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Late audio-vestibular consequences of radical radiotherapy to the parotid
Clinical Oncology (1992) 4:203-204 © 1992 The Royal College of Radiologists
Clinical Oncology
Correspondence Letters are published at the discretion o f the Editor. Opinions expressed by correspondents" are not necessarily those o f the Editor. Unduly long letters may be returned to the authors for shortening. Letters in response to a paper may be sent to the author of the paper so that the reply can be published in the same issue. Letters should be typed double spaced and should be signed by all authors personally. References should be given in the style specified in the Instruction to Authors at the front o f the Journal.
Acute Non-lymphocytic Leukaemia and Myelofibrosis Following Sequential Hemibody Irradiation for Prostatic Carcinoma SIR - Chin-Yee et al. [1] provide a lengthy discussion supporting the possibility of radiation leukaemogenesis in their case report. Whilst radiation oncologists must be cognizant of the potential toxicities of their treatments it is also important to maintain a balanced perspective recognizing competing explanations for observed patient outcomes. There were 509 men registered in our department with a primary diagnosis of prostate carcinoma from 1985-1990. In all, 381 received radiotherapy. Of these, 54 received radical radiotherapy to the prostate only, 273 received palliative (low dose) radiotherapy to metastases and 54 received both a radical and, at a later stage, palliative course(s) of radiotherapy. Four patients were subsequently diagnosed to have a lymphorecticular malignancy (Table l). Of note, half had received no therapeutic radiation and none had received chemotherapy. In very simplistic terms, 1.6% of non-irradiated patients developed a lymphoreticular malignancy compared with 0.5% of irradiated patients, and all of the latter occurred in those who had received high-dose radiotherapy only. Our sample is small but it is obviously plausible that these second malignancies may be coincidental following irradiation, or may even be associated with the primary diagnosis. Such associations are well described for a number of sites such as breast and uterus, lung and bladder, and retinoblastoma and osteosarcoma. P. GRAHAM
Department o f Radiation Oncology Westmead Hospital Westmead Australia 2145
References 1. Chin-Yee I, Porter AT, Lohmann RC. Acute non-lymphocytic leukaemia and myelofibrosis following sequential hemibody irradiation for prostatic carcinoma. Clin Oncol 1991; 3:28890. Late Audio-Vestibular Consequences of Radical Radiotherapy to the Parotid SIR We were interested to read the study of Singh and Slevin [1]. The hearing of 28 patients was tested to assess the effect upon the inner ear of a 3-week radical radiotherapy schedule used to treat pleomorphic adenomas. All patients had been treated at least 5 years previously. Twenty-three of 28 received a dose of 50 Gy or 16 fractions in 20 or 21 days. The remaining patients received 47.5 Gy ( n = l ) , 52.5 Gy (n=3) and 55 Gy ( n = l ) . Significant hearing loss was found in 55% (15/28). Three patients of 4 receiving doses greater than 50 Gy had notable deafness. In addition, 7 of 15 patients with hearing loss had semicircular paresis. These results contrast with those we published 3 years ago [2]. No hearing loss was seen in 18 patients tested. Seventeen were treated with 60 Gy in 30 fractions over 6 weeks (4 MeV X-rays). One received 55 Gy in 25 fractions (17 MeV electrons). Our conclusion was that a dose of 60 Gy given in daily 2 Gy fractions was unlikely to produce permanent hearing loss. The two series are similar in some ways. In the Manchester series 56% of treated patients at risk for late effects attended compared to 45% in Glasgow. Glasgow patients tended to be older at the time of testing (mean age 58 versus 65 years). Females predominate in both groups. A two field 'wedged pair' technique was used in Glasgow; in Manchester some patients were treated using a three field - -
approach but treatment depth at the centre of the horizontal contour (4-5 cm) was the same in both centres. The obvious difference between the two series is the daily fraction size used (3.3 Gy versus 2 Gy). Fraction size is an important factor in the expression of late damage in other neural tissues, such as spinal cord [3], brain [4] and optic chiasma [5]. Why should the inner ear be any different? Singh and Slevin use the local control rate of 94.8% in their centre as justification for giving treatment over 3 weeks, albeit with a high late morbidity. However, similar control rates have been reported from Edinburgh where pleomorphic adenomas were treated with doses of 50-60 Gy in 4-5 weeks [6]. Early results published from Hong Kong suggest that late temporal lobe necrosis as a complication of treatment of carcinoma of the nasopharynx can be reduced if the daily fraction size is reduced from 4.2 Gy to 2.5 Gy, even though the total dose was increased from 50.4 Gy to 60 Gy given over 6 weeks [7]. It is tempting to suggest that a high local control rate can be maintained in the treatment of pleomorphic adenoma with a low incidence of inner ear damage by protracting treatment beyond 15 fractions. Dawson and Orr [6] enunciated modern thinking that radiotherapy should be reserved for patients with pleomorphic adenoma in whom complete excision would probably result in seventh nerve damage. It is difficult to justify the use of a treatment for this benign tumour which exchanges damage to the seventh nerve with that to the eighth. Singh and Slevin state that patients are routinely warned that radical radiotherapy may result in late audio-vestibular damage. 'Tongue in cheek', we are tempted to suggest that patients should also be told that the incidence of damage is likely to be much less if a smaller daily fraction is given as part of a more protracted schedule.
Table 1. Case
Age (years)
Radiotherapy
Diagnosis interval (months)
Second diagnosis
1
71
39
Acute myeloid leukaemia
2
58
60
Small cell lymphoma
3 4
77 63
Pelvis 46 Gy + Prostate 20 Gy Pelvis 50 Gy + Prostate 20 Gy None None
29 1
Small cell lymphoma Chronic lymphatic leukaemia
204
Correspondence
Beatson Oncology Centre Western Infirmary Glasgow Gll 6NT R. A. EVANS Bridgend Hospital Mid Glamorgan K. C. Liu Prince of Wales Hospital Hong Kong T. AZHAR National University of Malaysia Kuala Lumpar Malaysia R. P:SVMONDS
-
References 1. Singh IP, Slevin NJ. Late Audio-vestibular consequences of a radical radiotherapy to the parotid. Clin Oncol 1991; 3:217-9. 2. Evans RA, Liu KC, Azhar T, et al. Assessment of permanent hearing impairment following radical megavoltage radiotherapy. J Laryngol Otol 1988; 102:588-9. 3. Wara WM, Phillips TL, Sheline HE, et al. Radiation tolerance of the spinal cord. Cancer 1975; 35:1558-62. 4. Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys 1980; 6:1215-28. 5. Harris JR, Levene MB. Visual complications following irradiation for pituitary adeomas and cranio-pharyngiomas. Radiology 1967; 120:167-71. 6. Dawson AK, Orr JA. Long term results of local excision and radiotherapy in pleomorphic adenoma of the parotid. Int J Radiat Oncol Biol Phys 1985; 11:451-5. 7. Lee WM, Ng SH, Ho JHC et al. Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma. Cancer 1988; 60:1535-42. Economical with the Radiotherapy 'Dose' S1R- Radiotherapy dose in North American literature is often expressed as an isolated numerical dose, as the dose per fraction adopted in many North American centres has been standardized at 2 Gy per day. Dose in the U K has traditionally and correctly been expressed as a 'package' i.e. numerical dose given in a number of fractions over an overall treatment time. The importance of this more complete
description of dose is emphasized when regimens using multiple fractions per day or split treatments are utilized. The most disappointing aspect of the paper by Krawczyk et al. [1] was not the results but their misleading expression of biological dose as a simple numerical dose. They express surprise that 'doses' of 60 Gy or less were associated with better results than larger 'doses'. The regimens used in their report varied in overall time from 1.5 weeks to 9.5 weeks, with some patients being treated thrice daily and others once. In this situation the relationship between local control and numerical dose is obviously meaningless. If one accepts the validity of a linear quadratic formulation which characterizes fractionation sensitivity and incorporates a time factor, then one can compare different fractionation approaches in terms of local effect. Two regimens which give similar local control rates for T2 glottic cancer are: 1. 52.5-55 Gy in 16 daily fractions (d/f 3.28-3.44 Gy) over 21 days (3 weeks) [2] 2. 63-65.5 Gy in 28-29 daily fractions (d/f 2.25 Gy) over 37-38 days (5.3 weeks) [3]
offered a choice of 2 repayment packages to suit their individual circumstances, with compound interest calculated on a yearly basis. 1. The radiotherapist uses a credit card with a fixed borrowing rate of 32.8% to be repaid over 3 years. Amount paid back (A) is calculated: 32.8,3 A = $2250 × (1 + Tff6-) = $5269 (5250) 2. The radiation oncologist uses a secured bank loan with a variable (inflationlinked) borrowing rate of at least 22.5% over 5.3 years. Amount paid back (B) is calculated: B = $2250 x (1 +" l~-ff) 22"5"53 = $6596 (6300-6525) Needless to say these amounts, A and B, are meaningless in isolation without details of repayment time and interest charges. Let us not be economical with the truth! N. J. SLEVIN
If we accept equivalence in terms of local tumour effect between the 2 regimens underlined then:
Christie Hospital Wilmslow Road Withington Manchester M20 9BX
D2 (1 + ~gg) should be similar to D1 (1 + ~ )
+ -~ ( T 2 - T 1 )
(D = total numerical dose, d = dose per fraction and T = overall time.) If we choose an cd[5 ratio of 25 Gy and assume a maximum time factor (Uc0 of 0.6 2 25 Gy per day [4] then 63 (1 + ~ ) should be 3.28, similar to 52.5 (1 + ~ - ) + 0.6 (37-21), i.e. 68.67 Gy will have a similar local tumour control to 68.99 Gy, despite the different total numerical doses used. Factitious Financial Footnote. A Clinical Oncologist/Radiotherapist and a Radiation Oncologist wish to borrow a $2250 lump sum to make a commercial killing. They are
References 1. Krawczyk J, Svoboda V, Foster L. The infuence of some factors on local control of early glottic cancer. Clin Oncol 1991;3:330-4. 2. SlevinNJ. Relative influences oftumour biological dose versus dose per fraction on late normal tissue morbidity following radiotherapy. Clin Oncol 1991; 3:352. 3. Mendenhall WM, Parsons JT, Million RR, et al. TI-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: Relationship of dose-fractionation factors to local control and complications. Int J Radia Oncol Biol Phys 1988;15:1267-73. 4. Withers HR, Taylor JMG, Maciejewski B. The harzard of accelerated tumour clonogen repopulation during radiotherapy. Acta Oncol 1988 ;27:131-46.
Clinical Oncology
Correspondence Letters are published at the discretion o f the Editor. Opinions expressed by correspondents" are not necessarily those o f the Editor. Unduly long letters may be returned to the authors for shortening. Letters in response to a paper may be sent to the author of the paper so that the reply can be published in the same issue. Letters should be typed double spaced and should be signed by all authors personally. References should be given in the style specified in the Instruction to Authors at the front o f the Journal.
Acute Non-lymphocytic Leukaemia and Myelofibrosis Following Sequential Hemibody Irradiation for Prostatic Carcinoma SIR - Chin-Yee et al. [1] provide a lengthy discussion supporting the possibility of radiation leukaemogenesis in their case report. Whilst radiation oncologists must be cognizant of the potential toxicities of their treatments it is also important to maintain a balanced perspective recognizing competing explanations for observed patient outcomes. There were 509 men registered in our department with a primary diagnosis of prostate carcinoma from 1985-1990. In all, 381 received radiotherapy. Of these, 54 received radical radiotherapy to the prostate only, 273 received palliative (low dose) radiotherapy to metastases and 54 received both a radical and, at a later stage, palliative course(s) of radiotherapy. Four patients were subsequently diagnosed to have a lymphorecticular malignancy (Table l). Of note, half had received no therapeutic radiation and none had received chemotherapy. In very simplistic terms, 1.6% of non-irradiated patients developed a lymphoreticular malignancy compared with 0.5% of irradiated patients, and all of the latter occurred in those who had received high-dose radiotherapy only. Our sample is small but it is obviously plausible that these second malignancies may be coincidental following irradiation, or may even be associated with the primary diagnosis. Such associations are well described for a number of sites such as breast and uterus, lung and bladder, and retinoblastoma and osteosarcoma. P. GRAHAM
Department o f Radiation Oncology Westmead Hospital Westmead Australia 2145
References 1. Chin-Yee I, Porter AT, Lohmann RC. Acute non-lymphocytic leukaemia and myelofibrosis following sequential hemibody irradiation for prostatic carcinoma. Clin Oncol 1991; 3:28890. Late Audio-Vestibular Consequences of Radical Radiotherapy to the Parotid SIR We were interested to read the study of Singh and Slevin [1]. The hearing of 28 patients was tested to assess the effect upon the inner ear of a 3-week radical radiotherapy schedule used to treat pleomorphic adenomas. All patients had been treated at least 5 years previously. Twenty-three of 28 received a dose of 50 Gy or 16 fractions in 20 or 21 days. The remaining patients received 47.5 Gy ( n = l ) , 52.5 Gy (n=3) and 55 Gy ( n = l ) . Significant hearing loss was found in 55% (15/28). Three patients of 4 receiving doses greater than 50 Gy had notable deafness. In addition, 7 of 15 patients with hearing loss had semicircular paresis. These results contrast with those we published 3 years ago [2]. No hearing loss was seen in 18 patients tested. Seventeen were treated with 60 Gy in 30 fractions over 6 weeks (4 MeV X-rays). One received 55 Gy in 25 fractions (17 MeV electrons). Our conclusion was that a dose of 60 Gy given in daily 2 Gy fractions was unlikely to produce permanent hearing loss. The two series are similar in some ways. In the Manchester series 56% of treated patients at risk for late effects attended compared to 45% in Glasgow. Glasgow patients tended to be older at the time of testing (mean age 58 versus 65 years). Females predominate in both groups. A two field 'wedged pair' technique was used in Glasgow; in Manchester some patients were treated using a three field - -
approach but treatment depth at the centre of the horizontal contour (4-5 cm) was the same in both centres. The obvious difference between the two series is the daily fraction size used (3.3 Gy versus 2 Gy). Fraction size is an important factor in the expression of late damage in other neural tissues, such as spinal cord [3], brain [4] and optic chiasma [5]. Why should the inner ear be any different? Singh and Slevin use the local control rate of 94.8% in their centre as justification for giving treatment over 3 weeks, albeit with a high late morbidity. However, similar control rates have been reported from Edinburgh where pleomorphic adenomas were treated with doses of 50-60 Gy in 4-5 weeks [6]. Early results published from Hong Kong suggest that late temporal lobe necrosis as a complication of treatment of carcinoma of the nasopharynx can be reduced if the daily fraction size is reduced from 4.2 Gy to 2.5 Gy, even though the total dose was increased from 50.4 Gy to 60 Gy given over 6 weeks [7]. It is tempting to suggest that a high local control rate can be maintained in the treatment of pleomorphic adenoma with a low incidence of inner ear damage by protracting treatment beyond 15 fractions. Dawson and Orr [6] enunciated modern thinking that radiotherapy should be reserved for patients with pleomorphic adenoma in whom complete excision would probably result in seventh nerve damage. It is difficult to justify the use of a treatment for this benign tumour which exchanges damage to the seventh nerve with that to the eighth. Singh and Slevin state that patients are routinely warned that radical radiotherapy may result in late audio-vestibular damage. 'Tongue in cheek', we are tempted to suggest that patients should also be told that the incidence of damage is likely to be much less if a smaller daily fraction is given as part of a more protracted schedule.
Table 1. Case
Age (years)
Radiotherapy
Diagnosis interval (months)
Second diagnosis
1
71
39
Acute myeloid leukaemia
2
58
60
Small cell lymphoma
3 4
77 63
Pelvis 46 Gy + Prostate 20 Gy Pelvis 50 Gy + Prostate 20 Gy None None
29 1
Small cell lymphoma Chronic lymphatic leukaemia
204
Correspondence
Beatson Oncology Centre Western Infirmary Glasgow Gll 6NT R. A. EVANS Bridgend Hospital Mid Glamorgan K. C. Liu Prince of Wales Hospital Hong Kong T. AZHAR National University of Malaysia Kuala Lumpar Malaysia R. P:SVMONDS
-
References 1. Singh IP, Slevin NJ. Late Audio-vestibular consequences of a radical radiotherapy to the parotid. Clin Oncol 1991; 3:217-9. 2. Evans RA, Liu KC, Azhar T, et al. Assessment of permanent hearing impairment following radical megavoltage radiotherapy. J Laryngol Otol 1988; 102:588-9. 3. Wara WM, Phillips TL, Sheline HE, et al. Radiation tolerance of the spinal cord. Cancer 1975; 35:1558-62. 4. Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys 1980; 6:1215-28. 5. Harris JR, Levene MB. Visual complications following irradiation for pituitary adeomas and cranio-pharyngiomas. Radiology 1967; 120:167-71. 6. Dawson AK, Orr JA. Long term results of local excision and radiotherapy in pleomorphic adenoma of the parotid. Int J Radiat Oncol Biol Phys 1985; 11:451-5. 7. Lee WM, Ng SH, Ho JHC et al. Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma. Cancer 1988; 60:1535-42. Economical with the Radiotherapy 'Dose' S1R- Radiotherapy dose in North American literature is often expressed as an isolated numerical dose, as the dose per fraction adopted in many North American centres has been standardized at 2 Gy per day. Dose in the U K has traditionally and correctly been expressed as a 'package' i.e. numerical dose given in a number of fractions over an overall treatment time. The importance of this more complete
description of dose is emphasized when regimens using multiple fractions per day or split treatments are utilized. The most disappointing aspect of the paper by Krawczyk et al. [1] was not the results but their misleading expression of biological dose as a simple numerical dose. They express surprise that 'doses' of 60 Gy or less were associated with better results than larger 'doses'. The regimens used in their report varied in overall time from 1.5 weeks to 9.5 weeks, with some patients being treated thrice daily and others once. In this situation the relationship between local control and numerical dose is obviously meaningless. If one accepts the validity of a linear quadratic formulation which characterizes fractionation sensitivity and incorporates a time factor, then one can compare different fractionation approaches in terms of local effect. Two regimens which give similar local control rates for T2 glottic cancer are: 1. 52.5-55 Gy in 16 daily fractions (d/f 3.28-3.44 Gy) over 21 days (3 weeks) [2] 2. 63-65.5 Gy in 28-29 daily fractions (d/f 2.25 Gy) over 37-38 days (5.3 weeks) [3]
offered a choice of 2 repayment packages to suit their individual circumstances, with compound interest calculated on a yearly basis. 1. The radiotherapist uses a credit card with a fixed borrowing rate of 32.8% to be repaid over 3 years. Amount paid back (A) is calculated: 32.8,3 A = $2250 × (1 + Tff6-) = $5269 (5250) 2. The radiation oncologist uses a secured bank loan with a variable (inflationlinked) borrowing rate of at least 22.5% over 5.3 years. Amount paid back (B) is calculated: B = $2250 x (1 +" l~-ff) 22"5"53 = $6596 (6300-6525) Needless to say these amounts, A and B, are meaningless in isolation without details of repayment time and interest charges. Let us not be economical with the truth! N. J. SLEVIN
If we accept equivalence in terms of local tumour effect between the 2 regimens underlined then:
Christie Hospital Wilmslow Road Withington Manchester M20 9BX
D2 (1 + ~gg) should be similar to D1 (1 + ~ )
+ -~ ( T 2 - T 1 )
(D = total numerical dose, d = dose per fraction and T = overall time.) If we choose an cd[5 ratio of 25 Gy and assume a maximum time factor (Uc0 of 0.6 2 25 Gy per day [4] then 63 (1 + ~ ) should be 3.28, similar to 52.5 (1 + ~ - ) + 0.6 (37-21), i.e. 68.67 Gy will have a similar local tumour control to 68.99 Gy, despite the different total numerical doses used. Factitious Financial Footnote. A Clinical Oncologist/Radiotherapist and a Radiation Oncologist wish to borrow a $2250 lump sum to make a commercial killing. They are
References 1. Krawczyk J, Svoboda V, Foster L. The infuence of some factors on local control of early glottic cancer. Clin Oncol 1991;3:330-4. 2. SlevinNJ. Relative influences oftumour biological dose versus dose per fraction on late normal tissue morbidity following radiotherapy. Clin Oncol 1991; 3:352. 3. Mendenhall WM, Parsons JT, Million RR, et al. TI-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: Relationship of dose-fractionation factors to local control and complications. Int J Radia Oncol Biol Phys 1988;15:1267-73. 4. Withers HR, Taylor JMG, Maciejewski B. The harzard of accelerated tumour clonogen repopulation during radiotherapy. Acta Oncol 1988 ;27:131-46.