The document discusses lung cancer incidence, mortality rates, and EGFR mutation rates in Jordan compared to global values. It also discusses molecular testing practices for NSCLC in Jordan, including which driver mutations are routinely tested, the tests used to detect EGFR mutations, and which exons are examined. Adjuvant EGFR therapy is not routinely used in Jordan for early-stage NSCLC. For progression on EGFR TKIs in mutated NSCLC, re-biopsy for T790M is done, and local therapies like stereotactic radiation are available treatment options.

2. Q1.COMPARING IT TO WORLD-WILD VALUES WHAT ARE THE
JORDANIAN INCIDENCE AND MORTALITY RATES FOR LUNG
CANCER IN GENERAL. AND WHAT ARE THE % OF EGFR
MUTATED NSCLC?
Q2. WHICH NSCLC PATIENTS DO WE ROUTINELY TEST FOR
DRIVERS MUTATIONS?
Q3.WHICH ARE NSCLC DRIVERS MUTATIONS THAT CAN BE
TESTED ?
Q4. ARE THE USED TESTS FOR EGFR MUTATINOS DETECTION
AND WHAT ARE THE EXAMINED EXONS IN THESE TESTS?
Q4. AMONG DIFFERENT INDICATIONS FOR EGFR TESTING AND
ANTI-EGFR TTT , DO WE USE THEM IN “ ADJUVANT “
SETTINGS?
Q5. HOW WE DEAL WITH “ROGRESSION ON TKI” AND WHAT
ARE THE AVAILABLE “LOCAL TREATMENT MODALITES “?

3. Q1.ARE JORDANIAN (INCIDENCE AND
MORTALITY ) RATES FOR LUNG
CANCER SIMILAR TO THOSE OF
INTERNATIONAL ONE? AND ALSO,
WHAT ABOUT THE RATE OF POSITVITY
OF EGFR MUTATIONS IN JORDAN?

5. Colon
8%(922)

7. 1ST most common cancer and 1ST
most common cancer related deaths in
WORLD-WILD MALES

8. 8TH
5T
H
Vs 3rd most
common cancer and
2nd most common
cancer related deaths
in WORLD-WILD
FEMALES.

9. Jordan
World-wild
A.INCIDENCE
2ND (9.1%)
(
2ND (11.4%
-BOTH SEX
1ST (16.5%)
1ST (14.3%)
-MALE
8TH (5.5%)
3RD (8.4%)
-FEMALE
B.MORTALITY:
1ST(15.2%)
1ST (18%)
-BOTH SEX
1ST (25%)
1ST (21.5%)
-MALE
5TH (5%)
2ND (13.7%)
-FEMALE

10. PREVALENCE OF SMOKING IN
JORDANIN MALES WAS 57 %
PREVALENCE OF SMOKING IN
JORDANIN FEMALES WAS 13 %
53 RD
4TH

11. PREVALENCE OF SMOKING IN JORDANIN ADULTS, BOTH SEXES
WAS 34.8% 16 TH

15. -Many systematic reviews and meta-analysis showed
that EGFR mutations are found in approximately 10%
of Caucasian patients with NSCLC and up to 50% of
Asian patients. While the overall pooled prevalence was
32% and it was higher in Females (43% vs 24%) and
Non-smoker(49% vs 21%) and Adeoncarcinoma 38%
vs 11.7%)
-Jordanian values -According to survey among differen
pulmonry cancers treating physicians - for EGFR
MUTATION was around 20%.

16. Q1.ARE JORDANIAN (INCIDENCE AND
MORTALITY ) RATES FOR LUNG CANCER
SIMILAR TO THOSE OF INTERNATIONAL ONE?
AND ALSO, WHAT ABOUT THE RATE OF
POSITVITY OF EGFR MUTATIONS IN JORDAN?
. DESPITE THAT INCIDENCE AND MORTLITY
RATES FOR LUNG CANCERS ARE LESS IN
JORDANIAN FEMALES . THEY ARE GENERALLY
SIMILAR TO THOSE WORLD-WILD VALUES IN
OVERALL POPULATION
.PERCENTAGES OF EGFR MUTATION IN
NSCLC AT JORDAN ARE AROUND 20%, WHICH
IS A MIDAY BETWEEN ASIAN AND

18. Q2.DURING OUR ROUTINE PRACTICE ,
DO WE USUALLY DO BIOMOLECULAR
TESTING FOR NSCLC-SQUAMOUS CELL
CARCINOMA?

19. DESPITE THAT, Most patients with the common EGFR
mutations are nonsmokers or former light smokers with
adenocarcinoma histology
AND THAT Certain characteristics OF SQUAMOUS such as
never smoking status, small biopsy specimens, and mixed histology
Are more likely to have EGFR-MUTATION
BUT, the cumulative incidence of targetable molecular
alterations in squamous cell carcinoma across all alterations ranges
from 2% to 10%.
THUS , DESPITE THE LOWER INCIDENCE OF EGFR MUTATION IN
SQUAMOUS –NSCLC . BUT NCCN Panel recommends that
:molecular testing should be considered in all patients with
metastatic NSCLC (non - squamous AND squamous cell carcinoma
)because these patients may also have actionable mutations , such as

21. Q1.DURING OUR ROUTINE PRACTICE ,
DO WE USUALLY DO BIOMOLECULAR
TESTING FOR NSCLC-SQUAMOUS CELL
CARCINOMA?
.EGFR MUTATION ANALYSIS IS USUALLY
ORDERED FOR METASTATIC NSCLC-NON
SQAMOUS CELL CARCINOMA SUBTYPE AND IN
SQUAMOUS CELL CARCINOMA WITH CERTAIN
CHARACTERISTICS SUCH AS “ never smoking status,
small biopsy specimens, and mixed histology “

22. Q2. WHAT ARE THE DRIVERS
MUTATIONS TESTS AVAILABLE
AND ROUTINELY DONE FOR
NSCLC AT JORDAN?

23. “Panel strongly advises broader molecular
profiling with the goal of identifying rare
driver mutations for which effective drugs
may already be available, or to appropriately
counsel patients regarding the availability of
clinical trials. Broad molecular profiling is
defined as molecular testing that identifies all
biomarkers identified in NSCL”

24. EGFR
AL
K
PDL-1

25. Q3. WHAT ARE THE DRIVERS
MUTATIONS TESTS AVAILABLE
AND ROUTINELY DONE FOR
NSCLC AT JORDAN?
.EGFR , ALK, PDL-1% TESTING ARE
THE TESTS THAT ARE AVAILABLE
AND USULLY PERFORMED AT
JORDAN DURING TREATING NSCLC-
PATIENTS

26. Q4. DO WE USE THE
RECOMMENDED TESTS FOR EGFR
MUTATION DETECTION AND WHAT
EXONS MUTATIONS DO WE
USUALLY TESTED ?

27. A.INITIAL NSCLC DIAGNOSIS:
the panel feels that plasma cfDNA/ctDNA DNA testing should not be used to
diagnose NSCLC; tissue should be used to diagnose NSCLC.Uunless: if 1) the
patient is not medically fit for invasive tissue sampling; or 2) there is insufficient
tissue for molecular analysis
B. MOLECULR MUTATION DETECTION:
. IHC is not recommended for detecting EGFR mutations.Real-time
PCR, Sanger sequencing (paired with tumor enrichment), and NGS
are the most commonly used methods to assess EGFR mutation
status.
C. AT DISEASE PROGRESSION:
.Data suggest that plasma genotyping (also known as plasma testing or liquid
biopsy) may be considered at progression instead of tissue biopsy to detect
whether patients have T790M; however, if plasma testing is negative, then tissue
biopsy is recomend
.the panel added content stating that NGS is preferred for detecting EGFR exon

28. EGFR EXON-MUTATIONS:
A. COMMON:
The most commonly described mutations in EGFR (exon 19 deletions, p.L858R
point mutation in exon 21) are associated with responsiveness to oral EGFR
tyrosine kinase inhibitor (TKI) therapy
B. LESS COMMON:
less commonly observed alterations in EGFR, which cumulatively account for
~10% of EGFR-mutation positive NSCLC (ie, exon 19 insertions, p.L861Q,
p.G719X, p.S768I) are also associated with responsiveness to certain EGFR TKIs
C. RESISTANCE MUTATION:
.Most EGFRex 20 alterations are a diverse group of in-frame duplication or
insertion mutations. ▪ These are generally associated with lack of response to first-,
second-, and third-generation EGFR TKI therapy.HOWEVER, some of exon 20
mutations are assosciated with repsonse to some TKIs
.EGFR p.T790M is most commonly observed as a mutation hat arises in response
to and as a mechanism of resistance to first- and second generation EGFR TKI. In
patients with progression on first- or second-generation TKI with p.T790M as the
primary mechanism of resistance, third generation TKIs are typically effective.

30. .COMMON : E.19 DELETIONS + E.21
L858R
.UN-COMMON: E.18 G719X + E.20
S7681+ E.21 L861Q
.RESISTANCE: T 790 M + E.20
INSERTIONS

33. Q4. DO WE USE THE
RECOMMENDED TESTS FOR
EGFR MUTATION DETECTION
AND WHAT EXONS MUTATIONS
DO WE USUALLY TESTED ?
.EGFR-MUTATIONS TESTING IS USUALLY
PERFORMED BY PCR TESTING . AND
,ALMOST ALL CLINICALLY
SIGNIFICANT EXONS MUTATIONS ARE
INVOLVED DURING TESTING, TURN-
AROUND TIME IS ABOUT 1 WEEK

34. Q5. DO WE USE ANTI -EGFR AS
ADJUVANT TREATMENT FOR EARLY
NSCLC IN OUR CLINICAL PRACTICE ?

35. 2. The NCCN Panel recommends atezolizumab as an adjuvant therapy
option for patients with completely resected (R0) stage IIB to IIIA or high-
risk stage IIA NSCLC and PD-L1 of 1% or more who have previously
received adjuvant chemotherapy based on clinical trial data and FDA
approval
3. The panel recommends osimertinib as an adjuvant therapy option for
patients with completely resected (R0) stage IB to IIIA EGFR mutation-
positive NSCLC who have previously received adjuvant chemotherapy or
are ineligible to receive platinum-based chemotherapy based on clinical
trial data and the FDA approval.
B. IF SURGICAL MARGINS ARE POSITIVE: in these patients, options
after an R1 OR R2 resection include: 1) re-resection and chemotherapy;
or 2) chemoradiation (either sequential or concurrent)
A,IF COMPLETE EXCISION:
1. NCCN recommends Postoperative chemotherapy for patients with T2ab,N0
tumors And who have high-risk features, including poorly differentiated tumors,
vascular invasion, wedge resection, tumors larger than 4 cm, visceral pleural
involvement, and unknown lymph node status (Nx)

38. The primary endpoint—DFS in patients with stage II and IIIA NSCLC—shows
good separation of the curves between patients receiving adjuvant osimertinib vs
placebo. The median DFS was not reached with osimertinib vs 20.4 months
with placeb

39. DFS in the overall study population (stage IB-IIIA), the median was not
reached with osimertinib vs 28.1 months with placebo
. At 12 months, 97% of patients in the osimertinib arm were disease free vs
69% on placebo. At 24 months, these rates were 89% vs 53%, and at 36
months, they were 79% vs 41%, respectively

40. In interim analysis, the median OS was not reached in either
arm and the OS curves very closely aligned, showing high rates
of survival in both arms. However, these OS data were very
immature (5% maturity) and not yet statistically significant.

42. Q5.DO WE USE ANTI -EGFR AS
ADJUVANT TREATMENT FOR EARLY
NSCLC IN OUR CLINICAL PRACTICE ?
.IT IS NOT YET A ROUTINE TO USE ANTI
EGFR “OSIMERTINIB” IN THE ADJUVANT
SETTING NSCLC

43. HOW DO WE DEAL WITH PROGRESSION
TO TKI IN EGFR MUTATED-NSCLC AND
WHAT ARE THE AVAILABLE LOCAL
THERAPY OPTIONS IN CASE OF
CONTINUATION OF EGFR-TKI?

44. .Continuation of Targeted Therapy After Progression on Initial Therapy
Patients may continue to derive benefit from EGFR TKIs, ALK inhibitors, or
ROS1 inhibitors after disease progression on first-line targeted therapy
in EGFR-MUTATED NSCLC : discontinuation of TKIs leads to more rapid
progression of disease (symptoms, size, Avidity PET scan) that is termed the flare
phenomenon
. Erlotinib, gefitinib, afatinib, dacomitinib, or osimertinib may be continued after
development of acquired resistance, but subsequent therapy with osimertinib is
also an option for select patients with EGFR T790M
.Furthermore, data show that when cancers start to progress, discontinuation of
the EGFR TKI can lead to a much more accelerated progression of the cancer
.Thus, continuing EGFR TKIs is beneficial in many patients even after their
cancers develop resistance to EGFR TKIs.

45. . local therapy should be considered (eg, SRS to brain metastases or other sites, SABR for
thoracic disease) …..IGTA therapy (eg, cryotherapy, microwave, radiofrequency) may be
an option for select patients not receiving SABR or definitive RT
A.RADIOTHERPAY TECHNIQUES:
a major paradigm shift from radiotherapy practice over the past 90 years when the goal
was to maximize tumor exposure to radiation with minimizing the surrounding normal
cells TOXICI
. because of technological advances in image guidance and treatment delivery techniques
that enable the delivery of large doses to tumors with reduced margins .thereby minimizing
doses to surrounding normal tissues .this led to The development of SRS and SBRT
. SRS: usually limited to brain lesions, is an extreme example of SBRT in that the entire
dose is typically given in a single fraction…….while, SABR: is defined as treatment of
tumors outside of the brain with 1–5 high dose fractions
B.IGTA:
. RFA: a needle-like RFA probe is placed inside the tumor. The radiofrequency waves
passing through the probe increase the temperature within tumor tissue, which results in
destruction of the tumor. performed under image guidance by interventional radiologists
. Cryotherapy : thin needle-like probe : (cryoprobe) is inserted through your skin and
directly into the cancerous tumor. A gas is pumped into the cryoprobe in order to freeze the

48. HOW DO WE DEAL WITH PROGRESSION
TO TKI IN EGFR MUTATED-NSCLC AND
WHAT ARE THE AVAILABLE LOCAL
THERAPY OPTIONS IN CASE OF
CONTINUATION OF EGFR-TKI?
-IN CASE OF PROGRESSION ON 1ST AND 2ND GENERTION TKI
:
WE SEND FOR T790M MUTATION, INITIALLY BY LIQUIDE
BIOPSY IF NE GATIVE WE REPEAT IT ON TISSUE BIOPSY
…IF POSITIVE WE SWITCH TO OSIMERTINIB AND IF
NEGATIVE WE START CHEMOTHEAPY
-IN CASE OF PROGRESSION ON OSIMERTINIB WE SWITCH
TO SYSTEMIC CHEMOTHERPAPY
-NOT ALL LOCAL THERAPY MODALITIES ARE READILY
AVAILABLE DURING OUR CLINICAL PRACTCE

49. . DESINCIDENCE AND MORTLITY RATES FOR LUNG CANCERS ARE
ARE GENERALLY SIMILAR TO THOSE WORLD-WILD VALUES IN
OVERALL POPULATION……..PERCENTAGES OF EGFR MUTATION IN
NSCLC AT JORDAN ARE AROUND 20%,.
..EGFR MUTATION ANALYSIS IS USUALLY ORDERED FOR
METASTATIC NSCLC-NON SQAMOUS CELL CARCINOMA SUBTYPE
AND IN SQUAMOUS CELL CARCINOMA WITH CERTAIN
CHARACTERISTICS SUCH AS “ never smoking status, small biopsy specimens,
and mixed histology
. .EGFR , ALK, PDL-1% TESTING ARE THE TESTS THAT ARE
AVAILABLE AND USULLY PERFORMED AT JORDAN DURING
TREATING NSCLC-PATIENTS
. EGFR-MUTATIONS TESTING IS USUALLY PERFORMED BY PCR
TESTING . AND ,ALMOST ALL CLINICALLY SIGNIFICANT EXONS
MUTATIONS ARE INVOLVED DURING TESTING, TURN-AROUND TIME
IS ABOUT 1 WEEK
.IT IS NOT YET A ROUTINE TO USE ANTI EGFR “OSIMERTINIB” IN
THE ADJUVANT SETTING NSCLC