0360.3016/92 $5.00 + .oO Copyright 0 1992 Pergamon Press Ltd.
In!. .I. Radiarion Oncoh~gy Rio/. Phvs., Vol. 23, pp. 641-652 Printed in the U.S.A. All rights reserved.
??Special Feature
IMPROVED DURING
PAIN MANAGEMENT WITH DAILY NURSING INTERVENTION RADIATION THERAPY FOR HEAD AND NECK CARCINOMA
N. A. JANJAN,
M.D.,*
D. E. WEISSMAN,
M.D.+ AND A. PAHULE,
R.N.*
Medical College of Wisconsin, Milwaukee, WI 53226 This study evaluated the response to a defined mouth care and analgesic treatment protocol for oropharyngeal mucositis in patients undergoing radiation therapy for head and neck carcinoma. Nineteen patients completed a 15 question pain survey before each radiation treatment. Patients were given instructions on the use of mouthwashes and a three-step analgesic protocol: acetaminophen, acetaminophen with codeine suspension, and oral morphine (20 mg/mL) for mild, moderate, and severe pain, respectively. Patients were seen daily by a radiation therapy nurse who reviewed the survey and prompt changes in the prescribed analgesic regimen were then made by a physician. Marked differences in control of pain related to radiation mucositis were observed when compared to patients from our prior study who used the same daily survey but had only sporadic nursing intervention and no analgesic protocol. Patients having daily nursing intervention reported fewer days of moderate/severe pain, had less pain throughout the day, and noted less disturbance in sleep, eating, and energy level. Weight loss of greater than 5 kg was noted in only three patients. Analgesics were used on 77% of treatment days and relieved all or most of the pain in 94% of these days. Daily review of a symptom survey by a radiation therapy nurse, combined with a well-defined strategy for mouth care, and analgesics results in improved pain management of radiation induced oropharyngeal mucositis because of prompt attention to patient needs. Future trials should incorporate defined strategies for oral care and analgesic use to control for possible bias in assessing efficacy. Cancer pain, Head and neck cancer, Radiation therapy.
reactions specifically have been a limiting factor in accelerated hyperfractionation regimens that incorporate a two-week break midway through prescribed therapy (20). Strategies in symptom management for radiation associated mucositis have generally included topical anesthetics and codeine elixirs ( 13). With this approach, pain related to radiation mucositis is moderate or severe in 37% of treatment days and is characterized as constant or present throughout most of the day in 58% of treatment days (21). Other approaches have used antimicrobial agents including benzydamine (BZD), nystatin, and chlorhexidine (4). Limitations include poor compliance with BZD due to a burning sensation, and failure of nys-
INTRODUCTION Radiation therapy has an established role in the management of head and neck malignancies. Applied as either
definitive treatment or as an adjunct to surgical management, radiation therapy is an effective treatment in securing local regional control for an anatomic and histologically heterogeneous group of neoplasms. Encompassing the primary tumor and draining lymphatics, radiation portals standardly treat significant volumes of mucosa within the upper aerodigestive tract. Symptomatic mucositis is routinely observed at the end of the second week of radiation correlating to a delivered dose of 2000 cGy with daily fractionation (2, 3, 14, 17). Mucosal inflammation peaks and plateaus during the fifth week of a six to seven week course of therapy. Mucositis and associated symptoms of xerostomia often result in poor oral hygiene and weight loss ( 11, 18, 19,2 1). Management of radiation mucositis is gaining greater significance in aggressive radiation schedules including hyperfractionation and accelerated fractionation (8, 10, 12, 15, 16, 20). Mucosal
tatin and chlorhexidine to affect mucosal reactions secondary to causes other than Candida. Reduction in se-
verity of observed mucositis has been documented with BZD, however, no consistent impact in analgesic efficacy has been reported. Presented is a study evaluating daily interaction with patients undergoing a course of radiation therapy for head and neck cancer. Daily pain diaries, detailing the devel-
* Department of Radiation Oncology. +Division of Cancer and Blood Diseases.
Acknowledgements-The authors gratefully acknowledge the assistance of J. Radtke, R.N., C. Jarmuz, R.N., and C. Krenz, R.N. in the completion of the study. Accepted for publication 3 1 December 199 1.
Reprint requests to: Dr. Nora Janjan, University of Texas M. D. Anderson Cancer Center, Division of Radiotherapy, Box 97, 15 15 Holcombe Blvd., Houston, TX 77031. 647
648
I. J. Radiation Oncology 0 Biology 0 Physics
opment and quality of symptoms associated with radiation therapy, were compared to total dose of radiation and independent physician assessment of mucosal reactions. The importance of reinforced instructions for oral hygiene and a well-defined strategy for analgesic administration were evaluated. METHODS
AND MATERIALS
Prior to initiation of radiation therapy in treatment of a head and neck malignancy, all patients were given written instructions regarding oral hygiene, nutrition, and analgesic prescriptions. These instructions were verbally explained by both physician and radiotherapy (RT) nurses. Oral hygiene was maintained using half-strength hydrogen peroxide and salt and soda rinses performed at a minimum of three times daily. Sucralfate suspension was administered three to four times daily (1, 5, 6). Analgesics were prescribed according to degree of pain including acetaminophen, acetaminophen with codeine, and oral morphine (20 mg/ml) elixirs for mild, moderate, and severe pain, respectively (Table 1). Respective levels of pain were determined by the patient’s verbal and written responses. A total of 19 patients were evaluated. Daily pain questionnaires were requested of each patient evaluating location, quality, and intensity of pain. Impact of reported pain upon functions including swallowing, speech, sleep, mood, and energy were directly asked within the questionnaire. The 15 question pain survey also specifically assessed efficacy and duration of response for each prescribed analgesic. Patients were seen daily by an RT nurse who collected and reviewed the survey and reinforced oral hygiene instructions. Appropriate changes in the analgesic regimen were prescribed based on reported level of pain; if inadequate pain control was indicated on the survey,
Volume 23, Number 3, 1992
was prescribed by a physician. This system allowed prompt response to the analgesic needs of the patient. Weekly evaluation under treatment was performed by the radiation oncologist who scored observed mucosal reactions without knowledge of the response on the daily pain survey. Specifically documented was the anatomic location of the mucosal reaction relative to the treatment portal, severity of mucositis, and total delivered dose. Mucosal reactions were scored on the basis of a four-point grid relating a range of early inflammation to confluent mucositis (Fig. 1). Weight was recorded weekly and continued alcohol or tobacco use was noted during the course of therapy. The patient’s response to the physician regarding the level of pain and analgesic efficacy were listed and compared to daily pain diary responses. The grid on the physician scoring sheet and visual analog scale on the patient diary were divided into thirds differentiating mild, moderate, and severe levels of pain. Responses from patient diaries and physician evaluation forms were chronologically assessed after completion of radiation. All patients received a total of 35 treatments, which were used as a common denominator for calculation of symptoms. The total number of treatment days reported with a given symptom divided by 35 total treatment days was used to relate the percent of the treatment course affected. A previously studied cohort of patients (N = 14; Group II) who had received routine instructions by physicians and nurses at the start of radiation therapy regarding oral
Patient Flow Sheet 1) Patient Name:
4)
Date of Birth 2) Diagnosis (histology/site): 3)
Site(s)
-5)
Number:
Diagnosis
Hospital: 6) Date of assessment:
Irradiated
the patient was clinically evaluated and if appropriate, the next analgesic level within the three tier system (Table 1)
Patient Date
Nasopharynx
7) Pt. cont. to smoke:
Oropharynx
8) Weight:
Hypopharynx Oral Cavity Paranasal R neck
Change +/- _ Abnormalities
List
_
9) CBC:
L neck ____ Supraclavicular ___
SMA
nl 12: “I _abn
2. Moderate pain:
3. Severe pain:
Starting dose 1st escalation 2nd escalation 3rd escalation 4th escalation 5th escalation
0.5 cc 0.75 cc 1.0 cc 1.5 cc 2 to 3 cc 4.5 to 6 cc
excellent
g”“d poor a) oral infection: type
Acetaminophen tablets or liquid: 1-2 tablets or 1.5 tablespoons (20 cc) liquid every 4 hours as needed for pain Acetaminophen with codeine 1.5 tablespoons (20 cc) to three tablespoons (40 cc) every 4 hours as needed for pain Morphine sulfate elixir (20 mg/cc) every 4 hours as needed for pain:
_
10) Oral Hygiene:
Table I. Three tier analgesic system determined by the level of pain reported by the patient 1. Mild pain:
1 1)
Chemotherapy: dates:
Yes_
_no
Latest:
_____
sinuses ____
-yes
Initial:
-
~ ____ Yes_
_
No _
______
No _
_
agents: 12)
Mucosal
13)
Pain
14)
Patient
reaction:
level: Diary: 123
(average
for
2
3
4
mild
moderate
severe
most
severe
0 ““ne
1 mild
2 moderate
3 severe
4 mat
severe
least
pain
worst 4
5
6
7
8
pain 9
10
pain pain
global Foods:
1
n”ne
week) worst least
15)
0
pain
liquids solids
Fig. 1. Physician scoring observed
Evaluation Sheet that was completed weekly, mucosal reactions and relating level of pain
reported by patient (independent of interaction with the nursing staff).
Improved pain management 0 N. A.
hygiene and nutrition were also evaluated (2 1). Analgesic prescriptions during the course of radiation were given according to standard practice ( 13). These patients completed pain questionnaires, but did not receive daily nursing intervention or analgesics prescribed according to the previously defined strategy and were used for comparison to the 19 patients in this study (Group I). Pain questionnaires had to be completed on more than 75% of treatment days to be eligible for evaluation, accounting for only 66% of Group II (14/2 1) patients (2 1). In contrast, all nineteen patients with daily nursing intervention completed pain diaries. RESULTS Patient populations Primary tumor location and delivered conventionally fractionated radiation for all patients evaluated are listed in Table 2. Common to all radiation portals was the inclusion of the posterior pharyngeal wall within the radiated volume. Symptoms described during radiation therapy correlated well with mucosal changes typical of radiation mucositis. The pain associated with radiation correlated with radiation field reductions routinely employed (Fig. 2). Group Z Mucosal pain localized to the throat for patients receiving daily nursing intervention (Group I) was noted in 57% of treatment days. Neck and mouth pain were reported during 28% and 11% of the treatment course, respectively. Pain with swallowing occurred in 40% of treatment days and correlated well to described pharyngeal pain (Fig. 3). Ability to eat was affected and dietary intake limited to liquids was reported over 2 1% of the treatment course. Mean weight loss equaled 3 kg; 42% of patients (8/ 19) sustained greater than a 2 kg weight loss; however, only 16% (3/ 19) experienced more than 5 kg loss in weight. Other functions affected included speech and energy level during 17% and 23% of the radiation course, respectively. Sleep was interrupted more than twice nightly during 26%
649
JANJANet al.
60
c 5o 2 a& 40 c ;
30
E g II
20
.-
10
o-
1234567 Week of Radiation
Fig. 2. Graphic demonstration of pharyngeal discomfort relative to week of radiation therapy. Patients were asymptomatic in first week of therapy; “percent change” relates to percent of patients relating complaints at the indicated week of radiation.
of the treatment and subjective assessment of mood was affected in 34% of the seven-week treatment (Table 3). Graphic representation of changes in mood correlated well with reported pharyngeal pain (Fig. 4). Mild pain was present in 43% of treatment days, moderate pain in 23%, and severe pain during only 6% of the treatment (Table 4). Administered analgesics included acetaminophen during 26% of treatment days, acetaminophen with codeine in 34%, and morphine during 17% of the radiation course. No sedation, respiratory compromise, aspiration or other effects of codeine or morphine
60 F
Pain with Swallowing
Table 2. Comparison of patient populations receiving daily (Group I) versus sporadic nursing intervention (Group II) for radiation mucositis
Patient number Mean age Sex Tumor location Oral cavity Oropharynx Supraglottic larynx/larynx Other Average total radiation dose Range of total radiation dose (cGy)
Group I
Group II
19 63 14 M/5 F
14 51 13 M/l F
7 2 7 3 6259 cGy 5040-7200
5 3 4 2 6381 cGy 5040-7020
IOI-
0:
1234567 Week of Radiation
Fig. 3. Graphic demonstration of pain with swallowing relative to week of radiation therapy. Patients were asymptomatic in first week of therapy; “percent change” indicates percent of patients symptomatic at the indicated week of radiation.
650
I. J. Radiation Oncology 0 Biology 0 Physics
Table 3. Symptoms during radiation therapy (RT) for patients receiving daily intervention (Group I)
1. Pain in: Throat Neck Mouth No pain during RT 2. Pain with swallowing severely limited diet (liquids only or less) Difficulty in: Talking Eating Mood Energy Sleep interrupted > twice/night 3. No. patients with >2 kg weight loss No. patients with >5 kg weight loss
No. of days affected: 35 treatment days
(%)
20 10 4 6 14 7 6 8 12 8 16 9 8119 3119
(57) (29) (11) (17) (40) (20) (17) (23) (34) (23) (46) (26) (42) (161
were observed. These analgesics relieved all or most of the pain in 94% of patients. The majority of patients (52%) reported sustained analgesia for greater than 2 hr with 56% of this group experiencing pain relief for more than 4 hr (Table 4). Group I vs. Group II The influence of daily nursing assessment of oral hygiene and pain management (Group I) was evaluated by comparing responses of patients receiving initial and sporadic instructions (Group II) (2 1). Primary tumor location and total radiation doses administered were comparable for the two groups (Table 2). Physician assessments of
+20l%-$W$cting r
Volume 23, Number 3, 1992 Table 4. Severity of pain for patients receiving intervention (Group I)
Pain intensity Mild Moderate Severe Pain frequency Occasionally Most of day Always present Analgesics 1. Medication Acetaminophen Acetaminophen with codeine Morphine sulfate 2. Medication taken round the clock 3. Analgesics relieved all or most of pain Analgesics relieved little or none of pain 4. Length of analgesia (hours) l-2 2-4 >4
daily nursing
No. of days affected 35 treatment days
(%)
15 8 2
(43) (23) (6)
16 6 2
(46) (17) (6)
9 12 6 4 33
(26) (34) (17) (11) (94)
2
(6)
2135 8135 IO/35
(6) (23) (29)
radiation-associated mucosal effects were also similar between the two groups with regard to time course and extent of observed inflammation. The two groups were similar in continued smoking or alcohol habits, secondary infections with Candida, and other mucosal irritants during the prescribed treatment. Sucralfate elixir (1, 5, 6) had been prescribed in both groups with similar rates of compliance. Viscous xylocaine was prescribed only in Group II patients and was used infrequently. The number of treatment days with mild and moderate pain were markedly different between the two groups. In the initial two weeks of radiation, before mucosal injury was evident, 50% of Group I and 60% of Group II experienced mild to moderate pain due either to tumor effects or postoperative healing (Table 5); moderate to severe
Table 5. Percentage of treatment days with mild and moderate pain versus week of radiation therapy (RT)
-
Week of Radiation Fig. 4. Chronologic evaluation of change in mood affected by radiation mucositis. Scale refers to level of mood ranging from content (+20) to depressed (- 10) as a function of reported pharyngeal pain during each week of radiation therapy.
Week RT
No intervention N= 14 (% days)
Daily intervention N= 19 (% days)
1 2 3 4 5 6 7 Week 3-7
30 50 90 95 90 90 75 x = 88%
51 60 64 76 86 74 66 x = 73%
Difference no vs. daily intervention (%) +21 +10 -26 -19 -4 -16 -9 -15
651
Improved pain management 0 N. A. JANJANet a/. Table 6. Percent of treatment
days with moderate and severe pain versus week of radiation therapy (RT) according to level of nursing intervention
Week RT
No intervention N= 14 (W days)
Daily intervention N= 19 (% days)
Difference no vs. daily intervention (%)
1 2 3 4 5 6 7
10 10 45 60 56 55 50
19 32 34 38 32 24 24
+9 +22 -11 -22 -24 -31 -26
Week 3-7
x = 53%
‘? = 30%
-15
pain was reported, however, in 32% of Group I and 10% of Group II patients in the first two weeks of radiation therapy (Table 6). Baseline levels of pain prior to radiation effects did not predict for subsequent difficulties in pain management. Pain during radiation therapy was reported to occur most or all of the day in 23% of treatment days for patients with daily intervention (Group I) in contrast to the 58% incidence among patients without daily intervention (Group II). A 19% decrease in treatment days with mucositis was observed during weeks three through seven of radiation therapy for patients receiving daily intervention. Improvement in pain control was most pronounced for moderate and severe pain levels with a 23% decrease in affected treatment days. Mean weight loss during radiation also differed in the two groups; only 42% of Group II as compared to 57% of Group I patients experienced more than a 2 kg loss in weight. Codeine and oxycodone products were used by 93% of Group II patients while only 14% used morphine; Group I by comparison, used codeine 34% of treatment days and morphine during 17% of the treatment (Table 7).
Table 7. Comparison of reported pain levels according to degree of nursing intervention No intervention N= 14 Pain noted most or all of day Mean weight loss > 5 kg Treatment days using codeine Treatment days using morphine sulfate
Daily intervention
Difference no vs. daily
(% days)
N= 19 (% days)
intervention (%)
58
23
-35
57
16
-41
93
34
-59
14
17
+3
* Patients were allowed to combine listed medications to achieve maximum control of experienced pain while minimizing secondary effects of analgesics.
DISCUSSION Radiation associated mucosal reactions are a predictable aspect of head and neck cancer irradiation first noted at the start of the third week of treatment following administration of 2000 cGy (2, 3, 14, 17). Numerous strategies have been proposed to either prevent ( 1,4-6,22) or treat (13) radiation-associated mucositis with limited observed efficacy (2 1). This study evaluated patients undergoing radiation therapy for head and neck cancer given a defined protocol for analgesic use and oral hygiene supported by daily nursing intervention. The importance of oral hygiene in reducing acute and late complications of radiation therapy to the head and neck region has been well described (4, 22). Aggressive oral hygiene acts to reduce oral flora, remove thickened secretions and debris, and increase moisture within the mouth. Pharyngeal pain represents a common denominator given the necessary inclusion of the pharyngeal wall in all head and neck radiation treatment portals. Recorded symptoms correlated exactly with observed mucositis during the course of therapy. Throat pain was therefore recorded during 57% of treatment days, affecting swallowing during 40% of the therapy and limiting dietary intake to liquids in 2 1% of treatment days. Weight loss totalling 5 kg or more occurred in 16% of patients evaluated. Correspondingly, 29% of patients experienced moderate to severe pain during the course of radiation. Effective analgesia was accomplished, however, in 94% of patients with codeine or morphine used over 5 1% of treatment days. Administered analgesics did not result in sedation, respiratory depression, aspiration, or other effects (7). Pertinent to a population with frequent alcohol dependency, no evidence of opioid psychologic dependence (addiction) was demonstrated during or following completion of the radiation course. The impact of a defined analgesic protocol and daily intervention was determined by comparison to a patient group receiving only initial and sporadic instructions (21). Notable improvements in pain control included a 34% improvement in oral intake, 15% reduction in weight loss totalling 2 kg or more, 35% reduction in pain duration, and 23% improvement in analgesic efficacy. Our results indicate that radiation mucositis can be treated effectively. Improvements in quality of life and nutritional status during the course of radiation therapy are observed with aggressive clinical management including a defined protocol for analgesic use and oral hygiene. This approach parallels that proven to be beneficial in mucositis related to bone marrow transplantation (4, 9). However, further work is necessary to determine optimal analgesic delivery and scheduling, and identify possible agents that may ameliorate radiation-induced inflammation. Future trials should incorporate defined strategies for oral care and analgesic used to control for these factors in assessing efficacy.
652
I. J. Radiation Oncology 0 Biology 0 Physics
Volume 23, Number 3, 1992
REFERENCES 1. Adams, S.; Toth, B.; Dudley, B. S. Evaluation of sucralfate
2.
3. 4.
5. 6. 7. 8.
9.
10.
11.
12.
as a compounded oral suspension for the treatment of stomatits. Clin. Pharmacol. Ther. 2: 178; 1985. Baker, D. G. The radiobiological basis for tissue reactions in the oral cavity following therapeutic x-irradiation. Arch. Otolaryngol. 108: 2 l-24; 1982. Dreizen, S. Description and incidence of oral complications. NC1 Monogr. 9: 11-15; 1990. Epstein, J. B. Infection prevention in bone marrow transplantation and radiation patients. NC1 Monogr. 9: 73-85; 1990. Ferraro, J. M. Sucralfate suspension for mouth ulcers. Drug. Intell. Clin. Pharm. 19: 480; 1985. Ferraro, J. M., Mattem, J. Q. A., II. Sucralfate suspension for stomatitis. Drug. Intell. Clin. Pharm. 18: 153; 1984. Fields, H. L. Analgesic drugs. In: Bonica, J. J., ed. Pain. New York, NY: McGraw-Hill Co; 1987: 251-279. Gray, A. J. Treatment of advanced head and neck cancer with accelerated fractionation. Int. J. Radiat. Oncol. Biol. Phys. 12: 9-12; 1986. Hill, H.; Kornell, J.; Saeger, L.; Jackson, T.; Pancho, M.; Sullivan, K.; Chapman, CR. Comparison of continuous infusion and patient-controlled analgesia in treatment of oral mucositis pain. Proc. ASCO 6: 268; 1987. Knee, R.; Fields, R. S.; Peters, L. J. Concomitant boost radiotherapy for advanced squamous cell carcinoma of the head and neck. Radiother. Oncol. 4: 1-7; 1985. Kuten, A.; Ben-Aryeh, H.; Berdicevky, I.; Ore, L.; Szargel, R.; Gutman, D.; Robinson, E.; Oral side effects of head and neck irradiation: correlation between clinical manifestations and laboratory data. Int. J. Radiat. Oncol. Biol. Phys. 12: 401-405; 1986. Meoz, R. T.; Fletcher, G. H.; Peters, L. J.; Barkley, H. T.; Thames, H. D. Twice-daily fractionation schemes for ad-
13. 14.
15.
16.
17. 18.
19.
20.
2 1.
22.
vanced head and neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 10: 831-836; 1984. Miaskowski, C. Management of mucositis during therapy. NC1 Monogr. 9: 95-98; 1990. Parsons, J. T. The effect of radiation on normal tissues of the head and neck. In: Million, R. R., Cassisi, N. J., eds. Management of head and neck cancer-a multidisciplinary approach. Philadelphia, PA: J. B. Lippincott Co.; 1984: 173177. Parsons, J. T.; Cassisi, N. J.; Million, R. R. Results of twice a day irradiation of squamous cell carcinomas of the head and neck. Int. J. Radiat. Oncol. Biol. Phys. 10: 2041-205 1; 1984. Parsons, J. T.; Mendenhall, W. M.; Cassisi, N. J.; Isaac& J. H.; Million, R. R. Hyperfractionation for head and neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 14: 649-658; 1988. Rubin, P. Radiation biology and radiation pathology syllabus. Chicago, IL: Waverly Press; 1975: 208-209. Spijkervet, F. K. L.; Saene, H. K. F.; van Panders, A. K.; Vermey, A.; Mehta, D. M. Scoring irradiation mucositis in head and neck cancer patients. J. Oral Pathol. Med. 18: 167-171; 1989. Tsujii, H. Quantitative dose-response analysis of salivary function following radiotherapy using sequential resialography. Int. J. Radiat. Oncol. Biol. Phys. 11: 1603-16 12; 1985. Wang, C. C.; Suit, H. D.; Blitzer, P. H.; Twice a day radiation therapy for supraglottic carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 12: 3-7; 1986. Weissman, D. E.; Janjan, N. A.; Byhardt, R. W. Assessment of pain during head and neck irradiation. J. Pain Symptom Management 4: 90-95; 1989. Wright, W. E. Pretreatment oral health care interventions for radiation patients. NC1 Monogr. 9: 57-59; 1990.
In!. .I. Radiarion Oncoh~gy Rio/. Phvs., Vol. 23, pp. 641-652 Printed in the U.S.A. All rights reserved.
??Special Feature
IMPROVED DURING
PAIN MANAGEMENT WITH DAILY NURSING INTERVENTION RADIATION THERAPY FOR HEAD AND NECK CARCINOMA
N. A. JANJAN,
M.D.,*
D. E. WEISSMAN,
M.D.+ AND A. PAHULE,
R.N.*
Medical College of Wisconsin, Milwaukee, WI 53226 This study evaluated the response to a defined mouth care and analgesic treatment protocol for oropharyngeal mucositis in patients undergoing radiation therapy for head and neck carcinoma. Nineteen patients completed a 15 question pain survey before each radiation treatment. Patients were given instructions on the use of mouthwashes and a three-step analgesic protocol: acetaminophen, acetaminophen with codeine suspension, and oral morphine (20 mg/mL) for mild, moderate, and severe pain, respectively. Patients were seen daily by a radiation therapy nurse who reviewed the survey and prompt changes in the prescribed analgesic regimen were then made by a physician. Marked differences in control of pain related to radiation mucositis were observed when compared to patients from our prior study who used the same daily survey but had only sporadic nursing intervention and no analgesic protocol. Patients having daily nursing intervention reported fewer days of moderate/severe pain, had less pain throughout the day, and noted less disturbance in sleep, eating, and energy level. Weight loss of greater than 5 kg was noted in only three patients. Analgesics were used on 77% of treatment days and relieved all or most of the pain in 94% of these days. Daily review of a symptom survey by a radiation therapy nurse, combined with a well-defined strategy for mouth care, and analgesics results in improved pain management of radiation induced oropharyngeal mucositis because of prompt attention to patient needs. Future trials should incorporate defined strategies for oral care and analgesic use to control for possible bias in assessing efficacy. Cancer pain, Head and neck cancer, Radiation therapy.
reactions specifically have been a limiting factor in accelerated hyperfractionation regimens that incorporate a two-week break midway through prescribed therapy (20). Strategies in symptom management for radiation associated mucositis have generally included topical anesthetics and codeine elixirs ( 13). With this approach, pain related to radiation mucositis is moderate or severe in 37% of treatment days and is characterized as constant or present throughout most of the day in 58% of treatment days (21). Other approaches have used antimicrobial agents including benzydamine (BZD), nystatin, and chlorhexidine (4). Limitations include poor compliance with BZD due to a burning sensation, and failure of nys-
INTRODUCTION Radiation therapy has an established role in the management of head and neck malignancies. Applied as either
definitive treatment or as an adjunct to surgical management, radiation therapy is an effective treatment in securing local regional control for an anatomic and histologically heterogeneous group of neoplasms. Encompassing the primary tumor and draining lymphatics, radiation portals standardly treat significant volumes of mucosa within the upper aerodigestive tract. Symptomatic mucositis is routinely observed at the end of the second week of radiation correlating to a delivered dose of 2000 cGy with daily fractionation (2, 3, 14, 17). Mucosal inflammation peaks and plateaus during the fifth week of a six to seven week course of therapy. Mucositis and associated symptoms of xerostomia often result in poor oral hygiene and weight loss ( 11, 18, 19,2 1). Management of radiation mucositis is gaining greater significance in aggressive radiation schedules including hyperfractionation and accelerated fractionation (8, 10, 12, 15, 16, 20). Mucosal
tatin and chlorhexidine to affect mucosal reactions secondary to causes other than Candida. Reduction in se-
verity of observed mucositis has been documented with BZD, however, no consistent impact in analgesic efficacy has been reported. Presented is a study evaluating daily interaction with patients undergoing a course of radiation therapy for head and neck cancer. Daily pain diaries, detailing the devel-
* Department of Radiation Oncology. +Division of Cancer and Blood Diseases.
Acknowledgements-The authors gratefully acknowledge the assistance of J. Radtke, R.N., C. Jarmuz, R.N., and C. Krenz, R.N. in the completion of the study. Accepted for publication 3 1 December 199 1.
Reprint requests to: Dr. Nora Janjan, University of Texas M. D. Anderson Cancer Center, Division of Radiotherapy, Box 97, 15 15 Holcombe Blvd., Houston, TX 77031. 647
648
I. J. Radiation Oncology 0 Biology 0 Physics
opment and quality of symptoms associated with radiation therapy, were compared to total dose of radiation and independent physician assessment of mucosal reactions. The importance of reinforced instructions for oral hygiene and a well-defined strategy for analgesic administration were evaluated. METHODS
AND MATERIALS
Prior to initiation of radiation therapy in treatment of a head and neck malignancy, all patients were given written instructions regarding oral hygiene, nutrition, and analgesic prescriptions. These instructions were verbally explained by both physician and radiotherapy (RT) nurses. Oral hygiene was maintained using half-strength hydrogen peroxide and salt and soda rinses performed at a minimum of three times daily. Sucralfate suspension was administered three to four times daily (1, 5, 6). Analgesics were prescribed according to degree of pain including acetaminophen, acetaminophen with codeine, and oral morphine (20 mg/ml) elixirs for mild, moderate, and severe pain, respectively (Table 1). Respective levels of pain were determined by the patient’s verbal and written responses. A total of 19 patients were evaluated. Daily pain questionnaires were requested of each patient evaluating location, quality, and intensity of pain. Impact of reported pain upon functions including swallowing, speech, sleep, mood, and energy were directly asked within the questionnaire. The 15 question pain survey also specifically assessed efficacy and duration of response for each prescribed analgesic. Patients were seen daily by an RT nurse who collected and reviewed the survey and reinforced oral hygiene instructions. Appropriate changes in the analgesic regimen were prescribed based on reported level of pain; if inadequate pain control was indicated on the survey,
Volume 23, Number 3, 1992
was prescribed by a physician. This system allowed prompt response to the analgesic needs of the patient. Weekly evaluation under treatment was performed by the radiation oncologist who scored observed mucosal reactions without knowledge of the response on the daily pain survey. Specifically documented was the anatomic location of the mucosal reaction relative to the treatment portal, severity of mucositis, and total delivered dose. Mucosal reactions were scored on the basis of a four-point grid relating a range of early inflammation to confluent mucositis (Fig. 1). Weight was recorded weekly and continued alcohol or tobacco use was noted during the course of therapy. The patient’s response to the physician regarding the level of pain and analgesic efficacy were listed and compared to daily pain diary responses. The grid on the physician scoring sheet and visual analog scale on the patient diary were divided into thirds differentiating mild, moderate, and severe levels of pain. Responses from patient diaries and physician evaluation forms were chronologically assessed after completion of radiation. All patients received a total of 35 treatments, which were used as a common denominator for calculation of symptoms. The total number of treatment days reported with a given symptom divided by 35 total treatment days was used to relate the percent of the treatment course affected. A previously studied cohort of patients (N = 14; Group II) who had received routine instructions by physicians and nurses at the start of radiation therapy regarding oral
Patient Flow Sheet 1) Patient Name:
4)
Date of Birth 2) Diagnosis (histology/site): 3)
Site(s)
-5)
Number:
Diagnosis
Hospital: 6) Date of assessment:
Irradiated
the patient was clinically evaluated and if appropriate, the next analgesic level within the three tier system (Table 1)
Patient Date
Nasopharynx
7) Pt. cont. to smoke:
Oropharynx
8) Weight:
Hypopharynx Oral Cavity Paranasal R neck
Change +/- _ Abnormalities
List
_
9) CBC:
L neck ____ Supraclavicular ___
SMA
nl 12: “I _abn
2. Moderate pain:
3. Severe pain:
Starting dose 1st escalation 2nd escalation 3rd escalation 4th escalation 5th escalation
0.5 cc 0.75 cc 1.0 cc 1.5 cc 2 to 3 cc 4.5 to 6 cc
excellent
g”“d poor a) oral infection: type
Acetaminophen tablets or liquid: 1-2 tablets or 1.5 tablespoons (20 cc) liquid every 4 hours as needed for pain Acetaminophen with codeine 1.5 tablespoons (20 cc) to three tablespoons (40 cc) every 4 hours as needed for pain Morphine sulfate elixir (20 mg/cc) every 4 hours as needed for pain:
_
10) Oral Hygiene:
Table I. Three tier analgesic system determined by the level of pain reported by the patient 1. Mild pain:
1 1)
Chemotherapy: dates:
Yes_
_no
Latest:
_____
sinuses ____
-yes
Initial:
-
~ ____ Yes_
_
No _
______
No _
_
agents: 12)
Mucosal
13)
Pain
14)
Patient
reaction:
level: Diary: 123
(average
for
2
3
4
mild
moderate
severe
most
severe
0 ““ne
1 mild
2 moderate
3 severe
4 mat
severe
least
pain
worst 4
5
6
7
8
pain 9
10
pain pain
global Foods:
1
n”ne
week) worst least
15)
0
pain
liquids solids
Fig. 1. Physician scoring observed
Evaluation Sheet that was completed weekly, mucosal reactions and relating level of pain
reported by patient (independent of interaction with the nursing staff).
Improved pain management 0 N. A.
hygiene and nutrition were also evaluated (2 1). Analgesic prescriptions during the course of radiation were given according to standard practice ( 13). These patients completed pain questionnaires, but did not receive daily nursing intervention or analgesics prescribed according to the previously defined strategy and were used for comparison to the 19 patients in this study (Group I). Pain questionnaires had to be completed on more than 75% of treatment days to be eligible for evaluation, accounting for only 66% of Group II (14/2 1) patients (2 1). In contrast, all nineteen patients with daily nursing intervention completed pain diaries. RESULTS Patient populations Primary tumor location and delivered conventionally fractionated radiation for all patients evaluated are listed in Table 2. Common to all radiation portals was the inclusion of the posterior pharyngeal wall within the radiated volume. Symptoms described during radiation therapy correlated well with mucosal changes typical of radiation mucositis. The pain associated with radiation correlated with radiation field reductions routinely employed (Fig. 2). Group Z Mucosal pain localized to the throat for patients receiving daily nursing intervention (Group I) was noted in 57% of treatment days. Neck and mouth pain were reported during 28% and 11% of the treatment course, respectively. Pain with swallowing occurred in 40% of treatment days and correlated well to described pharyngeal pain (Fig. 3). Ability to eat was affected and dietary intake limited to liquids was reported over 2 1% of the treatment course. Mean weight loss equaled 3 kg; 42% of patients (8/ 19) sustained greater than a 2 kg weight loss; however, only 16% (3/ 19) experienced more than 5 kg loss in weight. Other functions affected included speech and energy level during 17% and 23% of the radiation course, respectively. Sleep was interrupted more than twice nightly during 26%
649
JANJANet al.
60
c 5o 2 a& 40 c ;
30
E g II
20
.-
10
o-
1234567 Week of Radiation
Fig. 2. Graphic demonstration of pharyngeal discomfort relative to week of radiation therapy. Patients were asymptomatic in first week of therapy; “percent change” relates to percent of patients relating complaints at the indicated week of radiation.
of the treatment and subjective assessment of mood was affected in 34% of the seven-week treatment (Table 3). Graphic representation of changes in mood correlated well with reported pharyngeal pain (Fig. 4). Mild pain was present in 43% of treatment days, moderate pain in 23%, and severe pain during only 6% of the treatment (Table 4). Administered analgesics included acetaminophen during 26% of treatment days, acetaminophen with codeine in 34%, and morphine during 17% of the radiation course. No sedation, respiratory compromise, aspiration or other effects of codeine or morphine
60 F
Pain with Swallowing
Table 2. Comparison of patient populations receiving daily (Group I) versus sporadic nursing intervention (Group II) for radiation mucositis
Patient number Mean age Sex Tumor location Oral cavity Oropharynx Supraglottic larynx/larynx Other Average total radiation dose Range of total radiation dose (cGy)
Group I
Group II
19 63 14 M/5 F
14 51 13 M/l F
7 2 7 3 6259 cGy 5040-7200
5 3 4 2 6381 cGy 5040-7020
IOI-
0:
1234567 Week of Radiation
Fig. 3. Graphic demonstration of pain with swallowing relative to week of radiation therapy. Patients were asymptomatic in first week of therapy; “percent change” indicates percent of patients symptomatic at the indicated week of radiation.
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I. J. Radiation Oncology 0 Biology 0 Physics
Table 3. Symptoms during radiation therapy (RT) for patients receiving daily intervention (Group I)
1. Pain in: Throat Neck Mouth No pain during RT 2. Pain with swallowing severely limited diet (liquids only or less) Difficulty in: Talking Eating Mood Energy Sleep interrupted > twice/night 3. No. patients with >2 kg weight loss No. patients with >5 kg weight loss
No. of days affected: 35 treatment days
(%)
20 10 4 6 14 7 6 8 12 8 16 9 8119 3119
(57) (29) (11) (17) (40) (20) (17) (23) (34) (23) (46) (26) (42) (161
were observed. These analgesics relieved all or most of the pain in 94% of patients. The majority of patients (52%) reported sustained analgesia for greater than 2 hr with 56% of this group experiencing pain relief for more than 4 hr (Table 4). Group I vs. Group II The influence of daily nursing assessment of oral hygiene and pain management (Group I) was evaluated by comparing responses of patients receiving initial and sporadic instructions (Group II) (2 1). Primary tumor location and total radiation doses administered were comparable for the two groups (Table 2). Physician assessments of
+20l%-$W$cting r
Volume 23, Number 3, 1992 Table 4. Severity of pain for patients receiving intervention (Group I)
Pain intensity Mild Moderate Severe Pain frequency Occasionally Most of day Always present Analgesics 1. Medication Acetaminophen Acetaminophen with codeine Morphine sulfate 2. Medication taken round the clock 3. Analgesics relieved all or most of pain Analgesics relieved little or none of pain 4. Length of analgesia (hours) l-2 2-4 >4
daily nursing
No. of days affected 35 treatment days
(%)
15 8 2
(43) (23) (6)
16 6 2
(46) (17) (6)
9 12 6 4 33
(26) (34) (17) (11) (94)
2
(6)
2135 8135 IO/35
(6) (23) (29)
radiation-associated mucosal effects were also similar between the two groups with regard to time course and extent of observed inflammation. The two groups were similar in continued smoking or alcohol habits, secondary infections with Candida, and other mucosal irritants during the prescribed treatment. Sucralfate elixir (1, 5, 6) had been prescribed in both groups with similar rates of compliance. Viscous xylocaine was prescribed only in Group II patients and was used infrequently. The number of treatment days with mild and moderate pain were markedly different between the two groups. In the initial two weeks of radiation, before mucosal injury was evident, 50% of Group I and 60% of Group II experienced mild to moderate pain due either to tumor effects or postoperative healing (Table 5); moderate to severe
Table 5. Percentage of treatment days with mild and moderate pain versus week of radiation therapy (RT)
-
Week of Radiation Fig. 4. Chronologic evaluation of change in mood affected by radiation mucositis. Scale refers to level of mood ranging from content (+20) to depressed (- 10) as a function of reported pharyngeal pain during each week of radiation therapy.
Week RT
No intervention N= 14 (% days)
Daily intervention N= 19 (% days)
1 2 3 4 5 6 7 Week 3-7
30 50 90 95 90 90 75 x = 88%
51 60 64 76 86 74 66 x = 73%
Difference no vs. daily intervention (%) +21 +10 -26 -19 -4 -16 -9 -15
651
Improved pain management 0 N. A. JANJANet a/. Table 6. Percent of treatment
days with moderate and severe pain versus week of radiation therapy (RT) according to level of nursing intervention
Week RT
No intervention N= 14 (W days)
Daily intervention N= 19 (% days)
Difference no vs. daily intervention (%)
1 2 3 4 5 6 7
10 10 45 60 56 55 50
19 32 34 38 32 24 24
+9 +22 -11 -22 -24 -31 -26
Week 3-7
x = 53%
‘? = 30%
-15
pain was reported, however, in 32% of Group I and 10% of Group II patients in the first two weeks of radiation therapy (Table 6). Baseline levels of pain prior to radiation effects did not predict for subsequent difficulties in pain management. Pain during radiation therapy was reported to occur most or all of the day in 23% of treatment days for patients with daily intervention (Group I) in contrast to the 58% incidence among patients without daily intervention (Group II). A 19% decrease in treatment days with mucositis was observed during weeks three through seven of radiation therapy for patients receiving daily intervention. Improvement in pain control was most pronounced for moderate and severe pain levels with a 23% decrease in affected treatment days. Mean weight loss during radiation also differed in the two groups; only 42% of Group II as compared to 57% of Group I patients experienced more than a 2 kg loss in weight. Codeine and oxycodone products were used by 93% of Group II patients while only 14% used morphine; Group I by comparison, used codeine 34% of treatment days and morphine during 17% of the treatment (Table 7).
Table 7. Comparison of reported pain levels according to degree of nursing intervention No intervention N= 14 Pain noted most or all of day Mean weight loss > 5 kg Treatment days using codeine Treatment days using morphine sulfate
Daily intervention
Difference no vs. daily
(% days)
N= 19 (% days)
intervention (%)
58
23
-35
57
16
-41
93
34
-59
14
17
+3
* Patients were allowed to combine listed medications to achieve maximum control of experienced pain while minimizing secondary effects of analgesics.
DISCUSSION Radiation associated mucosal reactions are a predictable aspect of head and neck cancer irradiation first noted at the start of the third week of treatment following administration of 2000 cGy (2, 3, 14, 17). Numerous strategies have been proposed to either prevent ( 1,4-6,22) or treat (13) radiation-associated mucositis with limited observed efficacy (2 1). This study evaluated patients undergoing radiation therapy for head and neck cancer given a defined protocol for analgesic use and oral hygiene supported by daily nursing intervention. The importance of oral hygiene in reducing acute and late complications of radiation therapy to the head and neck region has been well described (4, 22). Aggressive oral hygiene acts to reduce oral flora, remove thickened secretions and debris, and increase moisture within the mouth. Pharyngeal pain represents a common denominator given the necessary inclusion of the pharyngeal wall in all head and neck radiation treatment portals. Recorded symptoms correlated exactly with observed mucositis during the course of therapy. Throat pain was therefore recorded during 57% of treatment days, affecting swallowing during 40% of the therapy and limiting dietary intake to liquids in 2 1% of treatment days. Weight loss totalling 5 kg or more occurred in 16% of patients evaluated. Correspondingly, 29% of patients experienced moderate to severe pain during the course of radiation. Effective analgesia was accomplished, however, in 94% of patients with codeine or morphine used over 5 1% of treatment days. Administered analgesics did not result in sedation, respiratory depression, aspiration, or other effects (7). Pertinent to a population with frequent alcohol dependency, no evidence of opioid psychologic dependence (addiction) was demonstrated during or following completion of the radiation course. The impact of a defined analgesic protocol and daily intervention was determined by comparison to a patient group receiving only initial and sporadic instructions (21). Notable improvements in pain control included a 34% improvement in oral intake, 15% reduction in weight loss totalling 2 kg or more, 35% reduction in pain duration, and 23% improvement in analgesic efficacy. Our results indicate that radiation mucositis can be treated effectively. Improvements in quality of life and nutritional status during the course of radiation therapy are observed with aggressive clinical management including a defined protocol for analgesic use and oral hygiene. This approach parallels that proven to be beneficial in mucositis related to bone marrow transplantation (4, 9). However, further work is necessary to determine optimal analgesic delivery and scheduling, and identify possible agents that may ameliorate radiation-induced inflammation. Future trials should incorporate defined strategies for oral care and analgesic used to control for these factors in assessing efficacy.
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