Oral cancer
BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7253.97 (Published 08 July 2000) Cite this as: BMJ 2000;321:97All rapid responses
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EDITOR -
Scully and Porter's interview of oral cancer(1) needs further
clarification with respect to the role of radiotherapy. The authors state
that cures with primary radiotherapy are uncommon. In fact, published
results suggest that brachytherapy achieves excellent local control rates
of over 80% for stage T1 and T2 cancers of the lip, tongue and floor of
mouth.(2-4) These results are comparable to surgical series and, moreover,
the functional and cosmetic results are excellent. For more advanced
tumours the results for both surgery and radiotherapy alone are less good,
and these tumours are often best managed with combined modality
therapy.(5)
Osteoradionecrosis of the mandible is undoubtedly a severe
consequence of radiotherapy. The risk of osteoradionecrosis is minimised
if the total dose to the mandible is restricted to less than 70Gy and by
careful dental supervision and avoidance of trauma and dental extractions.
The risk of radionecrosis with brachytherapy is critically dependent on
total dose, dose rate and volume of implant. Risks can be further reduced
by the use of tissue spacers to attenuate the dose to underlying bone.
Patients at high risk of radionecrosis (particularly tumours in close
proximity to bone) are best treated surgically.
Xerostomia is an unpleasant complication of treating the major
salivary glands with large field irradiation. Early stage disease,
however, can normally be irradiated with leteralised external beam
radiotherapy or brachytherapy sparing at least one major salivary gland.
Exciting new developments in the delivery of radiotherapy suggest that
even advanced lesions, where conventional treatment results in ablation of
parotid function bilaterally, can now be treated with sufficient sparing
of parotid gland function to maintain good saliva production.(6)
Current recommendations are that head and neck cancers should be
managed in a combined clinic with input from maxillofacial, ENT surgeons
and clinical oncologists together with the other members of the
multidisciplinary team.(5) Patients with oral cancer need to be fully
informed of the treatment alternatives, their respective results and side
effects before an individual's treatment approach is decided. This is best
done in the setting of a multidisciplinary clinic, where the relative
merits of different treatments can be discussed.
R Jena, specialist registrar, clinical oncology
S Russell, specialist registrar, clinical oncology
P Jani, consultant ENT surgeon
R Benson, consultant clinical oncologist
Addenbrookes Hospital NHS Trust, Cambridge CB2 2QQ
1. Scully C, Proter S. Oral Cancer BMJ 2000;321(7253):97-100
2. Jorgensen K, Elbrond O, Andersen AP. Carcinoma of the lip. A series of
869 cases. Acta Radiol Ther Phys Biol 1973;12(3):177-90
3. Mazeron JJ, Crook JM, Benck V, Marinello G, Martin M, Raynal M, et al.
Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue. Int
J Radiat Oncol Biol Phys 1990:19(6):1369-76
4. Pernot M, Hoffstetter S, Peiffert D, Luporsi E, Marchal C, Kozminski P,
et al. Epidermoid carcinomas of the floor of mouth treated by exclusive
radiation: statistical study of a series of 207 cases. Radiother Oncol
1995;35(3):177-85
5. British Association of Otolaryngologists Head and Neck Surgeons.
Effective head and neck cancer management. Consensus Document. 1998.
6. Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA. Dose, volume, and
function relationships in parotid salivary glands following conformal and
intensity-modulated irradiation of head and neck cancer. Int J Radiat
Oncol Biol Phys 1999:45(3):577-87.
Competing interests: No competing interests
Professors Scully and Portermay have produced an "ABC of oral
cancer"1. but it is certainly not an A to Z. The section on the role of
radiotherapy in the management of patients with oral cancer is woefully
inadequate. It
is inaccurate : interstitial therapy is not "brachiotherapy" it is
brachytherapy (and the term "plesiotherapy" is not in common usage). It
is presented badly : the photograph of radiation induced mucositis is so
out of focus that it is unrecognisable and of no educational value. It is
distorted : three lines are devoted to the complications of oral surgery
that may even involve mortality or major reconstruction of the face with
its disfigurement and functional impairment. On the other hand
radiotherapy side effects are awarded five full column inches and two
extra
stray sentences. External beam radiotherapy is damned in the sole
sentence describing it and which states only that it "is commonly
accompanied by side effects" which are detailed later. However, it
carries no mortality.
Even the section on management is woefully inadequate. Treatment is not
only "largely by surgery or radiotherapy". There is a considerable role
for post-operative radiotherapy ie a combined approach - barely alluded to
in the statement on "moderate dose radiotherapy" after neck dissection.
Lymph nodes can also be treated electively for suspected subclinical
disease.
The authors acknowledge with gratitude advice from a GP and a
maxillofacial surgical trainee. They would be advised to consult the
oncologist with whom it is hoped they work in accordance with one of
their recommendations that is useful in their review - ie the oncologist
member of their combined
clinic. They then might be able to reassure their currently mis-informed
readers that well planned and accurately delivered radiotherapy either by
external beam or brachytherapy in appropriate patients as advised by the
multidisciplinary team will result in cure rates that are no different
from surgery. For example, radiotherapy for floor of mouth cancer
results in 3 year disease-free survival rates varying from 85% for T1
disease to 13% for
T4 tumours (54% overall). For oral tongue these figures would be 64%, 5%
and 31% 2. Respectively.
Professor Alan Rodger & Dr Sidney Davis
William Buckland Radiotherapy Centre and Monash University.
References:
1. Scully C and Porter S. ABC of oral health. Oral Cancer. BMJ
2000 ; 321 : 97 - 100
2. Principles and Practice of Radiation Oncology. 2nd Ed. Ed. Perez
CA and Brady LW. Chapter 31. Oral Cavity by Wang CC pp 672 - 690. J B
Lippincott Co. Philadelphia 1992.
Competing interests: No competing interests
EDITOR – Scully and Porter give an interesting and
thorough coverage of oral cancer. (1) However they
state that cure of these cancers, especially larger
lesions, is uncommon with Radiotherapy. There are no
randomised trials comparing surgery with radiotherapy
in the treatment of oral cancer and therefore
comparisons can only be made on the evidence of
published series and retrospective review. Ildstat et.
al. retrospectively reviewed 163 patients with
carcinoma of the floor of mouth (2) and concluded that
radiotherapy alone and surgery alone resulted in
equivalent survival rates for early stage disease.
They also concluded that for advanced disease combined
modality treatment improved survival in the short
term. Akine et. al report local control rates of
between 80%-90% for both brachytherapy and surgery in
stage 1 carcinoma of the mobile tongue and conclude
that for T1 and T2 carcinomas of the tongue
brachytherapy and surgery are equivalent treatment
options. Looking at carcinoma of the base of tongue
treated with radiotherapy alone to the primary site of
disease Mendenhall et. al report local control rates
of 96%, 91% and 89% for T1-3 tumours respectively at
5 years but only 38% local control for T4 tumours.
Similarly in a series of 134 patients with carcinoma
of the base of tongue Hinerman et. al. reports local
control rates of 90%, 92%, 73% and 35% at 5 years for
T1 –T4 tumours respectively. Both Mendenhall and
Hinerman conclude that both local control and survival
are comparable with either treatment modality and that
morbidity with radiotherapy was lower. We agree that
more advanced lesions are best treated with primary
surgery but that this should be followed by
post-operative radiotherapy to the primary site for
advanced disease or for close or positive margins.
(6). We feel that the evidence suggests that surgery
and radiotherapy are equally effective in the
management of early stage oral cancers and are often
complimentary in more advanced disease and as such
optimal management is achieved only within the context
of the multidisciplinary clinic.
Richard J. Casasola Specialist Registrar
Department of Clinical Oncology Western General
Hospital Crewe Road Edinburgh
Charles G. Kelly Consultant Clinical Oncologist NCCT
Newcastle General Hospital, NE4 6BE
1. Scully C, Porter S. ABC of oral health, Oral
Cancer. BMJ 2000;321;97-100. (8 July)
2. Ildstad ST. Bigelow ME. Remensnyder JP. Intra-oral
cancer at the Massachusetts General Hospital. Squamous
cell carcinoma of the floor of the mouth. Annals of
Surgery. 197(1):34-41, 1983 Jan.
3. Akine Y. Tokita N. Ogino T. Tsukiyama I. Egawa S.
Saikawa M. Ohyama W. Yoshizumi T. Ebihara S. Stage
I-II carcinoma of the anterior two-thirds of the
tongue treated with different modalities: a
retrospective analysis of 244 patients. Radiotherapy & Oncology.
21(1):24-8, 1991 May.
4. Mendenhall WM. Stringer SP. Amdur RJ. Hinerman RW.
Moore-Higgs GJ. Cassisi NJ. Is radiation therapy a
preferred alternative to surgery for squamous cell
carcinoma of the base of tongue Journal of
Clinical Oncology. 18(1):35-42, 2000 Jan.
5. Hinerman RW. Parsons JT. Mendenhall WM. Stringer
SP. Cassisi NJ. Million RR. External beam irradiation
alone or combined with neck dissection for base of
tongue carcinoma: an alternative to primary surgery.
Laryngoscope. 104(12):1466-70, 1994 Dec.
6. Hicks WL Jr. Loree TR. Garcia RI. Maamoun S.
Marshall D. Orner JB. Bakamjian VY. Shedd DP. Squamous
cell carcinoma of the floor of mouth: a 20-year
review. Head & Neck. 19(5):400-5, 1997 Aug.
Competing interests: No competing interests
Dear Sir - I was rather disappointed with the content of the article
ABC of oral health-Oral cancer by Scully and Porter in the BMJ on the 8th
July 2000, The presentation gave a rather skewed impression of the outcome
of the approaches to management. The suggestion that specific
complications from surgery of oral cancer may include:- infections, etc
fails to appreciate the effect that surgery has on the patients function
and long term quality of life. Depending upon the site and extent of the
surgery many patients have difficulty eating, speaking and may well be
cosmetically disfigured 1, .
The authors rightly point out that adverse effects are common with
radiotherapy, however, cure is no less uncommon with radiotherapy alone
than it is with surgery alone. Both radiotherapy and surgery are equally
effective in managing small lesions. Large lesions usually have to be
treated with combined surgery and radiotherapy and if a planned combined
form of treatment is considered appropriate then it is probably better for
the patient to receive surgery and post operative radiotherapy 2.
Improvements in the delivery of radiotherapy have been made over the past
10 - 15 years with alterations of radiotherapy treatment schedules3. The
important factor for outcome is not the total dose but the combination of
the total dose, the number of fractions that the dose is delivered in and
the overall treatment time. With these newer treatment schedules tumour
control rates have improved slightly. Recent studies suggest that combined
chemo/radiotherapy also improves tumour response rates 4.
With regard to the complications of radiotherapy a high percentage of
patients will experience pain from mucositis. Tobacco smoking and oral
infections will enhance the severity of the mucositis. The severity of
mucositis that will develop can be reduced by cutting the dose of
radiation or cytotoxic drugs however, this will result in the tumour
being under treated. Xerostomia is an under rated side effect of
radiotherapy. The agents Pilocarpine and salivary substitutes are
effective on a small percentage of patients. Amifostine which may prevent
the development of xerostomia be of more value. Early studies in the USA
and Europe suggest that it significantly reduces the degree of xerostomia
5.
I feel that some of these points should have been brought out in the
article by Scully and Porter. Failure to give a balanced appraisal of
morbidity and survival from both surgery and radiotherapy detracts from
the value of an ABC article.
A. G. ROBERTSON
Consultant in Clinical Oncology
1) Finlay PM, Dawson F, Robertson AG and Soutar DS. An evaluation of
functional outcome after surgery and radiotherapy for intra-oral cancer.
British Journal of Oral and Maxillofacial Surgery 30: 14-17,1992
2) Kramer S, Gelber R D, Snow J B, Marcial V A, Lowry L D, Davis L W,
Chandler R. Combined Radiation Therapy and Surgery in the management of
advanced Head and Neck Cancer: Final report of study 73-03 of Radiation
Therapy Oncology Group. Head and Neck Surg (1987) ; 10: 19-30
3) Saunders MI. Head and neck cancer; altered fractionation
schedules, Oncologist 1999; 4: 11-16
4) Munro AJ. An overview of randomised controlled trials of avjuvant
chemotherapy in head and neck cancer. BJC 1995; 71: 83-91
5) Buntzel J, Kuttner K, Frohlich D, Glatzel M. Selective
cytoprotection with amifostine in concurrent radiochemotherapy for head
and neck cancer. Annals of Oncology 1998; 9:505-9
Competing interests: No competing interests
EDITOR. Although Scully and Porter’s recent review of oral cancer was
informative, a few additions would improve it. 1. In particular, as
radiotherapy is often unfamiliar even to many health professionals, a
number of points about this treatment and its side effects should be
clarified.
As pointed out in the article, radiation can be delivered by external
beam or implant brachytherapy. In fact the oral cavity is a particular
site where both are commonly used in combination, because of better
results with this approach. Implantation does require general anaesthesia
for placement of the needles. While brachytherapy used in conjunction with
external beam radiotherapy may only take a few days, when used as the sole
treatment it would typically take at least 4-5 days to deliver a curative
dose. In comparison, external beam radiotherapy usually takes up to 5-7
weeks, with treatment given as an outpatient each weekday.
Mucositis may begin after a number of weeks of treatment, and usually
resolves in the weeks afterwards. It is an expected consequence of
treatment. While it’s true that lowering the radiation dose could reduce
mucositis, this isn’t a practical solution, as the aim of treatment is to
give sufficient dose to kill the cancer. Good oral hygiene, avoiding
smoking and topical anaesthetics all reduce the symptoms of the mucositis,
but some patients may also require morphine and nasogastric (or
percutaneous) feeding.
As opposed to acute side effects such as mucositis, late
effects occur weeks to months after radiotherapy and may be permanent.
Xerostomia can be expected whenever a high enough dose of radiation is
given to the parotid glands. Although the authors provide a table of
causes of dry mouth, in a patient previously treated with radiotherapy the
radiation oncologist will usually be able to say whether radiotherapy is
the culprit (by reviewing the treatment given). Not all radiotherapy
treatments to the head and neck region, and not even all oral cavity
treatments, will cause xerostomia.
The risk of osteoradionecrosis of the mandible increases with total
dose and the size of the dose given with each individual treatment (i.e.
the fraction size). So for a given total dose, increasing the number of
fractions, decreases the risk of osteoradionecrosis. As the authors note
extraction of teeth after a high dose of radiotherapy has been received by
the mandible may precipitate osteoradionecrosis. To prevent this unhealthy
teeth need to be removed before radiotherapy. However if teeth later need
extraction antibiotics and hyperbaric oxygen may reduce the risks. Again
not all head and neck treatments deliver a high dose to the mandible and
if there is any doubt the treating radiation oncologist needs to be
contacted.
I agree that combined clinics offer the best outcomes for patients.
Multidisciplinary clinics have been a major advance in the treatment of a
range of cancers, including those of the head and neck region. The authors
state there are usually agreed treatment policies, but this underplays the
individualisation of care that occurs in these clinics. The choice of
treatment depends on factors such as the patient’s general condition, the
extent and location of the tumour and difference in functional and
cosmetic results. These decisions routinely involve discussions between
ENT and reconstructive surgeons, radiation and medical oncologists,
dentists and palliative care physicians.
Competing interests: No competing interests
A clinical oncologist will be of great help to Dr. Scully when he
publishes his book "ABC of Oral Health", particularly in the section on
oral cancer (1) The anatomical location of the mouth and lips needs more
precise definition. It is meaningless to say that cancer of the lip has a
good 5 year survival if the lip is not adequately described. The outer lip
is composed of the orbicularis muscle and is delineated by the junction of
the vermillion border with the skin (2). Tumours of the inner lip
consisting of the commissure and inner mucosa behave like buccal lesions
and have a poor prognosis. The oral cavity should be anatomically defined
to consist of the buccal mucosa, the gingiva and hard palate, the oral
tongue,floor of the mouth and retromolar trigone (3).
The first table in the article contains an error. Maxillary antral
carcinomas should not be classified as "uncommon" oral malignant neoplasms
(1). They usually spread superiorly to the orbit, optic nerves, or chiasma
of the brain (4). Tumours of the Nasal cavity can grow into the oral
cavity causing dental pain, loose teeth, or ill fitting dentures (2) and
should perhaps be placed in the table instead of the maxillary antral
carcinomas.
There are multitudinous controlled trials with various treatment
modalities and combinations of treatments for oral cancer. Not only
surgery, radiation therapy and chemotherapy. The use of chemotherapy
before other forms of therapy (neoadjuvant), during Radiation therapy
(adjuvant chemoradiotherapy), or after surgery and/or radiotherapy
(adjuvant)has been extensively investigated and published (2).
The statement "radio-resistant tumours" is unfortunate. Peters and
colleagues reported a prospective randomized trial in which an optimal
dose of radiotherapy was found to be at least 57.6 Gray (1.8
Gray/fraction). Doses of 52.2 Gray - 54 Gray were found to be suboptimal
in that patients had a higher recurrence rate than when the larger dose
was given (2). A misconception that verrucous carcinoma (which occurs in
the oral cavity and elsewhere) should not be irradiated arose from such a
statement in which Perez-Mesa stated that radiotherapy could make these
tumours more malignant and has been believed since 1966 by many throughout
the world (5).
It is not customary to refer to a lymph node undergoing "invasion". A
node can be said to contain metastases either by clinical palpation (N) or
after surgery has been done and it has been proven to be so by
histopathological analysis (pN). To say that "moderate dose radiotherapy
is sometimes used to `sterilise' such necks (1)," implies that
radiotherapy is not commonly used in an adequate dose to clinically
negative (non palpable nodes) necks. In carcinoma of the oral tongue not
irradiating the neck would be considered to be negligent even when there
is no palpable nodes because of the high incidence of occult metastases
(6).
There is no such thing as a "moderate" dose of radiotherapy. Too
little dose is harmful and useless and too much dose is dangerous and
destructive. To say that "cure is uncommon" after radiotherapy is not
true. Primary radiation therapy to both the tumour and the draining lymph
nodes is recommended for many oral cavity tumours and gives excellent
results - whether as brachytherapy (therapy which is "close") or
teletherapy (therapy from a distance). 5 year over-all survival for T1
tumours of the tongue is 70%; for T2 lesions 40% and for T3 tumours it is
as much as 25% (2). The term "brachiotherapy" is not correct and
"plesiotherapy" is used only for surface dose applications which is also
referred to as mold therapy. This form of therapy is hardly ever used in
oral cancer (7).
References:
1. Scully C., Porter S. Oral Cancer. ABC of Oral Health. eBMJ
2000:321:97-199.
2.Schantz S.P., Harrison L.B., Forastiere A.A. Tumors of the Nasal Cavity
and Paranasal Sinuses, Nasopharynx, Oral Cavity and Oropharynx. In. Cancer
- Principles and Practice of Oncology. De Vita V.T., Hellman S., Rosenberg
S.A. 5th Ed. 1997:741-801.
3.Dobbs J., Barret A., Ash D. Practical Radiotherapy Planning. 3rd Ed.
1999:108-120.
4.Moss T. In. Moss' Radiation Oncology. Ed. Cox J.T. 7th Ed. 1994:132-148.
5. Reinecke L., Thornley A.L. Case report - radiotherapy an effective
treatment for vaginal verrucous carcinoma. Br J Radiol. 1993:66:375-378.
Review.
6. Emami B. Oral Cavity. In Principles and Practice of Radiation Oncology.
3rd Ed. Perez C.A., Brady L.W. 1997:981-1002.
7. Williams J.F. Physics of Brachytherapy. In. Principles and Practice of
Radiation Oncology. 3rd Ed. Perez C.A., Brady L.W. 1997:405.
Competing interests: No competing interests
Sir, it is a great pity that your review articles often pass comments
on the efficacy of radiotherapy, without asking a radiation oncologist to
check the accuracy.
In the article by Scully and Porter, it is stated (when discussing
radiotherapy):
"However, adverse effects are common, cure is uncommon (especially for
large tumours), and subsequent surgery is more difficult and hazardous
(with survival further reduced)".
This is simply nonsense. Many series in the literature (for instance
Wang CC, et al, Int J Radiat Oncol Biol Phys 9:1185,1983)quote cure rates
for T1 and T2 tumours of the oral tongue, floor of mouth, soft palate,
retromolar trigone, buccal mucosa, and alveolar ridge of between 50% and
90% - hardly uncommon!
In many parts of the world, including parts of the UK, primary
radical radiotherapy is considered (with good reason) to be the treatment
of choice for oral cancer.
It would apper that a little more rigour is requierd in your article
review process.
Competing interests: No competing interests
Epidemiology of oral cancers should be emphasized
Editor - I have read with great interest the clinical review on oral cancer as published recently in your journal 1. While the clinical management has been presented in great details, obviously, the authors have played down the epidemiological patterns of this group of cancers. Understandably, Scully and Porter have mentioned correctly that most oral cancers are squamous cell carcinomas, being common in France and the developing world 1. However, when having indicated their aetiology, the authors have omitted such important dietary risk factors as hot foods and drinks, malnutrition and kerosene (as a cooking fuel) 2.
The notation of oral cancers in the review 1 is not entirely correct, either. For instance, the use of "mouth cancer" to describe all oral cancers is not exact since cancers of the mouth are a separate entity (see Table) when representing a subgroup of all oral cancers (ICD9, Dx:140-149). In the view of terminology, it would be better to present the group of oral cancers after the International Classification of Diseases (ICD 9th or 10th revision) as below.
Cancers of the lip, oral cavity and pharynx (ICD9, Dx)
Code
Cancer site
Lip
141
Tongue
Salivary glands
Mouth
Pharynx
By using such classification, the authors would have not missed to mention in their list of uncommon cancers 1, for instance, the cancer of the Waldeyer's tonsillar ring. And the fact that most cancers of the tongue are spindle-cell carcinomas 2 but not squamous one.
Apart from correcting the omissions, the authors would better justify and portray the increasing concern of oral cancers as emerging clinical problem by emphasizing on the spread of oral cancers worldwide and, especially, in Europe. The best case scenario of presenting the epidemiology of oral cancers would be to tabulate some age-standardized rates of mortality (e.g. as high as 13.28 per 100,000 in French males and as low as 0.513 in Greek males in 1990) and incidence (35.05 and 1.14 per 100,000, respectively) 3. Another approach might be to compare, for instance, the highest world incidence rate versus the lowest one (i.e. B. Rhin in France and Bombay in India versus S. Thames in UK and Denmark for males aged 35-64 in 1970-1980; etc.) 2. It is also very expressive a chart to be drawn on a comparative presentation of the highest age-specific incidence rates per 100,000 persons in males and females for Europe (i.e. France in 1990 3, see Figure).
Thus, by adding this accentuation on the epidemiology and, especially, on the standardization and presentation (tabular and/or graphical), the readers of your journal would be able to get a more complete picture of the spread of oral cancers worldwide. It is of note that an emphasis on epidemiology should be a requirement for further authors of clinical reviews in the "ABC" series of your journal. In this sense, I hope the authors of that review on oral cancer 1 would be also willing to add such emphasis in their book as foreseen to be published in autumn 2000, at least from a didactic point of view.
Sincerely,
Borislav D Dimitrov *, assistant professor of social medicine.
Department of Social Medicine, Higher Medical Institute, Plovdiv, 4000, Bulgaria
Present address: Laboratory of Biostatistics, Clinical Research Centre for Rare,
Diseases "Aldo e Cele Dacco", Mario Negri Institute for Pharmacological Research, Villa
Camozzi, Ranica (BG), 24020, Italy
e-mail: bdd11@usa.net
Conflict of interests: None
References
Competing interests: Editor