Hyperthermie und Radioonkologie:

Schwerpunkte der klinischen

Evolution

Lunchsymposium Dr. Sennewald Medizintechnik GmbH

DEGRO 2009, Bremen, 12. Juni 2009

Oliver J. Ott

Universitätsklinikum Erlangen, Strahlenklinik

University Cancer Center Erlangen

2

Bladder Cancer

Cervical Cancer

Head & Neck Cancer

Anal Canal Carcinoma

Colombo R et al. J Clin Oncol 2003 Harima Y et al. Int J Hyperthermia 2001

Datta NR et al. Int J Hyperthermia 1990 Kouloulias V et al. Am J Clin Oncol 2005

Hyperthermie Wirksam oder nicht?

3

Esophageal Cancer Malignant Melanoma

GBM

Head & Neck Cancer Head & Neck Cancer Cervical Cancer

Sugimachi K et al. Int J Hyperthermia 1992 Overgaard J et al. Lancet 1995 Sneed PK et al. IJROBP 1998

van der Zee C et al. Lancet 2000 Valdagni R et al. IJROBP 1994 Valdagni R et al. IJROBP 1994

Hyperthermie Wirksam oder nicht?

4

Breast Cancer Peritoneal Carcinomatosis

Superficial Tumours

Verwaal VJ et al. J Clin Oncol 2003 Vernon CC et al. IJROBP 1996

Jones E et al. J Clin Oncol 2005

Hyperthermie Wirksam oder nicht?

5

Rectal Cancer

6

Russian Trial: Flow Chart

T4NXM0 n = 115

R

A

N

D

O

M

10x 4 Gy n = 59

10x 4 Gy

+ Hyp. n = 56

RESECTABLE

Surgery n = 47

10x 4 Gy n = 68

YES

NO

Berdov BA et al. Int J Hyperthermia 1990;6:881-90

Rectal Cancer and Hyperthermia Randomised Trials

7

Berdov BA et al. Int J Hyperthermia 1990;6:881-90

Rectal Cancer and Hyperthermia Randomised Trials

Russian Trial: Results

Endpoint RT + HT RT alone P-Value

Complete Response 16 % 2 % < 0.05

Partial Response 54 % 34 % < 0.05

Resection Rate 55 % 26 % n.a.

Overall Survival (5y) 36 % 7 % < 0.05

n.a. = not available

8

German Trial: Flow Chart

Rau B et al. Viszeralchirurgie 2002;37:379-84 Schulze T et al.

Int J Hyperthermia 2006;22:301-18

Rectal Cancer and Hyperthermia Randomised Trials

uT3, uT4 n = 137

R

A

N

D

O

M

RCT n = 68

RCT +

RHT n

= 69

S

U

R

G

E

R

Y

C

H

E

M

O

9

German Trial: Results

Rau B et al. Viszeralchirurgie 2002;37:379-84 Schulze T et al.

Int J Hyperthermia 2006;22:301-18

Rectal Cancer and Hyperthermia Randomised Trials

Endpoint RCT + HT RCT alone P-Value

Response (CR + PR) 66 % 49 % < 0.05

Time to Progression 28 mo 20 mo < 0.05

Local Control (3y) 93 % 93 % n.s.

Overall Survival (3y) 89 % 80 % n.s.

n.s. = not significant

10

Recurrent Rectal Cancer and Hyperthermia Published Papers

Reference n Treatment Endpoint

Milani V et al. (2008) 24 Re-RT + RHT Feasibility

Hildebrand B et al. (2004) 9 CTX + RHT Feasibility,

Palliation

Juffermans et al. (2003) 53 Re-RT + RHT Feasibility,

Palliation

Schaffer et al. (2003) 13 Re-RT + RHT Feasibility

Rau B et al. (2000) 18 RCT + RHT Feasibility

Anscher et al. (2000) 3 RCT + RHT Feasibility

Experience of mankind 120 Feasibility

Recurrent Rectal Cancer Prognosis influenced by surgery

11 Dresen RC et al. Annals of Surgical Oncology 2008;15:1937–1947

N = 147 Neoadjuvant (C)RT, Surgery, IORT R0-Recection 57% 5y-Disease-free Survival 34.1%

12

Recurrent Rectal Cancer Phase II-Study (HyRec Trial)

1 2 3 4 5 6

Week

d2 d9 d23 d30

d 1-14 d 22-35

Radiotherapy PTV: depending on

former Tx Dose: 45 Gy

5-FU CIV (250 mg/m /d)

Oxaliplatin Bolus (50 mg/m /d)

Deep Regional Hyperthermia

R

E

S

E

C

T

I

O

N

d2 d9 d23 d30 d5 d12 d26 d33 d16 d19

Required Cases n =59

Ansprechpartner: Dr. O. Ott, Erlangen

HyRec Trial Current Status

13

04/2009: Protocol submitted to the German Cancer Aid Foundation to get Financial Support

14

Anal Carcinoma

15

Analkanalkarzinom Phase II-Studie: Design

Kouloulias et al. Am J Clin Oncol 2005;28:91–99

16

Analkanalkarzinom Phase II-Studie: Hyperthermie

Kouloulias et al. Am J Clin Oncol 2005;28:91–99

17

Analkanalkarzinom Phase II-Studie: Ergebnisse

Kouloulias et al. Am J Clin Oncol 2005;28:91–99

5-Jahres-Kolostomiefreiheit:

95% vs. 68%

zu Gunsten der Hyperthermie

Study-Design

Inclusion Criteria

• Squamous cell cancer

• Anal Canal + Margin

• Age > 18 Jahre

• All Stages except T1 N0

CONTROL - ARM:

EXPERIMENTAL - ARM:

Week

1 2 3 4 5 6

Chemotherapy

MMC: 10 mg/m2

5-FU: 1000 mg/m2/d

Radiotherapy

50.4-59 Gy

Radiotherapy

50.4-59Gy

Chemotherapy MMC: 10 mg/m2

5-FU: 1000 mg/m2/d

Hyperthermia

once/week

5 x 1.8-2 Gy/W

Ansprechpartner: Prof. Dr. G. Grabenbauer, Coburg

19

Prostate Cancer

20

Analkanalkarzinom Phase II-Studie: Hyperthermie

Van der Kwast et al. J Clin Oncol 2007;25:4178-4186

Prostatakarzinom Randomisierte, multizentrische Studie geplant

21

Flow Chart

R

A

N

D

O

M

PORT

PORT +

RHT

F

O

L

L

O

W

U

P

S

U

R

G

E

R

Y

PC (R0)

PC (R1/2)

Ansprechpartner: Prof. Dr. C. Belka, München; Prof. Dr. H.J. Feldmann, Fulda