Simultaneous chemoradiation: Accelerated hypofractionation

Int. .I. Radiation Oncology Biol. Phys.. Vol. 29, No. 5, pp. 1201-1202, 1994 Copyright 0 I994 Elsevier Science Ltd Printed in the USA. All rights reserved 0360-30 I6/94 $6.00 + .OO

Pergamon

??Correspondence

SIMULTANEOUS

CHEMORADIATION: HYPOFRACTIONATION

mz days 1 to 5 prior to radical surgery on Stage III and IV oral cavity cancer patients have obtained at least 3 out of 10 patients with severe wound complications. The therapeutic index has changed its ratio because of a change in tumor control and late toxicities. Our conclusion is this that simultaneous chemoradiation probably equates accelerated hypofractionation if the mechanism is supra-additive synergism. The study of treatment results and toxicities should be thoroughly established before using potentially worse treatments. Or if the risk is accepted because of better tumor results, there is a cheaper and more logical way of increasing the radiation local effect: raising the dose per fraction and keeping the treatment time as short as possible.

ACCELERATED

To the Editor: We have read several reports in Int J. Radiat. Oncol. Biol. PhJ:c-. lately concerning combinated chemoradiotherapy for head and neck cancer patients. Our humblest impression is that not a single review on late toxicities of such treatments has been dealt with. This comment is mainly focused on simultaneous chemoradiation. Sensitization is a complex term upon which authors do not agree. Steel CI al. (1) believe that to demonstrate a supraadditive effect of a certain cytostatic and radiation, data regarding both survival curves for each treatment modality should be carefully evaluated so not to misname a spurious effect observed because of the shape of such curves. Independent killing of different subpopulations in the radiation volume would obtain an increased cell kill even if not true sensitization were involved. The therapeutic index defines what amount of late damage is associated with a certain level of tumor control. It is clear that the interaction of chemoradiation obtains results superior to those with the same dose of radiation without chemotherapy. The results are higher in terms of tumor control. but also in toxicities. Publications regarding the matter refer to acute toxicities, but almost none deal with chronic ones. If. and only if there is a true mechanism of supra-additive synergism mainly involved in the interaction ofchemoradiation, then the nominal dose of radiation would be multiplied by a certain factor appliable and sensitive to different biological characteristics such as those implied by the linear quadratic model. What we mean is that a stronger enhancing effect would then be observed in tissues more sensitive to changes of fractionation because of the biologically augmented dose by chemotherapy: those tissues being lately projected effects ones, according to lower a/b ratios. For instance, let’s assume that a certain level of tumor control is obtained with 70 Gy, 2 Gy per fraction:

IGNACIO

ALASTUEY

JOSE MONTAGUT Servicio de Oncologia Radioterapica Hospital Vail d’tlebron, Barcelona,

Spain

1. Steel. G. G. Terminology in the description of drug radiation interactions. Int. J. Radial. Oncol. Biol. Phyx 5: I 145-I 150. 2. Taylor, J. The influence of dose and time on wound complications following post radiation neck dissection. Int. J. Radiat. Oncol. Biol. P~q:\. 23:4 l-46: 1992.

QUALITY OF LIFE AND NEUROPSYCHOLOGICAL FUNCTIONS IN LONG-TERM LOW-GRADE GLIOMA SURVIVORS To thr Editor: We read with interest the article by Kleinberg et al. (3) addressing the quality of survival in long-term disease-free survivors of intracranial gliomas, mainly anaplastic astrocytomas and glioblastomas. The Karnofsky Performance Status (KPS), the employment history, and the subjective memory function were the parameters used to assess the patients’ quality of life. All patients examined had received cranial radiotherapy and 83% had been treated with adjuvant chemotherapy. In contrast to the findings by others (I, 2, 4). the authors observed in their patients a relatively good performance status without a decline in neuropsychological functions. We recently published an article on cognitive functions and quality of life in long-term low-grade glioma survivors (6). These patients had been treated with radiotherapy 1 to 11 (mean 3.9) years previously after biopsy or surgery. A comprehensive somato-psychological examination took place, including the neurological and functional status (KPS), neuropsychological testing-to detect possible attentional, mnestic, verbal, visuo-spatial, and executive disturbances-and determination of the affective status, using the Profile of Mood States (POMS) and the Affect Balance Scale (ABS). Subjective information was obtained from the patients and their partners using a questionnaire, focusing on physical complaints, problems with daily life activities including cognitive functioning, the socio-economic status, social functioning and perceived social support, and evaluation of the overall health status and well-being. The total assessment was completed in one session and took approximately 2.5 h. In 13 of the 14 patients studied there was no significant neurological impairment and the KPS was at least 70. However. in contrast to these widely used parameters, more specific examination of cognitive functions (e.g.. memory function, word fluency, planning, and concentration) and the affective status (POMS) indicated that most patients had moderate to severe cognitive disturbances and suffered from fatigue, anger, and depressed moods. Moreover, a striking discrepancy was found between the patients’ self-reports on cognitive functioning and the test results;

I. For early and tumor effects (a/b = lo), ED = 70 (2 + lo), = 840 uu. 2. For late effects (a/b = 5), ED = 70 (2 + 5) = 490 uu. 3. If the same level of tumor control is obtained with 30 Gy plus simultaneous chemotherapy by 15 fractions of nominal 2 Gy augmented because of sensitization. then 15n(n + 10) = 840 uu, so that the dose n would be 4 Gy. 4. Late effects ED would be 60 (4 + 5) = 540. The therapeutic index would be worsened. For the argument’s sake, proliferation rates during treatment have not been taken into account: it is obvious that the same effect is obtained in 7 weeks in the first case and in 3 weeks in the combinated treatment. If this is considered, then n is between 3 and 4 Gy, and the index is less worsened. The conclusion is immediate; radiation sensitization would always increase the effect more on late normal than on tumor tissue. The approach would not be advisable from a theoretical point of view. There is a clinical aspect that proves this point. In an oncology contribution, Taylor d a/. (2) show results on wound complications following postradiation neck dissection. Table 3 indicates maximum grade of complication rate associated with total dose and fraction size. The highest percentage was 20% for 75-90 Gy total dose in 2.25-2.75 Gy per fraction. Our point is that any study involving simultaneous chemoradiation previous lo radical surgery that implies a proportion of wound complications of a serious order greater than the previously stated figure of 20% probably states the equivalent radiation dose being over 90 Gy in 2.25-2.75 Gy per fraction. Several Spanish unpublished results on the use of a 60-Gy shrinking field technique 2 Gy per day and fraction, with three to four cycles of cisplatin (CDDP) 100 mg/m* day I and fluorouracil (5-FU) 1000 mg/ 1201