Interventionelle Radiologie im Kontext von Oligometastasierung · klinik und poliklinik fÜr...

KLINIK UND POLIKLINIK FÜR RADIOLOGIE

INTERVENTIONELLE RADIOLOGIE

JENS RICKE


KLINIKUM DER UNIVERSITÄT MÜNCHEN®

CLOCC STUDY

Ruers et al. J Clin Oncol 33, 2015 (suppl; abstr 3501)

RF + Systemic treatment

± resection if an optionPatients with unresectable CRC liver metastases

N=152

Systemic treatment

± resection if an option

Randomization



RADIOFREQUENCY ARM

RF + Systemic

(N=57)

Treatment by RF 30 (52.6%)

RF + resection* 27 (47.4%)

RF procedure laparotomy 51 (89.5%)

laparoscopically 1 (1.8%)

percutaneously 4 (7.0%)

unknown 1 (1.8%)

Type of resection (N=27)

atypical resection or wedge 16 (59.3%)

2 or more segments

11 (40.7%)

Mean time in hospital 4.8 days*1 patient with resection only Ruers et al. J Clin Oncol 33, 2015 (suppl; abstr 3501)



TREATMENT INFORMATION

Treatment received

Assigned

Treatment FolfoxFolfox +

bevRF only

No

treatmentResection

RF + Systemic

(N=60)43

72%

8

13%

6*

10%

3**

5%

Systemic

(N=59)46

78%

13

22%

0

0%7***

12%

* 6 patients with RF only: : progression (2), intercurrent death (1), RF/surgery complications (3)

** 3 patients with no treatment: refusal, no treatment data received, bone metastases at baseline

*** 1 patient was resectable on initial CT imaging (ineligible)




OVERALL SURVIVAL

(years)

0 2 4 6 8 10 12

0

10

20

30

40

50

60

70

80

90

100

O N Number of patients at risk : Treatment

53 59 43 21 11 4 2

39 60 44 28 21 19 9

Systemic

RF+Systemic

Median (95% CI) 40.54 (27.50, 47.67) Systemic(Months) 45.60 (30.32, 67.75) RF+Systemic

8-year OS (95% CI) 8.9% ( 3.3, 18.1) Systemic35.9% (23.8, 48.2) RF+Systemic

HR = 0.58, 95% CI (0.38-0.88), P = 0.010 (Log-rank test)


Van Cutsem E, Cervantes A, Arnold D et al, ESMO Consensus 2016

Online Ann Oncol, July 2016

Van Cutsem E, Cervantes A, Arnold D et al, ESMO Consensus 2016Online Ann Oncol, July 2016

Deepness of response

∆ OS

No tumor shrinkage

PFS

PFS

∆ PFS

Tumor shrinkage

Lethaltumorload

Baseline tumor load

Time under treatment



VORTRAGSSTRUKTUR

Der Werkzeugkasten („LAT“)

Ablative Techniken

Locoregionäre Techniken

Patientenselektion

Tumorentität

Tumorbiologie

Kurative Intention oder Debulking?

Oder Palliation?





FIGURE 1: TOOLBOX OF ABLATIVE TREATMENTS

recommendation 15: local ablation techniques.

In patients with unresectable liver metastases only, or OMD, local ablation

techniques such as thermal ablation or high conformal radiation techniques

(e.g. SBRT, HDR-brachytherapy) can be considered. The decision should be

taken by an MDT based on local experience, tumour characteristics and

patient preference [IV, B].

In patients with lung only or OMD of the lung, ablative high conformal

radiation or thermal ablation may be considered if resection is limited by

comorbidity, the extent of lung parenchyma resection, or other factors [IV, B].



Local and ablative treatment

(including surgery)







Tanis Eur J Cancer 2014

LOKALE KONTROLLE NACH RESEKTION UND RFA



RFA:

lesion size > 30 mm (n = 6/28,

21.4%)

≤30 mm (n = 4/139, 2.9%)

Resektion:

<30 mm was 6.2% (n = 6/97)

No recurrences >30 mm (n = 0/13)

LOKALREZIDIVE PER GRUPPE

Tanis Eur J Cancer 2014





Welsh et al. Surgical Oncol 2008



CT-BRACHYTHERAPIE:LEBER, LUNGE, RETROPERITONEAL, MESENTERIAL, …



CT-BRACHYTHERAPIE:LEBER, LUNGE, RETROPERITONEAL, MESENTERIAL, …

Deutsche Akademie für Mikrotherapie









CRC NN-METASTASE: STABIL IN 2ND-LINE, CHEMO-PAUSE; 12 MONATS-F/U

CUP, NN-Metastase: Progress unter 1st-line-CTx; 6 Monats-F/U



Ricke et al. Int J Radiat Oncol Biol Phys 2010

Prospektiv randomisierte Dosisfindung

Primärer Endpunkt: lokale Kontrolle

Sekundärer Endpunkt: Gesamtüberleben, …

Tumorgröße 5 – 15cm

FFLP >90% nach 12 Mon. (>20Gy single fraction)



LOCAL CONTROL AFTER CT-BRACHYTHERAPY

CRC: 80 - 90% (12 months, 2-15cm) 1,2

Breast: >95% (12 months, 3-12cm) 3,4

Cholangiocellular/Adenoca: >80% 5,6

HCC: >90% (12 months, 5-15) 7, 8

GIST/Sarkoma: 80% 9

Melanoma: >80% 101,2 Collettini 2014, Ricke 20103,4 Collettini 2014, Wieners 20115,6 Kamphues 2012, Schnapauff 20127,8 Collettini 2012, Mohnike 20109 Bretschneider 2015 (in press)10 Bretschneider 2015



Professor Ricky Sharma

Chair of Radiation Oncology, University College London,

United Kingdom

COMBINED ANALYSIS OF:

on behalf of the FOXFIRE, SIRFLOX and FOXFIRE-Global

Investigators



PATIENT CHARACTERISTICS

Characteristic Chemo

(n = 549)

Chemo+SIRT

(n = 554)

Median age in years (range) 63 (23 – 89) 63 (28 – 90)

Male 65.8% 65.5%

WHO performance status

0

1

63.2%

36.4%

63.9%

35.7%

Extra-hepatic metastases 34.8% 35.9%

>25% liver involvement 30.6% 32.3%

Intent to treat with biologicals 54.5% 53.8%

Synchronous presentation with

liver mets

86.5% 87.2%

Primary tumour in situ 55.0% 50.2%



OVERALL SURVIVAL (N=1103)

0.00

0.25

0.50

0.75

1.00

Prop

ortion

Alive

554 417 247 91 35 17Chemo+SIRT549 419 242 88 33 12Chemo

No. at Risk

0 12 24 36 48 60

Time from Randomisation (months)

Chemo

Chemo+SIRT

0.00

0.25

0.50

0.75

1.00

Pro

port

ion

Alive

554 417 247 91 35 17Chemo+SIRT549 419 242 88 33 12Chemo

No. at Risk

0 12 24 36 48 60


Chemo

Chemo+SIRT

0.00

0.25

0.50

0.75

1.00

Pro

port

ion

Alive

554 417 247 91 35 17Chemo+SIRT549 419 242 88 33 12Chemo

No. at Risk

0 12 24 36 48 60


Chemo

Chemo+SIRT

n EventsMedian

549 41123.3 months

554 43322.6 months

HR: 1.04 (95% CI: 0.90–1.19) p=0.609



LIVER-SPECIFIC PROGRESSION-FREE SURVIVAL

First radiological progression within the liver

First progression extrahepatic or death without radiological progression having been documented

Cu

mu

lati

ve in

cid

ence

Cu

mu

lati

ve in

cid

ence



HR 0.51 (95% CI 0.43-0.62) p<0.001

HR 1.76 (95% CI 1.47-2.11) p<0.001

Patients in the Chemotherapy + SIRT arm had a lower risk of progression in the liver as a first event and a higher risk of non-liver progression as a first event



TREATMENT EFFECT ON OS WITHIN SUBGROUPS



Censored

276 223 150 54 22 7 2 1 0264 199 130 47 20 12 2 0At Risk (n)

n Median Survival

(95% CI) Chemo + SIRT 264 24.6 months (22.3–26.7)Chemo 276 26.6 months (24.8–29.9)Hazard Ratio 1.12 (0.92–1.36) p=0.279

0.0

0.2

0.4

0.6

0.8

1.0Pro

babili

ty o

f O

vera

ll Surv

ival

0 12 24 36 48 60 72 84 96

Time from Randomization (months)

Overall Survival for SF and FF-G Patients with Left-Sided Primary Tumours



Overall Survival for SF and FF-G Patients with Right-Sided Primary Tumours

Censored

n Median Survival

(95% CI) Chemo + SIRT 98 22.0 months (18.9–25.6)Chemo 81 17.1 months (13.9–19.9)Hazard Ratio 0.64 (0.46–0.89) p=0.007

0.0

0.2

0.4

0.6

0.8

1.0Pro

babili

ty o

f O

vera

ll Surv

ival

0 12 24 36 48 60 72 84 96

Time from Randomization (months)

81 51 15 6 2 1 098 78 43 14 5 3 1 1At Risk (n)

0

The treatment interaction by location for Overall Survival was highly significant (Chi-square: 9.49; p=0.002; HR: 0.548 [0.37–0.80])

REsect: Blinded assessment of surgical resectability of previously unresectable colorectal cancer liver metastases

following chemotherapy±Y90-RadioEmbolization

Benjamin Garlipp • Peter Gibbs • Guy van Hazel • Rohan Jeyarajah • Robert Martin Christiane Bruns • Hauke Lang • Derek Manas • Giuseppe Maria Ettorre

Fernando Pardo • Vincent Donckier • Christoph Benckert • Thomas van Gulik Diane Goéré • Michael Schön • Johann Pratschke • Wolf Bechstein • Shola Adeyemi

Max Seidensticker

Results

Characteristic FOLFOX (±bev)

alone

(n=228a)

FOLFOX (±bev)

+ SIRT

(n=244a)

BSA, m2 (SD) 1.87 (0.207) 1.87 (0.215)

Mean (SD) estimated tumor burden, % 17.6 (15.3) b 18.3 (16.6)c

Mean (SD) number of baseline hepatic target lesions 3.8 (1.2) b 3.8 (1.3)

Patients with extra-hepatic metastases, n (%) 91 (39.9) 99 (40.6)

Primary tumor in situ, n (%) 103 (45.2) 108 (44.3)

A total of 472 patients with similar baseline characteristics were

evaluable (mFOLFOX n=228; mFOLFOX + SIRT n = 244).

aNumber of patients with parameter unless stated otherwise; bn=227; cn=243

Results

Of patients deemed unresectable at baseline,

31.2% in the FOLFOX+SIRT arm vs. 22.7% in the FOLFOX arm

were converted to resectability (p<0.0001)



Hepatology 2013



PVE hat eine höhere Induktionskapazität..... Aber was ist mit der Tumorkontrolle?

Garlipp, Seidensticker, Hepatology 2013

0

20

40

60

80

100

120

RE

PVE

p<0,001

29 %

61%

Sekundäre Resektabilität nach RE





INCLUSION CRITERIA

Treatment failure w/ liver metastases of

CRC

Min. post 2nd line CTx (5-FU/FA,

Oxaliplatin, Irinotecan) and 1 monoclonal

antibody (Erbitux/Avastin)

>20% tumor load

No relevant extrahep. manifestations

Karnofsky 60%



SIRT VS. BSC

Median 5,5 vs. 2,1 months;

p<0,001

SIRTControl

Seidensticker R, Cardiovasc Intervent Radiol. 2012 Oct;35(5):1066-73



J Vasc Interv Radiol 2012; 23:96–105



EXCLUSION CRITERIA FOR RE (ALL PATIENTS)



OVERALL SURVIVAL NACH RE, N=224 (CRC)














Sex (f/m) 58 / 1

Mean Age (y, range) 57,4 (32 - 80)

Age (≤ vs. >60y) 37 / 22

Estrogen Receptor (pos/neg) 46 / 13

Progesteron Receptor (pos/neg) 34 / 25

In sum: Hormone Receptor (pos/neg) 49 / 10

Her2 neu (pos (triple)/neg) 20 / 39

Grading (1 / 2 / 3), 8 missing 4 / 26 / 21

Median time from first diagnosis to liver metastases (months, range)

45 (0 - 335,4)

Median time from first diagnosis liver metastases to first treatment in interventional radiology (months, range)

22 (1 - 294)

Mean number of liver metastases (n, range) 13 (1 - 88)

Mean maximum diameter of liver metastases (cm, range) 4,9 (1 - 14)

Mean tumor load (%, range) 8,2 (0,1 - 51,4)

Prior Chemotherapy (without hormones) (yes/no) 54 / 5

median lines (range) 2 (0 - 8)

Seidensticker BMC Cancer 2015



Other prior treatments (for metastases) (yes/no) 40 / 19detailed**surgery (for metastasis) 19radiotherapy 20Bisphophonates 24

Extrahepatic metastases (yes/no) 29 / 30site detailed**bones only 19bones 24pulmonary 6lymphatic nodes (others than axillary) 4peritoneal 1




GESAMTÜBERLEBEN AB LOKALABLATIVER THERAPIE

Median overall survival Months 95% CI

From first diagnosis 127,9 87,1 - 168,7

From first diagnosis liver metastases 56,3 44,5 - 67,9

From first treatment in Radiology 21,9 11,1 - 32,6



MULTIVARIAT: EINFLUß AUF GESAMTÜBERLEBEN

Variable set Hazard ratio 95% CIp-value

Extrahepatic metastases (yes/no) 0,57 0,21 - 1,60 0,286

Bone metastases only (yes/no) 0,91 0,39 - 2,10 0,82

Tumor load (≥ vs. < 2%) 4,32 1,63 - 11,44 0,003

Lines of chemotherapy (≥ vs. < 3) 1,57 0,73 - 3,38 0,244

CEA (≥ vs. < 6,2U/mL) 1,78 0,68 - 4,66 0,242

Under local control in FU (yes/no) 0,38 0,16 - 0,88 0,025

Best response overall (OR, RECIST) 5,88 2,27 - 15,27 < 0,001



69 YEARS, GOOD PS

Insuline-secreting pancreatic NET 08/2009,

Pancreas resection, hemihepatectomy

Recurrence after Surgery, Octreotide, DOTATATE,

Everolimus, Y90-Radioembolisation

Intermittent severe hypoglycemia

Continuous glucose infusion



MRI PRE BRACHY



CONTINUOUS GLUCOSE INFUSION40 GRAMS GLUCOSE/HOUR

8 weeks hospital stay, ECOG 0 (!)



IBT IN 2 SESSIONS, 2 WEEKS INTERVAL



IBT IN 2 SESSIONS, 2 WEEKS INTERVAL



NORMALIZED GLUCOSE LEVELS WITHOUT SUBSTITUTION, 1 WEEK AFTER 2ND SESSION OF IBT

Home at last !



09.12.2015 V. cava superior

SYNOVIAL SARKOMA, 34Y MALE

• Left lower extremity2009

• Repeated tumorresections

• 2015: systemic therapyw/ Ifosfamid/Cisplatin, Yondelis, no response

• Progressive inflowcongestion 12/15

• Weight loss 10kg in 4 months

• Fatigue Grade 3



Synovial sarkoma, 34y male



09.12.2015 12.01.2016V. cava superiorV. cava superior

SYNOVIAL SARKOMA, 34Y MALE



Der interdisziplinäre Werkzeugkasten ist entscheidend!

Keine örtliche oder Größenlimitation

Die onkologische Überlegung führt

Klein = thermisch oder SBRT, groß = IR & Strahlentherapie

Diffus = locoregionär (derzeit nur Radioembolisation)

…oder in Kombination mit Resektion (CLOCC)

Patientenselektion…

Tumorbiologie < biologisches Verhalten

Kurativ und palliativ

Immer multidisziplinär und potentiell kombiniert konzipiert

TAKE HOME



DANKE!

[email protected]

GOOGLE: RADIOLOGIE LMU

Date post:	09-Oct-2019
Category:	Documents
Upload:	others
View:	4 times
Download:	0 times

Interventionelle Radiologie im Kontext von Oligometastasierung · klinik und poliklinik fÜr...

Documents