Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study

Lei Du; Xin Xin Zhang; Lin Chun Feng; Jing Chen; Jun Yang; Hai Xia Liu; Shou Ping Xu; Chuan Bin Xie; Lin Ma

doi:10.1515/raon-2016-0001

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Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study

Radiology and Oncology

Volume 50 (2016): Issue 2 (June 2016)

By: Lei Du, Xin Xin Zhang, Lin Chun Feng, Jing Chen, Jun Yang, Hai Xia Liu, Shou Ping Xu, Chuan Bin Xie and Lin Ma

Open Access

|Feb 2016

Figures & Tables

Table 1

Distributions of patients in P67.5/P70 study according to the Union for International Cancer Control (UICC) 2002 staging system

Stage	N0	N1	N2	N3	Total
T1	6/16	13/27	11/15	3/3	33/61
T2	3/13	15/24	23/22	3/2	44/61
T3	2/8	15/11	18/18	3/3	38/40
T4	2/3	3/10	11/11	1/4	17/28
Total	13/40	46/72	63/66	10/12	132/190

Table 2

Patients’ characteristics

Characteristics	P67.5 study		P70 study		p

	n.	%.	n.	%.
Age (median)	15–75	(47)	10–81	(44)	0.527
Gender
Male	95	72.0	144	75.8	0.441
Female	37	28.0	46	24.2	0.441
Region
Northern China	110	83.3	159	83.7	0.933
Southern China	22	16.7	31	16.3	0.933
KPS
90–100	105	79.5	133	70.0	0.055
70–80	27	20.5	57	30.0	0.055
Pathology
WHO type I	2	1.5	3	1.6	0.964
WHO type II	130	98.5	187	98.4	0.964
UICC 2002 Stage
I	6	4.5	16	8.4	0.045
II	31	68	51.5	37.4
III	23.5	64	71	33.7
IVa-b	27	20.5	39	20.5

[i] KPS = Karnofsky performance status; UICC = Union for International Cancer Control; WHO = World Health Organization

Different survival rates for patients in the P67.5 study.

Table 3

BED of the two SMART regimens (Gy)

	BED (P67.5)	BED (P70)
Tumor OTT disregarded (α/β= 10Gy)	82.7	84.8
Tumor OTT taken into account (α/β= 10Gy)	62.9	62.0
Normal tissue (α/β= 5Gy)	97.9	99.7
Normal tissue (α/β= 3Gy)	118.1	119.5

[i] BED = biological effective dose; OTT = overall treatment time; SMART = simultaneous modulated accelerated radiation therapy

Table 4

Dosimetric data of organs at risk

	Mean value (Range)		p
	P67.5 study	P70 study	p
Beam-on time (s)	413.8 (336.0–521.7)	455.8 (358.0–696.0)	0.674
Couch travel (cm)	21.4 (18.0–27.0)	22.6 (17.0–28.7)	0.000
pGTVnx Dmean	70.2 (69.2–72.6)	72.3 (70.4–75.6)	0.000
pGTVnd Dmean	70.1 (69.2–72.7)	72.3 (70.1–75.6)	0.000
PTV1 Dmean	64.9 (63.1–67.3)	64.6 (62.1–70.5)	0.083
PTV2 Dmean	56.7 (55.7–59.8)	57.4 (54.7–61.7)	0.000
Brainstem Dmax	51.1 (35.9–69.1)	54.5 (41.6–71.9)	0.000
Spinal cord Dmax	40.6 (35.2–51.1)	41.5 (33.7–51.8)	0.003
Optic nerve Dmax
Left	29.0 (3.9–70.5)	38.3 (9.7–72.2)	0.000
Right	28.3 (4.6–70.8)	39.3 (9.2–72.9)	0.000
Eyeball Dmax
Left	19.4 (4.0–38.9)	29.6 (10.0–65.4)	0.000
Right	19.1 (5.3–38.8)	29.6 (11.2–57.7)	0.000
Lens Dmax
Left	3.2 (2.0–5.3)	4.1 (2.2–8.1)	0.000
Right	3.2 (2.2–8.3)	4.1 (2.2–8.3)	0.000
TMJ Dmean
Left	33.7 (22.6–60.4)	38.7 (22.9–58.5)	0.000
Right	33.1 (22.5–64.7)	38.2 (21.1–51.8)	0.000
Inner ear Dmean
Left	45.4 (27.4–67.1)	43.1 (12.3–58.0)	0.055
Right	44.7 (26.3–61.7)	44.4 (11.6–65.2)	0.815
Parotid gland Dmean
Left	30.8 (25.2–39.9)	31.2 (23.8–55.1)	0.334
Right	30.7 (22.9–65.2)	31.0 (22.0–47.9)	0.636
Oral cavity Dmean	34.2 (26.6–42.0)	38.8 (11.5–50.2)	0.000
L-E-T Dmean	32.7 (24.2–38.8)	38.7 (19.1–49.6)	0.000

[i] Dmean = mean dose (Gy); Dmax = maximum dose (Gy); L-E-T = Larynx-esophagus-trachea; pGTVnd = positive lymph nodes; pGTVnx = prescription doses delivered to the gross tumor volume; TMJ = Temporomandibular joint;

Table 5

Acute toxicities of normal organs [n (%)]

Toxicity	Grade 0		Grade 1		Grade 2		Grade 3		Grade 4		p

	P67.5	P70	P67.5	P70	P67.5	P70	P67.5	P70	P67.5	P70
Skin reaction	6 (4.5)	7 (3.7)	92 (69.7)	137 (72.1)	27 (20.5)	37 (19.5)	7 (5.3)	9 (4.7)	0 (0.0)	0 (0.0)	0.961
Mucositis	2 (1.5)	4 (2.1)	54 (40.9)	72 (37.9)	64 (48.5)	108 (56.8)	12 (9.1)	6 (3.2)	0 (0.0)	0 (0.0)	0.100
Xerostomia	4 (3.0)	9 (4.7)	33 (25.0)	100 (52.6)	95 (72.0)	81 (42.6)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0.000
Pharyngitis-esophagitis	0 (0.0)	7 (3.7)	51 (38.6)	83 (43.7)	79 (59.9)	99 (52.1)	2 (1.5)	1 (0.5)	0 (0.0)	0 (0.0)	0.072
Leucopenia	29 (22.0)	86 (45.3)	32 (24.2)	42 (22.1)	39 (29.6)	50 (26.3)	26 (19.7)	10 (5.3)	6 (4.5)	2 (1.0)	0.000
Anemia	66 (55.0)	175 (92.1)	44 (33.4)	14 (7.4)	18 (13.6)	1 (0.5)	4 (3.0)	0 (0)	0 (0.0)	0 (0)	0.000
Thrombocytopenia	103 (78.0)	180 (94.7)	16 (12.1)	7 (3.7)	5 (3.8)	2 (1.1)	5 (3.8)	1 (0.5)	3 (2.3)	0 (0)	0.000

Table 6

Patients with treatment failure

TNM stage	Failure time (month)	Failure site	Salvage treatment	Living status	Follow-up^{^*} (month)
1. T1N2M0	6	Bone	CT	Dead	17
2. T3N3bM0	7	Liver	CT	Dead	14
3. T2N2M0	8	Lung	CT+AT	Living	14
4. T1N2M0	9	Bone	CT+AT	Dead	12
5. T3N2M0	10	Lung	-	Dead	17
6. T1N2M0	10	Liver	CT	Living	16
7. T3N2M0	10	Local	RT	Dead	20
8. T3N1M0	12	Liver	CT	Dead	31
9. T3N2M0	13	Nodal	RT	Living	37
10. T1N3bM0	13	Nodal	BT	Living	26
11. T4N0M0	14	Liver	-	Dead	18
12. T3N1M0	21	Local	-	Dead	24
13. T3N1M0	22	Liver & Lung	CT	Living	33
14. T3N0M0	23	Local	CRT	Dead	33
15. T3N2M0	23	Nodal	CT	Living	27
16. T2N2M0	24	Nodal	CRT	Living	37

AT = anti-EGFR Mab therapy; BT = brachytherapy; CRT = concurrent chemoradiotherapy.CT = chemotherapy; RT = radiation therapy;

* The time from diagnosis.

Table 7

Summary of reported prospective studies on simultaneous modulated accelerated radiation therapy (SMART) for nasopharyngeal carcinoma (NPC)

Author	N	T3-4 tumor n (%)	Positive node n (%)	Fractionation patterns for GTV					LCR (%)

				Fraction	Prescription dose (Gy)	Fraction dose (Gy)	BED^{^*} (Gy) OTT disregarded	BED^{^*} (Gy)
Lee SW (2005)¹²	20	8 (40)	18 (90)	30	72	2.4	89.3	69.5	88.0 (2-y)
Lin SJ (2009)¹³	323	260 (80.5)	293 (90.7)	30 / 31	66 / 69.8	2.2 / 2.25	80.5 / 85.4	60.7 / 63.8	95.0 (3-y LRFS)
RTOG0225 (2009)¹⁴	68	23 (33.8)	50 (73.5)	33	70	2.12	84.8	62.0	92.6 (2-y)
Xiao WW (2011)¹⁵	81	81 (100)	56 (69.1)	30	68	2.27	83.4	63.6	94.9 (3-y)
Bakst RL (2011)¹⁶	25	16 (64)	20 (80)	30	70.2	2.34	86.6	66.8	91.0 (3-y)
Wang RS (2013)¹⁷	300	214 (71.3)	277 (92.3)	30–32	68–72	2.25–2.27	83.4–88.2	63.6–66.0	94.0 (4-y)
Author (2014)³	190	68 (35.8)	150 (78.9)	33	70	2.12	84.8	62.0	96.1 (2-y LRFS)
Current study	132	55 (41.7)	119 (90.2)	30	67.5	2.25	82.7	62.9	96.7 (2-y LRFS)

* α/β = 10Gy; OTT = overall treatment time; LCR = local control rate; LRFS = local relapse-free survival; y = year

References

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DOI: https://doi.org/10.1515/raon-2016-0001 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 218 - 225

Submitted on: Aug 31, 2015

Accepted on: Dec 9, 2015

Published online: Feb 7, 2016

Published in print: Jun 1, 2016

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

nasopharyngeal carcinoma,

simultaneous modulated accelerated radiation therapy,

helical tomotherapy,

acute toxicities, clinical outcome

Related subjects:

Medicine,

Clinical medicine,

Radiology

© 2016 Lei Du, Xin Xin Zhang, Lin Chun Feng, Jing Chen, Jun Yang, Hai Xia Liu, Shou Ping Xu, Chuan Bin Xie, Lin Ma, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Volume 50 (2016): Issue 2 (June 2016)