Management of Lung Cancer
By Dr Parneet Singh
1. Lung cancer is most commonly diagnosed at late stages. NSCLC stages at presentation range from 10% at stage I to 40% at stage IV.
2. Prognostic factors include patient performance status, weight loss, age, pulmonary function tests, tumor stage and molecular markers, completeness of resection, addition of chemotherapy and radiotherapy.
3. Treatment depends on stage - surgery or SBRT for stage I-II, chemotherapy and radiotherapy for stage III, chemotherapy and radiotherapy for consolidation or palliation in stage IV. Surgery provides the best chance for cure in early stages.
Christopher Azzoli, M.D., Assistant Member, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center: Current Modalities in the Treatment of Lung Cancer
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Christopher Azzoli, M.D., Assistant Member, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center: Current Modalities in the Treatment of Lung Cancer
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Carcinoma Larynx; Evidence based management
Staging - Surgery - Adjuvant therapy - Organ Preservation - Altered fractionation, chemotherapy - Radiotherapy (RT) techniques, Role of IMRT
Robert Sinha, M.D., Radiation Oncologist .Western Radiation Oncology - Dorothy Schneider Cancer Center - 2013 Mills-Peninsula Health Services Cancer Symposium
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
21 marzo 2014: Trattamenti stereo-RT e radiochirurgici come opzioni standard di trattamento: stato dell’arte in base a linee guida internazionali
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
6. Treatment of Lung Cancer Stage wise
• Stage I- Surgery ; SBRT
• Stage II- Surgery ; SBRT
• Stage III- CT+RT ; Surgery+/- CT+RT
• Stage IV – Chemotherapy +RT (consolidation and high
palliation)
6
7. Surgery
• Surgery is done in early stage NSCLC (stage I, II & IIIA )
• Only about 20% of patients suitable for curative surgery
• In these the tumor has not extended beyond broncho
pulmonary lymph nodes
• Lobar resection with hilar and mediastinal lymph node
sampling is the standard surgical treatment . 7
8. Surgery : PFT based algorithm
Surgery Type
Lobectomy /Lesser Pneumonectomy
FEV1 > 1.5 L
FEV1> 60%
DLCO > 60%
FEV1 > 2 L
FEV1> 60%
DLCO > 60%
Operate Operate•V/Q scan
•Calculated Post operative FEV1 & DLCO
< 40% > 40%
Exercise study
V02 max < 15 ml/kg/min V02 max > 15 ml/kg/min
Medically inoperable
Average risk
8
9. Types of surgery
Lobectomy
Single lobe of lung is removed
Bilobectomy
2 lobes of the lung are removed
Pneumonectomy
Removal of entire lung
When tumor extends close to carina T3N0
Wedge Resection
Removal of a small, pie shaped area of the
segment
Segmentectomy
A segment of the lung is removed
Chest Wall Resection
Removal of cancerous lung tissue for
cancers that have invaded the chest wall 9
16. Lymph node dissection
• Mediastinal lymph node dissection:
– Provides complete nodal staging.
– Identifies patients who require adjuvant radiotherapy.
– Improves survival.
– Improves local control.
• At least nodal sampling should be performed, if not complete
lymphadenectomy.
• Lobe specific Mediastinal nodal dissection in NSCLC:
– Right Side:
• Upper lobe (1,2,3,4,7)
• Middle lobe (1,2,3,4,7)
• Lower lobe (1,2,3,4,7,8,9)
– Left Side:
• Upper lobe (4,5,6,7)
• Lower lobe (4,5,6,7,8,9)
Shinichiro et al Surg today 2014
17. Complete Resection
• Free resection margins proved microscopically
• At least a lobe specific mediastinal nodal dissection with complete
hilar and intrapulmonary nodal dissection.
• At least 6 nodes should have been removed with 3 from
mediastinal nodes.
• Highest mediastinal node removed should be microscopically free.
Ramon et al Lung Cancer 2005 17
18. Criteria for inoperability
Tumor based criteria
Cytologically positive
effusions.
Vertebral body invasion.
Invasion or encasement of
great vessels.
Extensive involvement of
Carina or trachea.
Recurrent laryngeal nerve
paralysis.
Extensive mediastinal lymph
node metastasis.
Extensive N2 or any N3
disease
Patient related criteria
Cor pulmonale
CAD
Poor pulmonary function
Patient refusal
18
19. Segmentectomy or wedge resection vs
Lobectomy or Pneumonectomy
• Ginsberg et al Annals of Thoracic Surg,1995
• Three times higher recurrence rate in TI N0 with Limited
resections 15% vs 5%(p<.05)
• Morbidity, mortality equal in both arms.
• The Lung Cancer Study Group performed a randomized trial
of lobectomy vs limited surgical resection in patients with
T1N0or T2N0 NSCLC.
• Three times higher recurrence rate in TI N0 with Limited
resections 17% vs 6%(p = .008)
19
20. Results
• T1 tumors:
– 5year overall survival: 82%.
– 10 year overall survival: 74%.
• T2 tumors:
– 5year overall survival: 68%.
– 10 year overall survival: 60%
• Morbidity:
– 15% reduction in
spirometric values in
lobectomy
– 35% - 45% reduction after
pneumonectomy.
• Mortality:
– 5.9% perioperative
mortality for
pneumonectomy.
– 1.3% perioperative
mortality for lobectomy
Martini et al J Thor Cardiov Surg 1995
Watanabe Ann Thorac Surg 2004
20
21. Patterns of failure after Sx
• Patients who fail after surgery, present with extrathoracic disease 70% of the
time, local recurrence in 20% and local and distant metastasis in 10%.
• Tumors measuring 1-2 cm have a mediastinal nodal metastasis rate of 17%
as compared to those measuring 2 to 3 cm, when the rate is 37%
• Median overall survival was 9.1 years (stage T1) and 6.5 years (stage T2).
• Overall survival at 5 years was 72% (stage T1) and 55% (stage T2).
• Local recurrence-free survival at 5 years was 95% (stage T1) and 91% (stage
T2)
21
Martini et al J Thor Cardiov Surg 1995
Su et al J Thor Cardiov Surg 2014
22. Radiotherapy
Important role in the management of patients with non small cell
lung cancers
Radiotherapy (RT) series of Stage I patients treated definitively report
5-year survival rates ranging from 10% to 33% - Because of these
inferior outcomes, RT is only considered for patients who cannot
tolerate or refuse surgery
But with SBRT in stage I and stage II overall survival increased to 75-
80%
Intent - Radical
- Palliative
- Adjuvant
-Consolidation Onishi, IJROBP 201122
23. Role of radiotherapy
Localized early stage disease
( I, II,IIIa) (Resectable)
a) Alternative to surgery (medical
contraindication / patients
choice
b) As adjuvant to surgery
Locally advanced disease ( III)
(Unresectable)
Radical RT
― Alone
― With chemotherapy
Stage IV - treatment remains
palliative
– Symptoms palliation
– Local RT for consolidation
– RT to bone / brain mets
• Brachytherapy
― Alone (very early endobronchial
disease
― For boost or Palliative tratment
23
24. Modalities
Conventional 2 D planning
3 D planning –
a) 3 DCRT
b) IMRT
c) Gated RT
d) SBRT
Brachytherapy
24
25. Patient selection criteria for SBRT in early stage
• Medically inoperable – PFT ( FEV1 or DLCO<40%), DM/CAD,
cerebral disease, Pul. HTN
• Patient choice to avoid surgery
• PS 0-2
• Stage T1-2, N0 following PET-CT
• Max tumor size < 5cm
• Not adjacent to major vessels, heart, esophagus etc
25
26. Study fractionation Median
follow up
Local Control Overall survival Median
overall
survival
Other
Nyman et al Lung
Cancer 2006(74)
45Gy in 3 Fx
(BED 112.5),
43 mo 80%(2 years) OS 1/2/3/5 yr =
80/71/55/30%
39 mo
Van Zyp et
alRadiother and
Oncol 2009(70)
3 x 20Gy
(BED 180
15 mo 2yr LC 96% OS 1/2 yr =
83/62%
FFDM-90%
Timmerman
IJROBP 2009(70)
3 x 20Gy (T1),
3 x 22Gy (T2)
50 mo 3yr LC 88%, 3yr OS = 43% 32 mo FFDM 87%
DSS = 82%
FROG(118) 4 x 12-12.5Gy
(central)
3 x 22Gy
parenchymal
15 mo 2yr -93%, 2yr-74%, 2yr FFDM -
90%
2yr DFS 94%
26
27. SBRT vs Wedge resection in Stage I NSCLC
• 124 pts; T1-2N0MO
• 69 wedge resections, 58 SBRT
• SBRT prescribed as 48(T1) or 60(T2) Gy in 4 to 5 fractions
• Median follow up of 2.5 years
• No differences in DM, FFF, or CSS, but OS was higher with wedge
resection at 30 months.(87% vs 72%) p>.05
27
Inga et al JCO 2010
28. SBRT vs Surgery for Operable pts
Study Japan data (87 pts) Netherlands (177 pts)
Age 74 yrs 76 yrs
T1, T2 65, 22 pts (2.5 cm) 106, 71 pts (2.6 cm)
RT dose 42-72.5 Gy in 3-10 # 60 Gy in 3-8 #
Median FU 55 months 31.5 mo
5 yr OS 69.5% 51.3% (median: 61.5 mo)
5 yr LC (T1, T2) 92%, 73% 93% @ 3 yrs
Grade 3 RP 1.1% 2%
30 day mortality 0% 0%
28
Onishi, IJROBP 2011
Lagerwaard, IJROBP 2012
32. Technique for planning in 2 D RT
Pt taken on couch after explaining procedure and taking consent.
Position – supine with arms over head
No rigid immobilization required
2 cm margin around primary tumor & 1 cm margin around involved
regional lymph nodes
If mediatinal Lymph nodes or hilar lymph nodes involvement then
to go 1.5-2 cm across midline
32
33. UPPER LOBE PRIMARY
Field borders :
• Superior – cover I/L supraclav fossa
•Inferior – 4 cm below carina (2 VB
below carina)
•Medial – 3 cm across midline on
opp. side (opp. upper
mediastinal LN)
•Lateral – 2 cm margin
33
34. MIDDLE LOBE PRIMARY
Field borders :
• Superior – Thoracic inlet or SSN (if
no gross mediastinal nodes) but
cover I/L SCL fossa (if med. nodes
+)
•Inferior – 8-9 cm below carina
•Medial – 3 cm across midline on
opp. side (opp. Upper mediastinal
LN)
•Lateral – 2 cm margin
34
35. LOWER LOBE PRIMARY
Field borders :
• Superior –Thoracic inlet or SSN (if
no gross mediastinal nodes but cover
I/L SCL fossa (if med.nodes +)
•Inferior– vertebral origin of
diaphragm
•Medial – 3 cm across midline of
opp. side (opp.mediastinal LN)
•Lateral – 2 cm margin
35
39. Elective nodal irradiation
Irradiation of electively treated lymph nodes not necessery
Regional failure rates <10% where elective nodal areas not treated
Rationale for treating local tumor volume alone appears justified
when pt’s outcome not negatively impacted if regional lymph node
excluded
Rosenweig et al – IJROBP 2007
- 524 pt early stage treated to primary.
- No elective nodal irradiation.
- only 6.4% fail regionally. 39
40. Phase II
• Only primary tumour and ipsilateral hilum
• To reduce dose to cord
• To reduce dose to other critical structures
• Field arrangement like ant + post oblique or both oblique can
be used
41. Radical EBRT
Dose: 60-64 Gyin 30-32 # over 6 weeks
AP/PA portals treated till spinal cord tolerance ( ~ 45 Gy)
3 field techniques also used
Boost of 20 Gy delivered via oblique fields-3 fields anterior and posterior
oblique at 35-40 degrees with another anterior oblique at 50 degree
At Max Hospital – total dose of 60-64Gy/30-32#
41
42. Postoperative Radiotherapy(PORT)
Post-operative Radiotherapy (PORT):
– Indications:
– Residual disease post resection
– Incomplete resection (+ve / close margins)
– +ve mediastinal mets(N2 or N3)disease
In stage IA , IB , IIA - Additional radiotherapy is generally not needed if
there is no evidence of cancer in the surgical margins.
DOSE
50-54 Gy/ 25-27 fr/ 5-6 weeks
Phase I: 40 Gy/ 20 fr across the mediastinum
Phase II: 10-14 Gy/ 5-7 fr/2 cm margin (off cord).
PORT improves LRC but no ↑se in survival
Bradleyet al JCO 2005 42
43. • SEER (JCO 2006): 7,400 patients with stage II–III resected
NSCLC
• PORT used most often for patients <50 years, T3–4,larger T
size, increased N stage involved LN.
• Dose of 50 Gy f/b boost of 10 Gy to residual disease
• PORT improved 5-year OS for N2 patients(20→27%, HR
0.85)
• Reduced OS for N0 (41 → 31%, HR 1.2), and N1 (34 → 30%,
HR 1.1) patients.
44
44. Radiation for Medically Inoperable Early Stage
NSCLC
Author # PTs EBRT
Dose
(Gy)
%T1 %T2 Overall
5 yr
Survival
T1 5 yr
Survival
%
T2 5 Yr
Survival
%
Overall
Median
Survival
Local
Failure %
Haffty 1988 43 59 (con)
54 (split)
28 72 21% 28 mos 39
Noordijk
1988
50 60 (split) 50 50 16% 27( 4 yr) 15 4 yr
0 if>4cm
27 mos 70
Zhang
1989
44 55-70 14 86 32% 67 26 27 died
local failure
Talton
1990
77 60 3 75
22-T3
17% 50 18
Sandler
1990
77 32 32 53 3-6cm
12 > 6cm
17%
22%
30
3 yr
3-6 cm
17% 3 yr
20 mos 56 3 yr
Doseretz
1992
152 60-69 29 41
27-T3
10% 33-49
3 yr
22
3 yr
17 mos T1 30
T2 80
T3 86
Kaskowitz
1993
53 63.2 38 62 6% 20.9 49 3 yr
Slotman
1994
47 32-56
Hypofrac
32 68 25% 28 10 20 26
Graham
1995
103 56.8 34 66 13% 29 4 16.1 45
46. Palliative Disease
Aim:
– To achieve relief of symptoms only when disease is too advanced for
local control
Indications:
– T4 disease - For symptom palliation the dose and fractionation is tailored
to the condition depending upon the life expectancy : Extensive N2 or N3
disease
– Distant metastasis
– Weight loss > 12% of body weight
– Performance status -Poor
Treatment schedules chosen:
• If life expectancy is > 3-4 months : 30 Gy in 10# over 2 weeks
• If life expectancy is from days to 3 months :
– 20 Gy in 5# over 1 week
– 8 Gy in single fraction
47
47. Target volume for 3D planning
Modern treatment planning requires accurate target volume delineation:
1. The Gross Tumor Volume (GTV) - Primary tumors
- gross involved nodes + regional lymphnodes > 1cm in short axis
2. The Clinical Target Volume (CTV) - Areas suspected of subclinical
involvement ↓
- Margin around gross tumors (6mm for SCC & 8mm for adeno)
- Regional LNS(3mm for <2cm & 5mm for>2cm)
3. The Internal target volume for tumor motion 7mm-1.5cm fluroscopy based
4. At Max Hospital axially 0.5cm and cranio-caudal-1cm
BASED ON FLUROSCOPY
3. The Planning Target Volume (PTV)margin around ITV to compensate for
variation in treatment set up(5mm).
Grills et al IJROBP 2007
48
48. IMPACT OF CT WINDOW LEVEL
Countouring of primary tumor should always be done in lung window
rather than mediastinum window as it may lead to under estimation of
primary tumor
49. IMPACT OF PET ON RT PLANNING
Where ever possible PET should be fused with planning CT scan as it helps
to distinguish between tumor and atelectasis
50. Inter and intra-fractional organ motion
Respiratory motion is an important source of uncertainty for target
delineation
Interplay effect between tumor motion and leaf motion may increase
dosimetry uncertainty
Respiratory motion may affect dose to tumor as well as to normal structures
(lung, heart , esophagus, cord, etc)
Controlling tumor motion is of primary importance - reduction in margins
51
51. Tumor mobility
Two approaches to reduce the effect of respiratory motion: respiration
gating of the patient or controlling patient breathing
Patient’s breathing is monitored using a variety of devices & radiation is
delivered when the patient’s respiratory cycle reaches a specific phase
The patient’s breathing is altered by speaking to the patient(breath in-
breath out)
Breath-hold reduces tumor mobility but is poorly tolerated by patients with
lung cancer
Breath-hold or gating should take place with on-line monitoring
52
52. Respiratory Gating
• Conforms to target
• Higher doses to target tissue
• Less side effects from normal tissue
• Sharp dose gradient between target tissue and normal
tissue
• Misjudgment causes
• Underdose target
• Overdose normal tissue
53
53. Tracking Respiration
• External Marker
– Camera system
• Sends signal
• Reflected off markers
• Internal Markers
– Implanted gold
visicoil markers
54
54. Dose Volume Constraints
Organ RT Alone CT+RT CT/RT f/b Sx
Lung V20<40%
MLD<20Gy
V20<35%
V10<45%
V5<65%
MLD<20Gy
V20<20%
V10<40%
V5<55%
MLD<20Gy
Esophagus Dmax<75Gy
V60<50%
Dmax<75Gy
V55<50%
Dmax<75Gy
V55<50%
Cord 50 Gy 45Gy 45Gy
Heart V40<50% Same as RT alone Same as RT alone
Kidney 20Gy(<50% of
combined both
kidneys or <75% ofone
side of kidney if
another kidney is not
functional)
Same as RT Same as RT
Liver 30Gy(<40%) Same as RT Same as RT
Marks et al IJROBP 201055
55. Brachytherapy
Brachytherapy plays an important role in the palliative treatment of
obstructive disease
Brachytherapy used as definitive treatment in selected cases of early
endobronchial disease
Postoperative treatment of small residual peribronchial disease
Intraluminal brachytherapy alone can also be considered for the palliative
treatment of Endobronchial or endotracheal recurrent tumor growth in
previously irradiated areas
56
56. Technique
Uses Ir192 remote afterloading HDR brachytherapy
The total length of endobronchial component with 2 cm margins on either
side treated
Usual treatment length is 6-10 cm
Source is passed through a catheter placed transnasally under
bronchoscopic guidance.
Dose prescribed is 8 Gy in 2# after EBRT(depending on dose)
At max hospital 5-6Gy/1#
Dose is prescribed at 1 cm from the central axis of the source
57. Chemotherapy
Based upon the premise that 70% - 80% patients will have micrometastasis
during presentation
Situations where Chemotehrapy can be used:
• Neoadjuvant CT as an induction regimen
• Radical Concurrent CT wit Radiation
• Adjuvant chemotherapy with or without radiation
• Palliative chemotherapy in systemic disease
Currently platinum based combination chemotherapy regimen preferred
for the treatment NSCLC
58
58. Post op chemotherapy for high risk patients with
margin negative surgery
• Poorly differentiated histology
• Vascular invasion
• Wedge resection
• Tumor size>4 cm
• Incomplete nodal sampling
59
59. Chemoradiotherapy as a Primary Combined
Treatment of NSCLC
Aim
1) Exploiting additive effect on the locoregional tumor.
2) The control of micrometastases by chemotherapy component
3) Mutual enhancement
Types
Sequential
Concurrent
60
64. Chemotherapy at Max Hospital
• AdenoCarcinoma- Pemetrexed(500mg/m2)+ cisplatin(75mg/m2)/
Carboplatin (AUC-5)
• Squamous Cell carcinoma- Gemcitabine(1250mg/m2)+cisplatin or
Gemcitabine+ Carbopaltin or paclitaxel(50mg/m2)+Carboplatin
• For concurrent paclitaxel+ carboplatin (weekly) or cispaltin+
Etoposide(100mg/m2 D1-D3)
• NACT-3 cycles of chemo f/b reassessment
65
65. Anti-EGFR Targeted Agents: Biological Rationale
Activation of EGFR linked with
Increased cell proliferation
Angiogenesis
Metastasis
EGFR expression correlates with
Poor response to treatment
Disease progression
Poor survival
Agents that selectively target EGFR could inhibit and prevent the
pathogenesis of various cancers
66
66. EGFR
Gefitinib and erlotinib target the tyrosine kinase EGFR
Only about 10% of patients have a rapid and dramatic clinical response to
gefitinib
Efficacy may be attributed to somatic mutations in EGFR gene
Erlotinib has activity in NSCLC (10-15% of tumors will shrink; ~30-40% will
be stable)
Tarceva improves survival in patients with metastatic disease that have
failed first line chemotherapy
Rash and diarrhea - most common side effects
Gefitinib - 250 mg O.D. oral
Erlotinib- 150mg OD oral
N Engl J Med. 2004;350:2129-2139
Cancer Res. 1997;57:4838
67
67. ALK Mutation
• EML4-ALK gene fusions occur almost exclusively in carcinomas
arising in non-smokers
• About 4% of non-small-cell lung carcinomas involve an EML4-ALK
tyrosine kinase fusion gene.
• EML4-ALK mutation rarely occurs in combination with K-RAS or
EGFR mutations.
• Crizotinb and Ceretinib FDA approved
Matelli et al M J Pathol 200968
68. NSCLC Survival
Stage TNM 5-y Survival
Stage IA T1N0M0 65%
Stage IB T2N0M0 45%
Stage IIA T1N1M0 30%
Stage IIB T2N1M0
T3N0M0
28%
25%
Stage IIIA T1-2N2M0
T3N1-2M0
20%
18%-20%
Stage IIIB T4N0-3M0
T1-4N3M0
5%
5%
Stage IV Any T, Any N, M1 <1%
Non-small cell lung cancer survival rates by stage (2013, July 12). American Cancer
Society.
69
69. Radiotherapy: Toxicity
• The most common and significant radiation toxicity is radiation
pneumonitis.
• Occurs in two forms:
– Acute (1-6 months).
– Late (months to years).
• While acute radiation pneumonitis responds to corticosteroids, late
pneumonitis does not respond.
• Other toxicities encountered include, transverse myelitis, esophageal
strictures or perforation.
70. Acute Toxicities
• Usually during treatment or within 1 month
• Acute esophagitis starts in 3rd week of RT
• Treatment includes xylocaine and analgesics
• Nutritional status has to be kept in mind
• If it falls nasogastric tube or PEG insertion has to be done
• Bacterial and fungal infection has to be ruled out
• Cough –relieved with anti-tussive therapy
71
71. Late Toxicities
• Radiation Pneumonitis
• Pulmonary fibrosis
• Esophageal stenosis, ulceration, perforation and fistula
formation5-15%
• Cardiac- Pericarditis
• Spinal cord myelopathy
72
Gasper Cancer 2000
72. Radiation Pneumonitis
• Incidence of radiation pneumonitis is
related to:
– Dose.
– Fractionation.
– Volume of lung irradiated.
– Pre-treatment pulmonary
function.
– Administration of concurrent
chemotherapy
• Asymptomatic radiological findings
may be seen in 50% patients.
• Clinical radiation pneumonitis may
develop in as many as 20% patients.
Latent phase: Loss of type 2 pneumocytes,
Depletion of surfactant production and
resultant protein translocation into the alveoli
Edema of interstitial spaces
Thickening of alveolar septa
Acute clinical phase: Cough, dyspnea
Loss of capillaries and collagen deposition
Chronic restrictive changes
Pathophysiology of Radiation Pneumonitis
73. Pneumonitis grading.
• Grade 1: asymptomatic radiographic changes.
• Grade 2: changes requiring steroids or diuretics; dyspnea on
exertion
• Grade 3: requires oxygen; shortness of breath at rest
• Grade 4: requires assisted ventilation
• Grade 5: death
74
75. Conclusions
NSCLC accounts for more than 75% of all cases of lung cancer
Accurate staging of NSCLC is critical because treatment options depend on
the spread of the disease
Surgery /SBRT done for early stage NSCLC
Radiation has an important part to play in all stages & for radical treatment
as well as palliation
A number of other molecularly targeted drugs are being actively
investigated
Smoking cessation remains the only proven effective way to reduce the risk
lung cancer
76
77. NSCLC
Stage I & II
Fit
Unfit
Surgery
RT (± CCT)
Stage IV
Palliative RT / CCT
Supportive care
Medication
Brachytherapy
Stage III
Operable
Inoperable
Borderline
Surgery
Adjuvant RT ± CCT
Induction CCT
Fitness
for Sx
No
Fitness for
Surgery
Margins –ve,
+CT(4-6 Cycles)
Margins +ve,
Post op RT+CT
f/b CT
Conclusions
SBRT
78
78. SVC Syndrome
Extrinsic compression of SVC
or intracaval thrombosis
ETIOLOGY:
• Bronchogenic ca 80%
• Malignant lymphoma 15%
• Benign 2-5%
MANAGEMENT:
• General measures
• Radiation
• Decongestive measures
prior to starting RT
– I/V steroids
– Moist Oxygen
– Bronchodilators
• RT induced edema can
exacerbate symptoms in the
first few days
• RT doses will depend upon
the GC of the patient.
• Usual doses:
– 30 Gy in 10# in 2 weeks
– 20 Gy in 5 # in 1 week
– 8 Gy in SF
• Regimen selected depends
on patient age and GC.
79
79. Pancoast Tumors (SST)
• Lung tumors originating at apical pleuropulmonary groove (superior sulcus)
• CLINICAL:
Pancoast’s Syndrome:
- Pain in shoulder/ scapula medially
- Radicular pain in ulnar distribution
- Horner’s Syndrome
• MANAGEMENT
Resection
Extended en bloc resection
Preoperative RT:
– 50% - 60% become operable after preoperative RT.
Postoperative RT:
– no survival benefit
– However difficulty in obtaining clear resection margins make post op RT
necessary
80
80. • In patients with painful apical syndrome only:
RT : 30 Gy / 10 #
FIELD BORDERS:
Superior - C5 level
Inferior - 5 cm below carina
Laterally - include the full width of the upper 4 ribs.
Medially - entire mediastium.
Patient is then assessed for surgery.
• When surgery C.I.
Treatment goal is palliation of symptoms.
RT/CCT as the main therapeutic modalities.
81
81. Management
Resection
Extended en bloc resection of the chest wall including:
Posterior portions of first three ribs , part of upper thoracic vertebrae
(transverse processes) , intercostal nerves , lower trunk of brachial plexus
, stellate ganglion , lung (usually lobectomy)
Postoperative RT - No survival benefit has been found
However difficulty in obtaining clear resection margins make post
operative RT necessary with an aim to improve local control
Inoperable
N2 Nodal Disease
Extensive Vertebral Body Invasion
Superior Vena Cava Syndrome
Invasion of Subclavian Artery
Extensive Brachial Plexus Involvement
Medically Inoperable (COPD)
Distant Metastases
Treatment goal is palliation of symptoms.
RT/CCT are the main therapeutic modalities.
82