Combination of Chemotherapy and Transpupillary Thermotherapy for Retinoblastoma

Hee Kyung Yang; Jeong Hun Kim; Ho Kyung Choung; Seong Joon Kim; Young Suk Yu

doi:10.3341/jkos.2008.49.10.1619

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Yang, Kim, Choung, Kim, and Yu: Combination of Chemotherapy and Transpupillary Thermotherapy for Retinoblastoma

Original Article

J Korean Ophthalmol Soc 2008;49(10):1619-1628.

Published online: 7 September 2008

DOI: https://doi.org/10.3341/jkos.2008.49.10.1619

Combination of Chemotherapy and Transpupillary Thermotherapy for Retinoblastoma

Hee Kyung Yang, M.D.¹, Jeong Hun Kim, M.D.^1,², Ho Kyung Choung, M.D.^2,³, Seong Joon Kim, M.D.^1,², Young Suk Yu, M.D.^1,^2,

Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea

Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea

Department of Ophthalmology, Seoul National University Boramae Hospital, Seoul, Korea

Address reprint requests to Young Suk Yu, M.D., Ph.D. Department of Ophthalmology, Seoul National University College of Medicine #28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea Tel: 82-2-2072-2438, Fax: 82-2-741-3187, E-mail: ysyu@snu.ac.kr

Received 10 July 2007 Accepted 26 December 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To evaluate the results of transpupillary thermotherapy combined with chemotherapy for the treatment of retinoblastoma.

Methods

Retinoblastoma patients treated with chemotherapy and transpupillary thermotherapy from November, 2004 to October, 2007 were retrospectively reviewed. Local tumor control was assessed in terms of regression or recurrence, at 1 month after chemotherapy and each session of thermotherapy, as well as the final follow-up period.

Result

Fifty-nine tumors were treated in 15 eyes of 11 children. Age at diagnosis was 7.4±6.9 months. Mean tumor diameter at the time of diagnosis was 2.2±2.1 disc diameters (DD) and mean tumor diameter at the time of initial thermotherapy was 1.8±1.7DD. Mean number of thermotherapy sessions for each tumor was 1.3±0.5. Total tumor regression was obtained for 96.6% of tumors after a mean follow-up of 22.3±10.7 months. The initial tumor size before thermotherapy was significantly smaller in the group of tumors showing total regression after the first session of thermotherapy. The time required for total regression after initial thermotherapy was related to the initial tumor size before thermotherapy.

Conclusions

Transpupillary thermotherapy combined with chemotherapy is an effective modality for treating retinoblastoma, and the initial tumor diameter before treatment is a strong predictive factor of successful treatment response.

Keywords: Chemotherapy, Retinoblastoma, Transpupillary thermotherapy

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Figure 1.

Multiple retinoblastomas treated with initial chemotherapy and thermotherapy for all the tumors. (A) and (B) Retinoblastomas before any treatment. Initial base diameters were 1.5DD (A, white arrow) and 4DD (B, hollow arrow). Combined chemotherapy and thermotherapy were applied to both masses. (C) One month after initial thermotherapy combined with systemic chemotherapy, both masses showed total regression; DD=disc diameter.

Figure 2.

Multiple retinoblastomas treated with initial chemotherapy and further local thermotherapy for one tumor. (A) Two months after initial chemotherapy, showing no regression of the inferonasal 3DD mass, and partial regression of the 6DD macular mass. Thermotherapy was applied on the inferonasal mass (white arrow). (B) Immediately after thermotherapy, capillary dilatation and hemorrhage was found of the overlying vessels of the inferonasal mass (white arrow). (C) One month after thermotherapy, the inferonasal mass was much flattened down and showed nearly total regression; DD=disc diameter.

Figure 3.

Cumulative regression rate after increased number of transpupillary thermotherapy sessions combined with chemoreduction. A cumulative total of 72.9% (43/59), 89.8%(53/39), 96.6% (57/59) of tumors showed total regression after 1, 2, and 3 sessions of thermotherapy combined with chemotherapy.

Figure 4.

The distribution of initial tumor size (base diameter) before thermotherapy, according to the response pattern after one session of thermotherapy combined with systemic chemotherapy. Initial tumor size before thermo- therapy was smaller in the group of tumors that showed total regression after one session of thermotherapy combined with chemotherapy ( p=0.01); DD=disc diameter; SDV=standard deviation.

Figure 5.

Scattergram showing the relationship of initial tumor size (base diameter) before thermotherapy and the time to total tumor regression after initial thermotherapy (mo). The best fit line portrays the positive correlation with statistical significance (R²=0.424, p<0.01); DD=disc diameter; mo=months.

Table 1.

Patient characteristics

Total number of patients		11
Eyes		15
Gender	Male	7 (63.6%)
	Female	4 (36.4%)
Bilaterality of retinoblastoma	Bilateral	10 (90.9%)
	Unilateral	1 (9.1%)
Age at diagnosis (mo)		7.4±6.9 (1-21)
Follow-up (mo) after diagnosis		22.3±10.7 (7-38)
Bilaterality of thermotherapy	Bilateral	4 (36.4%)
	Unilateral*	7 (63.6%)
Status of eye	Enucleated	1 (6.7%)
	Preserved with active disease	0 (0%)
	Preserved with no active disease	14 (93.3%)
Average tumor numbers treated with thermotherapy per eye^†		4.1±3.0 (1-12)

^* Of the 7 patients who were treated unilaterally, 1 patient had unilateral retinoblastoma and 6 patients had the fellow eye enucleated at the time of diagnosis

^† At the time of initial session of thermotherapy; mo=months.

Table 2.

Tumor characteristics

Total number of tumors		59
Tumor size (DD)	Initial size at diagnosis, before chemotherapy	2.2±2.1 (0.2-10)
	Initial size before thermotherapy	1.8±1.7 (0.2-10)
Thermotherapy sessions		1.3±0.5 (1-3)
Initial thermotherapy after 1st cycle of chemotherapy* (mo)		3.3±4.2 (0-13)
Time to total regression after last thermotherapy^†(mo)		1.5±0.9 (1-5)
Follow-up after total regression of tumor^†(mo)		12.5±9.4 (0-32)
Tumor R-E classification	I-II	22 (37.3%)
	III-IV	37 (62.7%)
Tumor laterality	Right eye	39 (66.1%)
	Left eye	20 (33.9%)
Tumor location	Superior	32 (54.2%)
	Inferior	27 (45.8%)
	Temporal	22 (37.3%)
	Nasal	37 (62.7%)
	Posterior to equator	48 (81.4%)
	Anterior to equator	11 (18.6%)

^* Mean value of the 56 tumors that underwent primary chemotherapy

^† Mean value of the 57 tumors that totally regressed at the last follow-up examination; DD=disc diameter.

Table 3.

Power settings and durations of transpupillary thermotherapy (TTT) for increasing number of with systemic chemotherapy (CTx).TTT sessions combined

TTT	1 ^st session	2 ^nd session	3 ^rd session	Total
Total tumors	59	14	2	59
Tumor size (DD) before CTx*	2.2±2.1 (0.2-10)	3.5±2.4 (1.5-10)	6.0±1.4 (5-7)	2.2±2.1 (0.2-10)
Tumor size (DD) before TTT^†	1.8±1.7 (0.2-10)	3.1±2.5 (1-10)	5.5±0.7 (5-6)	1.8±1.7 (0.2-10)
Power (mW)	236±87 (80-600)	209±37 (175-300)	150±71 (100-200)	229±82 (80-600)
Duration (sec)	89±131 (4-736)	47±33 (4-105)	33±4 (30-36)	84±120 (4-736)
Energy (J)	28±68 (1-464)	9±7 (1-23)	8±6 (4-12)	25±62 (1-464)

^* Significance tested by one-way ANOVA ( p=0.02); thermotherapy

^† Significance tested by one-way ANOVA ( p<0.01); TTT=transpupillary; CTx=systemic chemotherapy.

Table 4.

Predictive variables of insufficient response after one session of thermotherapy combined with chemoreduction

Variable	p-value
Gender (Male/Female*)	0.60
Age at diagnosis	0.39
Bilaterality (Bilateral/Unilateral*)	0.48
R-E classification (III-IV/ I-II*)	0.17
Tumor location (Right/Left*)	0.79
Tumor location (Superior/Inferior*)	0.01^†
Tumor location (Temporal/Nasal*)	<0.01^†
Tumor location (Posterior/Anterior*)	0.88
Initial tumor Size	<0.01^‡
Initial tumor numbers per eye	0.60
Initial tumor size per eye	0.06
Energy applied per 1DD³	0.09

^* Reference variable

^‡ Significance tested by Pearson's chi-square test

^† Significance tested by Pearson’s independent t-test.

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