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