Table E-CTreatment characteristics

StudyLocalization or Staging MethodsComputerized Treatment Planning (system/vendor)Radiation Delivery Source (energy level)Duration of Treatment, Dose, Fractionation, BoostBeam Characteristics (number, shaping)Immobilization/Repositioning ProceduresScope of treatment (bilateral, lymph nodes in neck)Measures to reduce toxicity, e.g., moving salivary gland
560, Biagioli et al., 2007CTYes (Nomos.)Photons (6-MV)60 Gy, 2 Gy/frac, 5 frac/wk

Lifetime dose to spinal cord ≥ 60 Gy
GTV = gross tumor volume

PTV = GTV and areas at risk of microscopic disease expanded by 5–20-mm margin
580, Dirix et al., 2007CT, MRIYes (Helios, Cadplan, Eclipse)Photons (6-MV)60 Gy 2 Gy/frac, 5 frac/wk

IMRT boost 6 Gy, 2 Gy/frac in 10 pts

In regions where PTV and OAR overlapped (optic structures) underdosage of the PTV was tolerated

No elective irradiation of cervical LNs
Non-coplanar 6- field arrangement consisting of 5 fields of 6-MV photons and 1 filed of 10 or 18 MV photons from LA3-point fixation thermoplastic maskCTV included GTV plus margin (not defined) to account for microscopic disease at margin, encompassing resection cavity plus all paranasal sinuses that were invaded

PTV included CTV plus 5-mm margin
1010, Urbano et al., 2007CTYes (Helios, Cadplan, Eclipse or Helax- TMS and Pinnacle)Photons (6-MV)Dose level (DL) 1: Primary tumor site 63 Gy, 2.25 Gy/frac Elective nodal areas 51.8 Gy, 1.85 Gy/frac


DL 2: Primary tumor site 67.2 Gy, 2.4 Gy/frac Elective nodal areas 56 Gy, 2 Gy/frac

Mn Tx time:
DL1 = 39±3 days
DL2 = 38±1 days

Maximum mean dose to parotids 24 Gy where possible
5- and 7-beam arrangementsCustom-made cabulite head and neck maskCTV1 = entire larynx and hypopharynx complex, including thyroid cartilage, from 1 cm above the tip of the epiglottis to below the cricoid cartilage; adjacent sites invaded by tumor as well as all involved nodal areas and retropharyngeal nodes were included;

CTV2 = elective nodal volume, including uninvolved levels 2–5 and supraclavicular fossa nodes bilaterally;

PTV1/PTV2 = CTV1/CTV2 plus 3-mm margin
1420 Feng et al, 2007CTYes (in-house system)70 Gy, 2.0 Gy/frac to gross disease

59–63 Gy, 1.7–1.8 Gy/frac to low- and high-risk subclinical targets

Maximal mandibular dose < 72 Gy

Mean parotid gland dose ≥ 26 Gy

Mean noninvolved oral cavity dose ≥ 30 Gy
Inverse-planned beamlet (not further described)CTV = primary tumor and include lateral retropharyngeal (RP) nodes

PTV = CTV plus a 3- mm margin

Targets in low neck were included I IMRT plans, but anterior low neck fields abutting upper neck plans were not used
1430, Scrimger et al., 2007Yes (Helax v.6.02)Photons2 Gy/frac, 5 frac/wk initially, then 1.8–2.2 Gy/frac in SIB protocol

Planning goal to keep RT dose to spared portion of parotids as low as possible (mean dose to spared portion of parotid 18.4 Gy

Mean dose to all parotid tissue 27.1 Gy
7 gantry angles, 128-leaf MLCIn most patients, the CTV was immediately adjacent to the deep lobe of the parotid; entire target volume, including low neck, treated as 1 volume with no separate supraclavicular field

PTV = CTV plus 5-mm margin

PTV66 = areas of gross disease

PTV60 = high-risk operative bed

PTV54 = low-risk operative bed or undissected nodal regions
1500, Lee et al., 2007CT with contrastYes (MSKCC tx planning system)Photons (6-MV)70–72 Gy, 1.64- 2.12 Gy/frac, once daily with concomitant boost (n = 4) or SIB (n = 27)

When possible, a mean parotid dose of ≥ 26 Gy was achieved; efforts were made to prevent unwarranted hot spots within the glottic larynx
7-fieldThermoplastic head, neck, and shoulder maskGTV = any visible tumor on imaging studies and/or physical examination

CTV = GTV plus 5–10- mm margin, including levels II-IV nodal regions in the neck, retropharyngeal region in pts with clinically involved neck nodes, levels I-II in pts with node-positive disease at level II, and pts who had a primary hypopharyngeal tumor

PTV = GTV or high- risk CTV plus a 3-mm margin

In some cases a low- risk CTV and corresponding low-risk PTV involved the clinically uninvolved contralateral neck and base of skull
1770, Yao et al., 2007 (see 4630, Yao et al., 2005)CT, MRIYes (Corvus v.3.0, Nomos.)Photons50–74 Gy, 1.2- 1.25 Gy/frac, once daily (n = 83), twice-daily (n = 5), 2 with accelerated fractionation with noncomitant boostMultivane, intensity- modulating collimatorThermoplastic facemaskCTV1 = primary tumor and involved lymph nodes with margins

CTV2 = high-risk areas harboring microscopic disease, including soft tissue surrounding CTV1 and lymphatic areas with high risk of metastasis

CTV3 = areas with intermediate risk of microscopic disease
1780, Lee et al., 2007CT with or w/out contrastYes (MSKKC in- house)Photons (6-MV)30–70 Gy med 59 Gy

Dose constraints: Spinal cord 50 Gy
Beams chosen to ensure at least 95% of dose encompassed the target volumeThermoplastic maskGTV = any visible evidence of disease

CTV = at minimum the preoperative GTV and postop tumor bed

PTV = GTV and CTV plus 10–20-mm margins
1900, Ben- David et al., 2007CTYesPhotons70 Gy, 2 Gy/frac to gross tumor, 56–64 Gy, 1.6–1.8 Gy/frac to low- and high-risk targets

Maximal mandibular dose < 72 Gy

Mean parotid gland dose ≤ 26 Gy

Mean noninvolved oral cavity dose ≤ 30 Gy
Static multisegmental or inverse- planned beamlet (not further described)CTV = not described

PTV = CTV plus 5-mm margin
Radiation guards used in all pts with metallic dental restorations to reduce electron backscatter to adjacent soft tissue
1990, Yao et al., 2007CTYesPhotons50–70 Gy, 2 Gy/frac

Definitive IMRT pts received additional SIB of 10 Gy, 2 Gy/frac

High-risk postoperative sites (extracapsular extension, positive or close margins, tumor involvement of soft tissue or bone) received additional SIB of 4–6 Gy, 2 Gy/frac

No SIB given for intermediate-risk sites (w/out extracapsular extension, no positive or close margins, no soft tissue or bone involvement)
CTV1 = tumor bed, including preoperative primary tumor volumes and involved LNs

CTV2 = high-risk areas harboring microscopic disease, including normal structures immediately surrounding CTV1 with high risk of local tumor invasion (primary tumor CTV2) and high-risk lymphatic regions (lymphatic CTV2)

CTV3 = intermediate- risk lymphatic areas

PTV = CTV plus 5–8- mm margin
2180, Daly et al., 2007CTYes (Nomos.)Photons60–70 Gy, 1.8- 2.12 Gy/frac, once daily

Dose constraints: 1% of brainstem and optic nerves volume 54 Gy

< 1% temporal lobes volume 60 Gy

Half the contralateral parotid gland 25 Gy

Upper neck or high-risk subclinical region 60 Gy

Low neck and supraclavicular region 50–54 Gy
Continuous course RT delivered using an auto- sequence MLCPerforated, thermoplastic head maskGTV = gross extent of tumor

CTV = GTV plus margin of 10–20 mm for microscopic disease

PTV = CTV plus 3–5- mm margin to account for patient setup error

Elective neck radiation administered at the discretion of the treating physician (n = 10)

Two methods used to treat neck:

Primary tumor and upper neck above vocal cords treated with IMRT, anterior field for lower neck and supraclavicular fossae

Extended field IMRT for primary tumor plus all regional LNs including supraclavicular
2290, Yao et al., 2006CTYes (Nomos.)PhotonsDefinitive IMRT: 70–74 Gy to PTV1, 60 Gy tp PTV2, 50–54 Gy to PTV3

Adjuvant IMRT: 60–66 Gy to PTV1, 60 Gy to PTV2, 50–54 Gy to PTV3
Multivane intensity modulating collimatorCTV1 = primary tumor and involved cervical LNs

CTV2 = high-risk areas harboring microscopic disease

CTV3 = intermediate- risk lymphatic areas

PTV 1–2 = CTV 1–3 plus 5-mm margin
2370, Garden et al., 2007CTYes (CORVUS v.4.0, Nomos.)Photons (6-MV)66–70 Gy, 1.8–2.2 Gy/frac to CTV1

57–64 Gy, 1.9–2.1 Gy/frac to CTV2

54 Gy, 1,8 Gy/frac to CTV3

Concomitant boost 15–18 Gy in10 frac in 4 pts

Dose constraints: Parotid glands 26 Gy

Larynx 30–40 Gy
MLCCTV1 = gross disease with minimum 5-mm margin

CTV2 = CTV1 with additional margin

CTV3 = subclinical sites in both sides of upper neck

Lower neck treated with anterior field matched to inferior borders of IMRt delivery
2430, Vosmik et al., 2006CT (with or w/out contrast), MRI in some casesYes (CadPlan, Helios)Photons54–66 Gy, 1.8–2.2
Gy/frac, 6 wks

66 Gy to PTV66
60 Gy to PTV60
54 Gy to PTV54

With IMRT simultaneous integrated boost (SIB)

Dose constraints: Spinal cord maximum dose < 44 Gy

Brain stem maximum dose < 54 Gy mean dose < 28 Gy

Larynx (if not part of PTV) 67% volume < 50 Gy
Dynamic MLC, 2x26 leafsThermoplastic maskCTV, GTV, PTV defined according to ICRU Report 50

GTV = all macroscopic disease

CTV = gross disease plus 0.5–20-mm margin for microscopic disease

PTV = CTV plus 0.5–20-mm margin for setup errors
2770, Cheng et al., 2006CTYesPhotons (6-MV and 18-MV)70 Gy, 2 Gy/frac, 5 frac/wk

74.4 Gy, 1.2
Gy/frac, 2 frac daily, 10 frac/wk

Dose constraints: Spinal cord 43–44 Gy
Opposed fields with or w/out anterior fieldBilateral, off-cord or posterior cord boost, separate anterior field for low neck and supraclavicular fossa
Tumor dose NR

Mean dose to contra and ipsilateral parotid ave 22 Gy (SD 5 Gy) and 53 Gy (SD 7 Gy)

Mean dose to contra and ipsilat submandibular gland 57 Gy (SD 8) and 65 Gy (SD 7)
Bilateral neck in all 38
3320, Portaluri et al., 2006CT with or w/out contrastYes (Eclipse)Photons (6-MV)44–64 Gy to PTV1, 2 Gy/frac, 5 frac/wk

Boost to CTV2

Dose constraints: Median Dmax (overall population) Spinal cord 44 Gy

Ipsilateral parotid 48 Gy

Contralateral parotid 42 Gy
Multileaf collimator with 80 leaves, 11 fields (minimum 10, maximum 14)Head-and-shoulder maskCTV1 = tumor bed and bilateral LN levels depending on tumor site and stage

CTV2 = tumor bed and involved LNs

PTV1 and PTV2 = CTV1 and CTV 2 plus 4-mm margin
CT, MRI and PETVarian treatment-planning system (Eclipse®, Version 7.3.10, Varian Medical Systems, Hansen Way, Palo Alto CA, USA)6 MV photon beamsSimultaneous integrated boost (SIB) doses between 60 and 71 Gy (five fractions/week) with 2.0 (n = 8), 2.11 (n = 17), and 2.2 Gy (n = 4)/fraction to the boost volume (planning target volume, PTV1) were applied.

Organs at risk: Sp cd max <45
Gy, parotids mean <26 Gy, OC mean <35
Gy, nuchal tissue mean <45 Gy.

Mean total treatment time was 45.4 days (32–58 days).
5-field equiangular.Commercially available thermoplastic maskGTV with a margin of 10–15 mm was included in the SIB volume.
Elective lymph node regions (PTV2, 50–57 Gy) level 2–5 were included bilaterally.
IMRT: Varian Treatment planning system (Eclipse®, version 7.3.10, Varian medical system, Hansen Way, Palo Alto, CA, USA)IMRT: 6-MeV photon beamsIn all patients, SIB-IMRT technique was performed using the following schedules:
• 30 × 2.2/1.8 Gy to 66 Gy (PTV1)/54 Gy (PTV2; n = 28);
• 33 × 2.11/1.64 Gy to 69.6 Gy/54 Gy (n = 25);
• 30 × 2.11/1.8 Gy to 63.3/54 Gy (n = 3);
• 30–35 × 2.0 Gy to 60–70 Gy (n = 16 postoperative patients). In one case with large necrotic nodes, a higher SIB dose of 2.35 Gy per fraction to 75.2 Gy to the nodal GTV was chosen.

Dose to spinal cord, parotids, TMJ, brain, OC outside of PTV, nuchal tissue: Max <45 Gy, mean ≤26, <50, <40, mean <35, mean <45
Most were 5-field arrangements (n=61)

6-fields (n=5)

7-fields (n=7)

Sliding window MLC
Doses delivered to partial volumes of mandibular bone using IMRT with doses between 60–75Gy (mean 67) on average 7.8, 4.8, 0.9 and 0.3 cm3 were exposed to doses >60, 65, 70 and 75 Gy
respectively. [mean mandibular bone volume 58.4 cm3 (33–88cm3)
IMRT: Helios inverse treatment planning software with Cadplan® system version 6.27(Varian Medical Systems, Helsinki, Finland)IMRT: 6
MV photon beam
IMRT: Parotids excluded from PTV: Max 25 Gy 1st 5 patients and 16–20 Gy in rest of patients.

Dose constraints for spared submandibular glands varied 20–25 Gy.

Mean total dose to parotids and submand gl not treated as OAR was 49 Gy(45–54)
Conventional thermoplastic mask for immobilization in 1st 10 patients (Posicast®, Sinmed BV, EM Reenwijk, the Netherlands). Remaining pts stereotactic H & N immobilization device (BrainLab, Heinstetten, Germany).Both parotids spared in 7 (19%) patients, one contralateral parotid in 29 (81%).

Contralateral submandibular spared in 18 (50%) of patients.
3790, Ozsahin et al., 2006CT, MRIPhotons (6-MV) and electronsDefinitive tx: 70 Gy, 2 Gy/frac, 6 wks

Adjuvant RT: 66 Gy, 2 Gy/frac, 5 wks, 3 days

RT delivered as concomitant-boost accelerated schedule in single daily fracs M-Th, 2 frac on F

Parotids received ≥ 50 Gy in all pts
Thermoplastic maskSurgical margins, extracapsular nodal infiltration, regional nodesAmifostine 500 mg sc prior to each RT frac except Friday pm session
CTCorvus system (version 3.0)IMRT: To PTV 66–68 Gy (included deep lobe of parotid and posterior ½ of submandibular) To GTV 68–72 Gy 34 fractions over 7 weeksCastIMRT: CTV= GTV + 1 cm
PTV added 2 mm margin and included level 2 and 4 Cx LNs.
4290, Lau et al., 2006CT w/contrastYes (Pinnacle3)Photons (6-MV) and electrons70 Gy, 2 Gy/frac, 7 wks

50 Gy to areas of microscopic spread

Dose constraints: Spinal cord 36–40 Gy
Shaped lateral opposed fields, matching anterior low-neck field

0.5-cm multileaf collimator (MLC)
Hard plastic immobilization shellGTV = primary tumor and involved LNs

Upper and lower neck
CTInverse planning Corvus System version 3.0 (NOMOS. Corp, Sewickley, PA)Prescribed dose: GTV: 76 Gy. Nodal GTV: 72 PTV: 70
35 fractions over 7 weeks.
Fractional dose PTV: 2 Gy daily GTV: 2.17 Gy daily (SMART boost technique) Dose to lower neck 60 Gy if N0, 66 Gy if node-positive in 2 Gy daily fractions.
9 coplanar equally spaced beam anglesTailor-made thermoplastic cast from head to shoulders with neck support and mouth bite.IMRT: GTV includes whole NP, tumor extending out of NP, any skull-base erosion and intracranial disease. GTVn: enlarged neck nodes CTV: in some cases, just GTV (if close to critical structures), some were GTV + 5mm–1.5 cm. If palpable residual neck node present after IMRT completion, boost dose of up to 10 Gy may have been given.
4630 YaoCT, MRI, FDG-PETCorvus treatment planning system, NOMOS Version 3.0Definitive IMRT
Prescribed dose
PTV1 70–74 Gy
PTV2 60
PTV3 50–54
Postop high risk
Prescribed dose
PTV1 64–66
PTV2 60
PTV3 50–54
Postop intermediate risk
PTV1 60
PTV2 60
PTV3 50–54

Total (daily) dose SEB=sequential boost Definitive IMRT: SIB: CTV1/CTV2: 60 (2) CTV3: 54 (1.8) SEB: CTV1:10–14 (2)

High risk post op SIB: CTV1/CTV2: 60 (2) CTV3: 54 (1.8) SEB: CTV 1: 4–6 (2)

Intermed risk postop SIB: CTV 1/CTV 2: 60 (2) CTV 3: 54 (1.8) SEB: CTV1: no

Max to normal tissues: Sp cd 45 Gy Br stm 54 Optic n/chiasm 54 Retina 50 Temp lobes 60 Glottic larynx 2/3 < 50
Mandible 70 Parotid mean <30 or 50% of either <30.
Thermoplastic face maskCTV1: GTV with 5–10 mm margins CTV2: high-risk areas harboring microscopic disease (incl normal structures immediately surrounding CTV with high risk of local tumor invasion and high risk lymphatic regions.
CTV3: Intermediate-risk lymphatic areas.
5020, Nishimura et al., 2005CTIMRT treatment planning done by Cadplan Helios, Varian associates, Palo Alto, CA; Eclipse, Varian Medical Systems International Inc, Baden, Switzerland)

Treatment delivery by: Clinac-600C accelerator (Varian Associates)
4MV X-RayWhole neck irradiation with 46 to 50 Gy in 23–25 frac
IMRT boost to PTV to a total dose of 56 to70Gy in 28–35 frac (med, 68 Gy)

Dose constraints to spinal cord, brain, ipsilateral parotid gland, contralateral parotid glad: 40, 50, 25–30, 20–25 Gy
5 or 7 co-planar beams: angles of 60–75, 105–115, 135–150, 180, 210–225, 245–255m 285–300Type-S theromoplastic based system (med-tec, Orance City, IA)Bilateral and submandibular (Ib) and jugular chain (level II–IV) nodes were included in CTV.

The planning organ at risk volume a 3mm margin was added for the spide with no margin to parotid
5120, Wolden et al., 2006CT, MRI3DCRT (not specified)

IMRT (not specified)
IMRT 70 Gy total dose; accelerated fractionation/ 59 patients treated with hyperfractionated concomitant boost/ 15 patients dose painting (PTVm 1.8 Gy/frac 54 Gy total and PTVg 2.34 Gy/frac 70.2 Gy)IMRT Multiple beams tailored to patient anatomy and NPC distribution using dynamic multileaf collimatorsAquaplast masks for IMRTIMRT PTVg included GTV w/1-cm margin increase with the exception of posterior dimension to the primary tumor where a 5-mm margin was added. PTVm consisted of PTVg plus the area encompassing the nasopharynx and all cervical lymph nodes w/ a 5-mm margin.Limitation of parotid gland mean dose limited to 26 Gy when possible; cochlea dose reduced as much as possible
5210, Duthoy et al., 2005CT/MRIIMRT: End dose of 60 Gy in 4 patients, 66 Gy in 6 patients and 70 Gy in 29 patients all in 35 frac. Prescribed dose not reached in 2 patients (1 death after 21 frac and 1 was stopped due to liver mets)

3DCRT: 19 patients had 65Gy (61–70Gy) 1.8Gy/ frac 11 patients had noncoplanar beam w/ median dose of 66 Gy (54–66Gy) 2Gy/frac
3DCRT: 19 patients had coplanar beams 10 had non-coplanarNo elective radiation of cervical lymph nodes (ELNI)

3mm margin used for expansion from CTV to PTV
5310, Zheng et al., 2005CT, MRIPhotons (6-MV)66–72 Gy, 2 Gy/frac, once daily 5 days/wk, 6–7 wks

Dose constraints: Mean Dmax Gy(rng)
32 (19–45)
Spinal cord
24 (13–42)
Temporal lobe I
42 (17–68)
Temporal lobe C
23 (7–47)
Optic nerve I
36 (7–67)
Optic nerve C
31 (6–56)
Optic chiasm
31 (6–56)
Eyeball I
21 (2–39)
Eyeball C
15 (1–22)
5–7 static coplanar or noncoplanar beams with 3–7- mm block aperture margin from the PTV boundary, with wedges to improve dose conformity and homogeneity as neededGTV = primary tumor

CTV = GTV plus extent of subclinical microscopic disease, usually 5–10-mm margin

For high risk subclinical sites (eg, skull base, parapharyngeal space, oropharynx) 8–10 mm of CTV margin was delineated

PTV = CTV plus 2.5- mm margin

PRV (planning risk volume) = 2.5-mm margin around organs at risk
5330, Lu et al., 2005CTYesTotal to CTV 72 Gy, 1.7 Gy/frac, 6 wks

Initial dose to GTV 54 Gy, 1.8 Gy/frac, 5 frac/wk, 6 wks

Accelerated boost added 1.5 Gy/frac as second daily frac for 12 days

Dose constraints: Spinal cord 39.6 Gy
GTV = primary tumor plus draining anterior neck LNs

Clinically involved and uninvolved posterior neck

Boost target volume included primary tumor plus involved LNs plus 2-cm margin

Supraclavicular fossae
5420, Pan et al., 2005CTYes (UMPlan in-house)40–70 Gy med 64 GyPrimary tumor

Unilateral neck
5740, Thorstad et al., 2004CTYes (Nomos.)Photons (6-MV)Aquaplast face maskCTV1 = preop gross tumor volume plus 10-2—cm margin, including resection bed with invasion, or extracapsular extension by metastatic neck LNs

CTV2 = uninvolved cervical LNs
Amifostine 500 mg sc prior to each RT frac
6430, Kwong et al, 2004CTIMRT delivered with Mimic (NOMOS. Corporation)

Inverse planning by Corvus v3.0 (NOMOS. Corporation)
4 or 6 MVGTV: 68–70Gy to at least 95% and 70 Gy to macroscopically enlarged nodes in 2–2.06Gy/34 frac

PTV:66–68Gy to 95% 1.9–2.0Gy/frac

60–66Gy 2Gy daily frac from neck caudal to the chin or caudal to the most distal enlarged lymphnode. Organ atrisk Gy are listed in rightmost column.

Dose constraints to organs at risk: Spinal cord, [Eye, optic nerve, optic chiasm, temporal lobes, brain], brainstem, parotid glands, pituitary glands, [inner ears, middle ears, tempromandibular joints] – 40, 50, 50, 20, 25, 50 Gy
9 co-planar beam angels equally spaced. 0, 40, 80, 120, 160, 200, 240, 280, 320, 360 degreesCustom thermoplastic cast from head to shouldersPotential sites of local infiltration 1mm from GTV were included in CTV. CTV included: sphenoid sinus caudal to the base of pituitary fossa, cavernous sinuses on both sides, base of skull, including petrous temporal bones and excluding internal auditory canals and cochleae, inferior orbital fissures, foramen ovale and foramen spinosum, anterior half of the clivus and posterior third nasal cavity and antrum, medial pterygoid muscles and parapharyngeal space up to the styloid process and anterior one-half of the arch of the cervical vertebrae (C1) and prevertebral muscles inferior to C1.

Enlarged cervical lymph nodes were localized as separate GTV
CT/MRI3D planning (AcQPlan 3D RTP, Marconi Medical Systems)Salvage dose ranged from 16–38 Gy (median 24) with 2 Gy/fraction, one fraction daily, 5d/wk.

(Initial external beam RT doses: median to NPH 70 Gy, to negative neck 50, and to positive neck 68, fraction 2.0/d).
PTV= persistent disease + 5mm margin
7090, Chao et al., 2004CTi70 + or − 1.1 Gy to CTV1 definitive, 66.3 + or − 3.6Gy, CTV for definitive patients was 64+ or −4.2 Gy, and 66.3 + or − 3.6 Gy.

1.9 to 2.0 Gy/frac 5 frac/wk
CTV1 encompassed GTV and region adjacent to GTV, the surgical bed w/soft-tissue invasion, and regions with extracapsular extension by metastatic neck nodes, CTV2 was primarily prophylactically treated nodal stations.

Dose to each target volume was normalized to 80–90% of maximal isodose reference point.
7110, Sze et al., 2004CT w/out contrastYes (Helax TMS)70 Gy, 2 Gy/frac, 5 or 6 frac/wk, 7 wks

70 Gy to grossly enlarged LNs

50–60 Gy to supraclavicular fossae

med 46 days (rng 36–55 days
5–7 beamsRigid immobilzation deviceGTV-P = gross tumor volume plus adjoining involved retro-pharyngeal LNs

PTV = GTV-P and whole nasopharynx, plus 7–12-mm margin

Parapharyngeal spaces, posterior nasal fossae and maxillary sinuses, sphenoid and posterior ethmoid sinuses, base of skull and cavernous sinuses
7370, Lu et al., 2004CT, MRIYes (Nomos.)66–70 Gy, 1.8–2.8Gy/frac, 5 frac/wk

60 Gy to positive LNs in neck

Dose constraints: According to ICRU 50 guidelines

Brainstem mn dose 28 Gy

Optic chiasm mn dose 22 Gy

Optic nerves mn dose 19 Gy

Lens mn dose 4 Gy
Temporal lobes mn dose 22 Gy

Temporomandib28 Gy

Mandible mn dose 20 Gy

Pituitary mn dose 33 Gy
Dynamic multivane intensity modulating collimator (MIMiC) using segmental tomotherapy techniquesGTV = gross extent of tumor shown on imaging studies

CTV = GTV plus 5–10- and 10–15-cm margins
7570, Levendag et al., 2004CTYes (3D Cadplan)Photons (6-MV)70 Gy to gross primary tumor and involved neck LNs

46 Gy to uninvolved neck LNs
Dynamic multileaf collimator, abutted AP portal with midline shield for lower neckPVC head castCTV = primary tumor plus neck

PTV = CTV plus 5-mm margin

Unilateral and bilateral neck
7750, Liu et al., 2003CT, MRIYes (Pinnacle3)Photons (6- or 15- MV)60–77 Gy, 1.8 Gy/Frac, 5 frac/wk

70–77 Gy to primary tumor and positive neck LNs

60–65 Gy to CTV

50 Gy to clinically negative neck

Limit dose to 1% of volume of critical structures as follows: Brainstem and optic nerves 50 Gy

Spinal cord and optic chasm 45 Gy

Temporal lobes60 Gy

50% of contralateral parotid 25 gy
Static multisegmental multileaf collimator

Split-beam technique for anterior lower neck field
GTV = gross extent of tumor, including nasopharyngeal primary and retropharyngeal lymphadenopathy

CTV = GTV plus margin of potential microscopic spread
8250, Munter et al., 2003CT, MRIYes (KonRad, VIRTUOS)Photons (6- or 15- MV)55–72 Gy to primary PTV, GTV, positive LNs, 1.6–2.0 Gy/frac or 1.6–2.0 Gy/frac

IMRT boost or integrated boost also used

50–65 Gy to secondary PTV

Dose constraints: Cervical spinal cord 50 Gy

Brainstem 60 Gy

Optic nerve and chiasm 54 Gy

Protected parotid < 26 Gy
Integrated multileaf collimator, 5–9 beams (med 7)Scotch-Cast maskGTV = visible tumor in imaging studies

CTV = GTV plus 5-mm margin; in postop cases GTV included surgical bed and margins according to assessed risk Primary PTV = CTV plus 3-mm margin to compensate internal organ motion and setup variability

Secondary PTV = LNs or surgical neck levels at risk of sub clinical disease, including LN level II–V (depending on tumor site), retropharyngeal LNs, and in some cases level I

All pts with ipsilateral LN involvement also had contralateral neck RT

Tumor suspicious LNs and LN levels with radiographic evidence were defined as a target volume
8270 Braaksma 2003CTNon commercial inverse planning module “Optimize”

Computer planning purposes: Cadplan versions 2.7.9 and 3.1.2, Varian-Dosetek, Finland.

10 MV3DC
46 Gy to primary tumor and LN levels of neck (PTV1); then boosted to cumulative dose of 70 Gy primary tumor (PTV2).

Mean dose to R and L parotids was 29.2 and28.7, respectively.
PTV= CTV + 5mm margin
8370 Padovani 2003Focus logical, CMS, St Louis, MO6–18 MV3DC RT delivered in doses of 2 Gy/fraction at 5 fractions weekly.

Median dose PTV was 63 Gy (range 30–70).

Ipsilateral neck 60 Gy

Max dose to chiasma and CNS limited to 54 and 60 Gy, respec, ipsi optic n and retina 60 Gy.
NoncoplanarThermoplastic face maskCTV = pretx GTV and microscopic extension PTV= CTV plus additional uniform 5 mm expansion
Ipsi Cx LN in 5 pts; contra Cx LN in 1 pt.
8400 Amosson 2003CTNOMOS. Peacock10 MVIpsilat and contralat parotids had threshhold limits of 35 Gy and 25 Gy, respectively. (ave mean doses to ipsilat and contralat parotids were 24.2 and 19.1 Gy, respectively) No attempt made to avoid submandibular glands.
Sp cd 40 Mandible 58
n=13 with “Talon” fixation device

n=17 Reinforced Aquaplast mask.
9290 Teh 2002Daily fractions of 2.4 and 2 Gy to primary and secondary targets to a total dose of 60 and 50 Gy, respectively.
Overall tx course was five weeks (daily tx).
Dose to parotids limited- for midline tumors to 25 Gy, for unilateral tumors the ipsilat parotid was limited to 30–35 and contralat 25 Gy.
HELAX TMS6 MeVPrescription dose 51.3 Gy with 1.9 Gy/dMask fixationPlanning included pretherapeutic tumor extension and cx LN bilaterally
Jian 2002
CTFOCUS (computerized medical systems, Inc., St Louis, MO)6MV, 18MV and 9MeV40.8–43.2 Gy @ 1.2/frac, 2 frac/day, 6 hr interval betw doses with 6 MV. After 1 wk brk, off-cord 16.8–19.2, 1.2/frac, 2 frac/d with 18MV. Finally, an additional 14.4 Gy in 12 fracs off brnstm. Boost to upper neck by electron beam if necessary.

Total dose to primary tumor 74.4 Gy, to involved neck nodes 68–74.4 and to uninvolved neck nodes 50–60 Gy.

Dose constraints: Brstm 60–65 Gy Sp cd 50 Gy
NPH and upper neck
10740, Pommier et al, 2000CTElektra linear accelerator w/multileaf collimatorMixed X-ray 6 to 18 MV63.5 Gy (56–68) 2 Gy frac/5 frac wk6 to 15 (median 11 ) portals w/multileaf collimation field shapingThermoplastic face maskPTV including CTV plus 5 mm expansion Ipsilateral lymph nodes treated In 7 patientsPalatine prosthesis to protect floor of mouth Dose limited to 12 Gy for contralateral eye, 56 Gy to optic chiasm and contralateral optic nerve, 60 Gy to frontal CNS
11650, Kuppersmith et al., 1999CT with contrastYes14–71 Gy, 1.5–4.0 Gy/frac, 1 frac/day

Dose constraints:

Parotid glands 30 Gy
Dynamic multivane collimator, 40 beamsScrews in skull vertex attached top docking device
13270 Lawson 2008CT and PETEclipse (Varian Medical Systems)6 MVMean (median, range) total dose to gross dz: 70.14 Gy (70.29, 69.3–70.4). Per fraction to gross dz: 2.13 (2.13, 2.1–2.2). To remainder of clinically involved neck: 61.05 (63.03, 54.4–63.03). Per fraction to clinically invol neck: 1.85 (1.91, 1.7–1.95). Clinically uninvolved neck: 58.34 (57.75, 54.4–63.03). Per fraction to clinically uninvolved neck: 1.77 (1.75, 1.7–1.91).

5 daily fractions per week, to median (range) of 33 fractions (31–35).
CTV= PTV + 1–1.5 cm margins.
13340 Ikushima et al, 2008CT MRIClinac 2100C, Arian Alpatro4 and 10 MV30 Gy, 2.0 Gy daily fracThree to five ports with a 1.5 cm margin to CTV
16840, Wu et al, 2006CT, MRIElectron beamSimultaneous modulated accelerated RT-GTV, CTV70/2.5 Gy frac, 56/2.0 Gy frac With 28 frac within 6 weeksIMRT using split-beam technique w/middle and lower neck fields treated with single anterior field joined by CRT

Coplanar means positioned every 40 degrees from the posterior and lateral directions
BrainLAB noninvasive thermoplast mask and localizer frameCTV plus areas of potential microscopic spread including: nasopharynx, retropharyngeal nodes, clivus, skull base, pterygoid fossae, parapharyngeal space, inferior sphenoid sinus, posterior third of the nasal cavity and maxillary sinuses.

Included ipsilateral and contralateral neck nodes of level 1,2,3, 5
Brainstem, spinal cord, parotid glands, and lens specified at risk for inverse planning with different weights.
24330, Pfreunder et al., 2003CT5 MV linear acceleratorHnN compartments and lymphatic drainages were irradiated with 50.4 Gy/1.8 frac 5 frac/wk

GTV received 2nd 1.4 Gy frac after wk 4 of RT resulting in total 69.9 Gy in 5.5 weeks to GTV and 50.4 total to lymphatic drainage
Static wedge fieldsIndividualized masks for patient fixation
26140 Scorsetti 20016MV1–18 fractions (med 8) at median dose of 30 Gy (range 6–54). Second boost of 10–30 Gy to reduced target volume if good responders.PTV= GTV + 2–10 mm margin.
37660, Wendt et al, 2006CTMevatron KD2, Siemens Medical Solutions, Germany

Inverse planning software: Helax TMS, Nucletron, Europe w/KonRad, Siemens
5 frac/wk Median parotid gland dose 30 Gy or less in 37 or 39 patients and less than 26 in 29 patients rng 21–52.8 Gy.Bilateral 3D-C-IMRT using standard 7-portal arrangement. Each portal modified by # D metallic compensator

Lower neck and supraclavicular fossae (region II, IV, IV B) used single anterior field
Tumors of the nasopharynx, oropharynx, oral cavity, floor of mouth, gross primary tumor bed and lymph node down to the level of hyoid bone were irradiatedMedian dose to one parotid gland at aimed at 26Gy or less
38290, Anand et al., 2008CT, MRIYes (Plato ITPc or Primus)Photons (6-MV)Definitive IMRT 66 Gy, 1.9–2.0 Gy/frac, 33–35 frac to CTV1 and 70 Gy, 2.0–2.1 Gy/frac, to GTV for pts receiving CTx

70 Gy, 1.9–2.0 Gy/frac, 35–37 frac for pts receiving IMRT alone

Adjuvant IMRT 56–62 Gy toCTV1, 50–54 Gy to CTV2 and CTV3

50–52 Gy to supraclavicular region

Dose constraints: Median Dmax Gy (rng) Spinal cord 45 (37–48)

Brainstem 51 (33–58)

Optic nerve 24 (1–61)

Optic chiasm 26 (2–62)

Cochlea 42 (0.5–53)

Mandible 72 (28–77)
Multileaf collimator or compensators, 7–9 fields

Separate low anterior field with midline laryngeal block
Thermoplastic mask for head and neckGTV = primary tumor volume and metastatic LNs

CTV1 = GTV plus 10–12-mm margin

CTV2 = ipsilateral high risk but clinically negative LNs

CTV3 = contralateral uninvolved LNs

CTV1 for adjuvant IMRT included preop GTV and 15–20-mm margin to encompass surgical bed with soft tissue or bone invasion, or metastatic neck node regions with extracapsular extension

PTV = CTV1 plus 5-mm margin
38530, Studer et al., 2008CTDefinitive IMRT 69–72 Gy, 2.0–2.2 Gy/frac, 5 frac/wk

Postop IMRT 66 Gy, 2 Gy/frac, 5 frac/wk

All schedules based on SIB delivery
38640, Studer et al., 2008CTDefinitive IMRT 70–73 Gy, 2.1–2.2 Gy/frac, 33–35 frac to boost PTV

73 Gy, 2,2 Gy/frac, 33 frac to large GTVs

70 Gy, 2 Gy/frac, 35 frac in pts with CNS structures in the PTV

Adjuvant IMRT 60–66 Gy, 2 Gy/frac, 30–33 frac to boost PTV

Elective dose 54 Gy in most pts, 60–66 Gy prescribed for higher risk pts

All schedules based on SIB delivery
GTV = primary or total gross tumor volume
38840 Seung 2008CTADAC Pinnacle version 7.4; Phillips/ADAC6 MVSIB
prescribed dose 69.96 Gy (66–70) to PTV70/66; 59.4 Gy (59.4–60) to PTV59.4; and 54 (54–54.12) to PTV 54.
Median dose per frac: 2.12 (2.12–2.2) to PTV70/66; 1.8 (1.8–2.0) to PTV59.4 and 1.64 (1.64–1.8) to PTV54.
Normal tissue dose limitation max ≤45 to sp cd, and ≤54 brstm. Mean to parotids ≤26.
7–9 equally placed coplanar beamsAquaplast maskPrimary tumor and upper neck above VCs

GTV:gross extent of tumor and LNd > 1cm diameter.
CTV70:GTV plus margin for potential microscopic spread. CTV59.4 (highrisk CTV):CTV70 + retropharyngeal nodes and levels IB-V on LN positive side. PTV: CTV + margin 0.3–1 cm
38850 Caglar 2008ECLIPSE (Varian Medical Systems)IMRT 70 Gy at 2Gy/fraction to GTV, 64 to high-risk CTV, and 60 to low-risk CTV. Post op cases 64 Gy.
Parotid glands mean dose 26 Gy.
Sp cd dose 46 Gy.
thermoplasticGTV: for definitive cases = tumor and involved LNs High-risk CTV for definitive = GTV plus margin for subclinical dz and neck nodal regions at greatest risk of subclinical involvemt.
Low risk CTV included uninvolved Cx LNs.
PTV: CTV + 5 mm margin.
39000 Sanguineti 2008CTPinnacle36 MVEarly stage lesions (stage 1–2) hypofractionated schedule. Adv stage dz acc/hyperfrac 78 Gy to PTV1 at 1.3 Gy twice daily. Others rec’d conventional frac at 2 Gy/frac to PTV1.ThermoplasticCTV1=CTV + GTV CTV2=included tissue at high risk of containing microscopic dz. CTV3=included tissue at low risk of microsc dz. PTV1, PTV2 and PTV3 expanded the corresponding CTV by 5mm.
39020 Rosenthal 2008ADAC PinnacleTo primary site: 60–63/30 fx n=5
66/30 fx n=79
66–68/33 fx n=5
70/33 fx n=56
72/40 fx (concomitant boost) n=15
39300, Hoppe et al., 2008CT, MRIYes (MSKKC system)Photons (6-MV)70 Gy, 2.1 Gy/frac to PTV1

60 Gy, 2 Gy/frac to PTV2

54 Gy, 1.8 Gy/frac to PTV3

54 Gy to involved neck

All treated once daily, 5 days/wk

Dose constraints: Brainstem
< 50 Gy

Spinal cord
< 45 Gy

< 50 Gy

< 45 Gy

Optic nerve
< 54 Gy

Optic chiasm
< 54 Gy
Dynamic multileaf collimator with dynamic leaf sequencingCustom Aquaplast mask that also immobilizes shoulders when neck is treatedCTV1 = clinical tumor volume included gross disease with 3–5-mm margin

CTV2 = surgical bed and areas at high risk of microscopic disease

CTV3 = LN regions at risk

PTV1, 2, 3 = CTV 1, 2, 3 plus 5–10-mm margin, expanded 1-mm in areas adjacent to critical normal structures

Bilateral or ipsilateral neck irradiation for involved LNs
39390, Worden et al., 2008CT, PET70 Gy, 2 Gy/frac daily, 5 frac/wk to gross disease and 10–20-cm margins

59–63 Gy, 1.7–1.8 Gy/frac to tissue volumes at risk of harboring subclinical disease
Gross tumor volume plus 10–20-cm margins

Bilateral neck

From: Appendix E, Single-Arm Studies

Cover of Comparative Effectiveness and Safety of Radiotherapy Treatments for Head and Neck Cancer
Comparative Effectiveness and Safety of Radiotherapy Treatments for Head and Neck Cancer [Internet].
Comparative Effectiveness Reviews, No. 20.
Samson DJ, Ratko TA, Rothenberg BM, et al.

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