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Radiotherapy Unit, Meldola
Neoplasie del polmone e
trattamenti combinati
Donatella Arpa
Neoplasie del polmone e
trattamenti combinati
CHEMIOTERAPIA RADIOTERAPIA CHIRURGIA
IMMUNOTERAPIA
Definitive therapy for locally advanced NSCLC, generally combined with chemotherapy.
Definitive therapy for early stage .
Preoperative or postoperative therapy for selected patients treated with surgery.
Therapy for limited recurrence and metastases.
Neoplasie del polmone e trattamenti
combinati
Non-Small- Cell Lung Cancer
Unresectable IIIA-IIIB
Resectable IIIA
Locally Advanced Non-Small- Cell
Lung Cancer
Unresectable IIIA –IIIB NSCLC
Progression-free survival was significantly longer with
durvalumab than with placebo.
The secondary end points also favored durvalumab,
and safety was similar between the groups.
(Funded by AstraZeneca; PACIFIC ClinicalTrials.gov
number, NCT02125461.)
Optimal RT dose:RTOG 0617
a median survival of 28 months.
MS continues to range from 10 to 26 mo with a 5-year survival rate of less than 25%.
Previous work has demonstrated that Lengthening treatment time beyond 6 weeks has a negative impact on overall survival, likely due to accelerated repopulation of tumor cells.
Optimal RT dose…….
IS IT ENOUGH ???
Hyperfractionation
hypofractionation
Optimal RT dose…….
the analysis of Machtay demonstrated a moderate
linear relationship between lesional BED and overall
survival: for every 1 Gy increase in BED, there was
an absolute overall survival benefit ranging from
0.36% to 0.7%.
Non-Small- Cell Lung Cancer
Unresectable IIIA-IIIB
Resectable IIIA
Definitive therapy for locally advanced NSCLC, generally combined with chemotherapy.
Definitive therapy for early stage .
Preoperative or postoperative therapy for selected patients treated with surgery.
Therapy for limited recurrence and metastases.
Neoplasie del polmone e trattamenti
combinati
Despite having complete resection and adjuvant chemotherapy, up to 40% of resectable stage IIIA patients experience local tumor recurrence.
In order to improve local tumor control and survival, post-operative radiotherapy (PORT) has long been utilized to intensify local therapy.
Postoperative therapy (PORT)
Postoperative therapy (PORT)
Adverse effect on survival
by increasing the relative
risk of death by 21%,
translating to a 7%
reduction in 2-year OS from
55% to 48%.
Subgroup analysis
indicated a detriment in OS
for patients with stage I/II
N0-1 due to excess of toxicity
from PORT.
PORT for stage III-N2
disease trended toward, but
did not reach, a significant
survival benefit.
Is it true?
A significant flaw of the
PORT Meta-analysis was
the inclusion of historical
series with patients
treatments utilizing
antiquated techniques
that were potentially more
toxic than modern radiation
delivery with image
guidance, respiratory
motion assessment,
and higher dose
conformality.
Lally BE.Postoperative radiotherapy for stage II or III
nonsmall-cell lung cancer using the surveillance,
epidemiology, and end results database. J Clin Oncol 2006
Robinson CG. Postoperative radiotherapy for pathologic N2
non-small-cell lung cancer treated with adjuvant
chemotherapy: a review of the National Cancer Data Base.
J Clin Oncol 2015
Douillard JY Impact of postoperative radiation therapy on
survival in patients with complete resection and stage I, II,
or IIIA non-smallcell lung cancer treated with adjuvant
chemotherapy: the adjuvant Navelbine International
Trialist Association (ANITA) Randomized Trial. Int J
Radiat Oncol Biol Phys 2008,
Postoperative therapy (PORT)
Postoperative therapy (PORT) N2
In case of R1 resection (positive resection margin, chest wall),PORT should be considered
In completely resected early-stage NSCLC is not recommended
In case both ChT and RT are administered post-surgery, RT should be administered after ChT
Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up Annals of Oncology 28 (Supplement 4): iv1–iv21, 2017
Preoperative therapy
Therapeutic management options for stage III non-small cell lung cancerWorld J Clin Oncol 2017
February 10; 8(1): 1-20 ISSN 2218-4333
Surgical resection may not improve treatment
outcomes compared to definitive
radiotherapy. Within the context that
radiotherapy leads to lower morbidity and
mortality compared to surgery, definitive
chemoradiation is a reasonable treatment
option for patients with stage IIIA-N2
disease.
5-year OS and MS were not improved with the
induction chemoradiation.
Five-year PFS was significantly higher under the
intervention arm (22.4%) compared to
chemoradiation arm (11.1%).
Relatively high treatment-related deaths were
observed in the trimodality arm (7.9%) compared
to definitive chemoradiation arm (2.1%).
No significant differences were found for either
OS or PFS between the two groups, thus making
either strategies acceptable for resectable stage
IIIA, and select inoperable IIIA or IIIB patients.
RT
Oligoprogressive disease
Oligometastatic disease
Neoplasie del polmone e trattamenti
combinati
Oligoprogressive and oligometastatic
disease
Oligometastatic state : metastatic disease is
present at a limited number of anatomic sites is
being increasingly recognized.
Oligoprogressive state: disease progression at a
limited number of anatomic sites, with continued
response or stable disease at other sites of disease.
Such an oligoprogressive state is best described in
patients with NSCLC treated with molecular
targeted therapy.
Oligoprogressive and oligometastatic
disease
Radiotherapy :“Therapeutic Ratio”
The concept of therapeutic ratio is best
illustrated graphically, by making a direct
comparison of dose-response curves for both
tumor control and normal tissue complication
rates plotted as a function of dose.
Precise targeting
Imaging
Imaging
Contouring
Treatment volume
Icru 50, 62
Intrafraction modifications
Interfraction modifications
IGRT
Our experience
NSLC
25 Gy in 5 frazioni su T ed N 15 Gy in 3 frazioni
(con una disomogeneità interna sino a 37.5 Gy)
30 Gy in 5 frazioni su T
25gy in 5 frazioni su N
Ipofrazionamento della dose
Split course
I ciclo RT: 30 Gy in 5 frazioniT e 25 Gy in 5 frazioni N
(24-30/05/16)
II ciclo RT: 15 Gy in 3 frazioni 7-11/07/16
In
du
ctio
n C
T
Ra
dio
the
rap
y
Co
nso
lida
tio
n
CT
CDDP
75 mg/mq (1,21)
DOCETAXEL 75 mg/mq (1,21)
(2 cycles)
Accelerated
Hypofractio
nated RT (From 15th to 19th)
CDDP 75 mg/mq (1,21)
DOCETAXEL 75 mg/mq (1,21)
(2 cycles)
FBS and/or TBNA PET CT scan
Biopsy
Program protocol
T 30 Gy/5 fractions up to 40 Gy N 25 Gy/5 fractions up to 37.5 Gy
cT4 cN2 M0 squamous carcinoma
ycTx ycN0 M0
cT4 cN3 M0 adenocarcinoma
ycTx ycN0 M0
30/01/14 FBS ; ADENOK ALK TRASLOCATO
RT 2009, PROTOCOLLO IRST
ycTx ycN0 M0
Dal 29/03/2014- 2/04/14
25 gy in 5 frazioni con
dismogeneità 31.25 Gy
PD aprile 2015… avvio di
crizotinib
ypT0 ypN0(0/34) ypMx
cT4 cN3 M0 squamous carcinoma cT4 cN3 M0 adenocarcinoma
ycT0 ycN0 yMx
cT4 cN3 cM0 adenocarcinoma
ycT4 ycN0 cM0 adenocarcinoma
cT3cN2 cM0 large cell carcinoma
ycT0 ycN0 cM1 large cell carcinoma
Grade (No. = 19)
1 2 3-4
Toxicity (WHO/RTOG) No. % No. % No. %
Neutropenia - - 2 12.5 11 68.8
Leucopenia - - 2 12.5 8 50.1
Anemia - - 2 12.5 - -
Creatinine - - 3 18.8 - -
Fatigue - - 2 12.5 1 6.3
Mucositis - - 1 6.3 - -
Overall Chemoteraphy and
Radiotherapy Toxicity
No cases of acute pneumonia or esophagitis (G3/4)were observed
Overall Survival (median follow-up : 23 months, range 2-42)
2012/10/14
0.00
0.20
0.40
0.60
0.80
1.00
OS
0 6 12 18 24 30months
Median OS: 27.0 months (95% CI 9.6-not reached)
Pts at risk 23 20 11 10 6 4
Local Progression-Free
Survival
2012/09/14
Metastasis-Free Survival
0.00
0.20
0.40
0.60
0.80
1.00
Relg
ional F
ree S
urv
ival
0 6 12 18 24 30months
Median LPFS: 19.8 months (95% CI 9.7-not reached)
Pts at risk 17 16 10 7 3 2
0.00
0.20
0.40
0.60
0.80
1.00
Meta
sta
sis
Fre
e S
urv
ival
0 6 12 18months
Median MFS: 9.7 months (95% CI 5.8-not reached)
Pts at risk 17 13 5 4
Loc
al P
rog
ress
ion
Fre
e
Su
rviv
al
grazie