Volumetric modulated arc therapy for treatment of solid tumors: current insights

Figures & data

Figure 1 Flow chart – study selection diagram.

Table 1 VMAT in brain metastases

Study	Study design	Setting	Number of patients (treated lesions)	Technique, dose (fractionation)	Image guidance	Acute ≥ Grade 3 toxicity	Late ≥ Grade 2 toxicity	Median FUP, months (range)	Clinical outcome	LC rate	OS
Weber et al^Citation30	P	EXC, ADJ	29	VMAT–SIB 2 arcs, 40 Gy (4) WBRT, 30 Gy (3)	CBCT	0%	0%	5.4 (2.6–8.2)	Local failure: 13% Brain failure: 13% Metastases and brain local control: 74%	6 months: 77.9%	6 months: 55.1%
Awad et al^Citation31	R	EXC	30 (73)	VMAT–SIB 2 arcs, 50 Gy, range 20–70.8 (3.3) WBRT, 30 Gy, range 28.6–37.5 (2)	na	0%	Radionecrosis: 3%	3.5 (0.03–16.5)	Clinical benefit: 81.5%a	na	Median: 9.4 months
Nichol et al^Citation32	P	EXC	60	VMAT–SIB 2 arcs, Total dose and fractionation 47.5 (9.5) WBRT, 20 Gy (4)	Orthogonal kilovoltage imaging	Ataxia: 1.7% Radionecrosis: 1.7% Somnolence: 1.7% CTCAE	Nausea: 1.7% Neuropathy: 1.7% Headache: 1.7% Cognitive impairment: 3.3% Ataxia: 5% Motor weakness: 9.9% Radionecrosis: 13.3%	30.5	3 months objective response: 56%	12 months: 88% 36 months: 84%	Median: 10.1 months
Tsai et al^Citation33	P	PRO, EXC, ADJ	24	VMAT (2 full arcs and 2 noncoplanar arcs), PRO: 25 (2.5) ADJ, EXC: 30 (2.5–3)	na	na	na	4	Stable neurocognitive functions	na	na

Note:

a On 27 evaluable lesion.

Abbreviations: P, prospective study; R, retrospective study; EXC, exclusive; ADJ, adjuvant; PRO, prophylactic; VMAT, volumetric modulated arc therapy; SIB, simultaneous integrated boost; WBRT, whole-brain radiotherapy; CBCT, cone-beam computed tomography; na, not available; CTCAE, Common Terminology Criteria for Adverse Events scale; FUP, follow-up; LC, local control; OS, overall survival.

Table 2 VMAT in H&N cancers

Study	Study design	Setting	Number of patients (treated lesions)	Technique, dose (fraction)	Image guidance	Acute ≥ Grade 3 toxicity	Late ≥ Grade 2 toxicity	Median FUP, months (range)	Clinical outcome	LC rate	OS
Scorsetti et al^Citation43	R	EXC, ADJ	45	VMAT–SIB 1–2 arcs –EXC pts: 54.45–69.96 Gy (1.65–2.12) –ADJ pts: 54.45–66 Gy (1.65–2.0) – Sinonasal pts: 55 Gy (2.2)	CBCT	Dysphagia: 7% Mucositis: 28% Skin: 14% CTCAE	na	(2–6)	CR: 74% PR: 16% SD: 10%	na	na
Doornaert et al^Citation44	R	EXC	35	VMAT-SIB 2 arcs 75 Gy (2); 57.75 Gy (1.65)	OBI (kV) or CBCT	Laryngeal toxicity: 8% Moist desquamation: 28.5% Opioid analgesia: 49% Confluent mucositis: 50%	na	<6	na	na	na
Smet et al^Citation45	R	EXC ± CT	157	VMAT–SIB 2 arcs 79 pts Therapeutic doses: 72 Gy (2.4) Prophylactic doses: 40 or 46.4 or 49.6 Gy Versus IMRT; 78 pts Therapeutic doses: 72 Gy (2.4) Prophylactic doses: 40 or 46.4 or 49.6 Gy	na	VMAT: Mucositis: 49% Dysphagia: 63% Skin: 38% IMRT Mucositis: 54% Dysphagia: 74% Skin: 36% CTCAE	na	VMAT: 17.5 (4–36.7) IMRT: 34.9 (4.1–66.9)	na	VMAT 36 months: 84.9% IMRT 36 months: 72.7%	VMAT 36 months: 70.8% IMRT 36 months: 57.3%
Moncharmont et al^Citation46	R	EXC ADJ	150	VMAT–SIB 2 arcsa Therapeutic doses: 66–70 Gy (2–2.2) Prophylactic doses: 50 Gy (2)	na	Mucositis: 19% Dysphagia: 16% Skin: 16% Brachial plexitis: 3% CTCAE	Dysphagia: 20% Xerostomia: 19% Larynx stiff: 11% Skin fibrosis: 9% Plexitis: 2% Trismus: 2% Osteoradionecrosis of mandible: 2% Esophageal stenosis: 1% Trachea stenosis: 0.6%b	16	na	na	na
Ozdemir et al^Citation47	R	EXC	45	VMAT–SIB 19 pts or Dynamic IMRT 18 pts Therapeutic doses: 70 Gy (2.1) Prophylactic doses: 54 Gy (1.6)	kV-CBCT	Dysphagia: 8.9% Mucositis: 6.7% Gastrointestinal: 6.6% Hematologic: 2.2%	na	na	na	na	na
Guo et al^Citation48	P	EXC	205	VMAT–SIB 1 arc Therapeutic doses: 68–70 Gy (2.0–2.3) Prophylactic doses: 54–56 Gy (1.8)	na	Mucositis: 28% Hematologic (overall): 11% Dry mouth: 10% Vomiting: 10% Dermatitis: 5% Fever: 1%	Ear: 18% Xerostomia: 9% Skin: 2% Subcutaneous tissues: 2% Mandible: 1% Cranial nerve: 1% Spinal cord: 0.5%	37.3 (6.3–45.1)	na	36 months: 94.0%**	36 months: 97.0%

Notes:

a 122 pts;

b Any grade late toxicity;

** Locoregional relapse-free survival.

Abbreviations: VMAT, volumetric modulated arc therapy; SIB, simultaneous integrated boost; P, prospective study; R, retrospective study; EXC, exclusive; ADJ, adjuvant; CT, chemotherapy; pts, patients; CBCT, cone-beam computed tomography; OBI (kV), onboard imaging (kilovoltage); na, not available; FUP, follow-up; pts, patients; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; LC, local control; OS, overall survival; CTCAE, Common Terminology Criteria for Adverse Events scale; H&N, head-and-neck; IMRT, intensity-modulated radiotherapy.

Table 3 VMAT in thoracic neoplasms

Study	Tumor site	Study design	Setting	Number of patients	Technique, dose (fractionation)	Image guidance	Acute toxicity, Grade ≥3	Late toxicity, Grade ≥2	Median FUP, months (range)	Clinical outcome	LC rate	DFS	OS
Scorsetti et al^Citation49	Lung (NSCLC)	P	EXC	24	VMAT 2 partial arcs 66 Gy (2) in 22 pts; 60 Gy (2) in 1 pt; 50 Gy (2) for 1 pt	CBCT	0% RTOG	na	6	3 months PR >50%: 56% 3 months PR <50%: 22% 3 months SD: 22%	na	na	na
Kimura et al^Citation50	Mesothelioma	P	ADJ	17	VMAT–SIB 3 arcs 54 Gy (1.8)	na	Pneumonitis: 20%	na	11	na	12 months: 55.7%	12 months: 29.3%	12 months: 43.1%
Kim et al^Citation51	Breast	R	EXC	31	VMAT-SIB 3 arcs Whole breast: 50 Gy (2) Macroscopic disease: 60–70 Gy (2.4–2.8) followed by 10 Gy electron boost	na	0% RTOG	Pneumonitis: 3.2% RTOG	25.2	na	100%	na	na
De Rose et al^Citation52	Breast	P	ADJ	144	VMAT–SIB 2 partial arcs Whole breast: 40.5 Gy (2.7) Surgical bed: 48 (3.2)	CBCT/2D–2D matching	Skin: 1.4% RTOG	0% CTCAE	37 (24–55)	na	24 months: 99.3%	2 months: 99.3%	na

Abbreviations: NSCLC, nonsmall cell lung cancer; P, prospective study; R, retrospective study; EXC, exclusive; ADJ, adjuvant; VMAT, volumetric modulated arc therapy; SIB, simultaneous integrated boost; pts, patients; CBCT, cone-beam computed tomography; FUP, follow-up; PR, partial remission; SD, stable disease; na, not available; LC, local control; DFS, disease-free survival; OS, overall survival; RTOG, Radiation Therapy Oncology Group scale; CTCAE, Common Terminology Criteria for Adverse Events scale.

Table 4 VMAT in genitourinary tumors

Study	Tumor site	Study design	Setting	Number of patients	Technique, dose (fractionation)	Image guidance	Acute toxicity Grade ≥3	Late toxicity Grade ≥2	Median FUP, months (range)	LC rate	DFS	OS
Pesce et al^Citation61	Prostate	P	EXC, ADJ	45	VMAT 1 arc 76–78 (2)	CBCT	0 CTCAE	na	na	na	na	na
Alongi et al^Citation62	Prostate	R	EXC	70	VMAT–SIB 2 arcs Prostate: 71.4–74.2 (2.55–2.65) Seminal vesicles: 61.6–65.5 (2.2–2.3) Pelvic lymph nodes: 51.8 (1.85)	na	GU: 1%	na	11 (3.5–23)	na	na	na
Alongi et al^Citation63	Prostate	P	ADJ	39	VMAT–SIB 1 or 2 arcs 70–71.4 (2.5–2.55)	CBCT	0 RTOG	GI: 0% GU: 11% RTOG	22.8 (9–28)	na	na	na
Ng et al^Citation64	Prostate	R	EXC	23	VMAT–SIB 1–2 arcs Prostate: 72 (2.25) Seminal vesicles: 64 (2) Pelvic lymph nodes: 50 (1.56)	kV	0	GU: 4% GI: 9%	40.9 (30–54)	na	na	na
Sveistrup et al^Citation65	Prostate	P	EXC	87	VMAT 1 arc 78 (2)	Implanted markers and kV	GI: 8% GU: 53%a	GI: 4% GU: 16%a	12	na	na	na
Ishii et al^Citation66	Prostate	P	EXC	100	Two sequential treatments: VMAT–SIB 2 arcs Pelvic lymph nodes: 46.8 (1.8) Prostate: 52 (2) followed by VMAT 1 arc Prostate: 26 (2)	CBCT	0% CTCAE	na	≤3	na	na	na
Hegazy et al^Citation67	Prostate	P	EXC (83% ADT)	29	VMAT–SIB 2 arcs PTV1: 70 (2.5) PTV2: 56 (2) PTV3: 50.4 (1.8)	CBCT	GI: 0% GU: 0% RTOG	GI: 0% GU: 10% RTOG	42 (18–72)	na	24 months b-RFS: 90% 36 months b-RFS: 72%	36 months: 88% 48 months: 72%
Hesselberg et al^Citation68	Prostate	R	EXC, ADJ	113	VMAT–SIB 2–3 arcs EXC: 74–78 (2) ADJ: 50.4–66 (1.8–2)	Filming based on bony anatomy (daily); kV (once a week)	0% RTOG	GU: 0.8% RTOG	14
Alongi et al^Citation72	Endometrium	P	ADJ	50	VMAT–SIB 1–2 arcs, 54 (1.8), boost 66 (2.2)	CBCT	GI: 0% GU: 0% CTCAE	GI: 0% GU: 0% CTCAE	26 (12–39)	24 months: 100%	na	24 months: 96%
Macchia et al^Citation73	Endometrium	P	ADJ	70	VMAT–SIB 2 arcs PTV2: 45 (1.8) PTV1:   Level I: 55 (2.2)   Level II: 60 (2.4)	na	GI (Level I): 0% GI (Level II): 2.8%; GU (Level I): 0% GU (Level II): 0%; Skin (Level I): 0% Skin (Level II): 0% CTCAE	GI (Level I): 5.7% GI (Level II): 2.8%; GU (Level I): 0% GU (Level II): 0% CTCAE	25 (4–60)	36 months: 98.5%	36 months: 81.3%	36 months:93.9%

Note:

a PCSS: Prostate Cancer Symptom Scale questionnaire.

Abbreviations: P, prospective study; R, retrospective study; ADT, androgen deprivation therapy; EXC, exclusive; ADJ, adjuvant; VMAT, volumetric modulated arc therapy; SIB, simultaneous integrated boost; kV, kilovoltage X-ray imaging; CBCT, cone-beam computed tomography; GI, gastrointestinal; GU, genitourinary; FUP, follow-up; na, not available; LC, local control; DFS, disease-free survival; OS, overall survival; b-RFS, biochemical relapse-free survival; RTOG, Radiation Therapy Oncology Group scale; CTCAE, Common Terminology Criteria for Adverse Events scale.

Table 5 VMAT–SIB in anorectal cancer

Study	Tumor site	Study design	Setting	Number of patients	Technique, dose (fractionation)	Image guidance	Acute toxicity Grade ≥3	Late toxicity Grade ≥2	Median FUP, months (range)	Clinical outcome	LC rate	DFS	OS
Richetti et al^Citation75	Rectum	P	NA CRT	25a	VMAT 1 arc: 44 (2.0) or 45 (1.8)	na	GI: 8% CTCAE	na	na	Downstaging (at surgery, VMAT vs 3D-CRT): T 41% vs 26% –N 12% vs 21% Upstaging (at surgery): T 6% vs 11%–N 18% vs 11%–M 6% vs 0%	na	na	na
Dröge et al^Citation76	Rectum	R	NA CRT	81b	VMAT 2 arcs: 50.4 (1.8)	na	GU: 1% GI: 3% CTCAE	GI: 3% GU: 3% CTCAE	18.3 (4.0–59.2)	R0 resection: 98%	na	na	na
Picardi et al^Citation77	Rectum	P	NA CRT	18	VMAT–SIB 2 arcs: Nodal drainage: 45 (1.8) Disease: 57.5 (2.3)	MVPI	GI: 27.8% GU: 5.6% Leukopenia: 5.6% Skin: 5.6% CTCAE	na	61 (3–70)	PR: 72.2% CR: 22.2% ORR: 94.4% (pT0-mic: 61.1%) Not evaluated. 5.6%	12 months: 100% 36 months: 68.6% 60 months: 68.6%	12 months:88.9% 36 months: 66.7% 60 months: 66.7%	12 months: 85% 36 months: 63.8% 60 months: 63.8%
Tozzi et al^Citation78	Anus	R	EXC CRT	36c	VMAT–SIB 2–4 arcs Macroscopic disease: 59.4 (1.8); elective lymph nodes: 49.5 (1.5)	kV	GI: 8.3% Skin: 13.9% CTCAE	GI: 8% CTCAE	19 (7–59)	CR: 83.3% PR: 2% PD: 16.6% (refusal)	60 months: 78.1%	60 months: 85.7%	Mean actuarial survival: 52.8 months
Leon et al^Citation79	Anus	P	EXC CRT	11	VMAT/IMRT–SIB Macroscopic disease: 57.5 (2.13); clinical lymph nodes: 54 (2.0); elective lymph nodes: 48.6 (1.8)	na	GI: 36% HE: 54% Skin: 63% CTCAE	na	22 (12–27)	3 months CR: 91% 3 months TR: 73%	na	24 months: 73%	24 months: 88%
Weber et al^Citation80	Anus	R	EXC CRT	17d	VMAT 2–4 arcs: 50.4 (1.8)	na	Skin: 29.4% GI: 11.8% GU: 5.9% Leukopenia: 11.8% Anemia: 5.9% Thrombocytopenia: 5.9% CTCAE	na	15.3 (3.3–54)	na	24 months: 100%	24 months: 100%	24 months: 100%
ranco et al^Citation81	Anus	R	EXC CRT	39	VMAT–SIB 1–2 arcs: macroscopic disease: 50.4–54 (1.8); clinical lymph nodes: 50.4–54 (1.68–1.8); elective lymphnodes: 45 (1.5)	CBCT	GU: 2% GI: 5% Skin: 18% Leukopenia: 32% Neutropenia: 31% Thrombocytopenia: 13% CTCAE	na	21.5 (6–50)	na	24 months colostomy-free survival: 77.9%	12 months: 100% 24 months: 84.5%	12 months: 100% 24 months: 85.2%

Notes:

a 20 in the comparison group of 3D-CRT;

b 107 in the comparing group 3D-CRT;

c 28 in the comparing group 3D-CRT;

d 86 in the comparing group 3D-CRT.

Abbreviations: P, prospective study; R, retrospective study; EXC CRT, exclusive chemoradiation; HE, hematologic; NA CRT, neoadjuvant concurrent chemoradiation; PD, progressive disease; VMAT, volumetric modulated arc therapy; SIB, simultaneous integrated boost; IMRT, intensity-modulated radiotherapy; CBCT, cone-beam CT; MVPI, megavoltage portal imaging; FUP, follow-up; GI, gastrointestinal; GU, genitourinary; ORR, overall response rate; CR, complete response; PR, partial response; LR, local response; TR, total response; LC, local control; DFS, disease-free survival; OS, overall survival; na, not available; CTCAE, Common Terminology Criteria for Adverse Events scale; 3D-CRT, three- dimensional conformal radiotherapy.

Table 6 Stereotactic body radiation therapy (SBRT)–VMAT

Study	Tumor site	Study design	Setting	Number of patients (treated lesions)	Technique, dose (fractionation)	Image guidance	Acute toxicity Grade ≥3	Late toxicity Grade ≥2	Median FUP, months (range)	Clinical outcome	LC rate	DFS	OS
Scorsetti et al^Citation83	Abdominal lesions	R	EXC	37	SBRT–VMAT 45–75 Gya	CBCT	0% CTCAE	GI: 2.7% CTCAE	12 (6–22)	Lesions: CR: 3.0%b PR: 42.4% SD: 24.2%	79.2%	na	na
Deodato et al^Citation84	Various	P	EXC	20 (25)	SBRT–VMAT 12–26c	na	0% CTCAE	0%	12 (8–20)	Lesions: CR: 28% PR: 20% SD: 52%	85%	24 months: 88%	na
Scorsetti et al^Citation85	Liver	P	EXC	61 (76)	SBRT–VMAT 75 Gy (25)–67.5 Gy in 8% of lesions, 60 Gy in 5%, 52.5 Gy in 5%	CBCT	1.6% (chronic chest wall pain)	na	12 (2–26)	Lesions: CR: 47.4% PR: 21% SD: 26.3% PD: 5.3%	94.7%	na	Median: 19 months (16.3–21.7) 12 months: 83.5% 18 months: 65%
Deodato et al^Citation86	Various	P	EXC	65 (100)	SRS–VMAT 12–28 Gy (1)d	na	0% CTCAE	na	11 (1–38)	ORR + SD by morphological imaging: 95% ORR + SD by functional imaging: 98%	24 months: 72%	na	24 months: 71.8%
Scorsetti et al^Citation87	Prostate	P	EXC	72	SBRT–VMAT with FFF beams 35 Gy (7)	CBCT	GI: 0% GU: 0% CTCAE	GI: 0% GU: 1% CTCAE	14.5 (6–23)	na	na	na	na
Franceschini et al^Citation88	Thoracic node metastases	R	EXC	29 (32)	SBRT–VMAT with FFF beams 30–60 Gy (6–8)	CBCT	0%	6%	12 (2–35)	CR: 14 pts PR: 11 pts SD: 3 pts PD: 1 pt	na	Median: 9 months 12 months: 28% 24 months: 17%	Median: 18 months 12 months: 76% 24 months: 49%

Notes:

a In 3–6 fractions.

b Calculated on 33 patients.

c In 5 fractions.

d Median dose 18 Gy.

Abbreviations: P, prospective study; R, retrospective study; EXC, exclusive; SBRT, stereotactic body radiotherapy; VMAT, volumetric modulated arc therapy; FFF, flattening filter-free; CBCT, cone-beam CT; CR, complete remission; PR, partial remission; SD, stable disease; SRS, stereotactic radiosurgery; PD, progressive disease; pts, patients; CTCAE, Common Terminology Criteria for Adverse Events; GI, gastrointestinal; GU, genitourinary; FUP, follow-up; ORR, overall response rate; LC, local control; DFS, disease-free survival; OS, overall survival.

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