オリゴメタの臨床

東北大学大学院医学系研究科 放射線腫瘍学分野

神宮 啓一

2015.08.30. JASTRO summer seminar

☑ The author has no conflict of interest to disclose with respect to this presentation.

What is                 Oligometastasis/Oligo‐recurrence?

Oligometastases and Oligo‐recurrence: The New Era of Cancer TherapyJpn J Clin Oncol 2010;40(2)107–111Yuzuru Niibe and Kazushige Hayakawa

Schema of Sync-oligometastasis Schema of Oligo-recurrence

より改変引用

Oligometastases:1-5 metastatic or recurrent lesions that can be treated by local therapy. They can be divided into three states as follows1,2.

Oligometastases No.oflesions Primary site DFI

- Oligo-recurrence 1-5 controlled ≥ 6 months- Sync-oligometastasis 1-5 active 0 month- Unclassified oligometastasis 1-5 controlled < 6 months

DFI = Disease-free interval1 Niibe Y et al. Gynecol Oncol. 2006 Nov;103(2):435-8.2 Niibe Y et al. Pulm. Med. 2012;2012:261096.

Brain metastasis

Stereotactic Radiosurgery Plus Whole-Brain Radiation Therapy vs Stereotactic Radiosurgery Alone for Treatment of Brain Metastases: A Randomized Controlled Trial

Aoyama et al. JAMA. 2006;295(21):2483-2491. doi:10.1001/jama.295.21.2483

1 to 4 brain metastases, each less than 3 cm in diameter

JROSG 99‐1

SRS+WB SRS alone

The mean survival time was 7.5 months for patients receiving whole-brain radiation therapy (WBRT) plus stereotactic radiosurgery(SRS) and 8.0 months for patients receiving SRS alone. This difference was not significant (P = .42). There was a statistically significant decrease in brain tumor recurrence in the WBRT+SRS group (P = .003).

Figure Legend:

Stereotactic Radiosurgery Plus Whole-Brain Radiation Therapy vs Stereotactic Radiosurgery Alone for Treatment of Brain Metastases: A Randomized Controlled Trial

Aoyama et al. JAMA. 2006;295(21):2483-2491. doi:10.1001/jama.295.21.2483

There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.

SRS alone +whole brain RT Ope alone +whole brain RT

SRS+/‐WB Ope+/‐WB

whole brain RT (―) whole brain RT (+)

＊1‐3metastases

Time to intracranial progression at (A) new sites and (B) initial sites in patients treated initially by radiosurgery (RS) or surgery (S) after observation or adjuvant whole-brain

radiotherapy (WBRT).

Kocher M et al. JCO 2011;29:134-141

頭蓋内制御

局所制御

local+WBRT>>local only

(A) Survival with WHO performance score ≤ 2 and (B) overall survival after observation or adjuvant whole-brain radiotherapy (WBRT).

Kocher M et al. JCO 2011;29:134-141

local+WBRT=local only

Oligometastases of brain only in Patients with Non‐Small Cell Lung Cancer (NSCLC) Treated with Stereotactic Irradiation 

(STI): a Multi‐institutional Study in JapanNiibe, Shirato, et al. 

Patients:     in 1996‐2008① Sync‐oligometastasis group: patients with oligometastatic NSCLC with brain metastases  were performed SRS for metastases and curative therapy  for  primary lesions.

② oligo‐recurrence group: patients with NSCLC have metachronous metastases in brain after curative therapy for primary lesions. At recurrence, the patients have no relapse of the primary lesions. 

Sync-oligometastasis

Non‐brain metastasis

Results after resection of colorectal liver metastases

Author Patients (n)follow-up (months)

Median overall survival

(months )5-y survival (%)

Laurent C 156 29 40 36

Yan TD 120 30 39 36

Turrini O 119 66 40 28.5

de Haas RJ 234 40 84 61

Portier G 173 87 34 42

de Jong MC 1669 30 36 47.3

Martí J 236 68 42 47

Reuter NP 126 20 36.4 23

Reuter NP 183 34 79.2 55

Systematic review and meta‐analysis of follow‐up after hepatectomy for colorectal liver metastases

Clinical Score for Predicting Recurrence After Hepatic Resection for MetastaticColorectal Cancer  Analysis of 1001 Consecutive Cases

Fong Y, et al. Ann Surg. 1999;230(3):309‐18

Copyright ©1997 The American Association for Thoracic Surgery

J Thorac Cardiovasc Surg 1997;113:37‐49

Long‐term results of lung metastasectomy: prognostic analyses based on 5206 cases. The International Registry of Lung Metastases.

Overall survival, PME (pulmonary metastasectomy) vs. SABR.

Pulmonary oligometastases: Metastasectomyor stereotactic ablative radiotherapy?

Radiotherapy and Oncology, 2013; 107: 409 - 413

Materials and MethodsSex 31 females, 65 males

Age median 72 years (range 25-88)

DFI median 24, range 0-246 months

Oligometastatic state Oligo-recurrence :79 (82%)Sync-oligometastasis :10 (10%)Unclassified oligometastasis : 7 (7%)

No. of metastatic tumors solitary :76 (79%)multiple :20 (21%)

Tumor size median 1.9, range 0.6-4.2 cm

Stereotactic body radiotherapy for metastatic lung tumors with emphasis on the difference in oligometastatic state

3rd ESTRO forum in Barcelona

Tohoku University & St. Luke’s International Hospital & the University of Tokyo Hospital & Okayama University

Primary tumorsPrimary sites Colorectum :25 (26%)

Lung :24 (25%)Head and neck :8 (8%)Uterus :8 (8%)Others :31 (32%)

Pathology Adenocarcinoma :49 (51%)Squamous cell carcinoma :19 (20%)Others :12 (12%)Unknown :16 (17%)

Outcomes

3-year local control: 75%

3-year OS: 52%, median 41 mo

3-year RFS: 25%, median 16 mo

RFS comparison of oligometastatic states

p < 0.01

Oligo-recurrences, median 17 mo

Sync-oligometastases, median 6.5 mo

Hamamoto Y, et al.

Authors No. dose follow‐up period (median) outcomes

Norihisa et al.   43 48‐60/4‐5fr 27 mo 2‐y LC: 90%

Ricardi et al. 61 26‐45/1‐4fr 20 mo 3‐y LC: 83.5%

Hoff et al. 71 12‐30/ 1fr 14 mo 2‐y LC: 96%

Inoue et al. 22 40‐48Gy/4fr 25 mo 3‐y LC: 72%

Takahashi et al. 42 20‐56Gy/1‐7fr 20 mo 2‐y LC: 87%

Hamamoto et al. 31 48‐60 Gy/4‐5fr 18 mo 3‐y LC: 50%

Tohoku univ. 57 48‐60/4‐15fr 42 mo 3‐y LC: 53%

肺転移に対するSABRの局所制御率まとめ

Local control rate with SBRT for oligometastasis(non‐colorectal vs. colorectal)  

Tohoku univ.

Stereotactic body radiotherapy for colorectal liver metastases

Cancer 2001; 117: 4060‐4069

HCC

Colorectal liver meta

Br J Radiol;86:20130147

Isolated paraaortic lymph node recurrence after definitive irradiation for cervical carcinoma.

Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):442‐8

n=26 (including 7 pts without treatment)

5‐year; 30.8%

All 7 survivors had salvage treatment with radiation to the para‐aortic region and concurrent cisplatin‐based chemotherapy.

Cisplatin‐based CCRT was found to be associated with a good prognosis.

Image‐guided stereotactic body radiation therapy in patients with isolated para‐aortic lymph node metastases from uterine cervical and corpus cancer

Int J Radiat Oncol Biol Phys. 2009 May 1;74(1):147‐53. 

n=30

*25 patients received a cisplatin‐based regimen 

Post‐operative loco‐regional recurrent esophageal cancer

N=69

Local +/‐ lymph node recurrence

N=16MST=10.0 mo

Lymph node recurrence

N=53MST=28.5 mo

Single‐regionN=41

MST=42.0 mo

Multiple‐regionsN=12

MST=17.5 mo

p=0.001 (Log‐rank test)

p=0.04 (Log‐rank test)

The results of radiochemotherapy for postoperative loco‐regional recurrent esophageal cancer according to patterns of recurrence in Tohoku University Hospital

*All patients were performed concomitant chemotherapy

Unpublished data

Local‐rec << oligo‐lymph rec <<solitary oligo‐lymph rec

period (months)

prob

abili

ty

Cause-specific survival, 5-year: 43.3%Irradiated-field control , 5-year: 59.9%

Overall survival, 5-year: 39.2%

Progression-free survival, 5-year: 31.0%

Long‐Term Results of Radiochemotherapy for Solitary Lymph Node Metastasis After Curative Resection of Esophageal Cancer

Jingu K, et al.  Int J Radiat Oncol Biol Phys. 2012;83(1):172‐7Age years old

median 66.0

range 50-78

Gender No.

male 33

female 2

Initial pathological stage (UICC 2002) No.

I-II 20

III-IV 15

Histology No.

scc 33

adenoscuamous 2

Metastatic region No.

supraclavicular 6

mediastinal 24

abdominal 5

Performance Status (ECOG) No.

0 14

1 16

2 5

author year No. methods response rate

MST (months) 3-year OS

Raoul 1995 24 RT 65% 10.7 4.3%

Nemoto 2001 33RT (21)

CRT (12) 91% 7 12%

Shimada 2003 76CRT (47)

Chemo (17)RT (12)

34% 8 < 20%

Nishimura 2003 13 CRT 72% 9.5 19%

Yamashita 2005 16CRT (6)RT (10) 81% 13.8 19%

Maruyama 2010 23 CRT 60% 13 24%Nakamura 2008 22 CRT 82% 20.3 26.6%

Jingu 2012 30 CRT 72% 21.0 38.4%Jingu

(multi-lymph)2012 19 CRT 79% 17.5 17.5%

Jingu(single-lymph)

2012 35 CRT 80% 39 50.6%

*solitary means oligo‐recurrence.

Stereotactic Body Radiation Therapy (SBRT) for Treatment of Adrenal Gland Metastases from Non‐Small Cell Lung Cancer 

Strahlenther Onkol. 2011 Apr;187(4):245‐51.

Serious gastric ulcer event after stereotactic body radiotherapy (SBRT) delivered with concomitant vinorelbine in a patient with left adrenal metastasis of lung cancer Onishi et al. Acta Oncologica, 2012; 51: 624–628

＊Arrowheads shows the 90% isodose line for the prescribed dose of 60 Gy in 10 fractions.

  in 2 Gy standard fractionation (YESCARG‐1001, 10fx)

Duodenum

α/β = 4 Gy– 64 Gy to max. 25% of circumference– 100 Gy dose maximum in < 5%– 35 Gy to 50%– 35 Gy max. to nonadjacent duodenal wall

α/β = 3 Gy

BED<144Gy (<10cc)BED<105Gy (<100cc)

Liverα/β = 1 Gy– 20 Gy to 33%– 10 Gy to 50%

n.a.

Kidneysα/β = 2 Gy– 10 Gy to 75% (both kidneys)– 18 Gy to 50% (both kidneys)

α/β = 3 Gy

BED<60Gy (mean dose)

Colonα/β = 5 Gy– 62 Gy max. dose– 45 Gy max. on complete circumference

α/β = 3 GyBED<144Gy (<10cc)BED<105Gy (<100cc)

Spinal cord α/β = 2 Gy– 45 Gy max. dose

α/β = 2 GyBED<100Gy (max dose)

Dose-constraints for abdominal organs at risk

Strahlenther Onkol. 2012 Jan;188(1):35‐41

Dose limits for OARs

RTOG 0618, 3 fx ROSEL European trial, 3 or 5 fx JCOG, 4 fx (for PRV)

Lung V20 ≤10% V20 <5–10% V20 ≤20%

Esophagus ≤27 Gy (9 Gy/fx) 24 Gy (3 fx)27 Gy (5 fx)

≤40Gy (4 fx) ≤10cc≤35 Gy (4 fx) ≤ 1cc

Brachial plexus ≤24 Gy (8 Gy/fx) 24 Gy (3 fx)27 Gy (5 fx)

≤48Gy (4 fx) ≤ 1cc≤40Gy (4 fx) ≤10cc

Heart ≤30 Gy (10 Gy/fx) 24 Gy (3 fx)27 Gy (5 fx)

≤48Gy (4 fx) ≤ 1cc≤40Gy (4 fx) ≤10cc

Trachea, bronchus ≤30 Gy (10 Gy/fx) 30 Gy (3 fx)32 Gy (5 fx) ≤40Gy (4 fx) ≤10cc

Dose-constraints for thoracic organs at risk

Int J Radiat Oncol Biol Phys. 2011 Dec 1;81(5):1442‐57. 

Summary

• Oligo‐recurrence in brainIt is no need to add whole‐brain irradiation for 1‐3 brain metastases after SRT or surgery.

• Sync‐oligometastases and Oligo‐recurrenceSRT for oligometastases in lung or liver achieve 66～90% of local control. Oligo‐recurrence>> Sync‐oligometastases

• Oligo‐recurrence could be cure with (chemo)radiotherapyThe concept of oligo‐recurrence in lymph node might fit into postoperative esophageal cancer and uterine cervical cancer.Concurrent chemotherapy might be a favorable prognostic factor.

http://www.radiol.med.tohoku.ac.jp/chiryo/