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Head and neck glottic larynx squamous cell carcinoma definitive EBRT

Head and neck cancer treatment is complex and combined modality therapy is common. The involvement of an experienced multidisciplinary team (MDT) in the initial development and ongoing evaluation of the treatment plan, and the management of the sequelae associated with treatment is recommended. Patients should have appropriate access and care-pathways to supportive care services including inpatient, medical oncology and allied health care where appropriate.

Staging used in this protocol is based on the AJCC Cancer Staging Manual 7th edition. Newer guidelines, the AJCC Cancer Staging Manual 8th edition were implemented on January 1, 2018. Although the 8th edition provides additional prognostic information, at this time point it does not change management.

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  • Squamous cell carcinoma (SCC) of the glottic larynx
  • Stage I-II (T1N0M0 / T2N0M0) (AJCC Cancer Staging Manual 7th Edition)r
  • Good performance status ECOG 0-2

Cautions

Note

  • Tis can be considered in some circumstances depending on individual patient and tumour related factors.

Links to other regimens

  • Anxiety and depression are common in patients with cancer. A referral to a psychosocial practitioner should be considered.
Simulation Options Notes
Position
  • Supine
  
Arm/leg/head/neck/shoulder position
  • Head neutral or hyperextended with neck straight

Shoulders should be down as far as possible
Immobilisation and supports
  • Immobilisation mask
  • Neck support/ vacuum bag
  • Knee supports
  • Ankle supports
  
Organ pre-requisites
  • N/A
  
Contrast
  • N/A
  
Radiopaque markers
  • N/A
  
Bolus
  • Consider bolus

Consider use of bolus for anteriorly placed tumours (involving the anterior commissure) or if anatomy requires.
Other imaging
  • N/A
  
CT acquisition
  • 3D CT

≤3mm CT slice thickness.
Scan from the hard palate to manubriosternal joint.
Medications
  • N/A
  

Tis - T1N0

3DCRT/IMRT/VMAT
Phase Target area Dose prescription Prescription point Beam type Beam Energy Dose/# Fractions Scheduling
#/day #/fortnight
1 Larynx 63Gyr ICRU 50/83 Photons 4-6MV 2.25Gy 28 1 10
OR
1 Larynx 60Gyr ICRU 50/83 Photons 4-6MV 2.4Gy 25 1 10

T2N0

3DCRT/IMRT/VMAT
Phase Target area Dose prescription Prescription point Beam type Beam Energy Dose/# Fractions Scheduling
#/day #/fortnight
1 Larynx 66-70Gyrr ICRU 50/83 Photons 4-6MV 2Gy 33-35 1 6#/week (overall time 5-6 weeks)
OR
1 Larynx 65.25Gyr ICRU 50/83 Photons 4-6MV 2.25Gy 29 1 10

Prescription notes

  • Other schedules  may be considered including:
    • 64-68Gy in 32-34 fractionsr
    • 55Gy in 20 fractionsr
    • 66Gy in 30 fractions (2.2Gy/fraction) to 70Gy in 35 fractions (2.0Gy/fraction) (5 fractions per week in 6-7 weeks)r
  • These patients should be compensated for non-treatment days, i.e. public holidays or service days, as even short delays can be deleterious r
3DCRT/IMRT
GTV
  • Gross disease.
CTV
  • Entire larynx at level of GTV and 0.5-1cm superiorly and inferiorly.
PTV
  • CTV + 0.5-1cm margin as per department protocol.

2D traditional field borders for Tis/T1/T2: Link to 2D borders and lateral larynx DRR 

Margin ranges have been agreed by the Radiation Oncology reference committee and reflect safe clinical practice.

Target volume notes

  • The reduced PTV margins for 3DCRT/IMRT reflect the technological advancements and associated improved accuracy in in the conformal era. Whilst contouring is recommended, traditional field borders are still in place to account for organ motion (i.e. swallowing).
Modality Frequency Match point
  • kV/MV planar OR
  • Cone beam CT 
  • Daily
  • Bone
  • Check soft tissue alignment

Target verification recommendations reflect the minimum imaging required for the safe delivery this protocol.

Target verification notes

  • Departments should have a system in place to monitor change in patient contour due to weight loss or tumour shrinkage. For example, regular CBCT or repeat planning CT may be performed to check dose distribution. Repeat simulation and planning may be required if changes are not within departmental tolerances.
  • Consideration should be given to dose delivered from verification imaging and whether this needs to be accounted for in treatment planning, particularly with respect to critical OARs.

The side effects listed below are not a complete list of all possible side effects for this treatment and should only be used as a guide.

Acute: Short term side effects during or within a few weeks post radiotherapy (usually temporary)
Skin reaction / dermatitis

Including itch, erythema, dry or moist desquamation.

Read more about skin reactions
Mucositis

Read more about mucositis 
Fatigue

Read more about fatigue
Odynophagia
Dysphagia
Dysphonia
Cough
Stridor

An abnormal wheezing or high-pitched sound caused by an obstructed airway.

Late: Long term side effects - months post radiotherapy (may be permanent)
Skin changes

Including telangiectasia, atrophy and changes to skin pigmentation.
Dysphonia
Dysphagia

Including long-term feeding tube.
Carotid atherosclerosis
Hypothyroidism
Laryngeal necrosis and dysfunction
Soft tissue fibrosis and cramping
Second malignancy
Source Study & year published

Supports use

Yes/No/NA

 Is the radiation dose and fractionation consistent with  the protocol? Comments
Phase III trials

Yamazaki et al. 2006r

 Yes Yes

RCT - T1 only
RT Dose: CFX (60–66Gy in 30–33fx) vs HFX (56.25Gy in 25fx) or HFX (63Gy in 28fx)

Overgaard et al. 2003 (DAHANCA 6 & 7)r

 Yes Yes

RCT
5 vs 6 fx per week
Total dose: 66-68Gy in 33-34fx

Aaltonen et al. 2014r

 Yes Yes

RCT Laser vs RT (n= 60)
Overall voice quality similar in both arms.

Moon et al. 2014 (KROG 0201)r

 Yes Yes

CFX vs HFX - T1-2 (n = 156)
Closed early due to poor accrual
T1: CFX (66Gy in 33fx) vs HFX (63Gy in 28fx)
T2: CFX (70Gy in 35fx)  vs HFX (67.5Gy in 30fx)
HFX at least not inferior to CFX
Guidelines Date published/revised

Supports use

Yes/No/NA

 Is the radiation dose and fractionation consistent with  the protocol? Comments
Cancer Care Ontario 2009r Yes N/A  
Dutch National Guidelines 2002r Yes Yes

T1N0: 60Gy/25fx
T2N0: 70Gy/35fx or 68-70Gy/5.5 weeks if impaired vocal cord mobility
Royal College of Radiologists 2016r Yes Yes

T1/T2N0: 63Gy/28fx
NCCN 2017r Yes Yes

T1N0: 63Gy/28fx or 66Gy/33fx
T2N0: 65.25Gy/29fx or 70Gy/35fx

 

Efficacy

Radiotherapy alone vs surgery

For early-stage glottic laryngeal carcinomas surgery or RT have similar effectiveness. A number of systematic reviews of non-RCTs have shown endolaryngeal surgery (with or without laser) can provide similar voice and laryngeal function preservation and survival rates when compared to RT alone.rrr

Hypofractionation vs. standard fractionation

The ultimate goal in treating early glottic carcinoma is cure of the tumour, while preserving organ function, allowing the best voice quality possible, and without serious side effects. Dose per fraction and overall treatment time have been identified as factors that contribute to locoregional control.rr  Numerous studies have shown a locoregional control advantage for hypofractionated radiotherapy schedules when treating early stage glottic carcinoma, as compared to standard 2Gy per fraction daily treatments without an increase in serious complications.rrrrr Therefore the use of hypofractionated protocols over conventional schedules is considered standard of care.

The Japanese RCT reported significantly improved local control with hypofractionated radiotherapy (56.25-63Gy in 2.25Gy fractions) compared with 60-66Gy in 2Gy fractions.r In this trial, 180 patients with T1 glottic cancer, treated from 1993 to 2001, were randomised to either conventional or hypofractionated schedules. The dose prescribed for each schedule was dependent on the size of the tumour (in the hypofractionated arm 56.25Gy was prescribed if the tumour was </=2/3rds in length of the ipsilateral or bilateral vocal cords, vs 63Gy if the tumour occupied >2/3rds of the vocal cord). The 5 year local control was 77% vs 92% in the conventional and hypofractionated arms, respectively (p<0.004).

The DAHANCA group also reported improvement in 5 year locoregional control with an accelerated fractionated schedule.r 1476 patients were randomised to either 5 or 6 fractions of radiotherapy per week with the same total dose. The total dose delivered was 66-68Gy in 33-34 fractions, except for well-differentiated T1 glottic tumours which were treated with 62Gy. Of these patients 47% had laryngeal cancer, and 29% of patients overall had Stage I disease. Individual figures for LRC for early stage glottic cancer were not reported, but overall LRC improved from 60 to 70% (p=0.0005) in favour of the 6 fraction per week arm. There was no significant difference in overall survival. Disease-specific survival was 73% vs 66% for six and five fractions, respectively (p=0.01).

Toxicity

  • Several studies comparing conventional and hypofractionated dose schedules have reported similar outcomes for late normal tissue morbidity.rrr
  • In a large series reported by Chera et al. (n=585) there was a low rate (1.7%) of severe acute or late complications.r
  • The Japanese RCT by Yamazaki et al in 2006 demonstrated no statistically significant difference in acute skin/mucosal reactions or late toxicity between the conventional and hypofractionated dose schedules.r With a median follow-up of 64 months, no severe late complications were observed.

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The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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15 Dec 2018