htr J. Radiatwn Oncologr Biol. Phm Vol Pnnted tn the U.S A All rights reserved.
21,
pp.
0360-3016191 $3.00 + .@I Copyright 0 199 Pergamon Press plc
569-576
I
0 Original Contribution
PHOTON IRRADIATION OF UNRESECTABLE CARCINOMAS OF SALIVARY GLANDS C. C. WANG,
M.
D.*
AND MAX GOODMAN,
M.
D.?
Department of Radiation Oncology, Mass. General Hospital and the Departments of Pathology, Mass. General Hospital & Mass. Eye and Ear Infirmary, Boston, MA; and the Departments of Radiation Oncology and Pathology, Harvard Medical School
This paper presents our experience and the local control rates of a group of patients with inoperable and unresectable lesions treated by photon irradiation from 1980 through 1989. The patient material consists of a total of 24 patients, 9 with carcinoma arising from the parotid gland and 15 with lesions in the minor salivary glands, mainly the oral cavity and oropharynx. The pathologic slides were reviewed and malignancy of various ceil types confirmed. The 5year actuarial local control of parotid gland lesions after photon irradiation was 100% and the survival rate was 65%. For the minor salivary gland lesions, the 5-year actuarial local control was 78% and the survival rate with or without disease was 93%. Ail lesions were irradiated by accelerated hyperfractionated photons (bid) with 1.6 Gy per fraction, intermixed with various boost techniques including electron beam, intraoral cone, interstitial implant, and/or submental photons for a total of 65-70 Gy. Most treatment failures of parotid cancer were due to distant metastases. The present series showed excellent local control and satisfactory survival of inoperable and unresectabie salivary gland carcinomas after state-ofthe-art photon irradiation, comparable to that achieved by neutron irradiation. The late complications were minimal. A controlled randomized trial may be indicated. Salivary gland tumors, Accelerated hyperfractionation radiotherapy. INTRODUCTION
There were 9 patients with advanced carcinomas (2 T3 and 7 T4) arising in the parotid gland, 15 with TlA lesions of the minor salivary gland of the oral cavity and oropharynx (3 Tl , 4 T2, 4 T3 and 4 T4). The smaller lesions were considered unresectable because of the severe functional or cosmetic mutilation that might result after operation. The male to female ratio is 1:1.4. The mean age of the entire group was 71 years, ranging from 45 to 89. Pathologically, all various cell types were classified according to the WHO classification and reviewed by one of us (MG). These included squamous cell carcinoma (2), adenocystic carcinoma (7), adenocarcinoma (6), muco-epidermoid carcinoma (4), malignant pleomorphic adenoma (3), undifferentiated carcinoma (1)) acinic cell carcinoma (1). The patient profiles, radiation therapy data. and follow-up information are summarized in Table 2.
Carcinoma of the salivary gland is an uncommon malignancy and represents 2% to 3% of all head and neck neoplasms. Surgical resection with or without postoperative radiation therapy remains the treatment of choice for operable carcinomas of the major and minor salivary glands, which results in local control rates ranging from 50% to 80% (3,5,8). For the inoperable and unresectable lesions, which are rare in daily oncologic practice, high dose external photon or neutron radiation therapy is the preferred option for obtaining loco-regional control. METHODS
AND MATERIALS
This paper presents our experience and the local control and survival rates of a group of patients with unresectable carcinomas of the salivary gland treated by photon irradiation. From 1980-1989, a total of 24 patients were treated with photon irradiation at the Massachusetts General Hospital-Massachusetts Eye and Ear Infirmary. The extent of their primary tumors and regional nodes was staged according to the AJC staging system as shown in Table 1 (1).
Radiation therapy Of the entire group, all patients were treated with megavoltage radiations, either with a 6oCO machine or 4-6 MV photon from linear accelerator with an accelerated hyperfractionated schedule (1.6 Gy/f b.i.d.) as previously re-
Presented at the 32nd Meeting of ASTRO, Miami, Florida, 15-19 October 1990. *Radiation Therapist and Head of Clinical Services, Dept. of Radiation Medicine, Mass. General Hospital, Professor of Radiation Therapy, Harvard Medical School. tPathologist, Mass. Eye and Ear Infirmary and Assoc. Pathol-
ogist, Mass. General Hospital, Boston, MA, Assoc. Professor of Pathology, Harvard Medical School. Reprint requests to: C.C. Wang, M.D., Mass. General Hosp., Boston, MA 02114. Accepted for publication 22 February 1991.
569
570
I.J. Radiation Oncology 0 Biology 0 Physics Table 1. AJC staging of salivary gland carcinomas:
Tl T2 T3
August 1991, Volume 21, Number 3
1988
Tumor 2 cm or less in greatest dimension Tumor more than 2 cm-but not more than 4 cm in greatest dimension Tumor more than 4 cm but not more than 6 cm in greatest
dimension T4 Tumor more than 6 cm in greatest dimension NO No regional lymph node metastases Nl Metastasis in a single ipsilateral lymph node, 3 cm or less N2
in greatest dimension Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension N2a Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension
N2b Metastasis than 6 cm N2c Metastasis more than N3 Metastasis
in multiple ipsilateral lymph nodes, none more in greatest dimension in bilateral or contralateral lymph nodes, none 6 cm in greatest dimension in lymph node more than 6 cm in greatest dimen-
sion
ported (9), and intermixed with various boost techniques, for example, appositional electron beam, intra-oral cone, or interstitial brachytherapy. For the low grade lesions, the primary sites only were irradiated, whereas, for the high grade or poorly differentiated lesions with or without nodal disease, the primary sites and the regional lymph nodes were irradiated comprehensively. Depending on the extent of lesions and tolerance of treatments by the patients the doses to this group of tumors varied, ranging from 60 Gy to 78.9 Gy, with a median doses of 68.2 Gy.
Fig. 1. Diagram showing portal arrangement for localized parotid lesions using oblique wedge pair approach for 55 Gy.
Fig. 2. Diagram showing portal arrangement for advanced parotid lesions with nodal or propensity to cervical nodal metastases. (A) Simulation film showing AP PA portal covering the primary site and ipsilateral neck. (B) Diagram showing isodose distribution combining 40 Gy AP PA photons and ipsilateral electron beam to a dose of 65 Gy.
Unresectable salivary gland carcinoma 0 C.C. PHOTON IRRADlATlON OF UNRESECTABLE CARCINOMAS OF SALIVARY GLANDS A. PAROTID GLAND, ORAL CAVITY t? OROPHARYNX
571
WANG AND M. G~DMAN
PHOTON IRRADIATION OF UNRESECTABLE CARCINOMAS OF SALIVARY GLANDS B. PAROTID GLANDS (N=9)
(N=24)
1M)- -.._ *I,
85% (fl=4)
(n-11) '7
60-
___.
_______ l_l_l_.._ll_-.l.--_-_-II------(n-1 3)
63% (n-6)
i
60-
2 : ii P
40-
*O -
lmlcontrol
-------
overallsurvival
12
60-
g
40-
36
24
48
(kl)
(rl.3)
-
-
0 0
ii 0 L
65% __1__1__.__.__._____------.--.--.--.-
local
control
-I 60 1
months
Fig. 3. Diagram showing .5-year actuarial local control and survival rates of 24 patients after radiation therapy.
Figure 1 shows a typical portal arrangement for localized parotid lesion using wedge pair photon and appositional electron beam boost technique. Figure 2 shows radiation therapy portal for advanced parotid tumor used for treatment of local and regional nodes through opposed AP-PA photon and ipsilateral electron beams. Radiation therapy for tumors of the oral cavity and oropharynx was individualized, either through ipsilateral wedge pair, parallel opposing portals and various boost techniques depending on the extent of the primary and the status of the cervical nodes. Results of therapy The median follow-up of the entire group of patients was 43 months (range 8-107 months). Figure 3 shows the overall 5-year actuarial local control at the primary site and survival rates of 24 patients after radiation therapy. These rates were 85% and 83% respectively. For nine patients with unresectable parotid lesions, the 5-year actuarial local control at the primary site was 100% and the survival rate 65%, as shown in Figure 4. For 15 patients with unresectable lesions of the oral cavity and oropharynx, the corresponding local control rate was 78% and the survival rate, with and without disease, 93% as shown in Figure 5. Cervical lymph node metastases were managed by radiation Therapy, and surgery, and may effect patients’ survival. Because of small numbers, the differences in local control and survival rates among each cell type could not be elicited. Radiation complications in this group of patients were insignificant. No patients thus far developed osteoradione-
24
12
I
I
t
36
48
60
months
Fig. 4. Diagram showing 5-year actuarial local control at the primary site and survival rates of nine patients with unresectable
parotid carcinoma after radiation therapy.
crosis of the mandible, soft tissue ulceration, trismus, radiation myelitis, or excessive skin and/or subcutaneous fibrosis. Figure 6 (Case 3) and Figure 7 (Case 20) illustrate the appearance after high dose photon irradiation in the long term survivors.
PHOTON IRRADIATION OF UNRESECTAELE CARCINOMAS OF SALIVARY GLANDS C. ORAL CAVITY AND OROPHARYNX (N=15)
‘y--A__
(“_,o)
_~~._.~~~~_~~~~l.~._-~~.~~~~--~~l-l~.~~.
93% (ll=5)
\
80 -
76% (!l=3)
(k6)
60 E : k P
40 -
00 0
12
24
36
48
60
months
Fig. 5. Diagram showing 5-year actuarial local control at primary site and survival rates of 15 patients with unresectable minor salivary gland carcinomas after radiation therapy. (Note = patients living with carcinomas while primary uncontrolled.)
572
I.J. Radiation Oncology 0 Biology 0 Physics
August 1991, Volume 21, Number 3
Table 2. Summary of patient characteristics,
No. patient
TNM stage
Tumor extent
Path diagnosis
radiation therapy and follow-up Date of RT bid or qd dose/f/days
Age
Sex
Tumor site
1
60
M
Parotid
T3NO
6 x 4 cm lesion fixed with involvement of skin No nodes
Adenoca
7/2/848/l 3184 b.i.d. 69 Gy/ 38 f
NED 4114188
No
dead of heart attack
43.9 mos
2
45
F
Parotid
T3NO
6 x 8 cm mass fixed to skin No nodes
High gr. mucoepider. ca.
6/247127182 b.i.d. 60.9 Gyt 33 f
NED 3123183
Yes bone & lung
dead of dist. met. Primary under control until death
7.8 mos
3
70
F
Parotid
T4NO
8 x 7 cm mass fixed to mandible and skin No nodes
Sq. cell ca
2/l l/833124183 b.i.d. 75 Gyl 39 f
NED 8/l/90
No
living-skin & subcutaneous tissues showed mod. fibrosis asymptomatic
88 mos
4
79
F
Parotid
T4N2
8 cm mass fixed to mandible, temporal bone bulging into ext meatus. facial nerve intact
High gr. mucoepider. ca.
5/l 8/887115188 b.i.d. 69 Gyl 42
NED 6/l l/90
No
developed nodal recurrence under chemotherapy
22 mos
Follow-up status of 1”
DM
Remarks
Duration of follow-up
Ext. upper cerv. lympth node mets. 5
89
F
Parotid
T4NO
8 x 8 cm mass fixed distorting ext. auditory canal with ulceration facial nerve paretic No nodes
High gr mucoepider . ca.
11/10/83116184 b.i.d. 68.4 Gy/ 38 f
NED 4/10/85
No
died of ca. of breast with skull base mets.
15 mos
6
89
M
Parotid
T4NO
8x6x5cm fixed mass facial nerve intact No nodes
Undiff ca.
l/6/892114189 b.i.d. 61.3 Gy/ 33 f
NED 318190
No
aging with multifold med problems
12 mos
7
80
F
Parotid
T4NO
6 x 4cm mass No nodes
Acinic cell tumor
6/26/86816186 b.i.d. 60 Gyl 4of
NED 7124187
Yes
died of DM
12 mos
8
58
M
Parotid
T4NO
9.5 x 8 cm fixed mass paresis of VI nerve No nodes
Sq. cell ca
l/26/833/18/83 b.i.d. 70 Gyl 44f
NED 5/l l/84
Yes
died of distant mets
14 mos
(Continued)
Unresectable salivary gland carcinoma 0 C.C.
513
WANG ANDM. GOODMAN
Table 2. (Continued)
No. patient
Age
Sex
Tumor site
TNM stage
9
80
F
Parotid
T4NO
10
54
M
faucial tonsil
T3Nl
Tumor extent 7 X 8 cm fixed mass puckering of overlying skin facial nerve intact No nodes
Path diagnosis High gr mucoepider. ca.
Adenoid cystic ca.
Date of RT bid or qd dose/f/days 10/9/851 l/15/85 b.i.d. 68 Gy/ 44f
l/16/86 b.i.d. 67.2 Gyi 42 f
Follow-up status of 1”
DM
Remarks
Duration of follow-up
NED 9124190
No
living & well no radiation sequelae
44 mos
NED 613187
No
died of inter current dis
17 mos
11
58
M
base of tongue
T3NO
5 cm submuc. mass in ent. base of tong. No nodes
Adenoid cystic ca.
9/29/811212181 b.i.d. 78.9 Gyl 36 f
local dis. never cont. 2112190
Yes pulm. mets
living with cancer symbiotically, relatively painfree with productive life
98 mos
12
69
M
floor of mouth
TlNO
1.5 cm submucosal mass in ant. FOM tethered to adj. gum No nodes
Poorly diff. ca. (ductal
3/10/884/l 5188 b.i.d. dose 67.2 Gyl 42 f
NED 2/l 5189
No
died of intercurrent dis .
10 mos
type)
13
72
F
hard palate
T4NO
Large tumor mass in left alv. ridge and hard palate with ext. Mucosal ulceration. Tumor ext. to max. antrum & nasal cavity. No nodes
Mal. pleom. adenoma
7/7/838118183 b.i.d. 64 Gy/ 40f
NED 6/13/90
No
82 mos
14
64
M
buccal mucosa
TlNO
2 cm rec. mass after prev. ext. No nodes
Adenoid cystic ca.
10/30/8612116186 b.i.d. 41.6 Gyl24 f 30 Gy/brach
NED 6/l 8190
No
41 mos
15
68
F
Buccoging. ridge
T4Nl
3 cm mass in L buccoginv. sulcus, adj . cheek and FOM with ext. infil. into mandible 2.5 cm submandib. node
Adenoid cystic ca.
l/27/86317186 b.i.d. 67.4 Gyl 42 f
NED 6/l l/90
No
51 mos
(Continued)
I.J. Radiation Oncology 0 Biology ??Physics
574
August 1991, Volume 21, Number 3
Table 2. (Continued)
No. patient
Tumor site
TNM stage
Tumor extent
Path diagnosis
Date of RT bid or qd dose/f/days
Follow-up status of 1”
Duration of follow-up
Age
Sex
16
76
F
RMT
TlNO
2 cm exophy mass rt RMT area No nodes
Adenoid cystic ca.
9/29/821 l/9/82 b.i.d. 65 Gyl 29 f
NED 6/8lI39
No
17
74
M
Base of tongue
T3N2c
4.5 cm ulcer. mass in base of tongue mult. bilat cerv. nodes
Adenoca
6/6/887128188 b.i.d. 69 Gyl 43 f
NED 8llOl89
No
18
63
F
Soft palate
T2NO
3.5 cm superfical ulce. tumor in soft pal. and uvula No nodes
Cystadeno ca. with lymph. invas.
7/21/888126188 b.i.d. 68.5 Gyl 41 f
NED 7/30/9O
No
23 mos
19
72
F
R. oropharynx
T4N 1
Large tumor filling R oro pharyn. wall and soft pal. 3 cm ipsilat. neck node
Mal. pleomorphic adenoma
711218% 9/7/88 b.i.d. 67.2 Gyl 42 f
NED 319190
Yes lungs pelvic bone
20 mos
20
55
F
Buccal mucosa
T2NO
3 cm submucosal mass in upper but. mucosa, ext. to buccogin. sulcus No nodes
Adenoid cystic ca. with focal sq metaplasia
10/21/831217183 b.i.d. 73 Gyl 43 f
NED 2/l/88
No
50 mos
21
70
F
Buccal mucosa
T2NO
4 cm mass inv upper buccoginv. ridge & hard pal ext. to premax. space & canine fossa No nodes
Adenoid cystic ca.
10/9/801 l/21/80 b.i.d. 59.87 Gyl 35 f
NED lOl24l89
No
107 mos
22
81
M
Base of tongue
T3Nl
5 cm submuc. mass in BOT 2 cm subdigastric node
Mutinous adenoca
5/29/867117186 b.i.d. 67 Gyl 42 f
rec. ca. ca in BOT 3 yrs after rad. ther. 8/719O
Yes lung
48 mos
23
77
M
Buccal mucosa
T4NO
bulky 5-6 cm diam mass L cheek No nodes
Low gr muco-ep ca.
10/28/8612/19/86 b.i.d. 72Gyl4Q f
local ret recurrence
Yes lung
primary uncontrolled with dist. mets .
12 mos
24
75
F
Soft palate
T2NO
3.5 cm submuc mass lat left soft palate
Adenoid cystic ca.
4/3/845126184 b.i.d. 69 Gyi 30 f
local rec. 5126186
Yes lung
salvage surg for rec. Alive with+
66 mos
No nodes
DM
Remarks
78 mos
disease in the neck not controlled
pul. mets 1 l/24/89
12 mos
Unresectable salivary gland carcinoma ??C.C. WANGAND M.
Fig. 6. Photographs showing appearance of parotid carcinc rma. (A) Pretreatment; (B) 6.5 years after radiation therapy (Case 3).
DISCUSSION
GOODMAN
Fig. 7. Photographs showing appearance of adenocystic carcinoma of the buccogingival sulcus. (A) Pretreatment; (B) 5 years after radiation therapy (Case 20).
Salivary gland malignancies have diverse histopathology and clinical course. The prognosis is closely related to
irradiation series were carried out many years ago with antiquated equipment and some even with orthovoltage radiation with low doses and in patients in poor general
the stages, cell types and grade, site of origin and status of lymph nodes and resectability. These tumors are marked by their unpredictable clinical course and some are characterized by chronicity and tendency to multiple recurrences. Therefore, long term follow-up is required. Note that results of the local treatment method, either surgical or radiotherapeutic, should be judged by the efficacy of local tumor control and attendant complications rather than the patients survivorship per se. Recent reports (4,7) summarized the results of treatments among various radiation centers as published in the literature, and indicated that the local control rates for inoperable cancers of the parotid gland after neutron u-radiation were superior to those after conventional photon irradiation, that is, 68% (range 38%81%) versus 28% (range 12%-54%), respectively (4). Significant radiation complications after neutron irradiation occurred in 1 of 5 patients treated (2). Without a randomized trial, such information for comparison of these treatments must be taken with a grain of salt since most photon
physical health unfit for radical surgery. Data related to local control of inoperable minor salivary glands by irradiation were practically lacking. Any treatment results mostly were poor, primarily derived from anecdotal experiences with a small number of patients (6). Although the numbers in the series were small and the follow-up relatively short, our experience suggested that state of the art photon radiation therapy using the b.i.d. program can achieve good local control of unresectable salivary gland tumors and the local control rates were comparable to those claimed by neutron radiation therapy yet without significant radiation therapy complications. Unfortunately, patients with advanced tumors tend to develop distant metastases even if the primary tumor is controlled. Further therapeutic measures using adjuvant chemotherapy should be explored in the hope of improving patient survival. Likewise, for comparison of neutron radiation therapy and accelerated hyperfractionated radiation therapy, a controlled randomized trial is suggested.
576
I.J. Radiation
Oncology 0 Biology 0 Physics
August 1991, Volume 21, Number 3
REFERENCES 1. American Joint Committee on Cancer. Manual for staging of cancer, 3rd edition. Philadelphia: JB Lippincott Co., 1988: 51-53. 2. Batterman, J.J.; Mijnheer, B.J. The Amsterdam fast neutron radiotherapy project. A final report. Int. J. Radiat. Oncol. Biol. Phys. 12:2093-2099; 1986. 3. Borthne, A.; Kjellevold, K.; Kaalhus, 0.; Vermund, H. Salivary gland malignant neoplasms: treatment and prognosis. Int. J. Radiat. Oncol. Biol. Phys. 12:747-754; 1986. 4. Catterall, M.; Errington, R.D. The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 13:13131318; 1987. 5. Fu, K.K.; Leibel, S.A.; Levine, M.L.; Friedlander, L.M.; Boles, R.; Phillips, T.L. Carcinoma of the major and minor
salivary glands. Cancer 40:2882-2890;
1977.
6. Kadish, S.; Goodman, M.; Wang, C.C. Treatment of minor salivary gland malignancies of the upper food and air passage epithelium. Cancer 29: 1021-1026; 1972. Laramore, G.E. Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice? Int. J. Radiat. Oncol. Biol. Phys. 13:1421-1423; 1987. Ravasz, L.A.; Terhaard, C.H.J.; Hordijk, G.J. Radiotherapy in epithelial tumors of the parotid gland: case presentation and literature review. Int. J. Radiat. Oncol. Biol. Phys. 1955-59; 1990. Wang, C.C.; Blitzer, P.B.; Suit, H.D. Twice-a-day radiation therapy for cancer of the head and neck. Cancer 55:21002104; 1985.
21,
pp.
0360-3016191 $3.00 + .@I Copyright 0 199 Pergamon Press plc
569-576
I
0 Original Contribution
PHOTON IRRADIATION OF UNRESECTABLE CARCINOMAS OF SALIVARY GLANDS C. C. WANG,
M.
D.*
AND MAX GOODMAN,
M.
D.?
Department of Radiation Oncology, Mass. General Hospital and the Departments of Pathology, Mass. General Hospital & Mass. Eye and Ear Infirmary, Boston, MA; and the Departments of Radiation Oncology and Pathology, Harvard Medical School
This paper presents our experience and the local control rates of a group of patients with inoperable and unresectable lesions treated by photon irradiation from 1980 through 1989. The patient material consists of a total of 24 patients, 9 with carcinoma arising from the parotid gland and 15 with lesions in the minor salivary glands, mainly the oral cavity and oropharynx. The pathologic slides were reviewed and malignancy of various ceil types confirmed. The 5year actuarial local control of parotid gland lesions after photon irradiation was 100% and the survival rate was 65%. For the minor salivary gland lesions, the 5-year actuarial local control was 78% and the survival rate with or without disease was 93%. Ail lesions were irradiated by accelerated hyperfractionated photons (bid) with 1.6 Gy per fraction, intermixed with various boost techniques including electron beam, intraoral cone, interstitial implant, and/or submental photons for a total of 65-70 Gy. Most treatment failures of parotid cancer were due to distant metastases. The present series showed excellent local control and satisfactory survival of inoperable and unresectabie salivary gland carcinomas after state-ofthe-art photon irradiation, comparable to that achieved by neutron irradiation. The late complications were minimal. A controlled randomized trial may be indicated. Salivary gland tumors, Accelerated hyperfractionation radiotherapy. INTRODUCTION
There were 9 patients with advanced carcinomas (2 T3 and 7 T4) arising in the parotid gland, 15 with TlA lesions of the minor salivary gland of the oral cavity and oropharynx (3 Tl , 4 T2, 4 T3 and 4 T4). The smaller lesions were considered unresectable because of the severe functional or cosmetic mutilation that might result after operation. The male to female ratio is 1:1.4. The mean age of the entire group was 71 years, ranging from 45 to 89. Pathologically, all various cell types were classified according to the WHO classification and reviewed by one of us (MG). These included squamous cell carcinoma (2), adenocystic carcinoma (7), adenocarcinoma (6), muco-epidermoid carcinoma (4), malignant pleomorphic adenoma (3), undifferentiated carcinoma (1)) acinic cell carcinoma (1). The patient profiles, radiation therapy data. and follow-up information are summarized in Table 2.
Carcinoma of the salivary gland is an uncommon malignancy and represents 2% to 3% of all head and neck neoplasms. Surgical resection with or without postoperative radiation therapy remains the treatment of choice for operable carcinomas of the major and minor salivary glands, which results in local control rates ranging from 50% to 80% (3,5,8). For the inoperable and unresectable lesions, which are rare in daily oncologic practice, high dose external photon or neutron radiation therapy is the preferred option for obtaining loco-regional control. METHODS
AND MATERIALS
This paper presents our experience and the local control and survival rates of a group of patients with unresectable carcinomas of the salivary gland treated by photon irradiation. From 1980-1989, a total of 24 patients were treated with photon irradiation at the Massachusetts General Hospital-Massachusetts Eye and Ear Infirmary. The extent of their primary tumors and regional nodes was staged according to the AJC staging system as shown in Table 1 (1).
Radiation therapy Of the entire group, all patients were treated with megavoltage radiations, either with a 6oCO machine or 4-6 MV photon from linear accelerator with an accelerated hyperfractionated schedule (1.6 Gy/f b.i.d.) as previously re-
Presented at the 32nd Meeting of ASTRO, Miami, Florida, 15-19 October 1990. *Radiation Therapist and Head of Clinical Services, Dept. of Radiation Medicine, Mass. General Hospital, Professor of Radiation Therapy, Harvard Medical School. tPathologist, Mass. Eye and Ear Infirmary and Assoc. Pathol-
ogist, Mass. General Hospital, Boston, MA, Assoc. Professor of Pathology, Harvard Medical School. Reprint requests to: C.C. Wang, M.D., Mass. General Hosp., Boston, MA 02114. Accepted for publication 22 February 1991.
569
570
I.J. Radiation Oncology 0 Biology 0 Physics Table 1. AJC staging of salivary gland carcinomas:
Tl T2 T3
August 1991, Volume 21, Number 3
1988
Tumor 2 cm or less in greatest dimension Tumor more than 2 cm-but not more than 4 cm in greatest dimension Tumor more than 4 cm but not more than 6 cm in greatest
dimension T4 Tumor more than 6 cm in greatest dimension NO No regional lymph node metastases Nl Metastasis in a single ipsilateral lymph node, 3 cm or less N2
in greatest dimension Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension N2a Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension
N2b Metastasis than 6 cm N2c Metastasis more than N3 Metastasis
in multiple ipsilateral lymph nodes, none more in greatest dimension in bilateral or contralateral lymph nodes, none 6 cm in greatest dimension in lymph node more than 6 cm in greatest dimen-
sion
ported (9), and intermixed with various boost techniques, for example, appositional electron beam, intra-oral cone, or interstitial brachytherapy. For the low grade lesions, the primary sites only were irradiated, whereas, for the high grade or poorly differentiated lesions with or without nodal disease, the primary sites and the regional lymph nodes were irradiated comprehensively. Depending on the extent of lesions and tolerance of treatments by the patients the doses to this group of tumors varied, ranging from 60 Gy to 78.9 Gy, with a median doses of 68.2 Gy.
Fig. 1. Diagram showing portal arrangement for localized parotid lesions using oblique wedge pair approach for 55 Gy.
Fig. 2. Diagram showing portal arrangement for advanced parotid lesions with nodal or propensity to cervical nodal metastases. (A) Simulation film showing AP PA portal covering the primary site and ipsilateral neck. (B) Diagram showing isodose distribution combining 40 Gy AP PA photons and ipsilateral electron beam to a dose of 65 Gy.
Unresectable salivary gland carcinoma 0 C.C. PHOTON IRRADlATlON OF UNRESECTABLE CARCINOMAS OF SALIVARY GLANDS A. PAROTID GLAND, ORAL CAVITY t? OROPHARYNX
571
WANG AND M. G~DMAN
PHOTON IRRADIATION OF UNRESECTABLE CARCINOMAS OF SALIVARY GLANDS B. PAROTID GLANDS (N=9)
(N=24)
1M)- -.._ *I,
85% (fl=4)
(n-11) '7
60-
___.
_______ l_l_l_.._ll_-.l.--_-_-II------(n-1 3)
63% (n-6)
i
60-
2 : ii P
40-
*O -
lmlcontrol
-------
overallsurvival
12
60-
g
40-
36
24
48
(kl)
(rl.3)
-
-
0 0
ii 0 L
65% __1__1__.__.__._____------.--.--.--.-
local
control
-I 60 1
months
Fig. 3. Diagram showing .5-year actuarial local control and survival rates of 24 patients after radiation therapy.
Figure 1 shows a typical portal arrangement for localized parotid lesion using wedge pair photon and appositional electron beam boost technique. Figure 2 shows radiation therapy portal for advanced parotid tumor used for treatment of local and regional nodes through opposed AP-PA photon and ipsilateral electron beams. Radiation therapy for tumors of the oral cavity and oropharynx was individualized, either through ipsilateral wedge pair, parallel opposing portals and various boost techniques depending on the extent of the primary and the status of the cervical nodes. Results of therapy The median follow-up of the entire group of patients was 43 months (range 8-107 months). Figure 3 shows the overall 5-year actuarial local control at the primary site and survival rates of 24 patients after radiation therapy. These rates were 85% and 83% respectively. For nine patients with unresectable parotid lesions, the 5-year actuarial local control at the primary site was 100% and the survival rate 65%, as shown in Figure 4. For 15 patients with unresectable lesions of the oral cavity and oropharynx, the corresponding local control rate was 78% and the survival rate, with and without disease, 93% as shown in Figure 5. Cervical lymph node metastases were managed by radiation Therapy, and surgery, and may effect patients’ survival. Because of small numbers, the differences in local control and survival rates among each cell type could not be elicited. Radiation complications in this group of patients were insignificant. No patients thus far developed osteoradione-
24
12
I
I
t
36
48
60
months
Fig. 4. Diagram showing 5-year actuarial local control at the primary site and survival rates of nine patients with unresectable
parotid carcinoma after radiation therapy.
crosis of the mandible, soft tissue ulceration, trismus, radiation myelitis, or excessive skin and/or subcutaneous fibrosis. Figure 6 (Case 3) and Figure 7 (Case 20) illustrate the appearance after high dose photon irradiation in the long term survivors.
PHOTON IRRADIATION OF UNRESECTAELE CARCINOMAS OF SALIVARY GLANDS C. ORAL CAVITY AND OROPHARYNX (N=15)
‘y--A__
(“_,o)
_~~._.~~~~_~~~~l.~._-~~.~~~~--~~l-l~.~~.
93% (ll=5)
\
80 -
76% (!l=3)
(k6)
60 E : k P
40 -
00 0
12
24
36
48
60
months
Fig. 5. Diagram showing 5-year actuarial local control at primary site and survival rates of 15 patients with unresectable minor salivary gland carcinomas after radiation therapy. (Note = patients living with carcinomas while primary uncontrolled.)
572
I.J. Radiation Oncology 0 Biology 0 Physics
August 1991, Volume 21, Number 3
Table 2. Summary of patient characteristics,
No. patient
TNM stage
Tumor extent
Path diagnosis
radiation therapy and follow-up Date of RT bid or qd dose/f/days
Age
Sex
Tumor site
1
60
M
Parotid
T3NO
6 x 4 cm lesion fixed with involvement of skin No nodes
Adenoca
7/2/848/l 3184 b.i.d. 69 Gy/ 38 f
NED 4114188
No
dead of heart attack
43.9 mos
2
45
F
Parotid
T3NO
6 x 8 cm mass fixed to skin No nodes
High gr. mucoepider. ca.
6/247127182 b.i.d. 60.9 Gyt 33 f
NED 3123183
Yes bone & lung
dead of dist. met. Primary under control until death
7.8 mos
3
70
F
Parotid
T4NO
8 x 7 cm mass fixed to mandible and skin No nodes
Sq. cell ca
2/l l/833124183 b.i.d. 75 Gyl 39 f
NED 8/l/90
No
living-skin & subcutaneous tissues showed mod. fibrosis asymptomatic
88 mos
4
79
F
Parotid
T4N2
8 cm mass fixed to mandible, temporal bone bulging into ext meatus. facial nerve intact
High gr. mucoepider. ca.
5/l 8/887115188 b.i.d. 69 Gyl 42
NED 6/l l/90
No
developed nodal recurrence under chemotherapy
22 mos
Follow-up status of 1”
DM
Remarks
Duration of follow-up
Ext. upper cerv. lympth node mets. 5
89
F
Parotid
T4NO
8 x 8 cm mass fixed distorting ext. auditory canal with ulceration facial nerve paretic No nodes
High gr mucoepider . ca.
11/10/83116184 b.i.d. 68.4 Gy/ 38 f
NED 4/10/85
No
died of ca. of breast with skull base mets.
15 mos
6
89
M
Parotid
T4NO
8x6x5cm fixed mass facial nerve intact No nodes
Undiff ca.
l/6/892114189 b.i.d. 61.3 Gy/ 33 f
NED 318190
No
aging with multifold med problems
12 mos
7
80
F
Parotid
T4NO
6 x 4cm mass No nodes
Acinic cell tumor
6/26/86816186 b.i.d. 60 Gyl 4of
NED 7124187
Yes
died of DM
12 mos
8
58
M
Parotid
T4NO
9.5 x 8 cm fixed mass paresis of VI nerve No nodes
Sq. cell ca
l/26/833/18/83 b.i.d. 70 Gyl 44f
NED 5/l l/84
Yes
died of distant mets
14 mos
(Continued)
Unresectable salivary gland carcinoma 0 C.C.
513
WANG ANDM. GOODMAN
Table 2. (Continued)
No. patient
Age
Sex
Tumor site
TNM stage
9
80
F
Parotid
T4NO
10
54
M
faucial tonsil
T3Nl
Tumor extent 7 X 8 cm fixed mass puckering of overlying skin facial nerve intact No nodes
Path diagnosis High gr mucoepider. ca.
Adenoid cystic ca.
Date of RT bid or qd dose/f/days 10/9/851 l/15/85 b.i.d. 68 Gy/ 44f
l/16/86 b.i.d. 67.2 Gyi 42 f
Follow-up status of 1”
DM
Remarks
Duration of follow-up
NED 9124190
No
living & well no radiation sequelae
44 mos
NED 613187
No
died of inter current dis
17 mos
11
58
M
base of tongue
T3NO
5 cm submuc. mass in ent. base of tong. No nodes
Adenoid cystic ca.
9/29/811212181 b.i.d. 78.9 Gyl 36 f
local dis. never cont. 2112190
Yes pulm. mets
living with cancer symbiotically, relatively painfree with productive life
98 mos
12
69
M
floor of mouth
TlNO
1.5 cm submucosal mass in ant. FOM tethered to adj. gum No nodes
Poorly diff. ca. (ductal
3/10/884/l 5188 b.i.d. dose 67.2 Gyl 42 f
NED 2/l 5189
No
died of intercurrent dis .
10 mos
type)
13
72
F
hard palate
T4NO
Large tumor mass in left alv. ridge and hard palate with ext. Mucosal ulceration. Tumor ext. to max. antrum & nasal cavity. No nodes
Mal. pleom. adenoma
7/7/838118183 b.i.d. 64 Gy/ 40f
NED 6/13/90
No
82 mos
14
64
M
buccal mucosa
TlNO
2 cm rec. mass after prev. ext. No nodes
Adenoid cystic ca.
10/30/8612116186 b.i.d. 41.6 Gyl24 f 30 Gy/brach
NED 6/l 8190
No
41 mos
15
68
F
Buccoging. ridge
T4Nl
3 cm mass in L buccoginv. sulcus, adj . cheek and FOM with ext. infil. into mandible 2.5 cm submandib. node
Adenoid cystic ca.
l/27/86317186 b.i.d. 67.4 Gyl 42 f
NED 6/l l/90
No
51 mos
(Continued)
I.J. Radiation Oncology 0 Biology ??Physics
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August 1991, Volume 21, Number 3
Table 2. (Continued)
No. patient
Tumor site
TNM stage
Tumor extent
Path diagnosis
Date of RT bid or qd dose/f/days
Follow-up status of 1”
Duration of follow-up
Age
Sex
16
76
F
RMT
TlNO
2 cm exophy mass rt RMT area No nodes
Adenoid cystic ca.
9/29/821 l/9/82 b.i.d. 65 Gyl 29 f
NED 6/8lI39
No
17
74
M
Base of tongue
T3N2c
4.5 cm ulcer. mass in base of tongue mult. bilat cerv. nodes
Adenoca
6/6/887128188 b.i.d. 69 Gyl 43 f
NED 8llOl89
No
18
63
F
Soft palate
T2NO
3.5 cm superfical ulce. tumor in soft pal. and uvula No nodes
Cystadeno ca. with lymph. invas.
7/21/888126188 b.i.d. 68.5 Gyl 41 f
NED 7/30/9O
No
23 mos
19
72
F
R. oropharynx
T4N 1
Large tumor filling R oro pharyn. wall and soft pal. 3 cm ipsilat. neck node
Mal. pleomorphic adenoma
711218% 9/7/88 b.i.d. 67.2 Gyl 42 f
NED 319190
Yes lungs pelvic bone
20 mos
20
55
F
Buccal mucosa
T2NO
3 cm submucosal mass in upper but. mucosa, ext. to buccogin. sulcus No nodes
Adenoid cystic ca. with focal sq metaplasia
10/21/831217183 b.i.d. 73 Gyl 43 f
NED 2/l/88
No
50 mos
21
70
F
Buccal mucosa
T2NO
4 cm mass inv upper buccoginv. ridge & hard pal ext. to premax. space & canine fossa No nodes
Adenoid cystic ca.
10/9/801 l/21/80 b.i.d. 59.87 Gyl 35 f
NED lOl24l89
No
107 mos
22
81
M
Base of tongue
T3Nl
5 cm submuc. mass in BOT 2 cm subdigastric node
Mutinous adenoca
5/29/867117186 b.i.d. 67 Gyl 42 f
rec. ca. ca in BOT 3 yrs after rad. ther. 8/719O
Yes lung
48 mos
23
77
M
Buccal mucosa
T4NO
bulky 5-6 cm diam mass L cheek No nodes
Low gr muco-ep ca.
10/28/8612/19/86 b.i.d. 72Gyl4Q f
local ret recurrence
Yes lung
primary uncontrolled with dist. mets .
12 mos
24
75
F
Soft palate
T2NO
3.5 cm submuc mass lat left soft palate
Adenoid cystic ca.
4/3/845126184 b.i.d. 69 Gyi 30 f
local rec. 5126186
Yes lung
salvage surg for rec. Alive with+
66 mos
No nodes
DM
Remarks
78 mos
disease in the neck not controlled
pul. mets 1 l/24/89
12 mos
Unresectable salivary gland carcinoma ??C.C. WANGAND M.
Fig. 6. Photographs showing appearance of parotid carcinc rma. (A) Pretreatment; (B) 6.5 years after radiation therapy (Case 3).
DISCUSSION
GOODMAN
Fig. 7. Photographs showing appearance of adenocystic carcinoma of the buccogingival sulcus. (A) Pretreatment; (B) 5 years after radiation therapy (Case 20).
Salivary gland malignancies have diverse histopathology and clinical course. The prognosis is closely related to
irradiation series were carried out many years ago with antiquated equipment and some even with orthovoltage radiation with low doses and in patients in poor general
the stages, cell types and grade, site of origin and status of lymph nodes and resectability. These tumors are marked by their unpredictable clinical course and some are characterized by chronicity and tendency to multiple recurrences. Therefore, long term follow-up is required. Note that results of the local treatment method, either surgical or radiotherapeutic, should be judged by the efficacy of local tumor control and attendant complications rather than the patients survivorship per se. Recent reports (4,7) summarized the results of treatments among various radiation centers as published in the literature, and indicated that the local control rates for inoperable cancers of the parotid gland after neutron u-radiation were superior to those after conventional photon irradiation, that is, 68% (range 38%81%) versus 28% (range 12%-54%), respectively (4). Significant radiation complications after neutron irradiation occurred in 1 of 5 patients treated (2). Without a randomized trial, such information for comparison of these treatments must be taken with a grain of salt since most photon
physical health unfit for radical surgery. Data related to local control of inoperable minor salivary glands by irradiation were practically lacking. Any treatment results mostly were poor, primarily derived from anecdotal experiences with a small number of patients (6). Although the numbers in the series were small and the follow-up relatively short, our experience suggested that state of the art photon radiation therapy using the b.i.d. program can achieve good local control of unresectable salivary gland tumors and the local control rates were comparable to those claimed by neutron radiation therapy yet without significant radiation therapy complications. Unfortunately, patients with advanced tumors tend to develop distant metastases even if the primary tumor is controlled. Further therapeutic measures using adjuvant chemotherapy should be explored in the hope of improving patient survival. Likewise, for comparison of neutron radiation therapy and accelerated hyperfractionated radiation therapy, a controlled randomized trial is suggested.
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I.J. Radiation
Oncology 0 Biology 0 Physics
August 1991, Volume 21, Number 3
REFERENCES 1. American Joint Committee on Cancer. Manual for staging of cancer, 3rd edition. Philadelphia: JB Lippincott Co., 1988: 51-53. 2. Batterman, J.J.; Mijnheer, B.J. The Amsterdam fast neutron radiotherapy project. A final report. Int. J. Radiat. Oncol. Biol. Phys. 12:2093-2099; 1986. 3. Borthne, A.; Kjellevold, K.; Kaalhus, 0.; Vermund, H. Salivary gland malignant neoplasms: treatment and prognosis. Int. J. Radiat. Oncol. Biol. Phys. 12:747-754; 1986. 4. Catterall, M.; Errington, R.D. The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 13:13131318; 1987. 5. Fu, K.K.; Leibel, S.A.; Levine, M.L.; Friedlander, L.M.; Boles, R.; Phillips, T.L. Carcinoma of the major and minor
salivary glands. Cancer 40:2882-2890;
1977.
6. Kadish, S.; Goodman, M.; Wang, C.C. Treatment of minor salivary gland malignancies of the upper food and air passage epithelium. Cancer 29: 1021-1026; 1972. Laramore, G.E. Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice? Int. J. Radiat. Oncol. Biol. Phys. 13:1421-1423; 1987. Ravasz, L.A.; Terhaard, C.H.J.; Hordijk, G.J. Radiotherapy in epithelial tumors of the parotid gland: case presentation and literature review. Int. J. Radiat. Oncol. Biol. Phys. 1955-59; 1990. Wang, C.C.; Blitzer, P.B.; Suit, H.D. Twice-a-day radiation therapy for cancer of the head and neck. Cancer 55:21002104; 1985.
