Download pdf - Clinical Management Guidelines for Hodgkins · PDF file1 C. l. inical Management Guidelines for Hodgkins Lymphoma . W. e. s. t of Scotland Blood Cancer Network . Contents: Page . Initial

1

CClliinniiccaall MMaannaaggeemmeenntt GGuuiiddeelliinneess ffoorr HHooddggkkiinnss LLyymmpphhoommaa WWeesstt ooff SSccoottllaanndd BBlloooodd CCaanncceerr NNeettwwoorrkk

Contents:

Page Initial investigations required 2 Prognostic scoring systems 3 Clinical Management flow charts by stage of disease 4-7 Appendix 1 Scottish Executive recommendations for PET scanning in Hodgkins Lymphoma 8 (Updated Sept 2008) Prepared by: Dr Andrew Clark Approved by : Haemato-oncology MCN July 2009 Issue Date: July 2009 Review Date: July 2011 Reference/Version number

WoSCAN CMG HL version 3 (Includes Updated Scottish Executive PET guidance issued Sept 2008)

Replaces WoSCAN CMG HL version 2 Haemato-oncology MCN: 31st May 2007 RCAG Prescribing Advisory Subgroup: 31st August 2007

WoSCAN CMG Hodgkin’s Lymphoma version 3.0 (Updated July 2009) – Review Date July 2011

2

Essential Initial Investigations: History: Specific to Hodgkins Lymphoma- Presence of B symptoms i.e. Weight loss > 10% of body weight, drenching sweats, fever, Additional features e.g. itch, alcohol induced pain, symptoms of SVC obstruction Physical Examination: General Health including assessment of performance status, cachexia Evidence and extent of lymphadenopathy/hepatosplenomegaly Any evidence of SVC obstruction Blood Tests: FBC with differential white cell count. ESR U+Es LFTs / Albumin LDH Hepatitis B/ C /HIV testing Bone marrow aspirate and trephine biopsy. (This may be omitted in Stage 1A disease with normal FBC and ESR) Lymph Node Biopsy This is essential for accurate diagnosis and excision biopsy should always be performed when possible. Regional pathology review should be carried out by a specialist lymphoma pathology team. Pulmonary Function Tests: Recommended at baseline Imaging CXR and/or Ultrasound of neck may help in initial diagnosis. Echocardiogram: age >60yo/known history of cardiovascular disease/Hypertension/Diabetes CT Scan ; Neck, Chest, Abdomen, Pelvis N.B. Accurate measurements of all lymph node masses are essential for future comparisons and should be obtained at diagnosis. This is an absolute requirement of any radiology report in lymphoma patients. PET scanning is now funded for all patients at diagnosis. This investigation is useful in most patients but should not unduly delay treatment. The CT component, in machines capable of dual scanning (PET-CT), should ideally, at present, not replace a baseline diagnostic CT scan. EACH CASE SHOULD BE DISCUSSED AT AN MDT MEETING. (This could be a local MDT if clear adherence to CMG guidance but all problem/difficult cases should continue to be discussed on a regional basis)


3

Prognostic Scoring systems in Hodgkins lymphoma

Early stage: I. EORTC risk factors in localised disease A. Favourable (patients must have all features)

1. Clinical stage 1 or 2 2. Maximum of three nodal areas involved 3. Age less than 50yo 4. ESR< 50 mm/h 5. Mediastinal/thoracic mass ratio < 0.33 at D5/6

B. Unfavourable

1. Clinical stage 2 with 4 or more nodal areas involved 2. Age > 50yo 3. ESR >50 mm/h without B symptoms or > 30 mm/h with B symptoms 4. Mediastinal/thoracic ratio > 0.33 at D5/6

Advanced stage: Hasenclever Score

1. Age > 45 yo 2. Male sex 3. Serum Albumin < 40g/l 4. Hb < 10.5g/dl 5. Stage 4 disease 6. Leucocytosis, i.e WCC >15 x 109/l 7. Lymphopenia i.e. (< 0.6 x 109/l or < 8% of total WCC)


4

MMAANNAAGGEEMMEENNTT OOFF EEAARRLLYY SSTTAAGGEE HHOODDGGKKIINNSS LLYYMMPPHHOOMMAA

RADIOTHERAPY

ALONE Involved field

Clinical stage IA /IIAClassical Hodgkins

PRESENT ABSENT

ABVD X 4-6

+

IFRT (30-35Gy)

ABVD X 2-4

+

IFRT (30-35Gy)

RISK FACTORS (RF)1- ESR > 50 2- >3 Nodal areas 3- Bulk >5cm<10cm4- Age > 50yo

IF IN CR AND NO RESIDUAL MASS AFTER 6 x ABVD

NOT SUITABLE OR NO LOCAL ETHICAL

APPROVAL

CONSIDER RATHL STUDY IF STAGE IIA WITH ADVERSE

FEATURES (see advanced disease flow chart)

CONSIDER OMITTING IFRT

COMBINED MODALITY THERAPY

(Modified by RF)

Unsuitable for NCRI RAPID STUDY

Low bulk LP HD Stage IA

or/

Clinical stage IA HL

(Mass <5cm) PET scan confirms

localised disease AND unfit for chemotherapy

ALL PATIENTS: Baseline PET-CT scan /Consider trial availability

Consider for clinical trial

e.g.NCRI RAPID study

DEFINITION: Clinical stage IA / IIA (CSIA/IIA) No bulk disease

(Nodal masses <10cm, mediastinal masses <0.33 intrathoracic diameter D5/6)


5

TREATMENT 1. PROGNOSTIC INDEX (Hasenclever Score) STRATIFIED BY: 2. PERFORMANCE STATUS (PS) / AGE

All patients – Baseline PET-CT scan where feasible Consider trial availability

Elderly/frail patients or Patients with poor PS

Young patients Fit older patients

DEFINITION : CS IIB, III and IV BULKY DISEASE i.e.

a) Nodal mass >10cm b) Mediastinal mass > 0.33 of intrathoracic diameter at D5/6

SHIELD

RATHL study not possible: ABVD X 2

ALL patients should be enrolled inn the RATHL study where possible

PET-CT SCAN After 2 cycles

STUDY Registration

SHIELD STUDY

Chemotherapy

ABVD or Reduced intensity

chemotherapy e.g.ChlVPP

Either Or

>60yo <60yo frail/low PS

PET-CT SCAN After completion of treatment if no interim PET scan was performed

/or that scan was positive

NEGATIVE

Option to discuss Radiotherapy

(Case by case basis at MCN)

POSITIVE

RADIOTHERAPY (Involved field, 30-35Gy)

OR/ CONSIDER SALVAGE

THERAPY (Discuss individual cases at MCN )

PET negative Complete ABVD X 6

PET postive Dose Escalation e.g. BEACOPP14

Stop Therapy



6

MMAANNAAGGEEMMEENNTT OOFF RREELLAAPPSSEEDD OORR PPRRIIMMAARRYY RREEFFRRAACCTTOORRYY HHOODDGGKKIINNSS LLYYMMPPHHOOMMAA

RELAPSE POST RADIOTHERAPY

ALONE

PRIMARY REFRACTORY

DISEASE

RELAPSED DISEASE PREVIOUSLY TREATED BY CHEMOTHERAPY OR/ COMBINED MODALITIES

STANDARD CHEMOTHERAPY/ RADIOTHERAPY (by stage and site)

e.g. ABVD

PBSC COLLECTION (AFTER 2nd CYCLE)

SALVAGE CHEMOTHERAPY DHAP, IVE, ESHAP

X 2-3

ConsiderIFRT

ALONE

Local Disease

Extensive Disease

ALTERNATIVE CHEMOTHERAPY(Non cross reacting

e.g. Gemcitabine* or reinduction therapy

if >1yr in CR ) +/-

RADIOTHERAPY

Is patient fit for high dose chemotherapy?

YES

**CONSIDER STRATIFICATION OF FURTHER DOSE INTENSIFICATION DEPENDENT ON RISK FACTORS

(Requires discussion of individual cases at regional MDT) Primary refractory disease on CT / PET scanning Evidence of PET positive disease post salvage even if chemosensitive Bulky or advanced stage disease at relapse +/- need for consolidative radiotherapy Significant extranodal/bone disease at relapse

CONSIDER REDUCED INTENSITY

ALLOGRAFT

HIGH RISK (e.g. PET positive post salvage)

STANDARD OF CARE

NO

TISSUE TYPE PATIENTS AND SIBLINGS**

HIGH DOSE THERAPY BEAM CHEMOTHERAPY

PBSC RESCUE

* Unlicensed. Approval through local non-formulary process required.

7

MMAANNAAGGEEMMEENNTT OOFF HHOODDGGKKIINNSS LLYYMMPPHHOOMMAA RREELLAAPPSSEEDD PPOOSSTT AAUUTTOOGGRRAAFFTT

REINDUCTION SALVAGE CHEMOTHERAPY

Experimental Therapy

e.g. Gemcitabine*

Reduced Intensity Allograft

(Requires CR/VGPR)

Conventional Allograft

(Very high TRM)

FURTHER TREATMENT DEPENDENT ON :

1. Response 2. Age, 3. Fitness, 4. Time to relapse

* Unlicensed. Approval through local non-formulary process required.


8

Protocol for the use of PET scanning in Hodgkins Lymphoma In November 2002 the then Health Technology Board for Scotland (HTBS) published its Health Technology Assessment (HTA) that stated that:- All patients who require restaging of Hodgkin’s disease should be sent for a FDG-PET scan. Extension to the restaging of all patient with lymphoma should be investigated by further research. Significant additional new research into the use of PET scan in malignant lymphomas has since been published. Furthermore, the International Working Group for Non-Hodgkin’s lymphoma have recently proposed new response criteria and associated guidelines on the use of PET imaging in lymphomas (Juweid et al, 2007; Cheson et al, 2007). The undernoted protocol has been developed in light of the emerging evidence.

Indications for the use of PET scanning in Hodgkins Lymphoma Hodgkin’s disease (HD) (~ 230 new scans in Scotland each year) . 1. All newly diagnosed patients with Hodgkin’s disease (HD) being considered for curative therapy should have a baseline scan. 2. Early stage HD after 3 courses of treatment within the context of the NCRI trial. 3. Patients with advanced HD (stage IIB, III and IV) who need to be considered for a change to more intensive chemotherapy early in their treatment plan (after 2 cycles of chemotherapy). 4. All HD patients with residual masses post treatment who have not been shown to be PET negative at an interim scan. 5. Patients with relapsed HD undergoing further treatment with curative intent should be considered for baseline and post treatment scanning where this will influence management. References:- Barrington, S.F., Begent, J., Lynch, T., ete al (2008) Guidelines for the use of PET-CT in Children. Cheson, B.D., Pfister, B. Juweid et al (2007) Revised respnse criteria for malignant lymphoma. J. Clin. Oncol. 25 pp. 579-586. Facey, K., Bradbury, I., Laking, G. and Payne, E. (2007) Overview of the clinical effectiveness of positron emission tomography imaging in selected cancers. Health Technology Assessment. 11 (44)



9

Gallamani, A., Hutchings, M., Rigacci, L et al (2007 Early Interim Fluoro-2-deoxy-D-Glucose Positron Emission Tomography is prognostically superior to International Prognostic score in advance stage Hodgkin’s lymphoma: A report from a joint Italian-Danish Study. J. Clin. Oncol. 25 pp. 3746-3752. Hutchings M. Loft A. Hansen M. Pedersen LM. Buhl T. Jurlander J. Buus S. Keiding S. D'Amore F. Boesen AM. Berthelsen AK. Specht L. (2006) FDG-PET after two to three cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood. 107 (1) pp. 52-59. Juweid, M.E., Stoobants, S., Hoekstra, O.S. et al (2007) Use of positron emission tomography for response assessment of lymphoma: consensus of the imaging subcommittee of International Harmonisation Project in Lymphoma. J. Clin. Oncol. 25 pp. 571-578. Phase 3 trial – Using PET scans to help decide treatment options for early stage Hodgkin’s lymphoma – Chief Investigator Professor John Radford – supported by Leukaemia Research Fund. Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation. [Journal Article] Bone Marrow Transplantation. 38 (3) pp.211-216. 2006 Aug. Computed tomography and 18F-FDG positron emission tomography for therapy control of Hodgkin's and non-Hodgkin's lymphoma patients: when do we really need FDG-PET?. [Journal Article] Annals of Oncology. 16(9) pp.15241529. 2005 Sep. UKCCSG Hodgkin’s Lymphoma Working Group (2006) Interim Guidelines for Management of patient’s with early stage lymphocyte predominant Hodgkin’s lymphoma, version 2. Available at: http://www.ukccsg.org/members/workinggroups/hodgkins/treatmentguidelines/index.html UKCCSG Hodgkin’s Lymphoma Working Group (2006) Interim Guidelines for the management of classical Hodgkin’s lymphoma, version 3. Available at: http://www.ukccsg.org/members/workinggroups/hodgkins/treatmentguidelines/index.html Cancer and Genetics Proposed March 2008 : Approved Sept 2008

http://www.ukccsg.org/members/working_groups/hodgkins/treatment_guidelines/index.html

http://www.ukccsg.org/members/working_groups/hodgkins/treatment_guidelines/index.html