[PPT] - R di th R di th Radiotherapy Lymphomas Radiotherapy Lymphomas L PowerPoint Presentation

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R di th L h R di th L h Radiotherapy Lymphomas Radiotherapy Lymphomas

Mary Gospodarowicz MD Mary Gospodarowicz MD

Princess Margaret Hospital Princess Margaret Hospital University of Toronto, Toronto, Canada University of Toronto, Toronto, Canada

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Changing Landscape in Lymphoma Changing Landscape in Lymphoma Changing Landscape in Lymphoma Changing Landscape in Lymphoma

90% of cases in adults

90% of cases in adults

median age

median age -

64 yrs

64 yrs

2008 Statistics

2008 Statistics US US Canada Canada

66 120 new cases 7 000

66 120 new cases 7 000

19 160 deaths

19 160 deaths 3 100 3 100

19 160 deaths

19 160 deaths 3 100 3 100

@ 500 000 people living with lymphoma

@ 500 000 people living with lymphoma

90% B

90% B-cell cell 90% B 90% B cell cell

@ 40% DLBCL

@ 40% DLBCL

10% T

10% T-

cell

cell

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RT in Non RT in Non Hodgkin L mphoma Hodgkin L mphoma RT in Non RT in Non-Hodgkin Lymphoma Hodgkin Lymphoma

Challenges

Challenges Challenges Challenges

– Only 4 Only 4 -

6% of all cancers

6% of all cancers – Numerous distinct disease entities Numerous distinct disease entities Numerous distinct disease entities Numerous distinct disease entities

Mycosis fungoides

Mycosis fungoides

Primary brain lymphoma

Primary brain lymphoma y y p y y p

Gastric MALT

Gastric MALT

Burkitt’s

Burkitt’s

– Changing outcomes Changing outcomes – Little level 1 evidence to guide practice Little level 1 evidence to guide practice

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Radiation Therapy in Cancer Radiation Therapy in Cancer Radiation Therapy in Cancer Radiation Therapy in Cancer

Local therapy

Local therapy

Local therapy

Local therapy

–Proven most effective agent in Proven most effective agent in idi l l t t l idi l l t t l providing local tumour control providing local tumour control –Proven capable of curing localized Proven capable of curing localized disease in most cancers disease in most cancers –Compensates for diagnostic ambiguity Compensates for diagnostic ambiguity p g g y p g g y

‘histology agnostic’

‘histology agnostic’

–Few contraindications Few contraindications Few contraindications Few contraindications

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Radiation Therapy in Cancer Radiation Therapy in Cancer Radiation Therapy in Cancer Radiation Therapy in Cancer

Local therapy

Local therapy

Local therapy

Local therapy

Proven most effective agent in providing

Proven most effective agent in providing local tumour control local tumour control local tumour control local tumour control

Proven capable of curing localized disease

Proven capable of curing localized disease in most cancers in most cancers in most cancers in most cancers

Compensates for diagnostic ambiguity

Compensates for diagnostic ambiguity

‘histology agnostic’

‘histology agnostic’ histology agnostic histology agnostic

Few contraindications

Few contraindications

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RT in L mphomas RT in L mphomas RT in Lymphomas RT in Lymphomas

Obj ti f RT Obj ti f RT

Objective of RT

Objective of RT

– Almost always to achieve local control Almost always to achieve local control

Outcomes of interest

Outcomes of interest

– Pattern of failure Pattern of failure

Local control

Local control

Overall failure rate

Overall failure rate

– Survival Survival – Toxicity Toxicity

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Stage I&II Follicular Lymphoma 1967 Stage I&II Follicular Lymphoma 1967-99 99

Stage I Stage I-

II

II

668 pts

668 pts

Stage I&II Follicular Lymphoma 1967 Stage I&II Follicular Lymphoma 1967 99 99

Stage I

Stage I-

II RT alone

II RT alone

460 pts

460 pts

– median follow median follow-

up

up

12.5 yrs

12.5 yrs ed a

o

ed a

o

up up 5 y s 5 y s

range

range

up to 32 yrs

up to 32 yrs

Treatment

Treatment – IF RT 30 IF RT 30-35 Gy 35 Gy Treatment Treatment IF RT 30 IF RT 30 35 Gy 35 Gy

Relapse

Relapse

distant distant 89 % 89 %

distant

distant

89 %

89 %

distant + local

distant + local

6 %

6 %

isolated local relapse

isolated local relapse

5%

5%

isolated local relapse

isolated local relapse - 5% 5%

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PMH 1968 PMH 1968 1999 1999 PMH 1968 PMH 1968 – 1999 1999 Stage I Stage I-

II Follicular Lymphoma RT Alone

II Follicular Lymphoma RT Alone

460 patients 460 patients

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PMH 1968 PMH 1968 – – 1999 1999 St I St I II F lli l L h RT Al II F lli l L h RT Al Stage I Stage I-II Follicular Lymphoma RT Alone II Follicular Lymphoma RT Alone

70 80

No relapse Relapse

50 60 Age 30 40 5 10 15 20 25 30 35 20 Ti l f ll Time to relapse or follow-up

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Stage I-II MZL PMH 1989-2004

MALT 1989 MALT 1989 -

2004

2004

166 t t t d ith RT 166 t t t d ith RT

166 pts treated with RT

166 pts treated with RT

median follow

median follow-

up 7.6 yrs (0.6

up 7.6 yrs (0.6 – – 16.2) 16.2)

median age 60 yrs

median age 60 yrs (23 (23-

93)

93)

F : M = 2 : 1

F : M = 2 : 1 F : M 2 : 1 F : M 2 : 1

stage I

stage I 148 (89%) 148 (89%) t II t II 18 (11%) 18 (11%)

stage II

stage II 18 (11%) 18 (11%)

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Stage I-II MZL PMH 1989-2004

Presenting Sites Presenting Sites

Orbit and adnexa Orbit and adnexa 70 (42%) 70 (42%) Skin & soft tissues Skin & soft tissues 4 4 Salivary gland Salivary gland 28 (17%) 28 (17%) Breast Breast 4 4 St h St h 22 (13%) 22 (13%) R t R t 1 Stomach Stomach 22 (13%) 22 (13%) Rectum Rectum 1 Thyroid Thyroid 21 (13%) 21 (13%) Meninges Meninges 1 1 Other head & neck* Other head & neck* 6 Thymus Thymus 1 Other head & neck Other head & neck 6 Thymus Thymus 1 Lung Lung 4 4 Bladder Bladder 4 *nasopharynx

nasopharynx -

3,

3, maxillary

maxillary sinus

sinus -

1

1 larynx larynx -

1, Hypopharynx

1, Hypopharynx -

1

1

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Stage I/II MALT lymphoma Stage I/II MALT lymphoma -

Relapse

Relapse g y p g y p p

Relapse

Stomach/Thyroid (n=43)

2 yrs: 13/31 (52%) 5 yrs: 25/31 (81%) > 5 yrs: 6/31 (19%)

Other sites (n=123)

10-year RFR

Thyroid 95%

y ( )

Stomach 100% Salivary gland 68% Orbit 67%

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Stage I/IIE MALT lymphoma Stage I/IIE MALT lymphoma - Survival Survival Stage I/IIE MALT lymphoma Stage I/IIE MALT lymphoma Survival Survival

10 yr RFR 77%

— 10 yr OS - 87%

-- 10 yr CSS - 98%

…. 10 yr RFR- 77%

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Limited Limited-

stage mantle

stage mantle-

cell lymphoma

cell lymphoma g y p y p

Leitch et al Leitch et al Annals of Oncology 14: 1555 1561 2003 Leitch et al. Leitch et al. Annals of Oncology 14: 1555–1561, 2003

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Int J Radiat Oncol Biol Phys 65: 1185 91 2006 Int J Radiat Oncol Biol Phys 65: 1185–91, 2006

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Localized DLBCL Localized DLBCL Localized DLBCL Localized DLBCL

Heterogeneous disease

Phenotypic, molecular characteristics

Phenotypic, molecular characteristics Nodal vs extranodal presentations Nodal vs extranodal presentations

Nodal vs. extranodal presentations

Stage I vs. II (II localized vs.. extensive)

Stage I vs. II (II localized vs.. extensive) B symptoms symptoms

B-symptoms

symptoms

LDH

LDH A d f t t A d f t t

Age and performance status

Comorbidity

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Spectrum of Localized DLBL Spectrum of Localized DLBL Spectrum of Localized DLBL Spectrum of Localized DLBL

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PMH Experience 1984 PMH Experience 1984 2003 2003 PMH Experience 1984 PMH Experience 1984 -

2003

2003

600 patients with stage I

600 patients with stage I-

II

II

Age 15

Age 15 -

91

91 median median -

57 yrs

57 yrs

Follow

Follow-

up 0.4

up 0.4 – 22 yrs 22 yrs median median -

10.1 yrs

10.1 yrs y y

Stage I

317

317 B B-symptoms symptoms -

64

64

Stage II

Stage II -

283

283 Extranodal Extranodal -

354

354 g

Chemo 3/4 courses

Chemo 3/4 courses -

233

233

Chemo 5/6 courses

Chemo 5/6 courses - 336 336

Chemo 5/6 courses

Chemo 5/6 courses 336 336

median RT dose

median RT dose – – 35 Gy 35 Gy

pre

pre-rituximab rituximab

pre

pre rituximab rituximab

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Overall Survival Overall Survival Overall Survival Overall Survival

PMH DLBCL PMH DLBCL – – CMT 1984 CMT 1984-

2003

2003

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Survival by age Survival by age Survival by age Survival by age

PMH DLBCL PMH DLBCL – – CMT 1984 CMT 1984-

2003

2003

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Probability of Local Relapse Probability of Local Relapse Probability of Local Relapse Probability of Local Relapse

PMH DLBCL PMH DLBCL – – CMT 1984 CMT 1984-

2003

2003

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CHOP non CHOP non-

responders

responders p Probability of Death from Lymphoma Probability of Death from Lymphoma

PMH DLBCL PMH DLBCL – – CMT 1984 CMT 1984-

2003

2003

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Rituximab Era Rituximab Era

Rit i b Rit i b d ll i t d d t th d ll i t d d t th

Rituximab

Rituximab gradually introduced to the gradually introduced to the management of all DLBCL management of all DLBCL

Outcomes improved

Role of RT questioned

Role of RT questioned q

No level 1 evidence

For the benefit of RT

For the lack of benefit of RT

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Practice Practice G id li G id li Guidelines Guidelines

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T/NK T/NK-cell Nasal Lymphoma cell Nasal Lymphoma T/NK T/NK cell Nasal Lymphoma cell Nasal Lymphoma

Note: Non-randomized comparison Note: Non randomized comparison RT n=18 RT n=18 RT n=18 RT n=18 CMT n=61 CMT n=61

Cheung et al, IJRBOP 2002; 54: 182-90

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IELSG Testis Lymphoma IELSG Testis Lymphoma IELSG Testis Lymphoma IELSG Testis Lymphoma

Kaplan-Meier survival estimates

Actuarial risk of contralateral testicular failure by prophylactic scrotal RT

(l k t t 0 0027)

1.00

(log rank test, p=0.0027)

No scrotal XRT

0 50 0.75

No scrotal XRT

0.25 0.50

Prophylactic XRT

0.00 PFS 10 20 30

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RT RT - Refractory Refractory-Recurrent DLBCL Recurrent DLBCL RT RT Refractory Refractory Recurrent DLBCL Recurrent DLBCL

Martens et al, IJROBP 64: 1183 Martens et al, IJROBP 64: 1183-

7, 2006

7, 2006

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Int J Radiat Oncol Biol Phys, 51:148–155, 2001

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Austral Radiol 50:222–7, 2006

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RO Practice in Lymphomas RO Practice in Lymphomas RO Practice in Lymphomas RO Practice in Lymphomas

Change in radiation oncology practice

Change in radiation oncology practice g gy p g gy p

– Target volume rather than nodal region Target volume rather than nodal region treated treated – GTV, CTB, PTV defined and treated GTV, CTB, PTV defined and treated – Most practice in adjuvant setting Most practice in adjuvant setting

N GTV CTV N GTV CTV d d d d

No GTV, CTV non

No GTV, CTV non-

standard

standard

– Need to monitor and report RT relevant Need to monitor and report RT relevant

utcomes
utcomes
utcomes
utcomes
Local control

Local control

Patterns of relapse

Patterns of relapse

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RT Planning RT Planning

R i ti l Requires optimal pre-chemotherapy imaging imaging

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Current Standard Current Standard Current Standard Current Standard

Target

Target -

post chemotherapy CTV

post chemotherapy CTV

Dose and fractionation

Dose and fractionation

30 30 35 Gy in 15 35 Gy in 15 20 fractions 20 fractions – 30 30 – 35 Gy in 15 35 Gy in 15-20 fractions 20 fractions

3D CRT / IMRT

3D CRT / IMRT

–protect normal tissues protect normal tissues

CT planning

CT planning

CT planning

CT planning

Image guidance as required

Image guidance as required

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Role of RT Role of RT

All trials show improved local control

Very safe treatment

Minimal acute and late severe toxicity

Modern techniques

Modern techniques – – lower acute toxicity lower acute toxicity

Best local therapy cannot improve

Best local therapy cannot improve distant disease control distant disease control

If systemic therapy results in 100% local

If systemic therapy results in 100% local control control – – no need for RT no need for RT

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C rrent contro ersies C rrent contro ersies Current controversies Current controversies

L li d f lli l l h L li d f lli l l h

Localized follicular lymphoma

Localized follicular lymphoma

– Curable with RT or just very slow natural Curable with RT or just very slow natural hi t hi t history history

MALT

MALT

– Role of RT in rare presentations Role of RT in rare presentations – Need to learn more about the natural Need to learn more about the natural history history

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C rrent contro ersies C rrent contro ersies Current controversies Current controversies

L li d DLBCL L li d DLBCL

Localized DLBCL

Localized DLBCL

– Is RT needed in R Is RT needed in R-

CHOP era

CHOP era

Does it add to the chemotherapy

Does it add to the chemotherapy

– Must conduct studies that include optimal Must conduct studies that include optimal chemotherapy and ask RT question chemotherapy and ask RT question chemotherapy and ask RT question chemotherapy and ask RT question

Extranodal lymphomas

Extranodal lymphomas

– Differences btwn EN and N presentations Differences btwn EN and N presentations

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C rrent contro ersies C rrent contro ersies Current controversies Current controversies

R l f RT i FDG PET R l f RT i FDG PET

Role of RT in FDG PET era

Role of RT in FDG PET era

– Assessment of response to chemotherapy Assessment of response to chemotherapy i id i id t t t FDG PET t t t FDG PET using mid using mid-treatment FDG PET treatment FDG PET – Post chemotherapy PET assessed Post chemotherapy PET assessed response as selection factor for RT response as selection factor for RT response as selection factor for RT response as selection factor for RT

Role of RT in PET +ve and PET

Role of RT in PET +ve and PET – –ve cases ve cases

Patterns of failures in above situations

Patterns of failures in above situations

Patterns of failures in above situations

Patterns of failures in above situations

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Future Future Future Future

Biologic imaging

Biologic imaging g g g g g g

Disease extent

Disease extent

Response

Response p

Selection for adjuvant treatment

Selection for adjuvant treatment

Role of precision RT

Role of precision RT

Role of precision RT

Role of precision RT

Molecular disease characteristics

Molecular disease characteristics

D fi iti f di titi D fi iti f di titi

Definition of disease entities

Definition of disease entities

Impact on the management

Impact on the management

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