[Epidermoid cancer of the oropharynx].
Explore the source record for details and available documents.
Antineoplastic Agents↗
Biomedical subjects
J C Horiot
Publications and source records attributed to J C Horiot.
The influence of the boost in breast-conserving therapy on cosmetic outcome in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer.
PURPOSE: To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy (BCT). METHODS AND MATERIALS: In EORTC trial 22881/10882, 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. Patients having a microscopically complete tumor excision were randomized between no boost and a boost of 16 Gy. The cosmetic outcome was evaluated by a panel, scoring photographs of 731 patients taken soon after surgery and 3 years later, and by digitizer measurements, measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later. RESULTS: There was no difference in the cosmetic outcome between the two treatment arms after surgery, before the start of radiotherapy. At 3-year follow-up, both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result. The panel evaluation at 3 years showed that 86% of patients in the no-boost group had an excellent or good global result, compared to 71% of patients in the boost group (p = 0.0001). The digitizer measurements at 3 years showed a relative breast retraction assessment (pBRA) of 7.6 pBRA in the no-boost group, compared to 8.3 pBRA in the boost group, indicating a worse cosmetic result in the boost group at follow-up (p = 0.04). CONCLUSIONS: These results showed that a boost dose of 16 Gy had a negative, but limited, impact on the cosmetic outcome after 3 years.
Adult↗
Validation of the methods of cosmetic assessment after breast-conserving therapy in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer.
PURPOSE: To evaluate both qualitative and quantitative scoring methods for the cosmetic result after breast-conserving therapy (BCT), and to compare the usefulness and reliability of these methods. METHODS AND MATERIALS: In EORTC trial 22881/10882, stage I and II breast cancer patients were treated with tumorectomy and axillary dissection. A total of 5318 patients were randomized between no boost and a boost of 16 Gy following whole-breast irradiation of 50 Gy. The cosmetic result was assessed for 731 patients in two ways. A panel scored the qualitative appearance of the breast using photographs taken after surgery and 3 years later. Digitizer measurements of the displacement of the nipple were also made using these photographs in order to calculate the breast retraction assessment (BRA). The cosmetic results after 3-year follow-up were used to analyze the correlation between the panel evaluation and digitizer measurements. RESULTS: For the panel evaluation the intraobserver agreement for the global cosmetic score as measured by the simple Kappa statistic was 0.42, considered moderate agreement. The multiple Kappa statistic for interobserver agreement for the global cosmetic score was 0.28, considered fair agreement. The specific cosmetic items scored by the panel were all significantly related to the global cosmetic score; breast size and shape influenced the global score most. For the digitizer measurements, the standard deviation from the average value of 30.0 mm was 2.3 mm (7.7%) for the intraobserver variability and 2.6 mm (8.7%) for the interobserver variability. The two methods were significantly, though moderately, correlated; some items scored by the panel were only correlated to the digitizer measurements if the tumor was not located in the inferior quadrant of the breast. CONCLUSIONS: The intra- and interobserver variability of the digitizer evaluation of cosmesis was smaller than that of the panel evaluation. However, there are some treatment sequelae, such as disturbing scars and skin changes, that can not be evaluated by BRA measurements. Therefore, the methods of cosmetic evaluation used in a study must be chosen in a way that balances reliability and comprehensiveness.
Adult↗
[Preoperative radiotherapy of cancer of the rectum. What if Europe is right?].
Explore the source record for details and available documents.
Chemotherapy, Adjuvant↗
The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis.
PURPOSE: The aim of this study was to assess the potential of pre-treatment cell kinetic parameters to predict outcome in head and neck cancer patients treated by conventional radiotherapy. MATERIALS AND METHODS: Data from 11 different centers were pooled. Inclusion criteria were such that the patients received radiotherapy alone, and that the radiotherapy was given in an overall time of at least 6 weeks with a dose of at least 60 Gy. All patients received a tracer dose of either iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) intravenously prior to treatment and a tumor biopsy was taken several hours later. The cell kinetic parameters labeling index (LI), DNA synthesis time (Ts) and potential doubling time (Tpot) were subsequently calculated from flow cytometry data, obtained on the biopsies using antibodies against I/BrdUrd incorporated into DNA. Each center carried out their own flow cytometry analysis. RESULTS: From the 11 centers, a total of 476 patients conforming to the inclusion criteria were analyzed. Median values for overall time and total dose were 49 days and 69 Gy, respectively. Fifty one percent of patients had local recurrences and 53% patients had died, the majority from their disease. Median follow-up was 20 months; being 30 months for surviving patients. Multivariate analysis revealed that T-stage, maximum tumor diameter, differentiation grade, N-stage, tumor localization and overall time correlated with locoregional control, in decreasing order of significance. For the cell kinetic parameters, univariate analysis showed that only LI was significantly associated with local control (P=0.02), with higher values correlating with a worse outcome. Ts showed some evidence that patients with longer values did worse, but this was not significant (P=0.06). Tpot showed no trend (P=0.8). When assessing survival in a univariate analysis, neither LI nor Tpot associated with outcome (P=0.4, 0.4, respectively). Surprisingly, Ts did correlate with survival, with longer values being worse (P=0.02). In the multivariate analysis of local control, LI lost its significance (P=0.16). CONCLUSIONS: The only pretreatment kinetic parameter for which some evidence was found for an association with local control (the best end-point for testing the present hypothesis) was LI, not Tpot, and this evidence disappeared in a multivariate analysis. It therefore appears that pretreatment cell kinetic measurements carried out using flow cytometry, only provide a relatively weak predictor of outcome after radiotherapy in head and neck cancer.
Analysis of Variance↗
ARCON: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC.
BACKGROUND: Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours. AIM: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours. METHODS: The phase I/II study included three steps: accelerated fractionation (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11 ) and AF with both carbon and nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy. RESULTS: The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10%, neither in the lung parenchyma nor in the mediastinum. No significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps, of the 25 patients entered in the two Nicotinamide containing steps 10 (40%) developed grade 2 or greater reactions which significantly detracted from their quality of life. There was no significant difference in tumour clearance rate among the three steps. The percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively. CONCLUSION: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant difference in time to progression among the three study steps.
Administration, Inhalation↗
Effects of combined irradiation and doxorubicin treatment on cardiac function and antioxidant defenses in the rat.
Combined radiotherapy and chemotherapy have represented a major advance in the therapeutic management of cancer therapy. However, the combination of doxorubicin (DXR) and cardiac irradiation (IRR) could precipitate the unexpected expression of congestive heart failure. Oxidative lesions induced by IRR and DXR could represent one of the pathogenic factors of myocardial dysfunction. Our investigations were performed to evaluate in the rat: 1) cardiac functional changes, 2) cardiac and plasma peroxidative damage and antioxidant defenses variations, that occur 24 h (acute effects) and 30 d (middle term effects) following DXR treatment 1 mg/kg(-1)/day(-1) IP for 10 d and a 1 x 20 Gy cardiac gamma-irradiation. Our results showed that DXR affected heart reactivity as early as the end of its administration, although irradiation exerted no detectable effect. Antioxidant defenses disturbances in hearts of DXR treated rats were characterized by vitamins C and E decreases, catalase activity induction and an increase in lipid peroxidation. Moreover, plasma vitamin C consumption and the lower level of plasma lipid peroxidation attested to the efficient solicitation of antioxidant defenses that probably contributed to the preservation of cardiac function at 24 h. After 30 d, cardiac dysfunction became symptomatic at rest, resulting from DXR cardiac toxicity. In spite of the persistent activation of cardiac catalase activity, antioxidant deficiency and increased plasma and cardiac lipid peroxidation highlighted defenses overtaken. Thus, different physiopathological mechanisms are involved in heart disturbance at acute and middle terms, IRR and DXR acting on distinct targets without disclosing synergistic effects. After 30 d, cardiac and plasma biochemical abnormalities were emphasized by the combined DXR+IRR therapy, pointing out the severity of the damage. Oxidative damage to the heart induced both by irradiation and DXR, may be one of the pathogenic factors of myocardial dysfunction. There is the possibility that the deleterious effects might be limited by the use of pharmacologic antioxidant agents.
Animals↗
EORTC scientific strategy meeting 25-26 March 1999.
Explore the source record for details and available documents.
Belgium↗
Pre-operative chemoradiotherapy and total mesorectal excision surgery of rectal cancer: towards the eradication of pelvic failures?
Explore the source record for details and available documents.
Chemotherapy, Adjuvant↗
Radiation dose homogeneity in an EORTC multicenter trial on breast irradiation.
The influence of the radiation dose on local control and cosmetic outcome in breast-conserving treatment for breast cancer is investigated in EORTC trial 2288110882. In this study 50 Gy is administered to the whole breast, and the effect of an additional dose to the tumor-bearing area (boost dose) is evaluated. The purpose of this analysis is to document the dose homogeneity of the radiation dose as reported in the first 1915 treatment forms, received at the EORTC Data Center. The dose to the prescription Point (A) was within 95 and 110% of 50 Gy in all but 13 (99.3%) patients (median dose 50 Gy) and the minimum and maximum doses in the central plane of the breast were within 95% and 110% of the dose to point A in 82% of patients. The dose to the tumor excision area (point B) was within the homogeneity criteria in 97% of patients, and the boost doses were consistent with randomization in 93% of cases. These data, based on one-third of the randomized patients in trial 22881/10882, demonstrate a high level of homogeneity in radiation doses, despite a number of ambiguities in the protocol, which were efficiently clarified a few months after the beginning of the trial. This high level of consistency is a remarkable achievement given the number of centers, the number of patients, and the number of countries involved in this trial.
Adult↗
[Prevention of caries and osteoradionecrosis in patients irradiated in oncology. Critical review].
In this paper, various preventive measures regarding caries and osteoradionecrosis in irradiated patients with the head and neck cancer are discussed. Local application of high concentrations of fluoride gel as well as good oral hygiene are the most appropriate measures to implement.
Cariostatic Agents↗
Preoperative radiotherapy and surgery for endometrial carcinoma: prognostic significance of the sterilization of the specimen.
INTRODUCTION: We report a retrospective study on the analysis of the operative specimen after preoperative radiotherapy for FIGO (1971) stage I or II endometrial carcinoma. METHODS AND MATERIALS: From 1976 to 1996, 221 patients were treated with external radiotherapy (XRT) and/or low-dose-rate brachytherapy (BT) followed by surgery (S). Patients with cervical involvement (89 patients) or with high-grade tumors (49 patients) received XRT and BT. Patients stage FIGO Ia (89 patients) or with low-grade tumors (57 patients) received BT alone. Surgery was performed 5 to 6 weeks after irradiation. RESULTS: The mean follow-up is 78 months (12-216). The 5-year survival was 90% for FIGO Ia, 80% for FIGO Ib, and 84% for FIGO II (p = 0.51). According to the differentiation, 5-year survival was 87% for grade 1, 84% for grade 2, 84% for grade 3 (p = 0.10). Grade 3 complications were registered in 2% (no grade 4). The tumors were sterilized in 37 patients (17%), sterilized but with dystrophic glands in 34 patients (16%), only modified and altered in 21 patients (9.5%), with viable cells in 56 patients (26%). After preoperative radiotherapy, 37/148 specimens were sterilized (25%), 14/74 after brachytherapy and surgery (19%), 23/74 after external radiotherapy-brachytherapy and surgery (31%). According to the response of the specimen, 5-year survival was 87% when the tumor was sterilized, 96% when altered glands were present, 85% when modified, and 76% if residual tumor with viable cells was identified (p = 0.043). CONCLUSION: Preoperative radiotherapy followed by surgery is a safe and effective treatment of FIGO stage I or II endometrial carcinomas. BT with two uterine tubes seems to be of interest in the contribution of the treatment of the uterus to sterilize the specimen. The analysis of this new prognostic factor remains important to select a population with worst prognosis.
Adult↗
Conservative management of rectal adenocarcinoma by radiotherapy.
PURPOSE: The aim of this study was to analyze the experience of Centre GF Leclerc for conservative and curative treatment by radiotherapy of low rectal cancer. PATIENTS AND METHODS: A total of 151 patients received radiotherapy alone for rectal adenocarcinoma with curative intent. They were clinically staged according to size (T1 < 3 cm, and T2 > 3 cm) and depth of infiltration (A=superficial, and B=impaired mobility and T3 fixed). Over the past 6 years, rectal ultrasound (US) has been used systematically, compared with computed tomographic scan and magnetic resonance imaging when needed. Intracavitary contact X ray was given to 129 patients (69%), and brachytherapy in 45 of 151. External radiotherapy was used in 34 cases (22.5%). RESULTS: Complete response was obtained in 93%. Local failures were observed in 50 cases (28%); two occurred in pelvic nodes after intracavitary X rays. Size (tumors > 3 cm) and alteration of mobility significantly influenced the rate of local failure (p=0.009 and 0.007). The addition of external radiotherapy in patients with poor prognostic factors improved the local control rate. A total of 39 patients with recurrence were amenable to salvage surgery. After salvage treatment, the local control rate was 82% with unlimited follow-up. The 5-year actuarial survival rate was 57%, with a specific survival of 66%. There was no difference in local control or survival according to differentiation of the tumors and distance between anal margin and the inferior level of the lesion. Severe late effect (grade 3) was 3.8%. The sphincter preservation was obtained in 104 of 124 cases (84%). The sphincter function was judged to normal in 102 of 104 patients (98%). CONCLUSION: Intracavitary contact X ray is the treatment of choice for clinical Stage T1A rectal tumors. External radiotherapy significantly improved the results of treatment of tumors > 3 cm. Clinical staging and transrectal ultrasound allows a safe selection of indications. Radiotherapy alone may be proposed for selected cases as an alternative to mutilating surgery for small rectal adenocarcinoma.
Adenocarcinoma↗
Tumor response, mucosal reactions and late effects after conventional and hyperfractionated radiotherapy.
BACKGROUND: Relationships between normal tissue reactions and tumor response to radiotherapy have generally been investigated in retrospective studies, with the attendant difficulties such as different times of treatment and lack of standard scales for scoring of normal tissue reactions. This study analyses the correlation between normal tissue reactions and tumor response in a randomized trial of hyperfractionation versus conventional radiotherapy. MATERIALS AND METHODS: EORTC trial 22791, which accrued 325 T2-3, N0-1 and M0 oropharynx squamous cell carcinomas, compared conventional radiotherapy (70 Gy in 7 weeks) to a hyperfractionated regime (two daily irradiations of 1.15 Gy up to 80.5 Gy in 7 weeks). Acute and late toxicities were assessed according to the RTOG/EORTC scales. The variables were tumor regression at treatment completion, tumor control for unlimited follow-up, severity of acute mucosal reactions (grade of the peak reaction, time to onset of grade 2 mucositis, or duration of acute reactions of grade 3) and severity of late effects in normal tissues (late ulceration, cervical edema secondary to lymphatic drainage damage, late muscular fibrosis, or late mucosal necrosis as consequential damage). Kendall's rank correlation was used to assess the levels of significance of the correlation. The 95% confidence interval (95% CI) was calculated for each correlation tau-b coefficient. RESULTS: Irradiation doses and overall treatment times were consistent between the treatment arms. The time to onset of patchy mucosal reactions was inversely correlated to tumor regression at treatment completion in the hyperfractionated arm (arm 2) but not in the conventional fractionation arm (arm 1). The other significant correlations were restricted to the following pairs of end-points and patient subgroups: acute mucositis of grade 3 versus tumor regression at the end of treatment in arm 2 for T2 tumors, late ulceration versus tumor control in arm 2 and acute mucosal reactions versus late effects in normal tissues in arm 2 for T3 tumors. By and large, the 95% CIs for Kendall's tau-b included zero and did not include 0.5, an indication that the comparison had sufficient power to detect a difference, if indeed one existed. CONCLUSIONS: These results do not represent clinical evidence strong enough to demonstrate that individual differences in sensitivity influence the response of tumors to radiation.
Carcinoma, Squamous Cell↗
[Controlled clinical trials of hyperfractionated and accelerated radiotherapy in otorhinolaryngologic cancers].
From 1978 to March 1998, (1,867 patients) were accrued in head and neck trials comparing hyperfractionation (HF) and accelerated fractionation (AF) to classical fractionation (CF). Two randomized trials (867 pts) led to positive conclusions in favour of the HF & AF arms: 1) EORTC trial 22791 (356 patients, 1980-87) compared CF (70 Gy/35-40 fr/7-8 wks) to HF (80.5 Gy/70 fr/7 wks, using 2 fr x 1.15 Gy/day) in T2 T3, N0-N1 < 3 cm in oropharyngeal carcinoma. Locoregional control (LRC) was higher (p = 0.01) in HF versus CF. At 5 years, 56% of the patients are LRC free with HF versus 38% with CF on the latest update (February 1998). This improvement of LRC also resulted in a significant overall survival (p = 0.05). There was no difference in late normal tissue damage between the two treatment modalities. Overall, this is the largest improvement documented in a randomised trial for oropharyngeal cancers during the past decade. 2) EORTC trial 22851 (511 patients, 1985-1995) compared AF (72 Gy/45 fr/5 wks) to CF (70 Gy/35 fr/7 wks) in T2 T3 T4 head & neck cancers (hypopharynx excluded). Acute and late toxicity were increased in the AF arm. Late severe sequelae occurred in 14% of patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord. The AF arm is significantly better for locoregional control (p = 0.017) and for time to progression (p = 0.012) resulting in a 15% locoregional gain at 5 years over the CF arm. This improvement is of larger magnitude in patients with poorer prognosis (N3 any T, T4 any N) than in patients with more favourable stage. Multivariate analysis confirmed AF as an independent pronostic factor for local control (p = 0.03). Specific survival shows a non significant advantage (p = 0.06) in favour of the AF arm. This trial shows that accelerated radiotherapy is able to improve locoregional control in a large variety of head and neck squamous cell carcinomas. A less toxic scheme should however be investigated before moving AF schemes in standard practice. To conclude, these two schemes derived from experimental radiobiology concepts resulted in a significant improvement of locoregional control. Hyperfractionation resulted in an improved locoregional and survival benefit. Although HF is presently the most reliable regimen to improve locoregional control, the validity of the concept of AF is also confirmed. Better schemes of AF should now be evaluated to reduce late toxicity.
Acceleration↗
Carcinoma of the intact uterine cervix treated with radiotherapy alone: a French cooperative study: update and multivariate analysis of prognostics factors.
PURPOSE: To determine independent prognostic factors in a group of 1875 patients with invasive carcinoma of the intact uterine cervix treated with radiotherapy alone in a French cooperative study from 1970 to 1993. MATERIALS AND METHODS: Patients were staged according to the UICC-FIGO and MDAH substaging. The distribution per FIGO stage was Ia-Ib: 25.5%; IIa: 12%; IIb: 29%; IIIa: 5%; IIIb: 25%, and IV: 3.5%. Ninety-two percent had squamous cell carcinoma. The maximum diameter of the clinically detectable cervical disease was less than 3 cm in 24.5% of Stages I-II and in 10% of Stages III-IV, more than 5 cm in 13.5% of Stages I-II, and in 16% of Stages III-IV. Nodal involvement was shown on lymphangiogram in 16% of Stages I-II and in 32.5% of Stages III-IV. RESULTS: 1) Univariate analysis of Stages I and II: stage, cervical disease diameter, and nodal involvement are significant prognostic factors. Five-year specific survival rate (5ySS) is 83.5% in Stage Ib, 81% in IIa and 71% in IIb. Five-year disease-free survival rate (5yDFS) is 86% in tumors less of 3 cm, 76% in tumors of 3 to 5 cm, and 61.5% in tumor larger than 5 cm. Lymphangiogram strongly influences the 5-year pelvic disease-free survival rate (5yPDFS): respectively, 90% in nonpositive lymphangiogram vs. 65% when positive. A significant drop in specific and disease-free survival is observed (10 and 14%, respectively (p = 0.04) when comparing adenocarcinoma and squamous cell carcinoma. Age is a significant prognostic factor for specific survival because patients aged less than 30 years old have 91% vs. about 75% for patients over 30 years (p = 0.03). 2) Univariate analysis of Stages III-IV: Stage and positive lymphangiogram are predictive factors for relapse and death. The MDAH substaging is more reliable to predict the probability of pelvic disease-free survival in Stage III. At 5 years, the FIGO Stages IIIa and IIIb have a rather similar PDFS (65% vs. 59%). Conversely, the difference of survival rates between MDAH Stage IIIA and Stage IIIB is more demonstrative (69% vs. 47.5%). 3) Multivariate analysis (Cox P. H. R. model). Nodal involvement and stage remain significant for all three models in all stages (p < 0.0001). Age above 70 years influences specific survival for Stage I-II (p = 0.01). Tumors larger than 5 cm and adenocarcinoma also appear to be independent prognostic factors for specific and disease-free survival in Stage I-II (p = 0.05 and p = 0.005, respectively). CONCLUSIONS: The relevance of tumor size (less or greater than 4 cm) is now recognized in the 1995 revised FIGO staging in Stage Ib but unfortunately not in other stages. Tumor size per stage and nodal status should be systematically recorded to allow a better prediction of failure rates and to compare literature reports.
Adenocarcinoma↗
Age is not a limiting factor for radical radiotherapy in pelvic malignancies.
BACKGROUND AND PURPOSE: Pelvic radiotherapy (RT) toxicity in the elderly is poorly documented. We developed a study aiming to evaluate whether or not a limit of age could be identified beyond which toxicities in patients receiving pelvic RT were more frequent or more severe. MATERIAL AND METHODS: 1619 patients with pelvic cancers enrolled in nine EORTC trials, RT arms, were retrospectively studied. Patients were split into six age ranges from 50 years to 70 years and over. Survivals and late toxicity occurrence were calculated with the Kaplan-Meier method and comparison between age groups with the logrank test. A trend test was done to examine if chronological age had an impact on acute toxicity occurrence. RESULTS: Survival was comparable in each age group for prostate (P = 0.18), uterus (0.41), anal canal cancer (P = 0.6) and slightly better for the younger group of rectum cancer (P = 0.04). A total of 1722 acute and 514 late grade > or = 1 were recorded. Acute nausea/ vomiting, skin complications and performance status deterioration were significantly more frequent in younger patients. There was no trend toward more aged patients to experience diarrhea (P = 0.149) and after adjustment on RT dose, acute urinary complications were observed equally in each age range (P = 0.32). Eighty percent of patients were free of late complication at 5 years in each age range (P = 0.79). For the grade > 2 late side-effects, a plateau was observed after 1 year at near 9% without any difference (P = 0.06) nor trend (P = 0.13) between age-groups. CONCLUSION: Age per se is not a limiting factor for radical radiotherapy in pelvic malignancies.
Age Factors↗
Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial.
BACKGROUND AND PURPOSE: A 5 week-hyperfractionated and accelerated radiotherapy regimen without reduction of the total dose was developed to fight tumour repopulation during treatment and tumour hypoxia. The purpose of the study was to try to improve loco-regional control in high risk head and neck carcinoma treated with curative radiotherapy. METHODS AND MATERIALS: From 1985 to 1995, a randomised controlled trial of the EORTC Cooperative Group of Radiotherapy (EORTC 22851) compared the experimental regimen (72 Gy/45 fractions/5 weeks) to standard fractionation and overall treatment time (70 Gy/35 fractions/7 weeks) in T2, T3 and T4 head and neck cancers (hypopharynx excluded). The end-point criteria were local and loco-regional control, overall and disease-free survival, and acute and late toxicities. Five hundred twelve patients were accrued. RESULTS: Patients in the AF (accelerated fractionation) arm did significantly better with regard to loco-regional control (P = 0.02) resulting at 5 years in a 13% gain (95% CI 3-23% gain) in loco-regional control over the CF (conventional fractionation) arm. This improvement is of larger magnitude in patients with poorer prognosis (N2-3 any T, T4 any N) than in patients with more favourable stage. Multivariate analysis confirmed AF as an independent prognostic factor of good prognosis for loco-regional control (P = 0.03). Specific survival shows a trend (P = 0.06) in favour of the AF arm. ACUTE AND LATE TOXICITIES: Acute and late toxicity were increased in the AF arm. Late severe functional irradiation damage occurred in 14% of patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord. CONCLUSIONS: This trial shows that accelerated radiotherapy improves loco-regional control in head and neck squamous cell carcinomas. A less toxic scheme should, however, be investigated and documented before using accelerated radiotherapy as a standard regimen of curative radiotherapy for head and neck cancers.
Adult↗