OLIGOMETASTASISSS

1. PANEL DISCUSSION- YROC 2019
DR KANHU CHARAN PATRO
Oligometastatic Disease
WHERE ARE WE?
1

2. METASTASIS – OLDER DAYS
2

3. METASTASIS – OLDER DAYS
3

4. METASTASIS – MODERN ERA
4

5. MASKING AND UNMASKING
5

6. PANEL
6

7. 7

8. OLIGOMETASTATIC DISEASE
Solitary or few detectable metastatic lesions that are
usually confined to a single organ and may be more
than one organ
8

9. ALL METASTATIC TUMORS ARE SAME
WITH RESPECT TO SITE AND NUMBER?
9

10. Count the numbers- how many are oligo?
• 1
• 2
• 3
• 4
• 5
• Many
10
DR SAYAN PLEASE ?

11. 11

12. 12

13. 13
1 Vs >1 2 Vs >2 3 Vs >3
4 Vs >4
5 vs >5

14. 14
5 vs >5

15. 15
5 vs >5

16. PATTERN OF METASTASIS IN CA.LUNG [ADENO]
16
Thomas Klikovits /LUNG CANCER/2019
1. Bone metastases were more common in patients with central tumors,
2. Lung metastases were more common in those with peripheral tumors.
3. Central primary were associated with decreased median overall survival.
4. Bone metastases tend to appear together with adrenal and liver metastases,
5. Adrenal with skin,
6. Pleural with pericardial metastases more frequently than expected if
metastatic events occurred independently

17. 17

18. Conclusion
• Patients with 5 lesions
• Early detection aggressive treatment of patients
with a small number of metastatic lesions is
worth testing as an approach to improving long-
term survival.
18

19. THEORIES
19
DR SHANU JAIN PLEASE

20. V
20

21. 1995
21
Hellman created heaven for patients and
doctors

22. 22

23. SPECTRUM THEORY
Hellman and Weichselbaum described an
intermediate state exist between local and
widespread disease which they coined
“oligometastases”
(Hellman and Weichselbaum 1995)
23

24. SEED AND SOIL THEORY
24

25. SEED AND SOIL THEORY
1889 AD
Stephen Paget proposed his "seed and soil" theory of
cancer. He analyzed over 1000 autopsy records of
women who had breast cancer and found that the
patterns of metastasis were not random. Thus, he
proposed that tumor cells (the seeds) have a specific
affinity for specific organs (the soil), and metastasis
would only result if the seed and soil were compatible.

26. EXAMPLES
PRIMARY METASTATIC SITE
LUNG-NSCLC ADRENAL.BRAIN
LUNG-SCLC BRAIN
PROSTATE BONE
COLORECTAL LIVER
CERVIX NODE

27. CLONAL THEROY
27

29. Micro-RNA THEORY
29

31. 31

32. Why so?- DR ANAND PLEASE?
1. Improved imaging (role of PET-CT/FDG)
2. Increased availability of locoregional
treatments (radiofrequency, stereotactic
radiotherapy,vertebroplasty,minimally
invasive surgery)
3. Availability of more efficacious systemic
treatments (targeted therapies for oncogene
addicted NSCLC, immunotherapy)
4. Multidisciplinary approach
32

33. OLIGO-CLASSIFICATION
• Oligometastasis
–Synchronous oligometastasis
–Metachronus oligometastasis
• Oligopersistance
• Oligorecurrence
• Oligoprogressive 33
DR BIPRA DAS
PLEASE?

34. OLIGOMETASTASIS SPECTRUM-DEFINITIONS
Diane K. Reyes/ONCOTARGET/2015 2nd JAN 2019/OLIGO
34

35. M. Guckenberger ELCC 2016
Oligo meanings
35

36. Spectrum of Metastatic Disease
36

37. Oligometastases is the state in
which the patient shows distant
relapse in only a limited number
of regions
37

38. Oligo-recurrence has a primary
site of the cancer controlled,
meaning that all gross recurrent
or metastatic sites could be
treated using local therapy
38

39. SAME ORGAN VS DISTANT ORGAN
39

40. Synchronous oligometastatsis
Definition: De-novo presentation
of oligo-metasases
40

41. Synchronous oligometastasis
1.≤5 metastatic or recurrent lesions in the
presence of active primary lesions
2.Oligometastatic disease is detected at
the time of diagnosis of the primary
tumor, therefore there is an active
primary tumor
41

42. Metachronousoligometastaticdisease
Definition:
After period initial disease-free interval, new
presentation of oligo-metastases
42

43. Oligoprogressivedisease
• Definition: Majority of metastatic disease
controlled by systemic treatment, a few
‘resistant’ clones progress
43

44. INDUCED
OLIGOMETASTASIS/OLIGOPERSISTANCE
Induced oligometastasis occurs when
widespread micrometastatic disease is mostly
eradicated by systemic chemotherapy but
drug resistant clones are left behind, or tumor
foci is located in a site not accessed by
chemotherapy
44

45. FAVORABLE SECONDARY
• BONE AND SOFT TISSUE
• ADRENAL
45
DR DEEPANJAN PLEASE?

46. 46

47. Points of concern
1.Few data
2.Limited retrospective series
3.Different definition
4.Dynamic concept
5.NO RCT
47

48. HANDLING OLIGO
1. SBRT
2. RFA
3. SURGERY
4. BRACHYTHERAPY
5. INTRA ARTERIAL EMBOLIZATION
6. COMBINING WITH IMMUNOTHERAPY
48

49. HANDLING
• TREAT PRIMARY
• TREAT MET SITES
• TREAT BOTH
49

50. COMMON METASTATIC SITES
• BRAIN
• LIVER
• LUNG
• ADRENAL
• SPINE
50

51. FAVORABLE PRIMARY
• HORMONE RECEPTOR POSITIVE BREAST
CANCER
• ALK/EGFR/ ROS POSITIVE LUNG CANCER
• PROSTATE CANCER
• THYROID CANCER
• RCC
51

52. WHY SBRT FOR OLIGO?
52
DR JIBAK PLEASE

53. WHY SBRT FOR OLIGO?
• Ablative dose
• Better technology
• No delay in Systemic therapy
• Good number of studies
• High dose per fraction SBRT appears to be
mediated through pathways beyond DNA
damage and may enhance immune surveillance
of tumors
53

54. 54
LONGER TIME RADIATION EXPOSURE HINDERS THE REPAIR MECHANISM

55. 55
SHORTER DURATION TREATMENT RULES OUT REPOPULATION

56. 56
Massive vascular destruction no/minimal perfusion

57. 57
Massive vascular destruction no/minimal perfusion

58. 58
No cells exist to migrate from one phase to other

59. 59

60. ABSCOPAL THEORY
60

61. 61

62. 62

63. 1. Stereotactic body radiation therapy SBRT refers to an emerging
radiotherapy procedure that is highly effective in controlling
early stage primary and oligometastatic cancers at locations
throughout the abdominopelvic and thoracic cavities, and at
spinal and paraspinal sites.
2. The major feature that separates SBRT from conventional
radiation treatment is the delivery of large doses in a few
fractions, which results in a high biological effective dose BED
AAPM TASK GROUP 101
63

64. 64

65. MOSART- MULTI-ORGAN SITE ABLATIVE RADIATION THERAPY
DOSES USED IN NRG-BR001-OLIGOMETASTASIS
NRG-BR001 PROTOCOL
65

66. ONGOING OLIGOMETASTASIS TRIALS
JANA HEITMANN /JOURNAL OF THORACIC DISEASE/2018 66

67. Landmark trials
• Breast
– M1, MF07-01
• Prostate
– STAMPEDE
– HORRAD
• Colorectal-
– CLOCC
• Lung-
• Brain met-RTOG 9508
67

68. BREAST WITH OLIGO METS
68
DR ANAND PLEASE

69. 69

70. 70

71. 71

72. M1 TRIAL BREAST
NO ROLE OF LOCAL
SOS FOCAL[PALL]
ONLY GLOBAL[CHEMO]
BEYOND GLOBAL IS MORAL
LEARNT FROM M1 TRIAL
AND NEEDS MORE TRIAL
72

73. 73

74. 74

75. 75

76. 76

77. PROSTATE- ANY ROLE OF LOCAL
TREATMENT?
77
DR SHANU PLEASE

78. 78

79. 79
BENEFIT N LOW VOLUME DISEASE
STAMPEDE SHOWED NO BENEFIT
IN STAMPEDE OF METASTASIS

80. HORRARD TRIAL-METASTATIC PROSTATE
Liselotte M.S. Boeve/EUROPEAN ASSOCIATION OF UROLOGY/2018
The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary
bone mPCa did not show a significant difference in overall survival
BONE ONLY METASTASIS
ADT
VS
ADT + PROSTATE RT
432 patients with prostate-
specific antigen (PSA) >20
ng/ml and primary bone
mPCa on bone scan
between 2004 and 2014
None of the subgroups defined by
the different covariates showed a
significant difference in hazard
ratio (p > 0.05)
80
NO BENEFIT EVEN IN LOW VOLUME
DISEASE BUT RESULTS ARE BETTER

81. OLIGOMETASTASIS TO BRAIN
81

82. Ca lung with oligo brain
metastasis
CASE-1
82

83. History
1. c/o worsening headache, nausea- 1 month
2. Known c/o Ca lung left pT2N0M0– Lobectomy 2
yrs back.
3. HPE: Adenocarcinoma, Margins negative.
4. Pre OP PET CT showed no mediastinal nodes.
5. Was on followup.
83

84. Examination
• No e/o cranial nerve/motor deficits
• Bladder/ bowel habits normal.
• RS: NVBS, B/L air entry normal. No added
sounds
• P/A: soft . Non tender, no organomegaly
84

85. Workup-MRI
Intensely enhancing lesions with surrounding edema
in left CEREBELLUM (26x 22 mm), superior
cerebellum (16x15 mm) and high frontal region
(8x5mm) s/o metastasis.
85

86. 86

87. Workup
• Whole body FDG PET CT: No e/o disease
elsewhere in the body.
• Blocks review:
– EGFR +ve
– ALK - ve
– ROS1 -ve
87

88. Treatment
Options-
• TKI
• LOCAL SX/SRS
88
DR ANAND PLAESE?

89. OPTIONS
• WBRT
• SRS
• WBRT+SRS
• POST-OP SRS
• POST –OP WBRT
• BSC
• FAVORABLE PRIMARY
89

90. EGFR POSITIVE NSCLC WITH BRAIN MET
90
UPFRONT TKI
UPFRONT SRS
UPFRONT WBRT

91. 91

92. 6 months post RT
92

93. 24 months post RT
93

94. 30 months post RT
Enhancing lesion in dorsal pons and vermis, largest 11x7 mm
s/o metastasis.
PET CT: no extracranial disease
94

95. THOUGHTS
• UPFRONT EGFR INHIBITORS CAN NOT RREACH
THE BRAIN LIKE ERLOTINIB/ GEFITINIB/AFATINIB
• SANCTUARY SITE
• UPFRONT BRAIN RT INCREASES TOXICITY IN A
FOVOURABLE DISEASE
95

96. 96
UPFRONT SRS IS BETTER

97. 97
UPFRONT RT IS NOT BETTER

98. 98

99. BRAIN MET DOSE
• SITE
• SIZE
• PRIMARY
99
DR SAYAN PLEASE

100. DOSAGE SCHEDULE
100

101. • WBRT- 30Gy/ 10#/ 2 weeks
• fSRS – 6Gy x 5#
101

102. Whole Brain Radiation With
or Without SRS: RTOG 9508
333 patients randomized to WB alone (37.5
Gy in 15 fx) vs WB + SRS
• KPS >70; 1-3 lesions
• 75% controlled or absent primary site
• 10% breast primary (2/3 lung)
• SRS dose 15- 24 Gy (size dependent)
Andrews DW, Lancet 363, 2004
102

103. RTOG 9508: Results
Andrews DW, Lancet
363, 2004
Overall
Survival
Whole
Brain
5.7 mo
Whole Brain + SRS
6.5 mo (p=ns)
Overall
Survival
(Single lesion)
4.9 mo 6.5 mo (p=0.04)
Local
Control
(at one
year)
71% 82% (p=0.01)
Stable or
improved
KPS at 6
months
27% 43% (p0.03)
103

104. Survival in Patients with a Single Brain
Metastasis
Andrews DW, Lancet 363, 2004
RTOG 95-08 is the ONLY level 1 evidence to
demonstrate an overall survival benefit with
SBRT/SRS in oligometastatic disease 104
ADDITION OF SRS IS BETTER

105. 105
BOTH ARE SAME
THEN WHY NOT SRS?

106. 106

107. 107

108. 108
MAKE THE DOSE DOUBLE AND LESSEN YOUR TROUBLE

109. 109
MORIBUND PATIENT, EXTENSIVE METS WBRT.BSC
CHOOSE YOURSELF

110. SPINE SBRT
110
DR JIBAK PLEASE

111. 111

112. BRACHYTHERAPY
112

113. LUNG METS AND BRACHYTHERAPY
113

114. LIVER METS AND BRACHYTHERAPY
114

115. BRACHYTHERAPY
115
LETS PRACTICE AND POPULARISE BRACHYTHERAPY

116. PULMONARY METASTATECTOMY
116

117. 117

118. 118

119. 119

120. 120

121. IMMUNOSENSITIATION
RADIATION ACT LIKE AS VACCINE
121

122. 122

123. 123

124. 124

125. ASTRO STATEMENT
“It appears that the radiation helped turn the tumor into a
vaccine to stimulate an immune response. This heightened
immune response was able to keep the tumors stable. Longer
follow-up is needed to determine if this benefit of stable disease
will endure over time.”
125

126. 126
SOME FORM OF RADIATION BEFORE
IMMUNOTHERAPY ENHANCES ACTIVITY

127. summary
1. Within the metastatic setting, immunotherapy in
combination with radiotherapy may be synergistic and may
be an effective strategy to enhance the effect of
immunotherapy.
2. The radiation oncology community has begun to appreciate
the role of the immune response itself as an important
component in the treatment effect of radiotherapy.
3. Successful integration of immunotherapy into definitive
radiotherapy regimens may require a drastic alteration of
radiotherapy dosing and field design to maximize benefit
127

128. HANDLING ISOLATED ADRENAL METS
128
DR DIPANJAN PLEASE

129. 129

130. 130

131. Case study - 2
• 56 year male
• P/W – Rectal bleed -3month
• Sigmoidoscopy- ulcerative growth 3 cm from anal
verge
• Biopsy- adenocarcinoma
• Mri- abutting prostate, perirectal node
• CEA -112
• PET- single segment 7 hypodense lesion –SUV-4.2
• Biopsy not possible
• Radiologists sure about liver met
• Oligometastasis rectal malignancy
131

132. 132

133. Treatment options
1. Chemotherapy first and reassessment
2. SHORT /LONG-COURSE REGIME + SBRT F/B local
surgery-chemotherapy
3. SHORT/LONG COURSE REGIME + RFA F/B local
surgery-chemotherapy
4. SHORT /LONG COURSE REGIME F/B local surgery
and liver resection F/B-chemotherapy
133
DR BIPRA DAS PLEASE

134. Oligometastasis- colorectal- NCCN
134

135. Oligometastasis- colorectal- NCCN
135

136. Strategies for Metastatic Colorectal Cancer
Surgical Decision Making
Metastatic Disease
Assessment of Resectability
Tumor conference discussion
Resectable Unresectable
Neoadjuvant Surgery Chemotherapy
Ablative therapy
Adjuvant
?

137. 137

138. WHICH CHEMO?
FOLFOX VS FOLFIRI VS FOLFIXIRI
138

139. METASTATIC COLORECTAL CANCER-GONO TRIAL
The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an
increased, but manageable, toxicity in patients with metastatic colorectal cancer with
favorable prognostic characteristics
Alfredo Falcone/ Journal of Clinical oncology/2007
139
FOLFIRI IS BETTER WITH MORE SIDE EFFECTS

140. MCRC- FOLFOXIRI vs FOLFIRI - HORG STUDY
Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P ¼ 0.0001), diarrhoea (P ¼ 0.0001)
and neurosensory toxicity (P ¼ 0.001) compared with patients treated with FOLFIRI. The present study failed to
demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the
observed median OS is one of the best ever reported in the literature
J Souglakos/BJC/2006 10th JAN 2019/OLIGO
140
BOTH ARE SAME

141. OXALIPLATIN AND IRINOTECAN BASED
141

142. 142

143. 143

144. 144

145. CLOCC TRIAL
145

146. 146

147. LIVER CHANGES WITH OXALIPLATIN
12th JAN 2019/OLIGO
SINUSOIDAL OBSTRUCTION SYNDROME IS A MAJOR FEATURE OF HEPATIC LESIONS ASSOCIATED WITH
OXALIPLATIN NEOADJUVANT CHEMOTHERAPY FOR LIVER COLORECTAL METASTASES
147

148. LIVER CHANGES WITH IRINOTECAN
13th JAN 2019/OLIGO
STEATOHEPATITIS IS A MAJOR FEATURE OF HEPATIC LESIONS ASSOCIATED WITH IRINOTECAN
NEOADJUVANT CHEMOTHERAPY FOR LIVER COLORECTAL METASTASES
148

149. PRE-OP CHEMOTHERAPY
Advantages
• Allows time for other metastastic
sites to become clinically evident
• Allows for in vivo gauge of
chemoresponsiveness, facilitating
post-operative chemotherapy
planning
• Response may allow for easier
resection and increased rate of
negative surgical margins
• Response may be a prognostic factor
Disadvantages
• PROGRESSION
• Perioperative morbidity may be
increased because of
hepatotoxicity of chemotherapy
• Patient anxiety and desire to have
tumor resected as soon as
possible
149

150. Hepatectomy for Colorectal Metastases
Surgical Decision Making
Factor % p Hazard
> 1 Tumor 51 0.0004 1.5
CEA > 200 ng/ml 9 0.01 1.5
Size > 5 cm 45 0.01 1.4
Node + primary 60 0.02 1.3
Dz-free interval < 1 yr 49 0.03 1.3
Positive micro margin 11 0.004 1.7
Extrahepatic disease 9 0.003 1.7
PostopPreop
Fong et al, Ann Surg 1999; 230:309
Multivariate Analysis of Survival (N=1,001)
150

151. Hepatectomy for Colorectal Metastases
Surgical Decision Making
Survival
Score Median 5 year
0 74 months 60%
1 51 44
2 47 40
3 33 20
4 20 25
5 22 14
Fong et al, Ann Surg 1999; 230:309
The problem with scoring:
no one preoperative factor can be used to exclude
Preop Clinical Risk Score Predicts Survival
151

152. 152

153. Radiofrequency Ablation
• To treat tumors which do not meet resectability criteria, but disease
confined to the liver or stable extra-hepatic disease
• Not as a replacement for resection
• Expand the number of surgical candidates
• Solbiati L et al. Percutaneous radiofrequency ablation of hepatic
metastases from colorectal cancer: long-term results in 117 patients.
Radiology, 2001
– 117 patients
– 3-year survival 46%
– median survival 36 months
• Only 6 studies that reported at least 3-year survival were identified, with
results ranging from 37-58%
– McKay et al: Current role of radiofrequency ablation for the treatment of
colorectal liver metastases. BJS, 2006
153

154. 154

155. 155

156. 156

157. LAST LINE OF NEW DEVITA
157

158. 158