View
0
Download
0
Embed Size (px)
Current Controversies in
Radiation Therapy for Lung
Cancer
Optimal RT Dose :RTOG 7301
n = 378, stage III, KPS ≥ 50
RTOG-7301: Survival/Response
Total Number Median 2-Yr.
n Dose (cGy) Fractions (mos.) (%)
93 4,000 10(S) *(1-2-1) 8.5 10
97 4,000 20(C) 10.6 11
91 5,000 25(C) 9.5 19
84 6,000 30(C) 10.8 19
60 Gy in 6 weeks became the
standard dose for Stage III NSCLC
in the 70’s …80’s and 90’s
Overview of 74 Gy vs 60 Gy Dose
(Phase I/II Trials)
RTOG 0617- A 7501
Randomized Phase III Comparison of Standard-Dose (60 Gy)
Versus High-Dose (74 Gy) Conformal Radiotherapy with
Concurrent and Consolidation Carboplatin/Paclitaxel +/-
Cetuximab In Patients with Stage IIIA/IIIB Non-Small Cell Lung
Cancer (NSCLC)NCI Sponsored Cooperative Groups: RTOG, NCCTG, CALGB
Jeffrey D Bradley, Rebecca Paulus, Ritsuko Komaki, Gregory A. Masters, Kenneth Forster, Steven E. Schild, Jeffrey Bogart, Yolanda I. Garces, Samir
Narayan, Vivek Kavadi, Lucien A Nedzi, Jeff M. Michalski, Douglas Johnson, Robert M MacRae, Walter J Curran, and
Hak Choy
Bradley A-7501, ASCO ‘13
RTOG 0617 Overall Survival
S u rv
iv a l R
a te
( %
)
0
25
50
75
100
Months since Randomization
0 3 6 9 12 15 18
Patients at Risk Standard High dose
213 206
207 197
190 178
177 159
161 135
141 112
108 87
Dead
90 117
Total
213 206
HR=1.56 (1.19, 2.06) p=0.0007
Standard (60 Gy) High dose (74 Gy)
Median Survival Time
28.7 months 20.3 months
2 year Survival Rate
57.6%
44.3%
Bradley A-7501, ASCO ‘13
60 Gy
74 Gy
7
My Perspective on RT Dose and
RTOG 0617 60Gy
68Gy
6 3 G
y
7 4 G
y
More is not necessarily better (60 Gy > 74 Gy)
Less is “more” and clearly less toxic
1970 2014
CONVERT trial Concurrent ONce-daily VErsus twice-daily RadioTherapy:
A 2-arm randomised controlled trial of concurrent chemo-
radiotherapy comparing twice-daily and once-daily
radiotherapy schedules in patients with limited-stage small
cell lung cancer and good performance status
Corinne Faivre-Finn1, Michael Snee2, Linda Ashcroft3, Wiebke Appel4, Fabrice Barlesi5, Adi Bhatnagar6, Andrea Bezjak7, Felipe
Cardenal8, Pierre Fournel9, Susan Harden10, Cecile Le Pechoux11, Rhona McMenemin12, Nazia Mohammed13, Mary O'Brien14,
Jason Pantarotto15, Veerle Surmont16, Jan Van Meerbeeck16, Penella Woll17, Paul Lorigan1, Fiona Blackhall1
1. The University of Manchester, Institute of Cancer Sciences, Manchester, UK; 2. St James Hospital, Leeds, UK; 3. MAHSC-CTU, The Christie
NHS Foundation Trust, UK; 4. Royal Preston Hospital, UK; 5. CHU de Marseille, France; 6.Southampton General Hospital, UK; 7.Canadian Cancer
Trials Group, Princess Margaret Cancer Center, Toronto, Canada; 8. GECP , Institut Català d'Oncologia, Barcelona, Spain; 9. GFPC, Institut de
Cancérologie de la Loire, France; 10. Addenbrookes Hospital, Cambridge, UK; 11. Institut Gustave Roussy, Villejuif, France; 12. Freeman Hospital,
Newcastle-upon-Tyne, UK; 13. Beatson Cancer Centre, Glasgow, UK; 14. Royal Marsden Hospital, Surrey, UK; 15. Ottawa Health Research
Institute, Canada; 16. Universiteit Gent, Belgium; 17. Weston Park Hospital, Sheffield, UK
ASCO 2016, Presented by: Prof C Faivre-Finn
@finn_corinne
Study design multinational, phase III randomized study
ASCO 2016, Presented by: Prof C Faivre-Finn
RT 45Gy/30F/19D
L im
it e
d S
ta g
e S
m a
ll C
e ll
SD,PR,CRPCI
If
Overall survival
Presented by: Prof C Faivre-Finn
Median follow-up: 45 months
Overall
survival
(n=543)
BD OD Log-rank
Median
(months)
30 (24-34) 25 (21-31)
p=0.15
1-year 83% (78-87) 76% (71-
81)
2-year 56% (50-61) 51% (45-
57)
3-year 43% (37-49) 39% (33-
45)
Primary objective-survival at 2 years Trial hypothesis
Expected survival BD arm 44% Projected survival OD arm 56%
@finn_corinne
HR for death OD group =1.17 95% CI 0.95-1.45
AE
CTCAE v3.0 Arm
0
n (%)
1-2
n (%)
3-5
n (%)
P
(0,1,2 vs3,5)
Oesophagitis BD
OD
48 (18.9)
63 (25.7)
159 (62.6)
135 (55.1)
45 (18.5)
47 (19.2) 0.85
Pneumonitis BD
OD
198 (78.0)
187 (77.3)
51 (20.1)
49 (20.2)
5 (2.0)*
6 (2.4)* 0.70
Symptom Arm 0 1-2 3 4 p 0,1,2 vs 3,4
Dermatitis BD OD
233 (94.0) 216 (92.7)
15 (6.0) 17 (7.3)
- - -
Oesophagitis BD OD
219 (88.3) 191 (81.6)
29 (11.7) 39 (16.7)
- 4 (1.7)
- 0.06
Oesophageal stricture/fistula
BD OD
240 (91.8) 226 (97.0)
8 (3.2) 6 (2.6)
- 1 (0.4)
- 0.48
Pulmonary fibrosis
BD OD
125 (50.6) 120 (52.6)
119 (48.2) 106 (46.5)
3 (1.2) 2 (0.9)
- 1.00
Pneumonitis BD OD
171 (69.0) 154 (67.0)
71 (28.6) 70 (30.4)
5 (2.0) 5 (2.2)
1 (0.4) 1 (0.4) 0.90
Myelitis BD OD
247 (99.6) 223 (96.5)
1 (0.4)* 8 (3.5)*
- - -
Other BD OD
92 (37.4) 99 (42.7)
131 (53.3) 113 (48.7)
20 (8.1) 18 (7.8)
3 (1.2) 2 (0.9) 0.78
Acute & Late Toxicity
Immunotherapy is HOT!
Lung cancer clinical trials
Keynote 001 Pembrolizumab Trial: Percentage of Cells Expressing PD-L1
Garon, EB; NEJM, 2015
2nd line Patients: Check mate 017 Nivolumab vs. Docetaxel
Brahmer, J; NEJM, 2015
Radiation Therapy and the Abscopal Effect
Patient has visible tumor A, B, C, …
A
B
C
Radiation Therapy and the Abscopal Effect
Patient has visible tumor A, B, C, …
Treat tumor A alone with radiation A
B
C
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiBg9at6ObKAhXDOyYKHeDHAsAQjRwIBw&url=http://www.clker.com/clipart-black-lightning-bolt.html&bvm=bv.113370389,d.eWE&psig=AFQjCNHPHl-2Ub9lGeXZdJ27M2O6TJMtQw&ust=1454974449057365 http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiBg9at6ObKAhXDOyYKHeDHAsAQjRwIBw&url=http://www.clker.com/clipart-black-lightning-bolt.html&bvm=bv.113370389,d.eWE&psig=AFQjCNHPHl-2Ub9lGeXZdJ27M2O6TJMtQw&ust=1454974449057365
Radiation Therapy and the Abscopal Effect
Patient has visible tumor A, B, C, …
Treat tumor A alone with radiation
Tumors B, C, … regress
A
B
CC
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiBg9at6ObKAhXDOyYKHeDHAsAQjRwIBw&url=http://www.clker.com/clipart-black-lightning-bolt.html&bvm=bv.113370389,d.eWE&psig=AFQjCNHPHl-2Ub9lGeXZdJ27M2O6TJMtQw&ust=1454974449057365 http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiBg9at6ObKAhXDOyYKHeDHAsAQjRwIBw&url=http://www.clker.com/clipart-black-lightning-bolt.html&bvm=bv.113370389,d.eWE&psig=AFQjCNHPHl-2Ub9lGeXZdJ27M2O6TJMtQw&ust=1454974449057365
Radiation Therapy and the Abscopal Effect
Patient has visible tumor A, B, C, …
Treat tumor A alone with radiation
Tumors B, C, … regress
First described in 1953
Shown to be immune mediated over a decade ago
A
B
C
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiBg9at6ObKAhXDOyYKHeDHAsAQjRwIBw&url=http://www.clker.com/clipart-black-lightning-bolt.html&bvm=bv.113370389,d.eWE&psig=AFQjCNHPHl-2Ub9lGeXZdJ27M2O6TJMtQw&ust=1454974449057365 http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiBg9at6ObKAhXDOyYKHeDHAsAQjRwIBw&url=http://www.clker.com/clipart-black-lightning-bolt.html&bvm=bv.113370389,d.eWE&psig=AFQjCNHPHl-2Ub9lGeXZdJ27M2O6TJMtQw&ust=1454974449057365
RT Can Augment Immune Response
Shiao and Coussens. J Mammary Gland Biol Neoplasia. 2012.
Abscopal Effects
The Immune Mediated Abscopal Effect
Treatment of one tumor triggers the response of other (or all) tumors
IF this occurred in a reliable way, it would be extremely important
–Alas, it dose not
Mostly described in retrospective single patient case reports rather than
prospective series
