1. PANEL DISCUSSION ON CHALLENGES IN DISEASE RESPONSE STATUS
Case presenter: Dr. HH
Panelists: 1 2.
Moderator: Prof AB
Date:
Venue:

2. CASE 1

3. Case 1 27-year-old Malay lady
Presented to HSNZ in June 2011 with history of painless right neck swelling during her 2nd pregnancy
no B or compressive symptoms
HPE of right cervical LN (30/06/2011) in HSNZ
Classical Hodgkin Lymphoma (mixed cellularity)

4. 2012
After being informed her diagnosis, lost to follow up until February 2012
Presented again with fever, dyspnoea, orthopnoea & dysphagia
P/E: firm mass, 10cm x 15cm at right neck with features of SVCO
Blood Ix:
FBP (Hb 11.2, WBC 15.92, ANC 15.31, Lymph:, PLT 745), Reactive neutrophilia & thrombocytosis
LDH 536, ESR 99, normal RFT & LFT
Treated for chest infection & SVCO (antibiotic & IV Dexamethasone; commenced from HSNZ)
Default- about 7-8 mths

5. HSNZ Initial CT Neck & thorax (19/07/2011) in HSNZ
Right side of carvenous sinus slightly bulging, but no filling defect
Bilateral submandibular nodes less than 1 cm, right level II & III cervical nodes, largest measure 6mm & 1.6x1.5cm respectively
Large matted right supraclavicular nodes measures 4.8(AP)x6.7(W)x5.1(CC)cm.
Right IJV is small & compressed. Poor plane of demarcation with right CCA
4.6(AP)x4.0(W)x4.7(CC)cm heterogenously enhacing mass at apical & anterior segment of right upper lobe associated with opacities of adjacent lung parenchyma
Right paratrachea extends to pretrachea & precarina nodes measures 2.5x5.3x6.2cm. Subcarina node measures 1.8x4.1x4.3cm
CT Abdomen & Pelvis (28/02/2012) in HSNZ
Presence of hyperdense lesions seen at mainly at segment IVa, IVb and part of segment II and III.
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First target lesion: Large matted right supraclavicular nodes measures 4.8(AP)x6.7(W)x5.1(CC)cm.

6. Right supraclavicular nodes measures 4.8(AP)x6.7(W)x5.1(CC)cm
Large matted right supraclavicular nodes measures 4.8(AP)x6.7(W)x5.1(CC)cm

7. mass at apical & anterior segment of right upper lobe
4.6(AP)x4.0(W)x4.7(CC)cm heterogenously enhacing mass at apical & anterior segment of right upper lobe

8. hyperdense lesions mainly at segment IVa, IVb and part of segment II and III.
hyperdense lesions seen at mainly at segment IVa, IVb and part of segment II and III.

9. HUSM
CT scan repeated in HUSM on 06/03/2012 (patient already on IV Dexamathasone)
Neck:
Right submandibular (largest on right side 1.7cm) , bilateral posterior cervical group (largest on left side 2.0cm), bilateral supraclavicular nodes (largest on right side 1.6cm)
Along right jugular chain, matted together, 3.5cm & pushes the right neck vessels (CCA & IJV) anteriomedially
Thorax:
Matted nodes at anterior mediastinal, preaortic, precarina, subcarina & both hilar regions
Multiple lung nodules are seen in the right upper and middle lobes (largest 0.9cm anterior segment)
Bilateral axillary lymph nodes, largest on right side (2.3cm)
Abdomen
Solitary well-defined enhancing lesion is seen in segment IVa of liver, 0.5cm(AP)x0.5cm(W)
IMP: known case of Hodgkin Lymphoma with lung involvement, multiple neck & mediastinal lymphadenopathy – Stage IV

10. Right submandibular nodes; largest on right side measuring 1.7cm
There are multiple enlarged LN seen;
- Right submandibular nodes; largest on right side measuring 1.7cm [se4 image 27]
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11. Bilateral posterior cervical group; largest on the left side measuring 2.0cm
Bilateral posterior cervical group; largest on the left side measuring 2.0cm [se4 image 22]

12. right jugular chain which is matted together measuring approximately 3
right jugular chain which is matted together measuring approximately 3.5cm
Along the right jugular chain which is matted together measuring approximately 3.5cm [sec4 image 34]
It pushes the right neck vessels (CCA & IJV) anteromedially

13. Bilaterally axillary LN;
Largest on the right side measuring 2.3cm SHOWN HERE
Multiple enlarged anterior mediastinal LN
Lung infiltrated
Bilaterally axillary LN; largest on the right side measuring 2.3cm [se4 image 59]

14. HUSM BMAT for staging (04/03/2012)
No evidence of marrow infiltration by lymphoma cells
Final diagnosis: Classical Hodgkin Lymphoma (mixed cellularity) Ann Arbor Stage IVB (lung)

15. 2012 in HUSM
1st line chemotherapy ABVD regime (07/03/2012 – 27/06/2012)
Mid cycle CT Staging (neck, thorax, abdomen, pelvis) on 05/06/2012
Neck: no significant change in size of neck lymph nodes
Thorax: no significant changes in matted nodes at thoracic region, Multiple lung nodules still present
Abdomen:
ill-defined hypodense lesion noted in segment IVb of liver; 1.7cm x 3.9cm x 6.6cm
Previously seen solitary well-defined hypodense lesion in segment IVa of liver is currently not seen
Radiological impression: Hodgkin lymphoma with new liver lesion & no significant change in lymphadenopathies/lung nodules (progressive disease)
Issue to be discussed:
Cilinical response & radiological response
CHESON criteria.

16. Clinically, patient was well, no more palpable lymphadenopathy
FBC: acceptable (WBC 3.71, ANC 1.82, Hb 11.2, PLT 455)
LDH 283, Normal RFT & LFT

17. From hematological point of view:
Only achieved stable disease after 3 cycles of ABVD; chance to achieve better response with ABVD is small
Plan to switch to 2nd line chemotherapy i.e. ICE regime for 4 cycles then followed by BEAM & auto-SCT
ICE regime commenced on 12/07/2012 with stem cell mobilization & collection done after 2nd cycle of ICE
Failing to attain the criteria needed for a CR or PR, but not fulfilling those for progressive disease

18. CT staging (neck, thorax, abdomen, pelvis) done on 06/11/2012 – post ICE 4 cycles
IMP: Persistent lymphadenopathy, lung nodules, with no significant change from previous study

19. From hematological point of view:
most of lymph node already reduced in size, especially right supraclavicular nodes previously measures 4.8 (AP) x 6.7 (W) x 5.1 (CC) cm on 19/07/11 in HSNZ [Considered as 1st index lesion]; currently measure 2.3 cm (AP) x 2.3 cm (W) in latest CT Scan
ill-defined hypodense lesion noted in segment IVb of the liver measuring 1.7cm (AP) x 3.9 cm (W) x 6.6cm (CC) on CT Scan (05/06/12) [considered as 2nd index lesion], currently absent on latest CT scan
Impression: Partial Response (PR)
Patient was given 1 cycle of GemoX (06/12/2012), while awaiting for PET CT Scan appointment in Putrajaya.

20. PET CT on 06/02/2013 in Hospital Putrajaya:
Left thyroid lobe (SUV max 5.6), No significant CT changes
Clumps of subcentimetre mesenteric nodes just anterior to right psoas muscle at the level of L5 (SUV max 4.1)
Background FDG metabolism seen at subcentimetre right level II & V cervical nodes, matted nodes at anterior mediastinum (2.2x7.4cm), matted precarinal, subcarinal & aortopulmonary node (1.4x0.9cm)
IMP: FDG metabolism in the mesenteric nodes is likely due to residual lymphoma although infection cannot be excluded. Focal FDG hypermetabolism in left thyroid lobe warrants further investigation to diagnose or exclude malignancy
Assessment from hematological point of view:
Only small lesion in mesenteric.
Plan for BEAM & auto-SCT soon
Issue to be addressed:
Radiological response & clinical response

21. CASE 2

22. CASE 2 22-year-old Malay lady
Presented to ENT team in June 2011 with right neck swelling with history of progressively enlargement.
a/w fever, night sweat; no LOA, no LOW, no compressive symptoms
P/E: right neck swelling (supraclavicular) 8cmx6cm, firm & non tender. No hepatosplenomegaly
Blood Ix:
FBC (Hb 12.5, WBC 7.32, ANC 4.94, PLT 309)
LDH 425, ESR 62, normal RFT & LFT
biopsy (excisional biopsy) of right neck nodes (22/02/2011)
Classical Hodgkin Lymphoma (Mixed Cellularity type)

23. Initial CT Staging (Neck) on 21/02/2011 & (thorax, abdomen & pelvis) on 19/04/2011
Well-defined mixed solid cystic nodule arising from inferior pole of right thyroid gland 2.9cmx(AP)x3.3cm(W)x4.1cm(CC); thyroid mass slightly pushing trachea to the left, however is patent
Multiple enlarged LN in the cervical region; right posterior cervical , largest 1.89cm in short axis, Right infraclavicular, 3.0cm(AP)x3.8cm(W), small bilateral carotid space , submandibular nodes
Multiple enlarged matted LN right supraclavicular region with extension to involve right cervical chain, largest 3.7cmxX2.0cm
Multiple enlarged mediastinum nodes size ranging 0.9cm – 2.0cm
Multiple shotty lymph nodes in the abdominal region
IMP: Mediastinal and abdominal lymphadenopathies with right thyroid nodules

24. Largest nodes with necrotic centre measures 2.1cmX3.2cm
Right supraclavicular LN with extension to involve the right cervical chain nodes
Largest nodes with necrotic centre measures 2.1cmX3.2cm
Right supraclavicular LN with extension to involve the right cervical chain nodes
Largest nodes with necrotic centre measures 2.1cmX3.2cm {Ima 218c}

25. Right posterior cervical, largest measuring 1.89cm in short axis
Right posterior cervical, largest measuring 1.89cm in short axis {Im 162c}

26. Right infraclavicular 3.0cm
(AP)X3.8cm(W)
Right infraclavicular 3.0cm(AP)X3.8cm(W) {246}

27. Small bilateral carotid space
Small bilateral carotid space [im 183]

28. Submandibular nodes
Submandibular nodes [167]

29. On Rt, one LN abutting SVC
Multiple enlarged mediastinum nodes matted to form a mass anterior and left to the des aorta. 3.0cmx4.5cm .
On Rt, one LN abutting SVC
Multiple enlarged mediastinum nodes
Largest seen at preaortic area measuring 3.0cmx4.5cm {Im324c}

30. Anterior mediastinum mass is lobulated
Anterior mediastinum measuring 1.0cm {Im 308c}

31. Left pratrachea measuring 1.6cm
Left pratrachea measuring 1.6cm {Im306c}

32. Right hilar measuring 1.6 cm
Right hilar measuring 1.6 cm {Im382}

33. Precarina, 1.3cm
Precarina, 1.3cm

34. Carina, 1.3cm
Carina, 1.3cm {339}

35. Subcarina, 1.5cm
Subcarina, 1.5cm {356}

36. BMAT staging (02/05/2011): no evidence of infiltration by primary disease
Final diagnosis: Classical Hodgkin Lymphoma (mixed cellularity) Ann Arbor Stage IIIB

37. Treatment 1st line chemotherapy ABVD regime (21/04/2011 – 13/10/2011)
Mid cycle CT Staging (neck, thorax, abdomen, pelvis) on 20/07/2011
Partial response to treatment (partial regression of lymph nodes)
Hematological assessment: Partial Response (PR)
Haemato impression: PR

38. Smaller right supraclavicular lymph nodes, largest 1
Smaller right supraclavicular lymph nodes, largest 1.3cm; previous measurement 2.7cm(AP)x3.2cm(W)x4.1cm(CC)
Smaller right supraclavicular lymph nodes, largest 1.3cm (se4, im24); previous measurement 2.7cm(AP)x3.2cm(W)x4.1cm(CC)

39. Right paratracheal 0.9cm
Lesser & smaller mediastinal node as compare to previous study
- Right paratracheal 0.9cm (se4, im36)

40. Precarina 0.9cm
Precarina 0.9cm (se4, im38)

41. Anterior mediastinal mass is regressing in size
Anterior mediastinal node, 1.8cm (se4 im40)

42. Progress
2 months after completion of ABVD regime, she presented with recurrent right sided neck swelling with no B symptom, no compressive symptom
Blood Ix:
FBC (Hb 10.8, WBC 7.05, ANC 5.03, PLT 498)
LDH 272
FNAC of right LN (22/12/2011): compatible with Hodgkin lymphoma

43. Progress
Repeat CT Staging (Neck, thorax, abdomen & pelvis) on 03/01/2012 (Post ABVD 6 cycles)
Features of progressive disease (increased in size & number of lymph nodes at neck region)
PET CT was not done (financial reason)

44. The largest LN along the planes of right posterior jugular chain measuring 2.0cm(AP)x2.0cm(W)x3.0cm(CC) – level IV
The right neck nodes, notably the right supraclavicular LN have significantly increased in size & numbers.
The largest along the planes of right posterior jugular chain measuring 2.0cm(AP)x2.0cm(W)x3.0cm(CC) (se5/im227c) – level IV

45. Right posterior cervical chain (1.9cmx2.0cm)
Other significant enlarged LN
- Right posterior cervical chain (1.9cmx2.0cm) (se5/im180c)

46. Right posterior clavicular (1.3cmx2.1cm)
Right posterior clavicular (1.3cmx2.1cm) (se5/im260c)

47. Enlarged lobulated, peripherally enhacing necrotic anterior mediastinal nodes; measuring 4.2cm(AP)x1.9cm(W), slightly increased in size (previous 4.2cmx1.8cm).
Enlarged lobulated, peripherally enhacing necrotic anterior mediastinal nodes; measuring 4.2cm(AP)x1.9cm(W) (se5/im318), slightly increased in size (previous 4.2cmx1.8cm).

48. Salvage
Treatment plan; for curative intent with ICE chemo (2nd line chemotherapy) for 4 cycles then followed with high dose chemo + auto SCT
Commenced on ICE 1st cycle on 05/01/2012, stem cell mobilization & collection done after 3rd cycle of ICE

49. Response
CT staging (Neck, thorax, abdomen & pelvis) on 25/04/2012 post 4th ICE
Report: Good response of treatment (previously seen multiple lymph nodes have significantly reduced in size & numbers)
Haematological assessment: previously seen anterior mediastinal node measures 3.9cm x 1.4 cm (Se3 Im299) previously measures 4.2cm x 1.9 cm) in keeping with residual disease

50. Few right posterior jugular chain nodes with largest measuring 0
Few right posterior jugular chain nodes with largest measuring 0.7cm(AP)x1.1cm(W)x1.4cm(CC, previously was 1.0cm(AP)x1.0cm(W)x2.2cm(CC)
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Few right posterior jugular chain nodes with largest measuring 0.7cm(AP)x1.1cm(W)x1.4cm(CC), (Se3 Im206c) [previously was 1.0cm(AP)x1.0cm(W)x2.2cm(CC)]

51. Single right supraclavicular node measures 1.0cmx0.8cm
Single right supraclavicular node measures 1.0cmx0.8cm (Se3 Im217c)

52. Previously seen anterior mediastinal node measures 3. 9cmx1
Previously seen anterior mediastinal node measures 3.9cmx1.4cm (se3 Im299) (previously measures 4.2cmx1.9cm)
Previously seen anterior mediastinal node measures 3.9cmx1.4cm (se3 Im299) (previously measures 4.2cmx1.9cm)

53. Salvage
Proceed with IFRT (Involved-field radiotherapy) under oncology (mini- mantle radiotherapy), completed 15 courses on 05/07/2012
CT staging (Neck, thorax, abdomen & pelvis) on 07/08/2012 post IFRT
anterior mediastinal nodes are reducing in size, with the largest dimension is measured 2.2cm (W) x 1.1 cm (AP) [previous measures 3.9cm x 1.4cm], good response to treatment
PET CT Scan was not done
Assessment:
Reduction in nodes size in not enough to proceed with BEAM & auto SCT
PET CT was not done

54. Salvage For GDC 3-4 cycles (3rd line chemotherapy),
(11/09/2012 – 14/11/2012)
CT staging (Neck, thorax, abdomen & pelvis) on 09/12/2012 post 4th cycle of GDC
Subcentimeter cervical lymph node, Smaller size of anterior mediastinal lymph nodes
Residual disease

55. Previously seen anterior mediastinum LN are smaller in size, currently measures 1.7cmx0.8cm [Se2 Im42], previous measured 2.2cmx1.1cm
Previously seen anterior mediastinum LN are smaller in size, currently measures 1.7cmx0.8cm [Se2 Im42], previous measured 2.2cmx1.1cm

56. Patient is planned for PET CT Scan before finally proceeded with auto-SCT, however default follow up

57. Discussion Overall visit responseCT
PET
Bone Marrow
Physical Exam
B-Symptoms
Cheson criteria response criteria for malignant lymphoma