Analyses of Local Control of Pulmonary Oligometastases after Stereotactic Body Radiotherapy and Impact of Local Control on Survival

doi:10.21203/rs.3.rs-35650/v1

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Analyses of Local Control of Pulmonary Oligometastases after Stereotactic Body Radiotherapy and Impact of Local Control on Survival

https://doi.org/10.21203/rs.3.rs-35650/v1

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published 14 Oct, 2020

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Background

Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicenter retrospective study was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases and to investigate affecting factors for local control (LC).

Methods

The inclusion criteria was that SBRT for pulmonary oligometastases was the number of metastases was limited to 1 to 5, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED₁₀) of SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses.

Results

Data for 1378 patients with 1547 tumors from 68 institutions were analyzed. The median follow-up period was 24.2 months. One-year, 3-year and 5-year LC rates were 92.1%, 81.3% and 78.6%, respectively, and 1-year, 3-year and 5-year overall survival rates were 90.1%, 60.3% and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumor diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding esophagus origin) were significantly associated with lower LC rate. In survival analysis, local failure (p < 0.001), poorer performance status (1 vs. 0, p = 0.013; 2–3 vs. 0, p < 0.001), esophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma pathology of the primary lesion (vs. adenocarcinoma, p = 0.006) and increased maximum tumor diameter (p < 0.001) showed significant relationship with shorter survival.

Conclusions

LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure. Some important factors for achieving higher LC were revealed.

Cancer Biology

Oncology

pulmonary oligometastases

oligo-recurrence

sync-oligometastases

stereotactic body radiotherapy

local control

metastasis-directed therapy

During the past few decades, increasing attention has been paid to the importance of control of the primary site in metastatic disease. Some prospective trials and many retrospective studies for metastatic disease have shown improvement in the survival of patients treated with surgery or radiotherapy for the primary lesion, though systemic therapy has been the standard treatment [1–5]. In addition, aside from the activity of the primary lesion, a few metastases known as oligometastases which might be a good candidate for metastasis-directed therapy have gradually been recognized [6]. The survival benefit of primary lesion control was revealed only in prostate cancer patients with low metastatic burden (probably oligometastatic state) [7]. Some phase 2 studies revealed that intensive local therapy for the primary lesion and for all known oligometastases improved the overall survival and disease-free survival of patients and results of a future phase 3 trial are awaited [8–10]. In any case, control of primary lesion is important in oligometastatic state, therefore, the classification of oligometastases according to the activity of the primary lesion is important when metastasis-directed therapy is to be performed. Oligometastases have been classified into oligo-recurrences and sync-oligometastases according to the activity of the primary lesion at the time of initial appearance of oligometastases and patients with oligo-recurrences had longer survival [11, 12]. Recently, an investigation to determine whether there is a survival difference between patients with pulmonary oligo-recurrences and patients with sync-oligometastases after control of the primary lesion was performed in Japan and it was shown that patients with oligo-recurrences had a survival advantage [13]. The next question is whether successful local therapy for pulmonary oligometastases leads to longer survival or not and what factors affected local control (LC). The aim of this study was to identify factors affecting LC and to determine the survival benefit of LC after stereotactic body radiotherapy (SBRT) for pulmonary oligometastases. LC was secondary endpoint and these were secondary endpoint analyses and exploratory survival analyses of this large survey.

Eligibility and event definitions

The inclusion criteria were as follows: SBRT for pulmonary oligometastases was performed between January 2004 and June 2015, the number of metastasis was limited to 1 to 5 at the timing of emergence of the SBRT-targeted tumor, the primary lesion and other extrathoracic lesions were controlled before SBRT was performed, and the biological effective dose (BED₁₀) of SBRT was 75 Gy or more and dose per fraction was 4 Gy or more. Combination treatment with SBRT and surgery for each lesion was allowed. The exclusion criterion was local recurrence of a thoracic primary tumor. The following formula was used for calculation of BED₁₀: BED = nd [1 + d/(α/β)], where n is the number of fractions, d is dose per fraction and α/β ratio is 10 Gy for the tumors. Pulmonary oligometastasis was defined as the appearance of a solid tumor in the lung at the same time as or after treatment of the primary lesion. Local failure was defined as progression of the irradiated tumor, LC was defined as freedom from local failure, and locally controlled cohort was defined as freedom from any local failure of the irradiated tumor.

Ethics approval

This study was a retrospective, multicenter study in Japan. This study was conducted in 68 institutions in Japan. All of the institutions were health insurance-covered medical institutions that covered all citizens in Japan. This study was approved by the ethical committee of a senior facility (Ethics Committee of Toho University Omori Medical Center, reference number: 27–148). Informed consent was waived due to the study design, but all participating institutions were guaranteed the chance to opt out of participation in this study by giving information of this study via the Internet or posters, and opt-out consent was obtained from all patients.

Statistical analysis

Statistical analyses were performed using EZR, version 1.37 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a modified version of R commander (R Foundation for Statistical Computing, Vienna, Austria) [14]. Time to event was calculated from the first day of SBRT to the day an event was confirmed. Cumulative LC and overall survival (OS) rates were calculated using the Kaplan-Meier method, and the 95% confidence interval (95% CI) was calculated using Greenwood's formula. The Cox proportional hazards model was adjusted for LC analyses, and variables with a p-value of < 0.200 in univariate analyses (UVA) were regarded as potential factors and were put in multivariate analysis (MVA) with a stepwise backward elimination/forward addition approach using the Akaike information criterion (AIC) to build the best MVA model. A p-value < 0.050 was defined as significant.

Analyses of pretreatment prognostic factors for OS (primary endpoint) were reported elsewhere [13]. Because local failure was observed factor after SBRT, further analysis of OS was performed in this study to determine the effect of LC on OS. First, LC was analyzed as a time-dependent covariate. Previously reported covariates selected by the stepwise approach without changing continuous variables into categorical variables were used: PS, primary lesions, pathology of primary lesion, oligometastatic state and maximum tumor diameter. Local status was forced into this multivariate model as a time-dependent covariate. Secondary, as sensitivity analyses, the landmark analysis method was also used [15–16]. Six months, 1 year, 2 years and 3 years were set as landmark times. All local failures after the landmark time and all deaths before that time were ignored. Then a log-rank test was performed to compare locally controlled and locally failed cohorts with a p-value of ≤ 0.012 denoting significance. Lung adverse events (AEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Patient characteristics

A total of 1378 patients with 1547 tumors from 68 institutions were enrolled in this study. The baseline characteristics of the patients, primary tumors, oligometastatic tumors and SBRT are summarized in Table 1. Performance status (PS) and additional chemotherapy were judged at the timing of each SBRT if SBRT was performed asynchronously for two or more tumors. The dose calculation algorithm of type B was equivalent to Analytical Anisotropic Algorithm, type C was equivalent to Monte Carlo Algorithm and type A was an older generation algorithm such as Pencil Beam Convolution.

Table 1

Characteristics of patients, primary tumors, oligometastatic tumors and SBRT characteristics.
Characteristic	Distribution	Number (%)
All tumors		1547
Sex	Male	994(64.2)
	Female	553(35.7)
Age, years	Median, range, IQR	72; 16–93; 63–78
ECOG Performance Status	0	841 (54.3)
	1	529 (34.1)
	2	90 (5.8)
	3	19 (1.2)
	Missing	68 (4.3)
Primary lesion sites	Lung	451(29.1)
	Colorectum	391 (25.2)
	Head and Neck	126 (8.1)
	Esophagus	132 (8.5)
	Others	447 (28.8)
Pathology of primary lesion	Adenocarcinoma	861 (55.6)
	Squamous cell carcinoma	396 (25.5)
	Sarcoma	47 (3.0)
	Others	168 (10.8)
	Missing	75 (4.8)
Control method of primary lesion	Surgery	1222 (78.9)
	Chemoradiation	130 (8.4)
	Radiation (X-ray or particle)	70 (4.5)
	Others	44 (2.8)
	Missing	85 (5.4)
Disease-free interval, months	Median, range, IQR	17.5; 0-423.9; 8.0-34.3
Oligometastatic state	Oligo-recurrences	1157 (74.7)
	Sync-oligometastases	133 (8.5)
	Unclassified	133 (8.5)
	Missing	124 (8.0)
SBRT performed institution	Academic	642(41.4)
	Non-academic	905 (58.5)
Date SBRT was performed	2004–2009	518 (33.4)
	2010–2015	1029 (66.5)
Chemotherapy	Before SBRT	Yes, 591 (38.2) No, 945 (61.0) Missing, 11 (0.7)
	Concurrent with SBRT	Yes, 34 (2.7) No, 1513 (97.8)
	After SBRT	Yes, 242 (15.6) No, 998 (64.5) Missing, 307 (19.8)
Maximum tumor diameter, cm	Median, range, IQR	1.5; 0.3–6.5; 1.0–2.0
Number of oligometastases	1	1036 (66.9)
	2–5	503 (32.5)
	Missing	8 (0.5)
Lung lobe involved with treated tumor	Right upper lobe	293 (18.9)
Lung lobe involved with treated tumor	Right middle lobe	83 (5.3)
	Right lower lobe	321 (20.7)
	Left upper lobe	294 (19.0)
	Left lower lobe	226 (14.6)
	Unknown lobe	Right lung, 12; Left lung, 7
	Missing	311 (20.1)
Beams	Multiple static	1145 (74.0)
	Arc	401 (25.9)
	Missing	1 (0.0)
X-ray energy	4 MV only	202 (13.0)
	6 MV only	1179 (76.2)
	Others	160 (10.3)
	Missing	6 (0.3)
Field coplanarity	Coplanar field	1139 (73.6)
	Non-coplanar field	404 (26.1)
	Missing	4 (0.2)
Dose calculation algorithm	Type A	541 (34.9)
	Type B	799 (51.6)
	Type C	144 (9.3)
	Missing	63 (4.0)
Dose prescription	IC	1103 (71.2)
	D95 of PTV	317 (20.4)
	Others	127 (8.2)
BED₁₀ at isocenter, Gy₁₀	Median, range, IQR	105.6; 75.0-289.5; 105.6-126.9
OTT of SBRT, day	Median, range, IQR	7; 3–81; 4–11
Abbreviations: SBRT, stereotactic body radiotherapy; IQR, interquartile range; ECOG, Eastern Cooperative Oncology Group; IC, isocenter; D95 of PTV, dose covering 95% of planning target volume; BED, biological effective dose; OTT, overall treatment time.

Treatment outcomes

The median follow-up period for all patients was 24.2 months (range, 0.1-143.6 months; interquartile range [IQR], 13.7–42.7 months) and that for survivors was 26.9 months (range, 0.1-143.6 months; IQR, 14.7–49.4 months). Estimated 1-year, 3-year and 5-year LC rates were 92.1% (95% CI, 90.4–93.4%), 81.3% (95% CI, 78.8–83.6%) and 78.6% (95% CI, 75.6–81.2%), respectively (Fig. 1). Local failure of the irradiated tumor occurred in 222 tumors and the median interval from SBRT to local failure was 12.4 months (range, 2.9–98.6 months; IQR, 9.1–19.7 months). A total of 536 patients with 603 tumors died, and 10 deaths were caused by AEs of SBRT. Estimated 1-year, 3-year and 5-year OS rates were 90.1% (95% CI, 88.3–91.6%), 60.3% (95% CI, 57.1–63.3%) and 45.5% (95% CI, 41.8–49.1%), respectively (Fig. 1). The median survival period was 51.4 months (95% CI, 45.0-55.7 months). There were lung AEs reports from 1200 tumors in 1040 patients. Of those patients, 122 patients with 143 tumors (11.7%) had grade 2 or higher and 26 patients with 32 tumors (2.5%) had grade 3 or higher. Seven patients with 9 tumors had grade 5 of radiation pneumonitis and 3 patients with 4 tumors had grade 5 of hemoptysis.

Analyses for LC and survival

The results of UVA for LC are shown in Supplementary Table 1, and the results of MVA for LC are shown in Table 2. Maximum tumor diameter (per 1-cm increase; hazard ratio [HR], 1.297; 95% CI, 1.059–1.588; p = 0.011), type B dose calculation algorithm (ref. type A; HR, 0.592; 95% CI, 0.410–0.856; p = 0.005), overall treatment time (OTT) of SBRT (per 10-day prolongation; HR, 0.610; 95% CI, 0.385–0.966; p = 0.035) and primary lesions were significantly associated with LC. In regard to primary lesions, the LC rate for oligometastases from colorectal cancer was significantly lower than LC rate for oligometastases from lung cancer (ref. colorectum; HR, 0.413; 95% CI, 0.274–0.622; p < 0.001), head and neck cancer (ref. colorectum; HR, 0.194; 95% CI, 0.077–0.489; p < 0.001) and other cancers excluding esophagus (ref. colorectum; HR, 0.337; 95% CI, 0.208–0.546; p < 0.001). Kaplan-Meier LC curves according to oligometastases from colorectal cancer and oligometastases from other cancers are shown in Fig. 2 (p < 0.001).

Table 2

Multivariate Cox regression analysis for local control and overall survival
Factors	Covariate	Local control		Overall survival
Factors	Covariate	HR (95% CI)	P value	HR (95% CI)	P value
Local status	Controlled	-	-	reference
	Failed	-	-	2.390 (1.839–3.106)	< 0.001
ECOG PS	0	-	-	reference
	1	-	-	1.316 (1.059–1.635)	0.013
	2–3	-	-	2.008 (1.405–2.869)	< 0.001
Primary lesion sites	Colorectum	reference		reference
	Lung	0.413 (0.274–0.622)	< 0.001	0.936 (0.685–1.280)	0.681
	H&N	0.194 (0.077–0.489)	< 0.001	0.905 (0.556–1.474)	0.690
	Esophagus	0.618 (0.306–1.248)	0.179	1.650 (1.027–2.650)	0.038
	Others	0.337 (0.208–0.546)	< 0.001	1.291 (0.916–1.818)	0.143
Pathology of primary lesion	Adenoca.	-	-	reference
Pathology of primary lesion	SqCC	-	-	1.525 (1.122–2.072)	0.006
	Others	-	-	1.391 (0.988–1.960)	0.058
Oligometastatic state	Oligo-rec	-	-	reference
	Sync-oligo	-	-	1.391 (0.988–1.960)	0.058
	Unclassified	-	-	1.246 (0.905–1.714)	0.177
Chemotherapy concurrent with SBRT	Yes	1.969 (0.859–4.513)	0.109	-	-
Chemotherapy concurrent with SBRT	No	reference		-	-
Maximum tumor diameter	Per 1 cm	1.297 (1.059–1.588)	0.011	1.266 (1.131–1.417)	< 0.001
Dose calculation algorithm	Type A	reference		-	-
	Type B	0.592 (0.410–0.856)	0.005	-	-
	Type C	0.732 (0.371–1.445)	0.368	-	-
BED₁₀ at isocenter	Per 10 Gy₁₀	0.912 (0.828–1.006)	0.065	-	-
OTT of SBRT	Per 10 days	0.610 (0.385–0.966)	0.035	-	-
Abbreviations: HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; PS, performance status; H&N, head and neck; Adenoca., adenocarcinoma; SqCC, squamous cell carcinoma; Oligo-rec., oligo-recurrences; Sync-oligo, sync-oligometastases; SBRT, stereotactic body radiotherapy; BED, biological effective dose; OTT, overall treatment time.

In OS analyses, there were significant relationships of OS with local failed cohort (ref. local controlled cohort; HR, 2.390; 95% CI, 1.839–3.106; p < 0.001), PS of 1 (ref. PS of 0; HR, 1.316; 95% CI, 1.059–1.635; p = 0.013), PS of 2–3 (ref. PS 0; HR, 2.008; 95% CI, 1.405–2.869; p < 0.001), oligometastases from the esophagus (ref. colorectum; HR, 1.650; 95% CI, 1.027–2.650; p = 0.038), squamous cell carcinoma pathology of the primary lesion (ref. adenocarcinoma; HR, 1.525; 95% CI, 1.122–2.072; p = 0.006) and maximum oligometastatic tumor diameter (per 1-cm increase; HR, 1.266; 95% CI, 1.131–1.417; p < 0.001; Table 2). On the other hand, sync-oligometastases showed marginal significance (ref. oligo-recurrence, HR, 1.391; 95% CI, 0.988–1.960; p = 0.058). In landmark analyses, LC status of SBRT sites showed significant differences between the local controlled group and local failed group at all landmark time points (Fig. 3).

This study revealed the independent significance of OS benefit in a locally controlled cohort compared to that in a locally failed cohort by using SBRT for pulmonary oligometastases. In colorectal cancer, local failure of irradiated metastases have been reported to have correlation with worse OS [17]. Analyses of the large survey data in this study expanded the evidence into oligometastases from various primary cancer types. It will be certain that there is a situation in which metastasis-directed therapy works well, therefore, LC is important in that situation. The LC rate for patients who received SBRT for pulmonary metastases has been shown to be relatively high in prospective trials, but those results were not always obtained in a real world setting [18–20]. LC analyses in this study provide several key factors for successful LC by SBRT.

It is needed to be emphasized that SBRT consideration should be given to appropriate patients. In the present study, the inclusion criteria for patients included the criteria that the primary lesion and extrathoracic lesions needed to be controlled before SBRT and all pulmonary oligometastases were treated with local therapy. In a retrospective study in patients with synchronous oligometastatic (probably sync-oligometastases) epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer who were treated with an EGFR-tyrosine kinase inhibitor, OS improved only in patients who received local ablative therapy for the primary lesion and all oligometastatic lesions [21]. Then, the number of metastases and treatability of all lesions by local therapy will be important. In metastatic prostate cancer, survival benefit by definitive radiotherapy for primary lesion was seen only in low metastatic burden, and additional radiotherapy for all oligometastases showed retrospectively better castration-resistant prostate cancer-free survival than radiotherapy for only primary lesion [7, 22]. A recent consensus report proposed a maximum of five metastases and three organs as synchronous oligometastatic non-small cell lung cancer (probably sync-oligometastases) [23]. To work metastasis-directed therapy well, recent phase 2 trials required thoughtful eligibility criteria, treating primary lesion and all known oligometastases by local therapy [8–10, 24]. Appropriate selection of patients is important to obtain a benefit of SBRT.

The collaborative and detailed analyses of this study have also revealed some factors that affect LC. In MVA for LC showing that the primary site, maximum tumor diameter treated by SBRT and dose calculation algorithm were significant factors affecting LC confirmed previous findings [25–27]. Poor LC of metastatic lung tumors from the colorectum has been discussed because there were some reports of extremely low LC rates of colorectal metastases as well as reports of low LC rates of liver or bone metastases from the colorectum [27–32]. Interestingly, a German group reported that there was no significant difference in LC rates for colorectal metastasis and non-colorectal metastasis in the lung, but there was a significant difference in LC rates for those in the liver [20, 33]. In this study, a large crude difference of about 20% was found between LC rates for colorectal oligometastases and non-colorectal oligometastases were (Fig. 2). Analysis of SBRT for pulmonary oligometastases from colorectal cancer showed that dose escalation improved LC [34]. Consideration should be given to possible ways for improving LC of colorectal oligometastases. OTT of SBRT also showed a significant relationship with LC. OTT of SBRT would reflect the effect of reoxygenation, which has an influence on tumor radiosensitivity [35, 36]. SBRT sessions have often been performed on consecutive days in Japan. However an RTOG trial and another study required longer intervals in SBRT [23, 37]. Appropriate intervals each sessions such as 40 hours would contribute higher LC rate.

There are several limitations of this study. The retrospective nature of this study made all of the analyses subject to selection bias and confounding by indication. There was a considerable amount of missing data, SBRT methods varied from center to center, follow-up examinations were inconsistent, and there were unmeasured or uncontrolled factors. We could not investigate unlisted survey items such as a central lung tumor or not, patient’s comorbidities and dose–volume histogram analysis of the lung.

In conclusion, LC of pulmonary oligometastases by SBRT with a controlled primary lesion before SBRT had a survival benefit compared to the locally uncontrolled group and LC status showed the highest HR in multivariate analysis for OS. Therefore, LC is important and for achieving good LC, the use of a type A algorithm should be avoided and longer OTT of SBRT would contribute to higher LC rate, especially when treating large-size oligometastasis and colorectal oligometastasis.

LC, local control; SBRT, stereotactic body radiotherapy; BED, biological effective dose; OS, overall survival; CI, confidence interval; UVA, univariate analysis; MVA multivariate analysis; AIC, Akaike information criterion; AE, adverse event; PS, performance status; IQR, interquartile range; HR, hazard ratio; OTT, overall treatment time; EGFR, epidermal growth factor receptor

Ethics approval and consent to participate

This study was approved by the ethical committee of a senior facility (Ethics Committee of Toho University Omori Medical Center, reference number: 27-148). Informed consent was waived due to the study design.

Consent for publication

Not applicable.

Availability of data and materials

The datasets of this study are currently unavailable because it contains materials of unpublished manuscripts.

Competing interests

YN has received lecturer fees from Janssen Pharmaceutical K.K.

TY, MA, TS, KY, KY, HY, MO, YM, HO, KY, AN, KK, RO, AT and KJ declare no conflict of interest.

Funding

This study was supported by Grant-in-aid for research on radiation oncology of JASTRO 2015-2016.

Authors' contributions

Conception and design: YN and TY.

Provision of study patients: TY, YN, MA, TS, KY, KY, HY, MO, YM, HO, KY, AN, KK and RO.

Data analysis and interpretation: TY and KJ.

Manuscript draft: TY.

Manuscript editing and revision NY, MA, TS, KY, KY, HY, MO, YM, HO, KY, AN, KK, RO, AT and KJ.

Final approval of manuscript: All authors.

Acknowledgements

We acknowledge the collaboration of many radiation oncologists in Japan. We thank Drs. Akira Anbai, Gencho Kuga, Hajime Ikeda, Hideya Yamazaki, Hidekazu Tanaka, Hisashi Kaizu, Hiroki Kobayashi, Hisao Kakuhara, Ichiro Ogino, Imi Takanashi, Junichi Yokouchi, Kana Kobayashi, Katsuyuki Shirai, Keisuke Fujimoto, Kenji Nagata, Kentaro Yamamoto, Koda Ryuichi, Kosuke Amano, Koutaro Terashima, Masaaki Yamashina, Masayoshi Yamada, Michiko Imai, Miyako Myojin, Nanae Yamaguchi, Nobuhiko Yoshikawa, Nobuhisa Mabuchi, Osamu Suzuki, Saeko Hirota, Satoshi Itasaka, Seiji Kubota, Shigetoshi Shimamoto, Shinichi Ogawa, Shinya Takemoto, Shizuko Ohashi, Syuji Otsu, Takanori Fukuda, Takashi Sakamoto, Takashi Kawanaka, Takuya Yamazaki, Tetsuo Nonaka, Tetsuo Saito, Tetsuya Inoue, Toshiki Kawamura, Toshinori Soejima, Tomoyasu Kumano, Toru Sakayauchi, Tsunehiko Kan, Yasuhiro Dekura, Yasuo Matsumoto, Yoshiaki Okamoto, Yoshisuke Matsuoka, Yo Ushijima, Yuko Shirata, Yumi Sato, Yu Takada and Yutaka Naoi.

Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001;345:1655–9.
Le Scodan R, Stevens D, Brain E, Floiras JL, Cohen-Solal C, De La Lande B, Tubiana-Hulin M, Yacoub S, Gutierrez M, Ali D, Gardner M, Moisson P, et al. Breast cancer with synchronous metastases: survival impact of exclusive locoregional radiotherapy. J Clin Oncol. 2009;27:1375–81.
Xu H, Xia Z, Jia X, Chen K, Li D, Dai Y, Tao M, Mao Y. Primary Tumor Resection Is Associated with Improved Survival in Stage IV Colorectal Cancer: An Instrumental Variable Analysis. Sci Rep. 2015;5:16516.
Rusthoven CG, Jones BL, Flaig TW, Crawford ED, Koshy M, Sher DJ, Mahmood U, Chen RC, Chapin BF, Kavanagh BD, et al. Improved Survival With Prostate Radiation in Addition to Androgen Deprivation Therapy for Men With Newly Diagnosed Metastatic Prostate Cancer. J Clin Oncol. 2016;34:2835–42.
Tao L, Yuan C, Ma Z, Jiang B, Xiu D. Surgical resection of a primary tumor improves survival of metastatic pancreatic cancer: a population-based study. Cancer Manag Res. 2017;9:471–9.
Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13:8–10.
Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, Ritchie AWS, Attard G, Chowdhury S, Cross W, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353–66.
Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, Lambert B, Delrue L, Bultijnck R, Claeys T, et al. Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. J Clin Oncol. 2018;36:446–53.
Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016;17:1672–82.
Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, et al. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018;4:e173501.
Niibe Y, Hayakawa K. Oligometastases and oligo-recurrence: the new era of cancer therapy. Jpn J Clin Oncol. 2010;40:107–11.
Niibe Y, Chang JY. Novel insights of oligometastases and oligo-recurrence and review of the literature. Pulm Med. 2012;2012:261096.
Niibe Y, Yamamoto T, Onishi H, Yamashita H, Katsui K, Matsumoto Y, Oh RJ, Aoki M, Shintani T, Yamada K, et al. Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients. Anticancer Res. 2020;40:393–9.
Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013;48:452–8.
Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol. 1983;1:710–9.
Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011;4:363–71.
Franzese C, Comito T, Toska E, Tozzi A, Clerici E, De Rose F, Franceschini D, Navarria P, Reggiori G, Tomatis S, et al. Predictive factors for survival of oligometastatic colorectal cancer treated with Stereotactic body radiation therapy. Radiother Oncol. 2019;133:220–6.
Rusthoven KE, Kavanagh BD, Burri SH, Chen C, Cardenes H, Chidel MA, Pugh TJ, Kane M, Gaspar LE, Schefter TE. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol. 2009;27:1579–84.
Nuyttens JJ, van der Voort van Zyp NC, Verhoef C, Maat A, van Klaveren RJ, van der Holt B, Aerts J, Hoogeman M. Stereotactic body radiation therapy for oligometastases to the lung: a phase 2 study. Int J Radiat Oncol Biol Phys. 2015;91:337–43.
Rieber J, Streblow J, Uhlmann L, Flentje M, Duma M, Ernst I, Blanck O, Wittig A, Boda-Heggemann J, Krempien R, et al. Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases-A pooled analysis of the German working group “stereotactic radiotherapy”. Lung Cancer. 2016;97:51–8.
Xu Q, Zhou F, Liu H, Jiang T, Li X, Xu Y, Zhou C. Consolidative Local Ablative Therapy Improves the Survival of Patients With Synchronous Oligometastatic NSCLC Harboring EGFR Activating Mutation Treated With First-Line EGFR-TKIs. J Thorac Oncol. 2018;13:1383–92.
Tsumura H, Ishiyama H, Tabata KI, Sekiguchi A, Kawakami S, Satoh T, Kitano M, Iwamura M. Long-term outcomes of combining prostate brachytherapy and metastasis-directed radiotherapy in newly diagnosed oligometastatic prostate cancer: A retrospective cohort study. Prostate. 2019;79:506–14.
Dingemans AC, Hendriks LEL, Berghmans T, Levy A, Hasan B, Faivre-Finn C, Giaj-Levra M, Giaj-Levra N, Girard N, Greillier L, et al. Definition of Synchronous Oligometastatic Non-Small Cell Lung Cancer-A Consensus Report. J Thorac Oncol. 2019;14:2109–19.
Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393:2051–8.
Takeda A, Kunieda E, Ohashi T, Aoki Y, Koike N, Takeda T. Stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors from colorectal cancer and other primary cancers in comparison with primary lung cancer. Radiother Oncol. 2011;101:255–9.
Helou J, Thibault I, Poon I, et al. Stereotactic Ablative Radiation Therapy for Pulmonary Metastases: Histology, Dose, and Indication Matter. Int J Radiat Oncol Biol Phys. 2017;98:419–27. PubMed PMID:28463162.
Helou J, Thibault I, Poon I, Chiang A, Jain S, Soliman H, Erler D, Yeung L, Cheung P. Influence of Institutional Experience and Technological Advances on Outcome of Stereotactic Body Radiation Therapy for Oligometastatic Lung Disease. Int J Radiat Oncol Biol Phys. 2016;98:511–20.
Takeda A, Sanuki N, Tsurugai Y, Oku Y, Aoki Y. Stereotactic body radiotherapy for patients with oligometastases from colorectal cancer: risk-adapted dose prescription with a maximum dose of 83–100 Gy in five fractions. J Radiat Res. 2016;57:400–5.
Jingu K, Matsushita H, Yamamoto T, Umezawa R, Ishikawa Y, Takahashi N, Katagiri Y, Takeda K, Kadoya N. Stereotactic Radiotherapy for Pulmonary Oligometastases From Colorectal Cancer: A Systematic Review and Meta-Analysis. Technol Cancer Res Treat. 2018;17:1533033818794936.
Ahmed KA, Caudell JJ, El-Haddad G, Berglund AE, Welsh EA, Yue B, Hoffe SE, Naghavi AO, Abuodeh YA, Frakes JM. Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016;95:1399–404.
Ito K, Ogawa H, Shimizuguchi T, Nihei K, Furuya T, Tanaka H, Karasawa K. Stereotactic Body Radiotherapy for Spinal Metastases: Clinical Experience in 134 Cases From a Single Japanese Institution. Technol Cancer Res Treat. 2018;17:1533033818806472.
Hong JC, Ayala-Peacock DN, Lee J, Blackstock AW, Okunieff P, Sung MW, Weichselbaum RR, Kao J, Urbanic JJ, Milano MT, et al. Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis. PLoS One. 2018;13:e0195149.
Andratschke N, Alheid H, Allgäuer M, Becker G, Blanck O, Boda-Heggemann J, Brunner T, Duma M, Gerum S, Guckenberger M, et al. The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases. BMC Cancer. 2018;18:283.
Jingu K, Matsuo Y, Onishi H, Yamamoto T, Aoki M, Murakami Y, Yamashita H, Kakuhara H, Nemoto K, Sakayauchi T, et al. Dose Escalation Improves Outcome in Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Colorectal Cancer. Anticancer Res. 2017;37:2709–13.
Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004;4:437–47.
Kallman RF. The phenomenon of reoxygenation and its implications for fractionated radiotherapy. Radiology. 1972;105:135–42.
Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010;303:1070–6.

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Analyses of Local Control of Pulmonary Oligometastases after Stereotactic Body Radiotherapy and Impact of Local Control on Survival

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