstrated that
the total treatment time from the completion of surgery to the
completion of radiation may affect the likelihood of ultimate disease
control.
This study illustrated the impact of overall treatment time on 5-year LRC
rate
The rate of LRC at 5 years for
TPT < 11 weeks = 76%,
TPT 11 - 13 weeks = 62%
TPT >13 weeks = 38%
Hence, it is recommended that adjuvant radiation proceed as soon as
surgical wounds are well healed, optimally 4 to 6 weeks after completion
56. Induction chemotherapy
Generally not recommended in the standard management of resectable oral cavity
SCC.
For down staging tumors and enabling radical surgery
Technically unresectable oral cavity SCC ( T4a, T4b)
The balance b/n the extent of surgery required to achieve negative margins and
acceptable cosmetic and functional impairment defines the resctability of a tumor.
A combination of docetaxel, cisplatin, and 5-FU is the preferred induction regimen
for clinically fit patients with reported response rates of 17% to 50%
57. Induction cheomtherapy
In a trial conducted by Licitra et al., 94 patients with resectable advanced oral
cavity SCC were randomized to
Cisplatin + 5 FU ( 2 cycles) followed by surgery or upfront surgery
--------------------------------radiation therapy was reserved for high risk patients
Preoperative chemotherapy results in
- fewer mandibular resections
- decreased use of PORT
- there was no effect OS.
- response rates decrease with increasing stage in oral cancers
It is strongly recommended that the selection of patients for induction
chemotherapy be made in a multidisciplinary fashion.
58. Induction Chemotherapy
Patil MV et al. undertaken retrospective analysis of 721 patients with
technically unresectable oral cavity tumors who were treated with NACT during
the period from January 2008 - August 2012
Who were deemed technically unresectable??...........MDT based decision
- 74 ( 10.2 %) patients = Platinum + 5 FU + Docetaxel
- 647 ( 89.2 %) patients received 2 drug regimen = platinum + taxene
Buccal mucosa was the most common subsite (500 patients, 69.3 %)
After 2 cycles of chemotherapy, the patients were re-evaluated in the
multidisciplinary clinic ( average number of cycles received = 2)
59.
60. Cont’d
Response rate was evaluable in 618 patients & the overall response rate was 25.1%
The response rate with 3 drug regimen = 50%
2 drug regimen with docetaxel = 30.4% and with
paclitaxel = 17.2%
Resectability was achieved in a total of 310 patients
49 patients ( 66.21 %) taking 3 drug regimens
261 patients ( 40.34 %) taking 2 drug regimen patients.
Among patients who were resected 195 patients took CCRT ( 60 Gy, 30 #, weekly
cisplatin 30 mg/m2)
Among those non resected patients 167 were treated with CCRT ( 70 Gy, weekly
cisplatin), 3 patients were given definitive RT alone , and the rest were put on
palliative treatment.
61. Cont’d
After a median follow up of 28 months
The estimated median survival for those patients who didn’t receive
adjuvant Rx after surgery is 16.6 months but, it is unreached in those
patients who were treated with surgery plus adjuvant therapy
Patil MV et al.
after NACT
Surgically Rxed Non surgical
Rx
Whole
cohort
P value
Median OS 19.6 months 8.6 months 10.8 months 0.0001
2 year OS 47 % 20 %
2 year LRC 32 % 15 % 0.0001
62.
63.
64. Unresectable Disease
Chemotherapy combined with radiotherapy is the preferred treatment for
patients with unresectable locally advanced squamous cell carcinoma of the oral
cavity.
Tumors with one or more of the following characteristics
- encasement of the carotid artery
- skull base invasion
- involvement of the pre-vertebral fascia
A number of randomized trials and several meta-analyses have demonstrated
improved outcomes with concurrent chemotherapy as compared to sequential
treatment or radiation therapy alone for patients with locally advanced head-
and-neck cancers.
Extrapolating this trend for managing cases with OC-SCC…………??? ( low
number of cases of OCSCC were represented in this patient population)
65. Organ/function preserving treatment
No prospective studies have been conducted specifically investigating surgery
versus chemoradiation for oral cavity cancer
Over the past two decades some institutions has adopted a paradigm of upfront
organ function preservation using definitive CCRT for locally-advanced OC-SCC with
surgery reserved for salvage as necessary
Analysis of 20-year (1994 to 2014) experience of upfront CCRT for locally-advanced
OC-SCC from Chicago university was reported
Taxane and platinum-based induction chemotherapy was delivered prior to CRT on
several patients and lasted for a period of 6–8 weeks followed by FHX based CCRT
- Chemotherapy = 5 FU and hydroxyurea with other third agents.
- RT once or twice daily to a maximum dose of 70–75 Gy.
- IMRT was exclusively used after 2004
66. Cont’d
During the first decade of treatment, post-CRT neck dissection was
routinely performed for patients with N2- N3 neck disease;
In the second decade, post-CRT neck dissection was generally triggered by
any radiologicaly or clinically detected large or focally-abnormal lymph
node
Tumor outcomes were compared across treatment decades using the log-
rank test ( 1994 – 2003 Vs 2004 – 2014)
67.
68. Cont’d
Patients were followed for a median of 5.7 years
There was a trend to wards improved OS in the 2nd decade ( P = 0.1)
There was no significant difference in the LRC,PFS, and DC b/n decades of
treatment
ORN = 20 % and the most important risk factor was primary tumor of the FOM
Induction chemotherapy was not associated with LRC, DC, PFS or OS
Definitive CRT is a viable and feasible strategy for organ preservation for patients
with locally advanced OC-SCC.
N = 140 1st decade
( n = 64)
2004 – 2014
( IMRT) n = 76
Whole
cohort
T3/T4
disease
p value
for 1st & 2nd decades
5 yr OS 58.2 % 67.6 % 63.2 % 57.8 % 0.1
5 yr PFS 56.7 % 60.6 % 58.7 % 52.8 % 0.38
5yr LRC 77.3 % 79.8 % 76.8 % 72.8 % 0.9
5 yr DC 84 .3 % 89 .9 % 87.2 % 85 % 0.25
69.
70. Cont’d
Several retrospective studies have also investigated the efficacy and toxicity of organ
preservation for OC-SCC
The MSKCC reported their results for 73 patients with OC-SCC treated with definitive CRT
from 1990 to 2011.
With median follow-up of 73.1 months, 5-year OS was 15% and 5-year LRC was 37%.
Moreover, a recent National Cancer Database (NCDB) analysis reported 3-year OS of 37.8%
for 2091 patients receiving definitive CRT for OC-SCC
This discrepancy in oncologic outcomes among reports likely results from
- patient selection for definitive CRT which is usually limited to those with
high comorbidity or advanced disease
In fact, patients receiving definitive CRT in the NCDB analysis were found to be statistically
significantly more likely to be
older than 60,
treated at nonacademic centers,
have more comorbidities, and
have clinical T3/T4a as well as N2a-N2c diseases
73. Cont’d
Nutritional evaluation and rehabilitation as clinically indicated until
nutritional status is stabilized
Smoking cessation and alcohol counseling
In patients with cancer of the oral cavity, the risk of developing a second
primary cancer is well recognized.
Second primary cancers have an adverse effect on prognosis and are the
major cause of treatment failure in patients with early-stage disease.
The probability of developing a second metachronous malignancy at 5
years was 22% (18% for the subset of patients with oral cavity cancer)
74. Cont’d
Quitting tobacco and alcohol use greatly reduces the risk of developing
subsequent head and neck squamous cell carcinoma.
Individuals that have stopped smoking for 1 to 4 years have a 30%
decrease in risk of developing carcinoma of the head and neck compared
to those that continue to smoke.
For those that quit smoking beyond 20 years, the risk parallels that of
never smokers; a similar effect is seen with stopping the use of alcohol
Therefore, continued efforts toward tobacco and alcohol cessation are a
central strategy in the management of patients with oral squamous cell
carcinoma
75. Case critics
• Inadequate documentation
• Patient didn’t receive concurrent
chemotherapy
• The treatment beams on the opposed lateral
fields were not weighted.
76. References
1. Perez and Brady's Principles and Practice of Radiation Oncology, 7th Edition,
2. DeVita , Hellman, and Rosenberg’s Cancer Principles and Practice of Oncology, 11th
edition
3. Gunderson and Tepper clinical radition oncology 4th edition
4. Clinical radiation oncology, indications, techniques and results, 3rd edition
5. Upto date 2018
6. NCCN Guideline anal ca version 1.201
7. Scher ED, Romesser PB, Chen C, Ho F, Wuu Y, Sherman EJ, et al. Definitive
chemoradiation for primary oral cavity carcinoma: a single institution experience. Oral
Oncol 2015;51(7):709–15.
8. Spiotto MT, Jefferson G, Wenig B, Markiewicz M, Weichselbaum RR, Koshy M.
Differences in survival with surgery and postoperative radiotherapy compared with
definitive chemoradiotherapy for oral cavity cancer: a National Cancer Database
analysis. JAMA Otolaryngol Head Neck Surg 2017;143(7):691–9.
9. Google search
Editor's Notes
For example, primaries of the alveolar ridge and hard palate infrequently involve the neck, whereas occult neck metastasis is common (50%–60%) in patients with anterior tongue cancers.
However, extraction of healthy teeth does not reduce the risk of osteoradionecrosis and should be avoided
Multidisciplinary evaluation prior to treatment disposition helps to ensure that broad consensus treatment recommendations are made and interdisciplinary coordination of care is facilitated.
Once treatment has been completed, the multidisciplinary team should provide follow-up to the patient to ensure early detection of recurrent disease and adequate management of treatment sequelae
There is a lifelong risk of impaired healing that can lead to osteoradionecrosis, especially when teeth are extracted from hypovascularized and hypocellular bone.
Therefore, one objective of the pretherapy oral evaluation is to determine whether teeth in the proposed irradiated area can be reasonably maintained in a healthy state for the remainder of the patient’s life.
Medical, dental, and psychosocial issues that affect a person’s future dental health should be assessed at the pretherapy evaluation.
Patients who receive radiotherapy to major salivary glands are at lifelong risk for rampant caries.
Because of the numerous reported cases of progression of gingival recession and periodontal disease after RT, it may be difficult to assess the longevity of each tooth.
However, extraction of healthy teeth does not reduce the risk of osteoradionecrosis and should be avoided.
Consultation with the radiation oncologist is required before postirradiation extraction of teeth or invasive procedures that involve the exposure of irradiated bone
The overall health and functional status of the patient are important determinants in choosing between surgical and nonsurgical approaches.
The choice of treatment modality, either singly or in combination, depends on
- the stage and size of the tumor
- relevant patient factors such as performance status and toxixity
- comorbid disease, and convenience.
Treatment strategies are dictated by the anatomic subsite, tumor stage, histologic type, and patient factors such as medical comorbidities, performance status, and patient preference.
The outcome of intraoperative positive margins followed by immediate repeat resection revised to negative margins is associated with worse survival compared to negative margins achieved with initial resection (31% vs.
49%, respectively)
Buccal resections can often be performed with a transoral approach or with a lip-split incision to allow adequate exposure for mandibular or maxillary resection
The depth of tumor invasion has been reported to be the best predictor for regional metastasis in the cN0 neck.
Nevertheless, cutoffs for the extent of depth of invasion for which neck dissection is recommended remains ill defined.
The type of neck dissection (comprehensive or selective) is defined according to preoperative clinical staging, is determined at the discretion of the surgeon, and is based on the initial preoperative staging as follows:
N0 Selective neck dissection
Oral cavity at least levels I-III
Oropharynx at least levels II-IV
Hypopharynx at least levels II-IV and level VI when appropriate
Larynx at least levels II-IV and level VI when appropriate
N1-N2a-c Selective or comprehensive neck dissection
N3 Comprehensive neck dissection
Patients with advanced lesions involving the anterior tongue, floor of the mouth, or alveolus that approximate or cross the midline should undergo bilateral selective/modified neck dissection as necessary to achieve adequate tumor resection.
For oral cavity squamous cell carcinoma, SLN biopsy or the primary tumor depth of invasion is currently the best predictor of occult metastatic disease and should be used to guide decision making
Radical neck dissection (comprehensive neck dissection)
- the superficial and deep cervical fascia
- lymph nodes (levels I to V)
- the sternocleidomastoid muscle
- the omohyoid muscle,
- the internal and external jugular veins,
- cranial nerve XI, and the submandibular gland
A recent large randomized study in patients with cN0 oral cavity cancer compared neck dissection during surgery to observation of the neck and salvage neck dissection if nodal metastases appear at follow-up.
END resulted in higher rates of OS and DFS compared to therapeutic dissection at recurrence
Other analyses have shown that depth of invasion >4 mm is associated with increased risk of occult metastasis and late cervical recurrences.
In floor of the mouth tumors, a depth of invasion >1.5 mm is associated with 33% occult regional metastasis, whereas in buccal carcinomas, tumors of the maxillary alveolar ridge, and tumors of the hard palate, depth has not been extensively studied, and occult metastases are rare, occurring in 9% of patients and most often associated with T4 tumors.
Therefore, END is not indicated for early-stage buccal, maxillary alveolar ridge, or hard palate cancers in cN0 cases
Traditionally, indications for postoperative radiation therapy include multiple cervical metastases, positive or close margins, extracapsular extension, perineural invasion, advanced T stage, and mandibular bone involvement
The adverse clinicopathologic features in this study included
(a) close or positive margins,
(b) nerve involvement,
(c) ≥2 positive lymph nodes,
(d) largest node >3 cm,
(e) treatment delay >6 weeks, and
(f) Zubrod performance status ≥2.
There was a trend favoring CCRT in the subset of patients with stage III to IV disease, vascular embolism, perineural infiltration, and/or positive lymph nodes at levels IV and V with oral cavity or oropharyngeal primaries.
Several retrospective series have demonstrated an association between diminished outcomes and a delay beyond 6 weeks in initiating postoperative radiation
The achievement of pathologically negative marigns is significantly compromised with increasing T stage of the tumor.
More extensive procedures are required which are associated with a substantial amount of cosmetic deformity and functional morbidity.
Buccal mucosa primary, with diffuse margins and peritumoral
edema going up to or above the level of zygomatic arch and
without any satellite nodules.
2. Tongue primary {anterior 2/3rds} with the tumour extending
up to or below the level of the hyoid bone.
3. Extension of tumour of anterior two third of oral tongue to the
vallecula.
4. Extension of tumour into the high infratemporal fossa, as
defined by the extension of tumour above an axial plane passing
at the level of the sigmoid notch.
5. Extensive skin infiltration impacting the achievement of negative
margins
All patients were without any uncontrolled comorbidity and with adequate hematological, renal, and hepatic reserve were offered the chemotherapy
The response rate were significantly better with 3 drug regimen (p = 0.004) and in the 2 drug regimen, significantly better with docetaxel containing regimen (p = 0.025)
Many of the same series discussed above have also retrospectively compared the efficacy of definitive CRT to the paradigm of surgery followed by adjuvant RT or CRT for OC-SCC with conflicting results when considered as a whole
For instance, Spiotto et al. found 3-year OS to be statistically-significantly superior for patients in the NCDB receiving primary surgical resection compared to definitive CRT within propensity-score matched cohorts controlling for comorbidity, T-stage, N-stage, and tumor subsite among other factors . Similarly,
Gore et al. reported superior OS and disease-specific survival associated with surgery followed by adjuvant RT (n=54) compared to definitive CRT (n=50); however, the CRT group included a higher percentage of patients with stage III/IV disease (88% vs. 70%), and patients were treated at institutions with differing practice patterns .
Moreover, the Dana-Farber Cancer Institute reported their outcomes treating 30 patients with postoperative IMRT and 12 patients with definitive CRTfor OC-SCC and found significantly worse LRC at 2 years for the CRT group (91% vs. 64%) [13].
Notably, the majority of patients in their nonoperative group were excluded from surgery for disease that was too extensive for adequate resection or disease that would be associated with unacceptable postsurgical function indicating strong selection bias.
On the other hand, Tangthongkum et al. found statistically equivalent 5-year OS of 33% vs. 24% for patients receiving definitive concurrent CRT (n=61) or surgery with adjuvant RT/CRT (n=128), respectively