CME International Journal of

Radiation Oncology
biology physics

www.redjournal.org

Critical Review

Palliative Radiation Therapy for Head and Neck

Cancers
Amardeep S. Grewal, MD, Joshua Jones, MD, and Alexander Lin, MD
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania

Received Jan 14, 2019. Accepted for publication May 13, 2019.

Patients with advanced head and neck cancers who are not eligible for curative treatment represent a challenging cohort of
patients to manage given the complexity and severity of their presenting symptoms. Palliative radiation therapy, along with
other systemic and surgical measures, has the potential to significantly improve the quality of life of such patients. There is
little high-level evidence and a lack of consensus to direct the selection of an optimal palliative radiation regimen.
An ideal palliative radiation regimen should alleviate symptoms secondary to the cancer with minimal treatment toxicity
and side effects while improving a patient’s quality of life. This review presents the treatment approaches, outcomes, and
toxicities associated with different radiation regimens and proposes a multidisciplinary framework for the selection of an
individualized treatment regimen for patients that centers around patient prognosis, goals of care, logistics of treatment, and
the availability of other surgical and systemic therapies. Ó 2019 Elsevier Inc. All rights reserved.

Introduction directed therapy is thought to be associated with signifi-

cant treatment-related toxicity, including the burden
of daily treatments over many weeks. Such toxicity nega-
Head and neck cancers represent the sixth most common
tively affects the health and quality of life of these
cancer worldwide, with approximately 630,000 new pa-
patients and outweighs the benefit of potentially curative
tients receiving diagnoses annually.1 Although many ad-
therapy.
vances within the field of head and neck cancer have
improved curative-intent treatment, a lack of universal Supportive care measures used in patients with head
and neck cancer focus on managing the disease-associated
guidelines remains for palliative treatment. Disease- and
symptoms, including pain, dysphagia, dyspnea, bleeding,
health-related factors associated with the delivery of
and ulceration. Given the critical importance of the tissues
palliative-intent treatment include the presence of distant
of the head and neck to basic life function, such symptoms
metastatic disease at the time of initial presentation, very
significantly affect quality of life. Pain management with
advanced locoregional disease, prior extensive surgery
medications, anticholinergic blockade of secretions, tra-
or radiation therapy to the head and neck, patient comor-
cheostomy for airway protection, and feeding tube
bidities and poor performance status precluding tolerance
of curative-intent therapy, and patient choice. In such placement for nutritional supplementation represent some
of the common forms of care provided. For more symp-
patients, definitive, curative-intent treatment with cancer-
tomatic patients, palliative surgery or embolization

NotedAn online CME test for this article can be taken at https:// financial support for this work that could have influenced its outcome. We
academy.astro.org. confirm that the manuscript has been read and approved by all named
Corresponding author: Alexander Lin, MD; E-mail: alexander.lin@ authors and that there are no other persons who satisfied the criteria for
uphs.upenn.edu authorship but are not listed. We further confirm that the order of authors
Disclosures: We wish to confirm that there are no known conflicts of listed in the manuscript has been approved by all of us.
interest associated with this publication and there has been no significant

Int J Radiation Oncol Biol Phys, Vol. 105, No. 2, pp. 254e266, 2019
0360-3016/$ - see front matter Ó 2019 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ijrobp.2019.05.024
Volume 105  Number 2  2019 Palliative radiation therapy for head and neck cancers 255

Table 1 Studies of palliative radiation therapy for H&N cancers, organized chronologically by year published
Fx
Treatment size, BED, EQD2, Median
Study Type of study n Population regimen Gy Modality Gyy Gyy Response Rate OS, mo* Toxicity
Paris Prospective 37 27% stage 3 cycles of 14.8 3.7 2D 61 51 28% CR; 49% PR; 3 d
et al9 IVC; 63% Gy/4 fx, bid over 85% subjective
inoperable 2 d, with a 3- to palliative
4-wk break response
between cycles
Minatel Prospective 62 16% recurrent; 2 cycles of 25 2.5 2D 63 52 28% CR; 41% PR; 7 43% G3
et al30 74% stage IV Gy/10 fx, 81% symptom mucositis, 3%
with a 2-wk palliation G3 dyphagia
midtreatment
break; concurrent
bleomycin
Mohanti Retrospective 505 78% stage 20 Gy/5 fx in 1 wk 4 2D 28 23 37% PR; 6.7 100% patchy
et al22 IVA; 22% 47-59% mucositis at
stage IVB symptom 1-mo
response rate follow-up
Ghoshal. Prospective 25 72% stage IV 30 Gy/10 fx 3 2D 39 33 100% with >50% d 32% G2
et al24 in 2 wks patient reported mucositis
pain relief
at 4 wks
Corry Prospective 30 35% stage 3 cycles of 14 3.5 3D 57 47 6% CR; 47% PR; 5.7 33% G1; 11%
et al10 I-III; 65% Gy/4 fx, bid 44% improved G2, 0% G3
stage IV over 2 d, with QOL mucositis
a 4-wk break
between
cycles
Carrascoca Retrospective 7 14% stage III; 3 cycles of 14.8 3.7 2D 61 51 14% CR; 71% PR 4 14% G3
et al17 86% stage IV Gy/4 fx, bid over mucositis
2 d, with a 3- to
4-wk break
between cycles.
(þchemotherapy)
Porceddu Prospective 35 35% stage I-III; 30 Gy/5 fx, twice 6 d 48 40 56% CR and 9% 6.1 26% G3
et al18 65% stage IV weekly PR for primary mucositis;
and 44% CR 11% G3
and 19% PR dysphagia
for nodes; 62%
QOL and 67%
pain
improvement
Agarwal. Retrospective 110 78% T4 40 Gy/16 fx 2.5 2D 50 42 10% CR; 63% PR 12 (55% 14% G3 dermatitis,
et al28 PFS) 3% G4, 63% G3
mucositis
Al-mamgani Prospective 158 81% stage IV 50 Gy/16 fx 3.125 2D 65 54 45% CR; 28% PR 17 45% and 65% G3
et al29 þ dermatitis and
mucositis
Siddiqui Retrospective 44 48% recurrent; 13-18 Gy/1 fx or 6-18 SBRT 30-86 25-72 7% CR; 80% PR 5.6 (stage G4 mucositis,
et al33 23% stage 36-48 Gy/5-8 fx in patients with IVC) dysphagia,
I-IVB; 30% stage IVC EC fisutla,
stage IVC disease OC fistula
Ali et al25 Prospective 30 70% stage IV 30 Gy/10 fx 3 2D 39 33 26% CR; 47% PR Not 37% G2
in 2 wks reported mucositis
Kancherla Retrospective 33 91% stage 2 cycles of 20 4 3D 56 47 39%CR; 33% PR, 12 (42% OS) 6% and 9% G3
et al26 IVA-IVB Gy/5 fx, with 79% symptom mucositis and
a 2-wk break palliation esophagitis,
between cycles 18% IH*
Paliwal Retrospective 50 All patients 20 Gy/5 fx in 1 wk 4 2D 28 23 8% CR; 92% PR; d 4% G3 mucositis
et al23 with fixed 60-70%
nodes, symptom
stage IV; palliation
46% T4
Kawaguchi Retrospective 14 7% N1; 0% 35-42 Gy/3-5 fx d SBRT d d 36% CR; 64% PR 3 year OS: 100% G1/2
et al32 stage IV 79% oropharyngitis
(continued on next page)
256 Grewal et al. International Journal of Radiation Oncology  Biology  Physics

Table 1 (continued )
Fx
Treatment size, BED, EQD2, Median
Study Type of study n Population regimen Gy Modality Gyy Gyy Response Rate OS, mo* Toxicity
13
Lok et al Retrospective 75 55% stage IVC 3 cycles of 14.8 3.7 3D/ 61 51 66% subjective 5.7 5% G3 mucositis/
Gy/4 fx, bid IMRT pain response dermatitis
over 2 d, with
3- to 4-wk break
between cycles
Nguyen Retrospective 110 62% stage IV 24 Gy/3 fx, 1 8 3D/ 43 36 31% CR; 50% PR; 6.2 3 inpatient
et al20 fraction/wk IMRT 82% symptom hospitalizations
palliation
Khan Retrospective 21 81% de novo 35 Gy/5 7-8 SBRT 60-86 50-72 25% CR; 67% PR 12 (60% OS) d
et al34 primary fx to 48
H&N Gy/6 fx
cancers,
19%
recurrent
Fortin Prospective 32 66% T4, N3, 25 Gy/5 fx 5 IMRT 38 31 3- and 6-mo 6.5 13% G3 toxicity
et al21 or M1 in 1 wk improvement
in QOL: 59%
and 58%; pain
response: 71%
and 83%;
Murthy Prospective 126 70.6% stage 32 Gy/8 fx, 4 d 45 Gy 37 Gy 3.2% CR and 41% 5.5 1.2% G3
et al19 IVB twice weekly PR for mucositis
primary and
3.2% CR
and 62% PR for
nodes;
76% subjective
pain
improvement
Bledsoe Retrospective 65 15% stage III; 60 Gy/20 fx or 72 3 3D/ 78/94 65/78 50% CR, 41% PR 8.9 42% feeding
et al31 56% stage Gy/24 fx with IMRT among tube
IVA/IVB; 4- to 6-wk non-stage requirement
14% stage midtreatment IVC patients
IVC break
Gamez Retrospective 21 19% recurrent; 3 cycles of 14.8 3.7 3D/ 61 51 24% CR; 62% PR; 7 34.8% G2
et al16 52% stage Gy/4 fx, bid IMRT >76% symptom mucositis/
III-IVB; over 2 d, with palliation xerostomia
29% Stage a 3- to 4-wk
IVC break between
cycles.
(þchemotherapy)
Abbreviations: 2D Z 2-dimensional; 3D Z 3-dimensional; BED Z biologically effective dose; CR Z complete response; EC Z enterocutaneous;
EQD2 Z equivalent dose in 2 Gy; H&N Z head and neck; IMRT Z intensity modulated radiation therapy; OC Z oral cutaneous; OS Z overall survival;
QOL Z quality of life; PFS Z progression-free survival; PR Z partial response; SBRT Z stereotactic body radiation therapy.
* Other survival data reported in studies in which median OS is not reported.
y
For a/b Z 10 (tumor).

of bleeding vessels can also be performed.2,3 Multidisci- cancer-directed therapy with radiation therapy. The goal
plinary management of the supportive care these patients of a palliative treatment is to alleviate symptoms sec-
receive remains essential. Best supportive care is associ- ondary to the cancer with minimal treatment toxicity and
ated with a median survival of between 3 to 5 month- side effects.
sdshorter for patients who have received prior therapy.4
The use of palliative systemic therapy has the potential
to improve survival over supportive care alone, as Palliative radiation therapy
demonstrated by the median survival of 10.1 months with
the EXTREME regimen (cisplatin/carboplatin, 5- There have been many studies on the use of radiation
fluorouracil, and cetuximab) and of 14.9 months with therapy to mitigate disease-related symptoms and to
Pembrolizumab.5,6 improve patients’ speech, swallowing, breathing, and pain
A subset of patients not eligible for radical curative- and to mitigate ongoing bleeding and tumor ulceration.
intent therapy may still be candidates for palliative Although such studies advocate for the use of radiation
Volume 105  Number 2  2019 Palliative radiation therapy for head and neck cancers 257

therapy in the palliative setting, there is little high-level cells to repopulate before the next cycle. In addition, this
evidence to direct the selection of an optimal palliative regimen allows patients to complete all radiation for 1 cycle
radiation regimen. within 2 days, limiting the travel burden and time required
Curative-intent radiation therapy is delivered with doses in a health care facility for palliative treatment.
from 6000 to 7000 cGy divided into 180 to 200 cGy frac- The regimen was first studied in the head and neck
tions and is often delivered with concurrent chemotherapy. setting by Paris et al in 37 patients with head and neck
Such regimens, although curative, are often highly toxic.7 cancer.9 Patients included were medically inoperable, failed
Common side effects of treatment that are secondary to chemotherapy, or had metastatic disease. Twenty-one pa-
radiation damage to normal soft tissues include mucositis, tients completed all 3 cycles of radiation. An objective
dysphagia, xerostomia, dysgeusia, and radiation dermatitis. response rate of 77% was seen, with an improvement seen
Many palliative regimens aim to reduce the dose of radia- in those who completed more cycles. Average survival after
tion administered to below the threshold for producing therapy was 4.5 months. The majority of patients (85%)
severe side effects to optimize the balance between risk and endorsed subjective improvement in presenting symptoms.
benefit when cure is not the goal. Maintaining the delicate No major toxicities were seen, and expected side effects
balance of providing a sufficient dose for durable local including skin changes, dysphagia, and xerostomia peaked
control without causing significant morbidity is funda- 12 days after completion of each cycle. No late complica-
mental to the selection of each treatment regimen. tions were observed.
A similar QUAD shot approach was used by Corry
Overview of Palliative Regimens et al.10 In this study of 30 patients, 1400 cGy was admin-
istered over 2 days in twice-daily fractions. Patients
received up to 2 additional cycles if they demonstrated no
The treatment of head and neck cancers with palliative
tumor progression at the time of follow-up. All but 1 patient
radiation therapy has been studied in retrospective institu-
had metastatic disease, and two-thirds of the patients had an
tional studies and small phase 2 trials, as seen in Table 1.
Eastern Cooperative Oncology Group performance status
The treatment schedules used in these studies range from
of 2 to 3 at baseline. Fifty-three percent of patients
short courses with simple techniques to stereotactic radia-
completed all 3 cycles, and 50% of all patients had an
tion to conventionally fractionated, standard-length cour-
objective response. Median overall survival was 5.7
ses. Treatment durations range from 1 to 7 weeks, with
months, and 44% of patients endorsed improved quality of
many regimens including predetermined breaks between
life after completion of therapy. Patients also endorsed
cycles of radiation. Some regimens include the use of
improvements in dysphagia (33%) and pain (56%). No
chemotherapy. Treatment response rates, changes in quality
patients developed grade 3 toxicities, and the most common
of life, and toxicity profiles vary significantly based on
grade 1 and 2 toxicities were dermatitis (52%) and muco-
treatment regimen. We reviewed the literature to identify
sitis (67%). Similarly, low rates of grade 3 toxicities using
evidence to guide the development of a patient-centric
the QUAD shot approach have been shown in other retro-
framework for selection of an optimal regimen for the
spective analyses.11,12
palliative treatment of head and neck cancers. PubMed,
The significance of completing more cycles of the
EMBASE, MEDLINE, and Cochrane Library databases
QUAD shot regimen was reported by Lok et al in the
were searched for published studies on palliative radiation
largest retrospective study using QUAD shot.13 The study
for head and neck cancers from 1993 to 2018.
included 75 patients with pain, dysphagia, and bleeding
secondary to head and neck cancer, 40% of whom had prior
QUAD Shot radiation at the site of palliation. Thirty-seven percent of
patients completed at least 3 cycles of 1480 cGy, and some
One popular approach in the palliative treatment of head patients who tolerated and continued to respond to therapy
and neck cancers in North America is the “QUAD shot” received 5 cycles. Palliative response was significantly
regimen. This approach was introduced in the palliation of correlated with increasing number of cycles but not with
pelvic malignancies in RTOG 8502.8 The regimen consists prior radiation, chemotherapy, surgery, or disease stage.
of 370 cGy delivered twice daily for 2 consecutive days Palliative response was seen in 65% of patients, and median
(total of 1480c Gy/cycle), repeated every 3 to 4 weeks for a overall survival was 5.7 months. Grade 3 dermatitis and
total of 4400 cGy in 3 cycles. For patients who tolerate the functional mucositis were reported in 4 patients.
cycles well and who continue to respond, more than 3 cy- The properties of protons allow for significant dose
cles can be delivered. The cyclic nature of the regimen sparing of neighboring tissues and organs at risk and have
allows for disease response assessment after each course, at been studied in cases of head and neck reirradiation.14
which time a decision is made regarding whether to pro- Proton therapy has been used to deliver the QUAD shot
ceed with another course. The biologically equivalent dose regimen in a cohort of 26 patients, as described by Ma
administered in QUAD shot is below the threshold for et al.15 Eighty-eight percent of these patients had prior head
producing mucositis, and the separation between subse- and neck radiation. Overall palliative response was 73%,
quent cycles of radiation allows for depleted mucosal stem and the grade 1 acute toxicity rate was 58%.
258 Grewal et al. International Journal of Radiation Oncology  Biology  Physics

Addition of Concurrent Chemotherapy to QUAD 24 Gy in 3 Fractions

Shot
Higher-dose-per-fraction hypofractionated regimens have
There have been efforts to formally determine the response been studied in larger retrospective studies. The “0-7-21”
of radiosensitizing chemotherapy combined with the regimen from Canada delivered 24 Gy in 3 weekly fractions
QUAD shot regimen. Gamez et al similarly demonstrated and was studied in 110 patients, the majority of whom had
the tolerance of concurrent chemotherapy in a retrospective stage IV disease.20 This approach yielded high response
study of 21 patients with metastatic or recurrent head and rates of 82% and 81% for symptoms and tumor size,
neck cancer.16 The 2 most common indications for treat- respectively. However, toxicities from this regimen were
ment in this cohort were pain and dysphagia. All patients not reported.
received at least 1 cycle of QUAD shot radiation therapy
with carboplatin (AUC Z 2) or cetuximab 250 mg/m2 20-25 Gy in 5 Fractions
before each radiation cycle. Seventy-six percent of patients
completed all 3 cycles of radiation. Objective response was Short-course daily radiation regimens have been proposed and
high (85.7%), and the majority of complete responders described in studies, including a phase 2 trial by Fortin et al.21
(80%) completed all 3 cycles of radiation. Patients who In their study of 32 patients with advanced head and neck
completed all 3 cycles of radiation also had a 100% rate of cancer, patients received 2500 cGy in 5 fractions over the
presenting symptom resolution. Treatment was well toler- course of 1 week. Patients were treated with intensity modu-
ated with no grade 3 acute toxicities. All patients had at lated radiation therapy (IMRT), and the majority of patients
least a grade 1 toxicity, distributed among dermatitis, expressed improvement in global quality of life, physical
mucositis, and xerostomia. Thirty-five percent of patients functioning, swallowing, and pain compared with baseline.
had acute grade 2 toxicities, split between mucositis and Thirteen percent of patients experienced a grade 3 toxicity.
xerostomia. Two cases of late grade 2 xerostomia and Mohanti et al described a similar weeklong treatment in
dysgeusia were reported. Carrascosa et al similarly showed a large retrospective study of 505 patients.22 Patients were
a high response rate (95%) in 7 patients with head and neck treated with 2000 cGy in 5 fractions. Compared with Fortin
cancer treated with QUAD shot and concurrent paclitaxel et al, this regimen showed a lower objective response rate at
60 mg/m2.17 37% and a symptom response rate of 50%. In addition, all
patients in this cohort experienced patchy mucositis when
examined 1 month posttreatment. Paliwal et al used this
30-32 Gy in 5-8 Fractions same regimen of 2000 cGy in 5 fractions in a 50-patient
retrospective study.23
The “Hypo Trial” conducted by Porceddu et al was a
prospective multicenter trial of a hypofractionated pallia- 30 Gy in 10 Fractions
tive regimen for head and neck cancers in which patients
were given 3000 cGy in 5 fractions, with 2 fractions
Ghoshal et al studied a more conventional palliative
administered at least 3 days apart weekly.18 Of the 37 pa-
regimen of 3000 cGy in 10 fractions.24 Seventy-two percent
tients enrolled in the study, the majority (51%) had a World
of the 25 patients in this study had metastatic disease, with
Health Organization performance status of 1. The most
pain and dysphagia as the main indications for delivery of
common presenting symptom was dysphagia, seen in 18 of
palliative-intent radiation therapy. After treatment, symp-
39 patients. Overall, 80% of patients had an objective
toms were relieved by at least 50% for 90% of patients. All
response after treatment. Median survival was 6.1 months.
patients had either grade 1 or 2 mucositis after treatment.
Grade 3 mucositis was observed in 26% of patients, and
Ali et al reported similar outcomes with the regimen of
11% of patients experienced grade 3 dermatitis and
3000 cGy in 10 fractions in a prospective study of 30 pa-
dysphagia. Two patients had grade 4 dysphagia. Late grade
tients with symptomatic disease.25 All patients had >50%
3 toxicities of skin, mucosa, fibrosis, and xerostomia (all
pain relief and improvement in baseline dyspnea. A similar
n Z 1) were also observed in this cohort.
toxicity profile was also observed, with all patients having
Murthy et al studied a regimen with similar biological
grade 1 or 2 mucositis. Twenty-seven percent of patients in
dose equivalency and biweekly administration.19 Their
the cohort went on to receive further radiation in 200-cGy
regimen of 3200 cGy with 400 cGy fractions given twice a
fractions to a cumulative biologically effective dose of
week had a treatment completion rate of 74% in their
6600 cGy.
prospective study of 126 patients. Forty-two percent of
patients had a response at the primary site of disease, and
three-quarters of patients endorsed improvement in pain 40 Gy in 10 Fractions
from baseline. Only 1 case of grade 3 mucositis was re-
ported, and no long-term follow-up was reported owing to Two radiation regimens of 4000 cGy delivered over 10
significant travel burden for the majority of patients. fractions have been studied, each with slight variations in
Volume 105  Number 2  2019 Palliative radiation therapy for head and neck cancers 259

the design of treatment delivery. The first, studied by 3 weeks of treatment. Objective and symptom response
Kancherla et al, administered 2000 cGy over 5 days, fol- rate were high at 69% and 81%; however, toxicity levels
lowed by a 2-week break and then a second cycle of 2000 were on par with rates associated with curative intent
cGy in 1 week.26 There was a 72% objective response rate therapy, with 43% of all patients experiencing grade 3
and a 79% symptom response rate at 4 to 6 weeks after mucositis.
treatment completion among the 33 patients in this cohort. A similar high-dose, split-course accelerated hypo-
One- and 2-year overall survival were 42% and 35%, fractionated regimen was studied by Bledsoe et al.31 This
respectively. Grade 3 skin toxicity, mucositis, and esopha- approach used a regimen in which 6000 cGy to 7200 cGy
gitis were seen in 3%, 6%, and 9% of patients, respectively, was given in 20 to 24 fractions with a midtreatment 4- to
and 20% of all patients required hospitalization for toxicity 6-week break. The majority of the 65 patients had a
management. Karnofsky performance score of greater than 70 (74%).
Das et al prospectively studied 36 patients with stage IV Eleven percent of patients were unable to complete both
or recurrent head and neck cancer.27 Patients received 4000 courses of treatment owing to disease progression, patient
cGy in 10 fractions, with 2 fractions given each week. Sixty decline, or patient refusal. Ninety-one percent of evalu-
percent of patients had an improvement in performance able patients had an objective response at 3-month
status after treatments, and 88% of patients endorsed pain follow-up, and approximately 35% of patients
relief greater than 50%. No significant changes were noted continued to have local control at 4-year follow-up.
in head and neckespecific quality-of-life scores after Forty-two percent of patients required a feeding tube at
treatment. Similar to the toxicity profile seen by Kancherla some point during treatment secondary to mucositis and
et al, 21% of patients experienced grade 3 mucositis or dysphagia, and 20% of patients remained on tube feeds at
dermatitis. Forty-eight percent of patients were recom- their last follow-up. One patient developed late mucosal
mended a nasogastric tube during treatment owing to ulceration and necrosis 1.5 years after the completion of
oropharyngeal odynophagia. In an effort to reduce such treatment.
early mucosal toxicity, groups have studied the use of
smaller fractions with similar cumulative doses.28,29

40-50 Gy in 16 Fractions Stereotactic Body Radiation Therapy

In recent years, growing literature has emerged on the use

The Tata Group has reported on the delivery of 4000 cGy in
of stereotactic body radiation therapy (SBRT) for the
250-cGy fractions to 110 patients with incurable disease
treatment of recurrent head and neck cancers given the
and limited life expectancy.28 The most common baseline
severe toxicity profile associated with conventionally frac-
symptoms in this cohort were pain (99%) and dysphagia
tionated radiation therapy. There remain few studies
(88%). Seventy-three percent of patients had an objective
investigating the role of SBRT in patients with untreated
response, and 74% of patients had >50% symptom relief.
primary head and neck cancers who are unable to tolerate
With the use of smaller fractions of radiation, 63% and 3%
standard curative treatment. The few studies published
of patients still developed grade 3 and grade 4 mucositis,
consist of asymptomatic patients with early-stage disease
respectively.
who are treated to provide local control rather than symp-
A higher dose per fraction of 312.5 cGy was used in the
tom palliation. A retrospective series from Japan showed
“Christie scheme,” in which patients were treated to a cu-
local control of 71% and overall survival of 79% in a cohort
mulative dose of 5000 cGy.29 A 73% response rate was
of 14 elderly patients treated with 3500 to 4200 cGy in 3 to
seen in the cohort of 158 patients unsuitable for curative
5 fractions.32 All patients had an objective response. These
treatment. Seventy-seven percent of the 62 patients sur-
patients all had nonmetastatic disease, and only 1 patient
viving past 1 year had pain relief, and 47% of such patients
had N1 nodal involvement.
had improvement in their performance status. Grade 3 skin
Similarly, Siddiqui et al used SBRT to treat 10 patients
and mucosal toxicities were seen in 45% and 65% of pa-
with primary head and neck cancer with 1300 to 1800 cGy
tients, respectively, with severe late toxicity seen in 5% of
in a single fraction or 3600 to 4800 cGy in 5 to 8 frac-
patients.
tions.33 Median overall survival was 29 months for these
patients. A number of patients treated with SBRT devel-
Higher-Dose (50-72 Gy) Regimens oped grade 4 toxicities including mucositis, dysphagia,
esophagocutaneous and orocutaneous fistulas, and osteo-
Higher cumulative dose palliative regimens administered necrosis. Khan et al similarly showed high response rates in
in small fraction sizes have been studied in patients with a cohort of 21 patients receiving SBRT for de novo head
good performance status but are not amenable to curative and neck cancers.34 No toxicity data was reported in their
intent therapy. Minatel et al treated 58 patients with 5000 cohort of patients treated with SBRT.
cGy in 20 fractions with a 2-week break after the first In the setting of reirradiation, a multi-institutional re-
2500 cGy.30 Patients received bleomycin during the first view of SBRT for recurrent or second primary head and
260 Grewal et al. International Journal of Radiation Oncology  Biology  Physics

neck cancers showed a 2-year overall survival rate of 16.3% expression levels greater than 50%. Similarly, nivolumab
for patients.35 was shown to improve overall survival (median overall sur-
vival 7.7 vs 5.1 months) in CheckMate-141, a phase 3 trial
comparing nivolumab to a single-agent investigator’s choice
Comparative Studies of Palliative Radiation of second-line therapy (methotrexate, docetaxel, or cetux-
Regimens imab). Post hoc exploratory analyses from Checkmate-141
indicated significantly increased overall survival in patients
In examining the comparisons among these distinct with human papillomavirus (HPV)-positive tumors treated
palliative regimens, 2 single-institutional studies have with nivolumab (median overall survival of 9.1 vs 4.4
highlighted differences between response and toxicity months), and PD-L1 expression greater than 1%. Both trials
based on fractionation scheme. Chen et al reviewed 60 showed reduced toxicity of immunotherapy over conven-
patients treated with palliative intent for incurable and tional systemic therapy in the second-line recurrent or met-
recurrent head and neck cancers.5 The regimens used to astatic setting. Based off these promising results,
treat patients included QUAD shot, 7000 cGy in 35 pembrolizumab was moved to the frontline recurrent or
fractions, 3000 cGy in 10 fractions, 3750 cGy in 15 metastatic setting and compared with the EXTREME
fractions, and 2000 cGy in 5 fractions. Rates of palli- regimen (cisplatin or carboplatin, 5-fluorouracil, and cetux-
ative response for these regimens were 83%, 77%, imab) in KEYNOTE-048.6 Initial results from KEYNOTE-
67%, 86%, and 60%, respectively. Although these 048 showed single-agent pembrolizumab prolonging
regimens yielded similarly high response rates, the survival in patients with a PD-L1 combined positive score of
toxicity profiles varied significantly, with 9% grade 3 greater than 1 (median overall survival 12.3 vs 10.3 months)
toxicity in the QUAD shotetreated patients compared and 20 (14.9 vs 10.7 months). Pembrolizumab was associated
with 38%, 42%, 29%, and 20% in patients treated with with fewer grade 3 to 5 adverse events compared with the
7000 cGy in 35 fractions, 3000 cGy in 10 fractions, EXTREME regimen (17% vs 69%) and more durable re-
3750 cGy in 15 fractions, and 2000 cGy in 5 fractions, sponses (median 20.9 vs 4.5 months).
respectively. Patients receiving palliative radiation therapy for head
Stevens et al compared outcomes of 148 patients treated and neck cancer may also be candidates for immuno-
with palliative radiation therapy.36 The most common ra- therapy. Although there remains a relative paucity of data
diation schedule was 5000 cGy in 20 fractions; however, investigating immunotherapy with palliative radiation
other patients received 2400 cGy in 3 fractions, 6000 cGy therapy, the administration of concurrent and adjuvant
in 25 fractions, 3000 cGy in 10 fractions, 6000 cGy in 30 immunotherapy with radiation therapy was studied in
fractions, and 7000 cGy in 35 fractions. Radiation regimens RTOG 3504, in which nivolumab was deemed to be safe to
were prescribed based on provider judgment of patient administer with concomitant cetuximab and radiation
tolerability. Only 58% of patients scheduled to receive 7000 therapy.39 Pembrolizumab has also been shown to be safe to
cGy in 35 fractions were able to complete this course. On administer with concurrent radiation and cisplatin (40 mg/
multivariate analysis, radiation dose was found to be an m2) in patients with both HPV-positive and HPV-negative
independent predictor of treatment response and survival. head and neck cancers.40
This analysis was unable to capture the reasoning behind
provider dose selection, including judgment of patient
performance status and expected dose tolerance for each
patient at initial consultation. Discussion

Patients with advanced head and neck cancers represent a

Immunotherapy challenging cohort of patients to manage given the
complexity and severity of their presenting symptoms.
Along with the palliative radiation regimens noted earlier, Radiation therapy, along with other measures including
many patients ineligible for definitive concurrent chemo- chemotherapy, palliative care, and interventional proced-
radiation and with metastatic or recurrent head and neck ures have the potential to significantly improve the quality
cancers may be candidates for immunotherapy with or of life of these patients. Although some studies support the
without radiation therapy. The role of immunotherapy in the use of radiation therapy in the palliative setting, no
second-line treatment of metastatic and recurrent head and consensus exists to guide provider selection of appropriate
neck cancers was established in the KEYNOTE-040 and regimens for individual patients. Radiation regimens vary
CheckMate 141 trials.37,38 Pembrolizumab, studied in in treatment length from 3 days to conventional 7-week
KEYNOTE-040, showed a modest improvement in overall courses. Providers often select regimens based off a ho-
survival over standard-of-care second-line systemic therapy listic assessment of a patient. Performance status, comor-
(investigator’s choice of methotrexate, docetaxel, or cetux- bidities, disease burden, risk of acute toxicity, prior
imab), with a median overall survival of 8.4 versus 6.9 treatment, delivery of concurrent systemic therapy, logis-
months. This benefit was most evident in patients with PD-L1 tics regarding the delivery of treatment, and patient goals
Volume 105  Number 2  2019 Palliative radiation therapy for head and neck cancers 261

of care are all important considerations in determining an opportunity for patients with mucosal toxicity to recover
regimen selection. before further insults are caused by additional radiation
therapy. Patients deemed to be unsuitable for additional
Performance status radiation therapy may still benefit from the initial cycle of
treatment, as demonstrated in prior studies.7,11
Patients with a poorer performance status are likely to
have difficulty with protracted courses of radiation ther- Option of nonradiation palliative therapies
apy, which are associated with the burden of daily trips
for treatment. Patients with a poor performance status The discussion of patients in a multidisciplinary environ-
may also suffer more from toxicities from a protracted ment allows for the assessment of whether other non-
and high cumulative dose course of radiation treatment, radiation palliative treatments, such as surgery or systemic
as demonstrated by studies showing high rates of naso- therapy, are options if radiation therapy does not achieve
gastric tube requirement and mucositis in such pa- the desired effect. Patients who are candidates for systemic
tients.24-27 Likewise, concurrent administration of therapy may benefit from shorter courses of radiation
systemic therapy can exacerbate known and introduce therapy so that the toxicities of radiation do not delay the
new toxicities of radiation therapy, making this combi- start of systemic therapy. Patients eligible for immuno-
nation more challenging in patients with poorer perfor- therapy may receive immunotherapy before, during, or after
mance status.12 SBRT in the upfront de novo palliative radiation therapy, as demonstrated by the safety profile of
radiation setting, although an attractive approach for both pembrolizumab and nivolumab with concurrent ther-
treatment given the short treatment course, deserves apy.39,40 There is some suggestion of improved efficacy of
additional investigation regarding safety in this tenuous immunotherapy when administered closely with radiation
population given the high rates of grade 4 toxicities seen therapy.43,44 Those patients without other treatment options
in retrospective studies.29 and with survival anticipated to be many months to a year
may benefit from more protracted courses of radiation that
Patient prognostication provide a higher total dose.

Patient prognosis is another piece of information that pro- Goals of care

viders should consider when selecting dose. Patient prog-
nostication remains a challenge for providers, who often One potential structured approach to elicit patient values
overestimate survival by a factor of 3 of more.41 Different and priorities and determine and personalize treatment
tools, including nomograms, are now available to aid in plans involves asking patients 4 questions: (1) “What are
making prognostication more objective.42 Patient prognosis your most important goals if your health situation
aids in determining the desired duration of palliation from worsens?”; (2) “What do you value most?”; (3) “What
radiation treatment. Patients treated with protracted courses abilities are so critical to your life that you can’t imagine
tend to have more durable responses to treatment, as seen living without them?”; and (4) “If you become sicker, how
by median survivals in the 6- to 17-month range.25-27 These much are you willing to go through for the possibility of
patients are also more likely to experience higher rates of gaining more time?”45 The answers to these questions have
toxicity from treatment; however, with a greater predicted the potential to allow providers to ensure that a shared
longevity, the toxicity may represent an inconvenience decision is made that is concordant with a patient’s outlook
more than a significant detriment in quality of life, as it and goals. Other approaches, including more general con-
may be for patients with limited life expectancy. For pa- versations with patients and their families, may also help
tients with good performance status who are believed to both providers and patients.
have a favorable prognosis (life expectancy >1 year), a
more protracted course of radiation may be beneficial Best practices to consider
because late toxicity may be exacerbated by hypofractio-
nated courses.22,24 As seen in Figure 1, radiation regimen selection for palli-
ation cannot be based on patient prognosis alone. Consid-
Adaptive treatment eration of advanced care planning, goals of care, and an
assessment of other palliative treatment options is para-
A practical feature offered with some palliative regimens is mount to shared decision-making between the patient and
the flexibility offered with cyclic and split courses. Regi- the multidisciplinary care team.
mens with this built-in break, such as QUAD shot or 8 Gy x For patients with symptomatic disease and with poorer
3 delivered weeks apart, allow providers to assess a pa- prognoses of less than 4 months, the QUAD shot regimen,
tient’s response and tolerability to an initial course of ra- 2400 cGy in 3 fractions, or 2000 cGy in 5 fractions allow
diation therapy and determine whether the patient would for symptom palliation, are associated with less severe
benefit from additional treatment. This break also provides treatment toxicities, and reduce travel burden for patients.
262 Grewal et al. International Journal of Radiation Oncology  Biology  Physics

Patient referred for palliative H&N radiotherapy,

deemed not to be a candidate for curative therapy

Assess performance status, comorbidities, cancer stage, burd

burden of metastatic disease (oligometastatic state), tumor
histology, p16 status, prior oncologic therapies

Patient discussion in
multidisciplinary setting (Medical
Oncology, Radiation Oncology,
ENT, Palliative Care, Nutrition, and
Speech-Language Pathologists) Patientt Pro
Prognosis

<4 months 4-12

4 12 m
mo
months
onths >12 mon
months

Option of non- Non -radiation

diatio palliative Range off effective
eff
ffe non- Feww or no non-
Other non -radiation palliative therapies
therapies (surgery, radiation palliative radiation palliative
radiation therapies (surgery, therapies (surgery, (surgery, systemic therapy) may be
systemic therapy) may
palliative be available systemic therapy) systemic therapy) available
therapies

Durable palliation &

Dura Durable palliation
palli & Pursue aggressive
Pur
Comfort, symptom Comfort, symptom comfort, treatment,
Goals of Care Patient does not comfort,
relief, minimize risk relief, minimize risk comfortable with ~4 understands risk of
wish to pursue any comfortable with ~4
and Advanced of new toxicity,
treatment, focused
of new toxicity, weeks of daily RT, weeks of daily RT, short term QOL
reduced travel and reduced travel and
Care Planning# hospital burden on comfort care avoid severe toxicity avoid severe toxicity detriment due to
hospital burden from treatment from treatment treatment toxicity

Hospice
ospic

QUAD
AD Shot
Sh 30-50Gy /5
/5-20
2 fractions 70Gy in 35 fra
fractions SBRT
BRT
Treatment (3.7Gy BID for 2 days) x 3 +/- chemotherapy (Consider in context
Options or 21Gy/3 fractions of reirradiation)
or 20Gy/5 fractions*
+/- chemotherapy **

Fig. 1. Framework incorporating patient prognostication, goals of care, and nonradiation palliative therapy options in
selecting appropriate palliative regimens for patients with head and neck cancers. )Can be explored with 4 questions of
values and priorities. yUseful for short-course palliation for symptoms (ie, bleeding) when patient is eligible for systemic
therapy. zPossible increase in treatment toxicity without a proven benefit. §Only if neighboring organs at risk can allow
additional dose from such a treatment.

Patients with good responses to the initial cycle of QUAD additional treatment-related toxicity might instead benefit
shot should proceed with additional cycles, but patients from the QUAD shot or 2400 cGy in 3 fractions approach.
who experience difficulty with the first cycle can opt to A more protracted regimen of 7000 cGy in 35 fractions
forego additional radiation therapy. These regimens are also may be suitable for patients with a prognosis of greater than
better suited for patients who have difficulty with the 1 year who have goals of care that align with aggressive
positioning required for radiation treatment (ie, difficulty palliation. Although QUAD shot and 3000 Gy in 10 frac-
breathing or severe, difficult-to-control pain while lying flat tions can be used for patients whose goals of care align
in a thermoplastic mask). Longer courses are inappropriate better with such regimens, these regimens are unlikely to
for this cohort of patients because they are likely to cause provide durable responses in patients with better prognoses
greater harm secondary to treatment-related toxicity. and may necessitate additional treatments in the future.
Patients with an intermediate prognosis of 4 to 12 Although high-dose regimens are associated with higher
months who don’t have other treatment options may benefit rates of acute toxicity, concerns of late toxicity are
from a conventional palliative course of 2000 cGy in 5 important to consider when hypofractionation is used in
fractions or a more protracted course of 5000 cGy in 20 this subset of patients. Such regimens should also be
fractions. 2000 cGy in 5 fractions can be used to provide considered for patients with untreated or previously treated
patients with cancer-related symptoms, such as bleeding HPV-positive oropharyngeal cancers and those with oligo-
with palliation, and if they are eligible, can allow them to metastatic disease to address the primary tumor, as dis-
proceed with systemic therapy without a significant delay. cussed below.
Such regimens, when administered without scheduled
treatment breaks, allow patients to complete therapy within
a relatively short period of time and offer tumor and HPV-associated head and neck cancer
symptom responses with less toxicity than higher-dose
regimens. Those patients whose goals of care align with The rise of HPV-associated oropharyngeal cancers has led
treatments that provide comfort with minimal risk of to an increase in the number of patients younger than 60
Volume 105  Number 2  2019 Palliative radiation therapy for head and neck cancers 263

years of age with better performance status presenting for reirradiation. Carotid blowout is an infrequent but serious
care.46 Although many patients presenting with HPV- complication of reirradiation for head and neck cancers,
positive cancers are treated with curative intent therapy, with an incidence of 2.6% in a pooled analysis of 1554
some patients present with metastases or locally advanced patients treated with reirradiation.53 Such episodes are
disease and are only candidates for palliative-intent therapy. often fatal, and discussion of such treatment toxicities and
For such a patient with good performance status and a death is an integral part of informed consent for reirradia-
radiosensitive tumor, a protracted course of radiation ther- tion. Furthermore, discussion of other treatment options,
apy, similar to that which is offered in a definitive approach including immunotherapy and salvage surgery, are essential
(70 Gy in 35 fractions), offers the potential for durable within a multidisciplinary setting.
cancer control. Patient selection for palliative reirradiation should be
Although it is known that the risk of cancer progression based on interval from prior course of radiation and the ability
for patients with HPV-positive oropharyngeal carcinoma is to deliver sufficient dose to control disease while sparing
reduced compared with patients with HPV-negative dis- organs at risk from significant toxicity. An interval of 6
ease, approximately 10% to 25% of patients with HPV- months from initial course of radiation, as used in RTOG 96-
positive disease will experience a recurrence.47 Patients 10 and RTOG 99-11, is a minimum threshold used at many
with HPV-positive oropharyngeal cancer recurrences have centers. Patients with recurrences that occur earlier than 6
improved survival compared with patients with HPV- months out from initial radiation course may harbor disease
negative recurrences (2-year overall survival 55% vs that is relatively radioresistant because the initial course of
28%), and hence durable control is similarly required for radiation therapy likely never induced a significant thera-
patients with HPV-positive recurrences.48 Such patients peutic response. As such, further radiation therapy is likely to
respond well to immunotherapy, as demonstrated by the cause more harm than provide benefit. Reirradiation at sites
CHECKMATE-141 trial, and treatment options include close to serial organs, such as the spinal cord, brain stem, optic
immunotherapy followed by palliative radiation at pro- chiasm, and optic nerves, requires careful treatment planning
gression, palliative radiation followed by immunotherapy at to minimize the cumulative dose to such structures. Reirra-
progression, or the use of a concurrent therapy approach.38 diation to sites close to these critical organs at risk should be
Reirradiation for HPV-positive cancers is associated with administered using standard fractionation as opposed to
improved overall and progression-free survival.49 Given the accelerated hypofractionation. Regardless of fractionation
improved prognosis of such patients, a reirradiation course scheme used, treatment planning in the setting of reirradiation
of 70 Gy in 35 fractions can be considered if organs at risk necessitates the calculation of equivalent dose in 2 Gy for all
are within reirradiation dose constraints. organs at risk to determine whether such a course can be
safely administered. To minimize the risk of serious toxicity
in patients receiving reirradiation, a conservative cumulative
Reirradiation dose constraint of 60 Gy to critical serial organs can be used,
as seen in Table 2. Although patients with greater intervals
Patients with a history of head and neck radiation may from initial course of radiation therapy may experience some
benefit from reirradiation in the palliative setting for re- tissue recovery, a cumulative dose constraint greater than 60
currences and new primary cancers. Although there is a Gy has the potential to increase the risk of late toxicity.54
paucity of data regarding palliative-intent reirradiation, Minimizing cumulative dose to as low as reasonably
RTOG 96 to 10 and RTOG 99 to 11, trials of curative-intent achievable is a goal for sequential organs at risk.
salvage reirradiation, assessed the outcomes of patients Recurrences at areas farther away from critical serial
after 1.5 Gy bid to 60 Gy, with 5-FU and hydoxyurea, and organs at risk may be amenable to SBRT, which should be
cisplatin and paclitaxel, respectively.50,51 Eligible patients performed on clinical trial if possible. A multi-institutional
had a minimum 6-month interval from their prior course of comparison of reirradiation with IMRT and SBRT showed
radiation. Results from these studies highlight the guarded worse survival (2-year overall survival 39.1 vs 18.6
prognosis for patients with recurrent disease treated with months) with SBRT in patients more than 2 years out from
reirradiation, with a 2-year overall survival rate of 15.2% in treatment with unresected tumors.35 Furthermore, patients
RTOG 96 to 10 and 25.9% in RTOG 99 to 11. In this cohort with tumor recurrences less than 2 years out from initial
of patients, better outcomes were observed in patients with treatment had poor outcomes regardless of treatment with
an interval of greater than 1 year from the first course of IMRT or SBRT (2-year overall survival 16.8%). As such,
radiation. A separate multi-institutional review of 412 pa- all treatment options should be discussed with patients to
tients treated with reirradiation with IMRT similarly found allow for an informed, shared decision.
improved outcomes (2-year overall survival 61.9%) in pa-
tients with resected tumors and an interval of than 2 years Oligometastatic and oligorecurrent disease
between radiation courses.52 Adverse events from these
trials of reirradiation included fatal oropharyngeal hemor- Patients presenting with oligometastatic and oligorecurrent
rhages and carotid blowout in RTOG 99 to 11, highlighting head and neck cancer may benefit from aggressive pallia-
the potential severity of toxicity associated with tion of their limited metastatic disease. Initial findings from
264 Grewal et al. International Journal of Radiation Oncology  Biology  Physics

the SABR-COMET trial of stereotactic ablative radiation Table 2 Authors suggested maximum dose constraints on
therapy in patients with up to 5 metastatic sites from any H&N organs at risk
primary tumor site showed improvements in progression-
Palliative Palliative de
free survival (12 vs 6 months, P < .01) and overall survival reirradiation novo RT
(41 vs 28 months, P Z .09) when sites of metastases were
treated with radiation.55 Sun et al similarly reported 5-year Cumulative Cumulative
Organ at Risk dose (EQD2) dose (EQD2)
survival rates of 20% in select patients with head and neck
cancer who underwent oligometastasis-directed surgery of Spinal cord 60 Gy 50 Gy
stereotactic radiation to metastases.56 Given the improved Brain stem 60 Gy 54 Gy
overall survival in patients with oligometastatic disease, Carotid artery ALARA ALARA
Mandible ALARA ALARA
treatment to the primary head and neck tumor should pro-
Optic nerve 60 Gy 54 Gy
vide durable response, and as such, a course of 70 Gy in 35 Optic chiasm 60 Gy 54 Gy
fractions should be considered in patients with a good Constrictors Mean dose: Mean dose: <50 Gy
performance status. Metastases should also be addressed in ALARA
patients with oligometastatic and oligorecurrent disease. Brachial plexus 70 Gy* 60 Gy
Given the good life expectancy for such patients, wedge
resection, metastectomy, or stereotactic approaches should Abbreviations: ALARA Z as low as reasonably achievable; H&N
Z head and neck; RT Z radiation therapy; EQD2 Z equivalent dose
be considered over conventional palliative radiation doses in 2 Gy.
(30 Gy in 10 fractions or 20 Gy in 4-5 fractions) to sites of * There may be situations when it is appropriate to exceed the cu-
metastatic disease. mulative constraint (eg, plexus previously received full dose, and
recurrent disease involves or invades plexus). Clinical discussion be-
tween provider and patient is recommended to discuss the risks and
Treatment volumes benefits of reirradiation in this setting, with clinical decision-making
based on the results of such a discussion.
Appropriate volume selection has the potential to minimize
treatment-related toxicity. While no consensus guidelines in
contouring remain for palliative head and neck cancer, most who had received support from a palliative care team.57
providers strive to treat both disease that is actively causing Early palliative care integrated within a patient’s onco-
symptoms and disease that has the potential to cause logic care has the potential to improve patient quality of
symptoms if untreated. Such anticipatory planning is life, reduce depressive symptoms, and improve survival, as
essential in the palliative setting. Elective nodal volumes shown in a trial of 151 patients with advanced lung can-
are excluded in the palliative setting because they increase cer.58 Although it remains uncertain whether similar ben-
the radiation field size and introduce the possibility for efits are seen in patients with other cancers, a known value
worse treatment-related toxicity. of early palliative care is the delivery of holistic mental and
physical care to patients during a vulnerable time in their
Treatment planning lives.

Earlier studies in the palliative setting generally used Future directions

simpler techniques, such as 2-dimensional and 3-
dimensional planning, with parallel-opposed fields. Current trials under active enrollment include studies of
Although such planning is simpler and reduces time to SBRT with concurrent administration of immunotherapy
initiation of treatment, this field arrangement can increase (NCT03539198) and of proton therapy in the setting
mucosal radiation dose. The goal of a palliative course of of reirradiation (NCT03217188).59,60 Patients with recur-
radiation therapy is to minimize toxicity, and as such, rent head and neck cancer should be considered for such
IMRT should be considered, given its greater ability to clinical trials, with discussion and enrollment as clinically
spare critical structures in the head and neck from radiation indicated via the patient and the patient’s multidisciplinary
dose than less conformal techniques. care team.
There remains a paucity of data regarding the level of
Early palliative care treatment toxicity patients are willing to accept to achieve
palliation. The role of patient-reported outcomes in the
All patients seen in consultation for palliative radiation palliative setting will be instrumental in guiding future
should be referred to palliative care. Several studies have practitioners because patient-reported toxicity can differ
shown the benefits of earlier involvement of a palliative substantially from provider-assessed toxicity. Radiation
care team in the treatment of patients with advanced cancer. regimens resulting in significantly worse patient-reported
Shuman et al noted improved scores measuring the end-of- outcomes may need to be modified to ensure that palliation
life experience among patients with head and neck cancer is achieved.
Volume 105  Number 2  2019 Palliative radiation therapy for head and neck cancers 265

Conclusions 13. Lok BH, Jiang G, Gutiontov S, et al. Palliative head and neck radio-
therapy with the RTOG 8502 regimen for incurable primary or met-
astatic cancers. Oral Oncol 2015;51:957-962.
The results from the studies above demonstrate the value 14. Phan J, Sio TT, Nguyen TP, et al. Reirradiation of head and neck
of palliative radiation therapy in the treatment of patients cancers with proton therapy: Outcomes and analyses. Int J Radiat
with locoregionally advanced and metastatic head and Oncol Biol Phys 2016;96:30-41.
15. Ma J, Lok BH, Zong J, et al. Proton radiotherapy for recurrent or
neck cancers. Short, cyclic, hypofractionated courses are metastatic head and neck cancers with palliative quad shot. Int J Part
promising regimens for patients with poor performance Ther 2018;4:10-19.
status and worse prognosis, and protracted courses that 16. Gamez ME, Agarwal M, Hu KS, Lukens JN, Harrison LB. Hypo-
dose escalate with smaller fraction sizes are advanta- fractionated palliative radiotherapy with concurrent radiosensitizing
geous for patients with a better performance status and chemotherapy for advanced head and neck cancer using the “QUAD-
SHOT regimen. Anticancer Res 2017;37:685-691.
greater expected longevity. A collaborative approach 17. Carrascosa LA, Yashar CM, Paris KJ, Larocca RV, Faught SR,
from the onset with teams from palliative care, hospice, Spanos WJ. Palliation of pelvic and head and neck cancer with
otorhinolaryngology, medical oncology, and radiation paclitaxel and a novel radiotherapy regimen. J Palliat Med 2007;10:
oncology is essential to developing a comprehensive plan 877-881.
for patients with advanced and incurable head and neck 18. Porceddu SV, Rosser B, Burmeister BH, et al. Hypofractionated
radiotherapy for the palliation of advanced head and neck cancer in
cancers. Reaching consensus recommendations for pa- patients unsuitable for curative treatment e “Hypo Trial. Radiother
tients from such a group allows patients to have contin- Oncol 2007;85:456-462.
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results. Agarwal J. Twice-weekly palliative radiotherapy for locally
very advanced head and neck cancers. Indian J Cancer 2016;53:138-
141.
20. Nguyen NT, Doerwald-Munoz L, Zhang H, et al. 0-7-21 hypo-
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