Abstract
Purpose or Objective
Developments of local and systemic therapies have
improved the prognosis of metastatic NSCLC.
Oligometastatic patients may especially benefit from a
more aggressive treatment approach. However, the
concept of “oligometastasis” is complex: e.g. limited
progression or resistance of disease to systemic
treatment. This study aimed to evaluate the outcome of
stereotactic radiotherapy (SRT) to oligoprogressive or
oligoresistant NSCLC in patients receiving concurrent
immuno- or targeted therapy.
Material and Methods
The retrospective international multicenter register study
(TOaSTT) collected data on metastatic NSCLC patients
receiving SRT concurrent (≤30d) to immuno- or targeted
therapy. Patients were grouped in: patients treated for ≤5
metastases without additional metastases
(oligoprogression), treated for ≤5 progressive metastases
with controlled disease of all other metastases
(oligopersistent), and patients with mixed response/
uncontrolled disease. SRT was performed to ≤5
extracranial or cranial lesions. Overall survival (OS) was
analyzed using Kaplan-Meier survival curves and log rank
testing. Secondary outcomes were progression free
survival (PFS), local control (LC), time to switch of
systemic therapy after SRT and toxicity as defined by the
CTCAE v4 criteria.
Results
SRT of 192 lesions in 108 patients was performed between
7/2009 and 5/2018 in 16 clinics. Median age was 63y
(range 33-80). 75% had synchronous metastatic disease,
driver mutations were: EGFR 41%, ALK 14%, other 21%,
unknown/no 24%. Median follow-up was 18.7 (range 1-102) mo. The majority had metastases in 1-3 organs. 90% were
ECOG 0-1. Median 1 (range 1-5) metastasis was treated
with SRT; 69% cranial and 31% body SRT. Targeted
therapies were started a median 5.8mo before SRT in 69%,
during SRT in 8%, and a median 14d after SRT in 23% of
patients. 60% received an ALK- or EGFR-TKI, 31%
nivolumab or pembrolizumab, 8% bevacizumab.
Oligoprogressive and oligopersistent patients showed
improved OS compared to advanced metastatic disease
(p=0.008) (Fig.1). PFS was best in oligoprogressive
patients; median 20.1 vs 7 and 4.4 mo., respectively
(p=0.006). LC was median 21.0, 12.0 und 9.0mo: no sign.
difference between groups. After 1y, 86%, 47% and 39% in
the 3 groups continued the same immuno- or targeted
therapy as before SRT. Grade 3 and 4 acute toxicity were
observed in 6% and 1% (n=1, headache), late toxicity in 3%
and 1% (n=1, hemiparesis), respectively.
Conclusion
This study observed excellent survival with limited toxicity
when definitive SRT to a limited number of metastases was
combined with targeted- or immunotherapy in
oligoprogressive and oligopersistent NSCLC patients. Highdose
local radiotherapy of metastatic sites allowed
continuation of targeted-, or immunotherapy for minimum
1 year in 39% to 86%, with best results observed in
oligoprogressive patients. These observations need to be
further evaluated within prospective trials.
Developments of local and systemic therapies have
improved the prognosis of metastatic NSCLC.
Oligometastatic patients may especially benefit from a
more aggressive treatment approach. However, the
concept of “oligometastasis” is complex: e.g. limited
progression or resistance of disease to systemic
treatment. This study aimed to evaluate the outcome of
stereotactic radiotherapy (SRT) to oligoprogressive or
oligoresistant NSCLC in patients receiving concurrent
immuno- or targeted therapy.
Material and Methods
The retrospective international multicenter register study
(TOaSTT) collected data on metastatic NSCLC patients
receiving SRT concurrent (≤30d) to immuno- or targeted
therapy. Patients were grouped in: patients treated for ≤5
metastases without additional metastases
(oligoprogression), treated for ≤5 progressive metastases
with controlled disease of all other metastases
(oligopersistent), and patients with mixed response/
uncontrolled disease. SRT was performed to ≤5
extracranial or cranial lesions. Overall survival (OS) was
analyzed using Kaplan-Meier survival curves and log rank
testing. Secondary outcomes were progression free
survival (PFS), local control (LC), time to switch of
systemic therapy after SRT and toxicity as defined by the
CTCAE v4 criteria.
Results
SRT of 192 lesions in 108 patients was performed between
7/2009 and 5/2018 in 16 clinics. Median age was 63y
(range 33-80). 75% had synchronous metastatic disease,
driver mutations were: EGFR 41%, ALK 14%, other 21%,
unknown/no 24%. Median follow-up was 18.7 (range 1-102) mo. The majority had metastases in 1-3 organs. 90% were
ECOG 0-1. Median 1 (range 1-5) metastasis was treated
with SRT; 69% cranial and 31% body SRT. Targeted
therapies were started a median 5.8mo before SRT in 69%,
during SRT in 8%, and a median 14d after SRT in 23% of
patients. 60% received an ALK- or EGFR-TKI, 31%
nivolumab or pembrolizumab, 8% bevacizumab.
Oligoprogressive and oligopersistent patients showed
improved OS compared to advanced metastatic disease
(p=0.008) (Fig.1). PFS was best in oligoprogressive
patients; median 20.1 vs 7 and 4.4 mo., respectively
(p=0.006). LC was median 21.0, 12.0 und 9.0mo: no sign.
difference between groups. After 1y, 86%, 47% and 39% in
the 3 groups continued the same immuno- or targeted
therapy as before SRT. Grade 3 and 4 acute toxicity were
observed in 6% and 1% (n=1, headache), late toxicity in 3%
and 1% (n=1, hemiparesis), respectively.
Conclusion
This study observed excellent survival with limited toxicity
when definitive SRT to a limited number of metastases was
combined with targeted- or immunotherapy in
oligoprogressive and oligopersistent NSCLC patients. Highdose
local radiotherapy of metastatic sites allowed
continuation of targeted-, or immunotherapy for minimum
1 year in 39% to 86%, with best results observed in
oligoprogressive patients. These observations need to be
further evaluated within prospective trials.
| Original language | English |
|---|---|
| Pages (from-to) | S23-S24 |
| Journal | Radiotherapy and Oncology |
| Volume | 133 |
| DOIs | |
| Publication status | Published - Apr 2019 |