To report long-term results of randomized trial comparing 2 accelerated fractionations of definitive radiation therapy assessing the need to irradiate during weekend in patients with head and neck ...squamous cell carcinoma.
A total of 345 patients with SCC of the oral cavity, larynx, and oro- or hypo-pharynx, stage T2-4N0-1M0, were randomized to receive continuous accelerated irradiation (CAIR: once per day, 7 days per week) or concomitant accelerated boost (CB: once per day, 3 days per week, and twice per day, 2 days per week). Total dose ranged from 66.6-72 Gy, dose per fraction was 1.8 Gy, number of fractions ranged from 37-40 fractions, and overall treatment time ranged from 37-40 days.
No differences for all trial end-points were noted. At 5 and 10 years, the actuarial rates of local-regional control were 63% and 60% for CAIR vs 65% and 60% for CB, and the corresponding overall survival were 40% and 25% vs 44% and 25%, respectively. Confluent mucositis was the main acute toxicity, with an incidence of 89% in CAIR and 86% in CB patients. The 5-year rate of grade 3-4 late radiation morbidity was 6% for both regimens.
Results of this trial indicate that the effects of accelerated fractionation can be achieve by delivering twice-per-day irradiation on weekday(s). This trial has also confirmed that an accelerated, 6-weeks schedule is a reasonable option for patients with intermediate-stage head-and-neck squamous cell carcinoma because of the associated high cure rate and minimal severe late toxicity.
Summary Background Irradiation of salivary glands during the treatment of head and neck cancer may lead to an alteration in the amount of saliva produced. Because of this, patients can suffer dryness ...of the mouth with oral discomfort, taste disturbance and dental decay. Aim The aim of this study is to estimate late toxicity dependence on radiotherapy method. The main goal is to investigate the correlations between the radiation doses in salivary glands and their salivary excretion fractions (SEF) measured by dynamic scintigraphy. Materials/Methods In 40 patients with pharyngeal and laryngeal cancer irradiated by IMRT or conformal 3D to a total dose of 62.5–72.0Gy, parotid SEFs were measured. Parotid dose-volume histograms were obtained from 3D computer treatment planning. SEF measurements were performed before (baseline), and 6 weeks and 6 months after radiotherapy by 185MBq 99 Tc injected intravenously and next SEF rates were analysed in relation to radiation doses accumulated. The late radiation toxicity of salivary glands was tested according to the CTC v. 3.0 and SOMA-LENT scales. The non-parametric Mann Whitney test was used for the estimation of relationships. Results Pre- and post-treatment SEFs were measured in 31 patients treated by IMRT and in 9 patients treated by 3D CRT. Six weeks after radiotherapy SEF was generally lower by 34%, and 6 months after irradiation by 29.3% in IMRT technique. In 3D CRT relatively it was lower: after 6 weeks by average 52% and after 6 months by 35.5%. Late radiation toxicity of salivary glands was observed at a similar level according to CTC and SOMA-LENT scales in both methods of radiotherapy. Conclusions The level of SEF in parotid glands measured 6 weeks after radiotherapy clearly reflects the dose-response relationship of irradiated salivary tissue; 6 months later changes of SEF are the result of partial recovery of parotids. The results of sparing salivary glands can be optimized in the future; that is, a further reduction of xerostomia can be achieved by using improved IMRT techniques and focusing on sparing major and minor salivary glands.
The EORTC/RTOG late effects classification has been used for many years and covers nearly all organs and tissues, which may develop late radiation injuries. Dische developed a scoring system for ...radiation toxicity in which each clinical sign or symptom, that is characteristic for disturbance of function in an irradiated organ, is given scores for severity individually. EORTC and RTOG formed working groups to up-date their systems, for the recording of late injury to normal tissues, to be used in future clinical trials. The resulting system is called LENT-SOMA (1993).
In preparation for the introduction of the LENT-SOMA scale into clinical practice at the Centre of Oncology-Institute in Gliwice, we followed a sizeable cohort of patients using two scoring systems for the assessment of delayed radiation toxicity at each follow-up examination which took place every 6 months for up to 5 years after curative radiotherapy for head and neck cancer.
The analysed material comprised of 113 patients with oral cavity, pharyngeal or supraglottic cancer (T2-4N0-1) irradiated by conventional methods (18 patients), continuous accelerated irradiation (CAIR) (52 patients) or concomitant boost (CB) (43 patients). Total dose was in the range of 66–74 Gy. Delayed radiation toxicity was evaluated by two classification systems, those of Dische and LENT-SOMA, in the mucosal membranes, skin, larynx, salivary glands and spinal cord every 6 months after completion of radiotherapy treatment. The values in every scale were normalised (as a proportion of the maximum intensity for all symptoms) which permitted statistical comparison of the scales by use of the Wilcoxon test.
Analysis of all materials indicated a difference in the intensity of late radiation toxicity as estimated by the Dische and LENT-SOMA scales. The intensity of delayed radiation toxicity in the normalised Dische scale, for mucosal membranes and for skin, had higher values than observed in the LENT-SOMA system for the majority of examined patients. In the case of the larynx and salivary glands, the opposite situation was noted. The extent of conformity between normalised scales was evaluated in the case of the spinal cord.
The scoring systems of Dische and LENT-SOMA can not be interchangeably used, in clinical practice, for the estimation of delayed radiation toxicity in tissues of the head and neck region. The sensitivity of the scoring systems is similar only for the evaluation of radiation reactions in spinal cord.
Data charts of 64 patients with stage I glottic cancer treated with Manchester irradiation modality in the 1st Radiotherapy Clinic of MSC Memorial Institute in Gliwice has been retrospectively ...analyzed. There were 55 males and 9 females at median age 63 years (range from 37 to 83 years). In 40 (62%) patients pathological subtype of squamous cell cancer has not been established. In 19 (30%) patients microscopic examination revealed keratinizing and in 5 (8%) non-keratinizing type of neoplasm. In 49 (77%) patients the tumour involved only one vocal cord, in 11 (17%) both, in 3 (5%) vocal cord and commissure and 1 (1%) patient both cords and commissure. All patients were treated with 60Co machines (36 patients - 56%) or high energy photons (28 patients - 44%). Radiotherapy was conducted with so-called Manchester modality with one daily fraction of 3Gy to a total dose of 51-54 Gy. Overall treatment time varied between 21 and 23 days. Acute mucosal reaction was evaluated with the morphological-functional Dische scale as well as with the EORTC/RTOG scoring system. The criteria of treatment efficacy were: 5-year local control, 5-year survival without serious complications (3 and 4 EORTC) and 5-year survival after salvage surgery in relapsed patients. In 63 patients complete regression of the tumour was observed up to 6 months of follow-up. One patient failed at the time of radiotherapy ending. In one case distant metastases to lungs were noticed. In 6 patients local relapses were discovered of which 3 were successfully salvaged with the surgery. In one patient, 18 months after radiotherapy massive oedema of laryngeal mucosa occurred. In this case tracheostomy was needed. 5-year local control, local control after salvage surgery and survival without serious complication rates are 89%, 97% and 95% respectively. 1. Radiotherapy with Manchester modality is a safe and effective treatment of stage I glottic cancer. 2. Despite hypofractionation the risk of severe complication is comparable to conventional irradiation to 60 Gy in 30 fractions. 3. Because of shorter overall treatment time this modality might be recommended in cases of early glottic cancer. 4. After radiotherapy the function of the larynx is preserved.
To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation (CAIR) compared to a conventional treatment (5 days per week) in a randomized trial.
One ...hundred patients with squamous cell carcinoma of the head and neck in stage T(2-4)N(0-1)M(0) were entered into the trial between December 1, 1993 and June 30, 1996. Dose per fraction of 2.0 Gy (to the end of 1994), and 1.8 Gy (since January 1, 1995) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66-72 Gy (depending on tumour stage). The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm.
Actuarial 3-year local tumour control was 82% in the CAIR and 37% in the control group (P<0.0001) with reduction in local recurrence rate of 83%. Actuarial 3-year overall survival was 78 and 32% (P<0.0001), respectively. Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm. After 2.0 Gy fractions five of 23 patients (22%) in the CAIR developed early necroses over a period of 2-4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions (CLE). For this reason dose per fraction was lowered to 1. 8 Gy and the CLE was not observed again until now. Thus the overall rate of CLE decreased to 10%.
The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends. A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation, however tolerable by patients. Relatively high rate (22%) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy.
