B. Pilecki

Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer – report on 3-year tumour control and normal tissue toxicity

Purpose: 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. Materials and methods: One hundred patients with squamous cell carcinoma of the head and neck in stage T2‐4N0‐1M0 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. Results: 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%. Conclusions: 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. q 2000 Elsevier Science Ireland Ltd. All rights reserved.

Randomized clinical trial on accelerated 7 days per week fractionation in radiotherapy for head and neck cancer. Preliminary report on acute toxicity

PURPOSE Toxicity of an accelerated 7 days per week fractionation schedule (arm A) was evaluated and compared with a conventional 5 days per week treatment (arm B) in a randomized trial. MATERIALS AND METHODS Forty-four patients with squamous cell carcinoma of the head and neck in stage T2-4Nzero-1Mzero were included in the study. Total dose and dose per fraction of 2.0 Gy given once-a-day at 24 h intervals were the same in both arms of the trial. The only difference was the overall treatment time being 5 weeks in arm A and 7 weeks in arm B. RESULTS Analysis of severe mucosal reactions shows significant difference between arm A and B, with regard to both maximum score and duration of severe mucositis. Confluent mucositis (score > 15 according to the Dische system) lasting longer than 3 weeks developed in 48% of patients in arm A and only in 5% in arm B. In group A seven (30%) late effects (osteo- and soft tissue necrosis) occurred during 7-12 month follow-up with two reactions (10%) in group B being suspected as late effects. There was significant association between acute reactions and late effects in arm A, suggesting that the late effects are consequential. CONCLUSION The high incidence of severe acute reactions and consequential late effects suggests that the accelerated treatment in arm A (using daily fractions of 2.0 Gy, 7 days per week) gives unacceptable toxicity.

Acute mucositis in the stimulated oral mucosa of patients during radiotherapy for head and neck cancer

In 16 patients treated for squamous cell carcinoma of the oral cavity or oropharynx with an accelerated split course regimen, acute mucosal reactions were significantly less in the left buccal mucosa which had been repeatedly painted with 2% silver-nitrate solution for several days before radiotherapy than in the unpainted right buccal mucosa.

A comparison of two scoring systems for late radiation toxicity in patients after radiotherapy for head and neck cancer

Summary Background 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). Aim 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. Materials/Methods 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. Results 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. Conclusions 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.

Radiation-free weekend rescued! Continuous accelerated irradiation of 7-days per week is equal to accelerated fractionation with concomitant boost of 7 fractions in 5-days per week: report on phase 3 clinical trial in head-and-neck cancer patients.

PURPOSE 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. METHODS AND MATERIALS 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. RESULTS 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. CONCLUSIONS 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.

The influence of radiation technique on xerostomia in head and neck cancer patients – prospective study

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.

72. Cancer of oropharynx and nasopharynx – clinical prognostic factors analysis

Analysis contains 110 cases of oropharyngeal and 112 cases of nasopharyngeal cancers who were treated beetwen 1990–1998 in MSC Centre of Oncology-Institute, branch Gliwice. Main part of histopatological findings in oropharyngeal area were squamous cancers, but undifferentiated type was slightly dominated than squamous in nasopharyngeal region. More than half of cases in both localisations were locally advanced [T3,T4] and similar, nearly 1/3 cases were without nodal metastases. Comparisons beetwen mean tumor volumes indicate on bigger cancer volume, when primary tumor was located in oropharyngeal area, but mean nodal volume was much higher in nasopharyngeal cancer. Kinetics of distant metastases were much higher in nasopharyngeal location of primary tumor especially in undifferentiated cases. Radiotherapy was the main type of treatment which was realised in palliative and radical schedule with conventional and unconventional fractionation scheme. Following clinical factors were underdone evaluation: T-stage and primary tumor volume, N-stage with amount and volume of nodes, conglomerates of nodes presence, M-stage, type of histological structure and treatment factors: tumor and nodal total doses and kind of fractionation. Statistical methods which were used contained: single- and multivariate analysis and logistic regression model. Conclusion „Hierarchy of importance” of the factors which were analysed and their influences on treatment results are different in both localisations.

THE ESTIMATION OF LATE RADIATION REACTION OF SALIVARY GLANDS IN PATIENTS WITH SQUAMOUS CELL CANCER IRRADIATED IN HEAD&NECK REGION – THE PROSPECTIVE STUDY

Purpose: The purpose of this study is to estimate the late radiation toxicity of salivary glands in patients with squamous cell cancer irradiated by conventional (3D CRT) or accelerated method (CAIR or CB).The special goal there is to analyse the influence of method of contouring the glands on the values of accumulated doses. Materials: In 65 patients with pharyngeal and laryngeal cancer irradiated to total dose in range 62.5-72,O Gy the estimation of late radiation toxicity of salivary glands was provided. All patients were irradiated by conventional (3D CRT) or accelerated method (CAIR or CB). There were used two methods of contouring parotids: whole organs and whole parotids including superficial part. The late radiation reaction was estimated after 3, 6 and every 6 months after final treatment with using CTC version 3.0 classification. The non parametric Mann-Whitney and Spearman test was used for the estimation of relationships. Results: We have observed the middle level of xerostomia connecting with change of amount and consistency of saliva after irradiation. The contouring of whole parotids including superficial part of organ had significant influence on decrease of mean, median and modal doses in whole organs. In our material we had: mean doses=29,93 Gy, median doses=29,18 Gy and modal doses =28,85 for whole parotids. Conclusions: Xerostomy is the most troublesome symptom in patients with squamous cell cancer in H&N region. The contouring of whole parotids including superficial part had significant influence on decrease of mean, median and modal doses in whole organ in the correlation to the group of patients with contouring only whole parotids.This prospective study is being continued.

22/Rola radioterapii jako leczenia samodzielnego i skojarzonego oraz wpływu wybranych sposobów frakcjonowania dawki promieniowania u chorych na zaawansowanego raka części nosowej i ustnej gardła

Celem pracy jest ocena porownawcza skuteczności leczenia samodzielnego i skojarzonego promieniami oraz sposobow frakcjonowania dawki promieniowania u chorych na raka gornej i środkowej cześci gardla dokonana w oparciu o retrospektywny material kliniczny. Analizą objeto 283 chorych leczonych w latach 1989–2001 w Instytucie Onkologii w Gliwicach, u ktorych radioterapia miala charakter radykalnego leczenia samodzielnego lub skojarzonego z chemioterapią. Podstawowym kryterium doboru byl III i IV stopien klinicznego zaawansowania (z wykluczeniem postaci uogolnionej M1). Leczenie skojarzone: chemioterapia i radioterapia bylo prowadzone u 82 chorych. Chemioterapie stosowano w sekwencji z radioterapią, jako leczenie indukcyjne w 34 przypadkach, rownoczesne w 25 i uzupelniające w 23. W przypadkach leczenia skojarzonego: indukcyjnego i uzupelniającego dawke promieniowania podawano w oparciu o konwencjonalny system frakcjonowania (26 chorych), hiperfrakcjonowanie (21 chorych) albo frakcjonowanie przyśpieszone (10 chorych), natomiast u 25 chorych, u ktorych przeprowadzono jednoczasową chemioradioterapie zastosowano tylko frakcjonowanie przyśpieszone. Samodzielną radioterapie przeprowadzono w oparciu o frakcjonowanie przyspieszone – 94 chorych, konwencjonalne – 85 chorych, hiperfrakcjonowanie – 22 chorych. Zaobserwowano znamiennie korzystny wplyw leczenia skojarzonego na dlugośc przezycia calkowitego, przezycia bez objawow nowotworu oraz wyleczalnośc ogniska pierwotnego i przerzutowo zmienionych wezlow chlonnych szyi. Spośrod wszystkich sekwencji leczenia skojarzonego, najwiekszą skutecznością cechowalo sie leczenie jednoczesne, ktore w 3-letnim okresie obserwacji wykazywalo 18% przewage w odsetku wyleczen miejscowych i wezlowych w porownaniu do chemioterapii indukcyjnej i radioterapii oraz prawie 30% zysk w porownaniu do chemioterapii uzupelniającej i radioterapii. Na podstawie uzyskanych wynikow mozna przypuszczac, ze najbardziej optymalnym sposobem postepowania w stopniu III i IV raka cześci ustnej i nosowej gardla, a zwlaszcza w przypadkach wystepowania rozleglych zmian przerzutowych w wezlach chlonnych szyi i/lub naciekach pozatorebkowych – jest jednoczesne leczenie skojarzone polegające na przyśpieszonym sposobie frakcjonowania dawki promieniowania i chemioterapii opartej o Cisplatyne.

93/Ocena skuteczności leczenia wspomagającego octanem megestrolu u chorych na nowotwory regionu głowy i szyi, leczonych za pomocą przyśpieszonej radioterapii

Cel badania Celem badania byla ocena skuteczności leczenia wspomagającego octanem megestrolu u chorych na nowotwory regionu glowy i szyi, leczonych za pomocą radykalnej radioterapii (CAIR, CB) lub jednoczesnej chemio – i radioterapii. Efektem ubocznym wymienionych, agresywnych metod leczenia jest czesto znaczna utrata masy ciala prowadząca do niedozywienia i w konsekwencji do przerw w napromienianiu. Material i metoda Do badania zakwalifikowano 30 osob. Protokol badania zakladal podawanie 800 mg (20 ml) octanu megestrolu w postaci zawiesiny doustnej w jednej dawce dobowej przez caly okres leczenia promieniami. Ocenie poddano wplyw leku na takie parametry jak: stan odzywienia, stezenie hemoglobiny, laknienie, zmysl smaku i zmysl powonienia, ostry odczyn popromienny, szeroko pojeta jakośc zycia. Stan odzywienia oceniano na podstawie pomiarow antropometrycznych (masa ciala, grubośc faldu skornego nad mieśniem trojglowym ramienia, obwod środkowej cześci ramienia), badan biochemicznych (stezenie albumin w surowicy krwi, ilośc kreatyniny w dobowej zbiorce moczu) oraz calkowitej liczby limfocytow (CLL) w 1 ml krwi obwodowej. Stezenia hemoglobiny monitorowano w oparciu o wyniki rutynowych badan krwi prowadzonych w trakcie hospitalizacji. Ocena laknienia, zmyslow smaku i powonienia oraz jakości zycia oparta zostala na subiektywnych odczuciach pacjentow zawartych w wypelnianym przez nich kwestionariuszu. Nasilenie ostrego odczynu popromiennego blon śluzowych mierzono przy pomocy skali Dische. Wyniki U 18 pacjentow (60%) zaobserwowano wzrost masy ciala w trakcie leczenia, średnio o 1.5 kg. W 3 przypadkach (10%) masa ciala nie ulegla zmianie. U pozostalych 9 chorych (30%) zanotowano spadek masy ciala. Nalezy jednak podkreślic, ze w zadnym z ocenianych przypadkow ubytek nie przekroczyl 5% wyjściowej masy ciala. Poprawe laknienia zaobserwowano u 27 chorych (90%). Maksymalne nasilenie ostrego odczynu popromiennego wynosilo średnio 9 punktow w 24 punktowej skali wg. Dische. W wiekszości ocenionych przypadkow doszlo w trakcie radioterapii do zmniejszenia stezenia hemoglobiny oraz CLL – szczegolnie duze spadki odnotowano w grupie pacjentow leczonych przy pomocy jednoczasowej chemioradioterapii. Wnioski Wydaje sie, ze octan megestrolu poprawia tolerancje agresywnej radioterapii oraz jednoczesnej chemio – i radioterapii i jest cenną skladową leczenia wspomagającego.