Tissue Reactions In Patients Research Articles

Individual Sensitivity for Radiotherapy-related Adverse Tissue Reactions in Patients Treated Twice for Metachronous Cancers.

The role of genetics in susceptibility to radiotherapy-induced toxicities is unclear. A strong impact of genetics should cause correlated toxicities in patients with metachronous double radiotherapy. We ascertained information about demographics, lifestyle, radiotherapy and early toxicities in irradiated tissues for a retrospective cohort of 98 patients from 2 hospitals who underwent two metachronous radiotherapeutic treatments (2007-2022) of different anatomical regions. European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group (EORTC/RTOG) toxicity scores per organ system were combined to a single mean score. We considered as genetic component the variation of toxicity not explained by radiation dose to the tumor, age at radiotherapy, sex, smoking status, and surgery. Variance components of toxicity were evaluated by ordinal logistic regression with random intercept. Common site combinations were breast/contralateral breast (N = 16), breast/endometrium (N = 6), and cervix/breast (N = 5). Mean toxicity over exposed tissues was 0.70 (range, 0-3). Prescribed radiation dose was significantly associated with mean toxicity, with a 5% (95% CI 3-8) increase of the odds for a higher toxicity level per Gy. Sex, surgery, age and smoking were not. There was no genetic contribution to risk of toxicities after adjustment. Toxicity levels were not more similar within patients than between patients, suggesting a negligible impact of genotype on radiotherapy-related toxicities.

Outcome of revision surgery for adverse local tissue reactions in patients with recalled total hip arthroplasty.

Recalls of total hip arthroplasty (THA) implants, including metal-on-metal (MoM) THA and dual taper stems, due to increased risk of adverse local tissue reaction (ALTR), represent a challenge for both surgeons and patients. This study aims to analyze the revision surgery outcomes for ALTR in patients with recalled THA implants. A total of 118 consecutive patients who underwent revision surgery due to ALTR with recalled THA were analyzed. Sub-group analysis was performed for recalled MoM THAs, head-neck modular stems, and dual taper neck-stems. At a mean follow-up of 6.6years, the complication and reoperation rates of the recalled THAs were 32.2% and 25.4% respectively. The most common post-revision complication was dislocation (16%). Revision of modular taper corrosion THA and high-grade intraoperative tissue damage were risk factors associated with post-revision complications. This study reports high complication and reoperation rates of recalled THAs at mid-term follow-up. The high revision surgery complication rates in both groups suggest the importance of a systematic evaluation of all THA patients with at-risk implants. Level III, case control retrospective analysis.

Comparison of Asymptomatic and Symptomatic Adverse Local Tissue Reaction in Patients With Head-Neck Taper Corrosion

BackgroundDiagnosis of adverse local tissue reaction (ALTR) in metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to head-neck taper corrosion is challenging. The purpose of this study is to compare differences between asymptomatic and symptomatic ALTR in an observational cohort, including presentation, metal ion differences, and metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) findings. MethodsWe performed a retrospective review of an observational cohort of 492 MoP THA patients at increased risk of developing ALTR. Ninety-four patients underwent revision arthroplasty for ALTR. Patients were stratified into symptomatic and asymptomatic ALTR groups. Presentation, metal ion levels, and imaging findings were compared. ResultsFor patients with confirmed ALTR, 41% were asymptomatic. There was a statistically significant difference in the serum chromium levels between symptomatic and asymptomatic ALTR patients (2.2 μg/L vs 3.1 μg/L, P = .05). There was no statistically significant difference between the serum cobalt levels or MRI findings in these 2 groups. We observed that extracapsular disease associated with ALTR could be misinterpreted as trochanteric bursitis. ConclusionAlmost half of the MoP THA ALTR cases identified were asymptomatic. Cobalt levels could not differentiate between symptomatic and asymptomatic pseudotumor formation. Symptomatic and asymptomatic MoP ALTRs have similar MARS MRI characteristics. Our findings suggest that it is essential to risk stratify patients who could potentially have ALTR based on implant type, symptoms, ion levels, and MARS MRI.

Sensitivity and Specificity of Serum and Synovial Fluid Markers in Diagnosis of Infection in Head-Neck Taper Corrosion of Metal-On-Polyethylene Total Hip Arthroplasty

BackgroundThe accurate diagnosis of periprosthetic joint infection (PJI) in the setting of adverse local tissue reactions in patients with metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to head-neck taper junction corrosion is challenging as it frequently has the appearance of purulence. The aim of this study is to evaluate the utility of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and synovial fluid markers in diagnosing PJI in failed MoP THA due to head-neck taper corrosion. MethodsA total of 89 consecutive patients with MoP THA with head-neck taper corrosion in 2 groups was evaluated: (1) infection group (n = 11) and (2) noninfection group (n = 78). All patients had highly crossed polyethylene with cobalt chromium femoral heads and had preoperative synovial fluid aspiration. In addition, serum cobalt and chromium levels were analyzed. ResultsThe optimal cutoff value for synovial white blood cell was 2144 with 93% sensitivity and 84% specificity. Neutrophil count optimal cutoff value was 82% with 93% sensitivity and 82% specificity. Receiver operating characteristic analysis of ESR and CRP determined optimal cutoff at 57 mm/h and 35 mg/L with 57% sensitivity and 94% specificity and 93% sensitivity and 76% specificity, respectively. There were no significant differences in metal ion levels between the infected and noninfected groups. ConclusionThe results of this study suggest that ESR and CRP are useful in excluding PJI, whereas both synovial white blood cell count and neutrophil percentage in hip aspirate are useful markers for diagnosing infection in MoP THA patients with head-neck taper corrosion associated adverse local tissue reaction.

Taper Corrosion and Adverse Local Tissue Reactions in Patients with a Modular Knee Prosthesis.

Background:Corrosion has been documented in modular knee implants, but it has not been related to negative patient outcomes. We performed an observational retrieval investigation of 13 Stryker Triathlon TS modular knee implants, 3 of which were revised because of osteolysis and adverse local tissue reactions secondary to fretting corrosion at the modular junctions.Methods:Modular surfaces were examined for the presence and severity of corrosion, and factors that may influence the development of corrosion were investigated. Scanning electron microscopy and energy-dispersive x-ray spectroscopy were performed to evaluate implants with severe corrosion, and tissue samples were sent for histopathological analysis.Results:Mild to severe corrosion was present in association with 62% of modular tibial components and 75% of modular femoral components. Although tibial corrosion was less prevalent than femoral corrosion, it occurred earlier and with greater severity. Scanning electron microscopy and energy-dispersive x-ray spectroscopy demonstrated the appearances of fretting and corrosion of the modular junctions. Histopathological analysis of specimens from the 3 patients with adverse local tissue reactions demonstrated severe reactions to metal debris, including 1 reaction that was consistent with an aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL).Conclusions:To our knowledge, ALVAL and pseudotumors have not previously been reported secondary to corrosion of modular knee replacements. The threaded taper design and the release of cobalt-chromium ions and/or debris are implicated in the occurrence of the adverse local tissue reactions, osteolysis, and soft-tissue damage that we observed in our investigation. Clinicians should be aware of this possible complication associated with modular knee implants.Clinical Relevance:This article should raise clinician awareness of adverse local tissue reactions secondary to corrosion, potentially resulting in earlier recognition of this complication.

The Cobalt/Chromium Ratio Provides Similar Diagnostic Value to a Low Cobalt Threshold in Predicting Adverse Local Tissue Reactions in Patients With Metal-on-Metal Hip Arthroplasty

BackgroundA higher cobalt/chromium (Co/Cr) ratio is thought to be associated with corrosion of the trunnion and increased adverse local tissue reaction (ALTR) risk in patients treated with metal-on-metal (MoM) hip arthroplasty. The main aim of this study was to investigate the diagnostic value of Co/Cr ratio in identifying ALTR in patients treated with MoM hip resurfacing arthroplasty and total hip arthroplasty (THA). MethodsA total of 310 unilateral patients were included. All patients received a metal artifact reduction sequence magnetic resonance imaging to detect ALTR. Blood Co and Cr levels were measured. ResultsMoM THA patients had a higher Co/Cr ratio than MoM hip resurfacing arthroplasty patients (1.7, interquartile range 1.2-3.1 vs 0.9, interquartile range 0.7-1.3, P < .001). The continuous Co/Cr ratio, continuous Co, and Co ≥ 7 ppb were predictive of ALTR when tested in receiver-operating characteristic analyses. The most sensitive and specific cutoffs were found to be 1.4 for Co/Cr ratio (sensitivity = 80.0%; specificity = 48.7%) and 2.4 ppb for Co (sensitivity = 77.8%; specificity = 46.2%). In multivariate analysis, continuous Co, Co ≥ 7 ppb, and the receiver-operating characteristic analysis–generated cutoffs were associated with ALTR prevalence. ConclusionBlood metal ions are strong, but not perfect, predictors of ALTR in patients with MoM hip arthroplasty. Higher Co/Cr ratios are associated with increased risk for ALTR in MoM THA. However, blood Co levels alone are as good a predictor of ALTR as the Co/Cr ratio. The most ALTR-sensitive cutoffs are lower than previously reported in the literature.

The Fate of Elevated Metal Ion Levels After Revision Surgery for Head-Neck Taper Corrosion in Patients With Metal-on-Polyethylene Total Hip Arthroplasty

BackgroundElevated metal ion levels have been associated with the presence of adverse local tissue reactions in patients with metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to corrosion at head-neck taper junction. Patients are frequently concerned with their elevated systemic metal ion levels. This study investigated the rate of decline of serum cobalt and chromium ion levels after revision surgery. MethodsA total of 39 patients with MoP THA were revised because of the presence of symptomatic adverse local tissue reactions on magnetic resonance imaging with elevated serum metal ion levels. The time between initial implantation of MoP THA (index surgery) and revision surgery was considered the duration of metal exposure. The prerevision measure of ion level was considered the intensity of exposure. Prerevision median serum Co and Cr levels, as well as revision serum Co/Cr ratio, were reported. ResultsThe median serum levels of cobalt and cobalt-to-chromium ratio significantly decreased from prerevision levels of 8.2 μg/L (0.2-56.1 μg/L) and 5.6 μg/L (0.1-53.3 μg/L) to 3.1 μg/L (0.2-14 μg/L) and 1.7 μg/L (0.4-3.8 μg/L) at postrevision (P < .01), respectively. The rate of decline of Co was 0.45% per day during the first month. For chromium, the rate of decline was slower with 0.08% per day during the first month. ConclusionAt 3 months after revision surgery, cobalt and chromium ion levels declined by 34% and 8% of prerevision level, respectively. This study provides evidence-based practical information for surgeons to provide MoP THA patients when considering revision surgery for head-neck taper corrosion.

Sensitivity and Specificity of Metal Ion Levels in Predicting “Pseudotumors” due to Taper Corrosion in Patients With Dual Taper Modular Total Hip Arthroplasty

BackgroundCurrently, no serum metal ion threshold exists to identify adverse tissue reactions in total hip arthroplasty (THA) patients with taper corrosion. Our study aims to investigate the sensitivity and specificity of serum metal ions in detecting taper corrosion related pseudotumors in patients with dual taper modular THA. MethodsA total of 148 patients with dual taper modular THA were investigated: (1) 90 patients with pseudotumors detected with metal artifact reduction sequence-magnetic resonance imaging (MARS-MRI) and (2) 58 patients without pseudotumors on MARS-MRI. Receiver operating characteristic curves were constructed to determine the sensitivity and specificity using different metal ion thresholds. The severity of intraoperative tissue damage was correlated with preoperative metal ion levels. ResultsPseudotumor was associated with higher cobalt (5.0 μg/L vs 3.7 μg/L, P < .01) and Co/Cr ratio (6.0 vs 3.7, P < .01). The sensitivity and specificity for cobalt level of 2.8 μg/L and Co/Cr ratio of 3.8 in detecting taper corrosion–related pseudotumors on MARS-MRI was 88% and 32% and 70% and 50%, respectively. Higher intraoperative tissue damage grades demonstrated significantly higher Co/Cr ratios (8.6 vs 3.4, P = .03). ConclusionAlthough metal ion levels alone should not be relied on as the sole parameter to determine revision surgery, cobalt level >2.8 μg/L and the Co/Cr ratio >3.8 are useful clinical diagnostic adjuncts in the systematic clinical evaluation for taper corrosion–related adverse tissue reactions in patients with dual modular taper THA.

Genetic alterations in periprosthetic soft-tissue masses from patients with metal-on-metal hip replacement

Adverse soft tissue reactions in patients with metal-on-metal (MoM) hip replacement are associated with cobalt (Co) and chromium (Cr) particles released from the implant. Exposing the patients to long periods of increased metal ions concentrations resulting from the wear of these implants poses an increased risk of genotoxicity/mutagenicity. A variable proportion of patients develop periprosthetic soft-tissue masses or pseudotumors at the site of the implant. There is a concern that exposure to increased metal ions could increase the risk of cancer. In order to investigate whether the periprosthetic soft-tissue mass harbours any cancer- related genetic alterations, we studied DNA isolated from periprosthetic tissues of 20 patients with MoM hip replacement, for copy number alterations and mutations in hotspot regions of 50 cancer genes using aCGH and amplicon-based next generation sequencing.Our results showed copy number gains at 12q14.3 and 21q21.1in tumour from patient diagnosed with liposarcoma. Copy number alterations in periprosthetic tissues were seen in three other patients, one had a region of gain at 9q24.1 affecting JAK2 and INSL6, and two patients had region of gain at 6p21.1, affecting RUNX2. Mutation analysis showed V1578del mutation in NOTCH1 in two patients. The copy number alterations and mutations seen in periprosthetic soft-tissue masses are earlier reported in either haematological malignancies or in osteoblast related bone dysplasia. The presence of genetic anomalies was associated with longer in-situ time of the implant. Our findings warrant the need of similar studies in larger patient cohorts to evaluate the risk of development of neoplastic alterations in periprosthetic tissues of patients with MoM hip replacement.

Otto Aufranc Award: Large Heads Do Not Increase Damage at the Head-neck Taper of Metal-on-polyethylene Total Hip Arthroplasties.

Fretting and corrosion at head-neck junctions of total hip arthroplasties (THAs) have been associated with adverse local tissue reactions in patients with both metal-on-polyethylene (MoP) and metal-on-metal (MoM) prostheses. Femoral head size contributes to the severity of fretting and corrosion in large-diameter MoM THAs, but its impact on such damage in MoP THAs remains unknown. (1) Is femoral head size associated with increased fretting or corrosion at the head-neck junction in MoP total hips? (2) Is duration of implantation associated with increased fretting or corrosion? The severity of fretting/corrosion on surfaces of head tapers and stem trunnions was visually examined in 154 MoP THAs retrieved as part of 3282 revision surgeries performed at our institution between January 1, 2007, and December 31, 2013. Fretting and corrosion damage were subjectively graded by two independent observers on a 1 to 4 scale, and their relations to head size, alloy combinations, taper/trunnion design, length of implantation (LOI), and location were investigated. Differences in scores never exceeded one grade, and this occurred in only 17% of examined implants. With the available implants, the study provided 88% power to detect differences of 0.5 in fretting or corrosion scores in these analyses. Fretting and corrosion of the tapers and the trunnions were not affected by head size (p = 0.247, p = 0.471, p = 0.837, and p = 0.868, respectively), although taper/trunnion design affected taper fretting (p = 0.005) and corrosion (p = 0.0031) and trunnion fretting (p = 0.0028). Head taper fretting (observed in 73% of heads) increased with LOI, but head taper corrosion (noted in 93% of heads) was not affected. Trunnion fretting (observed in 86% of stems) was more severe in mixed-alloy combinations and with increased LOI and was more severe proximally. Trunnion corrosion (noted in 72% of stems) was also location-dependent with greater corrosion distally. Fretting and corrosion are regular occurrences in MoP THAs, but neither damage type was related to femoral head size. Conversely, taper design, LOI, and alloy combination affected the severity of both fretting and corrosion. Although it has been suggested that trunnion corrosion seen in MoP bearings is a function of larger diameter heads, our data suggest that larger femoral heads may be used for increased damage at the modular junction of MoP THAs.

The Symmetry of Adverse Local Tissue Reactions in Patients with Bilateral Simultaneous and Sequential ASR Hip Replacement

The purpose of this study was to evaluate whether patients with bilateral metal-on-metal (MoM) hip replacements have symmetric adverse local tissue reactions (ALTRs) at follow-up. An MRI of both hips was performed at a mean time of six years after surgery in 43 patients. The prevalence and severity of ALTRs were found to be similar in simultaneous hips but differences were observed in sequential hips. The order and timing of sequential hip arthroplasties did not affect the severity of ALTRs. Thus, in addition to metal ion exposure from an earlier MoM implant other factors may also play a role in the progression of ALTRs. Bilateral implants should be given special consideration in risk stratification algorithms for management of patients with MoM hip arthroplasty.

Soft tissue reactions in patients with bone anchored hearing aids.

To establish the incidence and correlation between the degree of soft tissue reaction and the body mass index (BMI) according to age and gender after a bone anchored hearing aid (BAHA) implant. We did a 1-9-year follow-up for the all the patients who underwent surgery in our department with BAHA implant system. Soft tissue reactions were classified in accordance with the Holgers classification on regular patient visits. BMI was calculated for each patient, and changes were recorded at least once a year. 47 patients were evaluated. 58% were operated on for chronic otitis with mixed or conductive hearing loss; 20% had unilateral or bilateral atresia and 16% had single sided deafness (SSD); other indications were otosclerosis and syndromic patients. The grade of Holgers classification significantly correlated at a 0.001 level with BMI (Spearmans rho 0.452). Holgers grade also differed significantly between the sexes-skin reactions in females were less frequent. An ANOVA test did not reveal any statistical difference between patients with dissimilar indications for BAHA. If performed carefully, BAHA surgery produces a favorable outcome. The Holgers grade may change as time passes. If skin reactions appear, they can be treated through local or systemic therapy, and they may turn into a normal grade. Adipose patients should be treated with special care because they are more prone to soft tissue reactions.

Radiogenomics: The Promise of Personalized Treatment in Radiation Oncology?

Significant variability exists in normal tissue reactions in patients with cancer receiving radiotherapy, with a subpopulation exhibiting increased toxicity to ionizing radiation. Genomic studies have proposed that single nucleotide polymorphisms in DNA repair genes, cytokines, and reactive oxygen species may play a role in clinical radiosensitivity. Additional research examining the association between genetic variants and radiation-induced inflammation and fibrosis may spur the development of targeted therapy in radiation oncology, which could increase cure rates and limit toxicity. As more people become long-term cancer survivors, oncology nurses must aggressively assess and manage late treatment side effects to optimize patient functioning and quality of life. The purpose of the current article is to describe the effect of ionizing radiation on normal and irradiated tissue, discuss genetic mutations that are proposed to influence radiosensitivity, and identify future areas of research on the association between genetics and radiation toxicity.

Repeated metal ion measurements in patients with high risk metal-on-metal hip replacement

Conventional follow-up methods are not sufficient to identify adverse soft tissue reactions in patients with metal-on-metal hip replacements. The national guidelines regarding metal ion measurements are debatable. The aims of our study were to investigate (1) if there is a clinically significant change in whole blood (WB) cobalt (Co) or chrome (Cr) levels in repeated WB assessment in patients operated on with ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) in the repeated WB metal ion assessment. We identified all patients (n = 254) with unilateral ASR implants who had second blood sample taken eight to 16 months after the first. WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with a high risk HR device. In contrast to this, 50 % of patients with THRs had metal ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group. In patients with a high risk HR, repeated metal ion measurement did not provide useful information for clinical decision-making. In patients with a LD MoM THR repeated measurements revealed a large number of patients with metal ion levels exceeding SUL and might thus be clinically beneficial.

IBD and related diagnostically difficult entities of the colon

This lecture (review) summarises current diagnostic problems and advances with regard to patterns of inflammation and dysplasia in inflammatory bowel disease (IBD), particularly ulcerative colitis and Crohn’s disease. In a small percentage of cases, a definite diagnosis of ulcerative colitis or Crohn’s disease cannot be established in which the term ‘indeterminate colitis’ has been used. Most cases of indeterminate colitis are related to fulminant colitis, a condition in which the classic features of ulcerative colitis or Crohn’s disease may be obscured by severe ulceration with early fissuring ulceration, transmural inflammation, and relative rectal sparing. Several studies suggest that ileal/anal pouch anastomosis procedure is safe and effective in patients with indeterminate (fulminant) colitis. In biopsy studies, there are a number of exceptions to the classic principles in IBD pathology that may lead to diagnostic confusion and simulate Crohn’s-like tissue reactions in patients with ulcerative colitis. For instance, skip lesions may occur in patients with ulcerative colitis in the follow settings: long-term oral or topical therapy, and on initial presentation in paediatric patients. Patients with IBD are at increased risk for the development of dysplasia and carcinoma. Dysplasia in IBD is classified as flat or elevated, and then microscopically as negative, indefinite, low or high grade. In addition to the conventional (intestinal) type of dysplasia, other less common and more diagnostically difficult types of dysplasia, such as serrated dysplasia and mucinous hypervillous epithelium, may occur in some patients with IBD. There is recent evidence to suggest that patients with flat low grade dysplasia should also be considered strongly for colectomy. Elevated lesions in IBD (DALM) are subdivided into adenoma-like and non-adenoma-like based on their endoscopic appearance. Regardless of the grade of dysplasia, adenoma-like lesions may be treated adequately by polypectomy if there are no other areas of flat dysplasia in the patient. The surveillance and treatment options for patients with flat and elevated dysplasia in IBD will be reviewed in detail.

Comparison of chromosomal radiosensitivity of normal cells with and without HRS-like response and normal tissue reactions in patients with cervix cancer

Purpose: In our previous study, using the micronucleus (MN) assay, the low- and high-dose radiation response of fibroblasts and keratinocytes from cancer patients was assessed. We reported that a hyper-radiosensitivity (HRS)-like phenomenon was observed for fibroblasts of two and keratinocytes of four of the 40 patients studied. In this paper, we report the comparison of these in vitro results and normal tissue reactions in patients with cervix cancer and answer the question of the predictive value of the MN assay.Materials and methods: Of the 40 patients with cervix cancer whose cells were previously studied in vitro, 32 received radiotherapy. The treated group included two patients with HRS-like positive fibroblasts and four patients with HRS-like positive keratinocytes. In 26 patients both types of cells were HRS-like negative. The in vitro results (MN induction measured in patients' fibroblasts and keratinocytes after in vitroγ-irradiation with doses ranging from 0.05–4 Gy) were compared with the maximum grade of acute and late reactions.Results: Five of the six patients whose cells demonstrated low-dose chromosomal hypersensitivity in vitro, did not suffer from any mild or severe side effects after radiotherapy. Although individual variations in the grade scores of normal-tissue reactions were observed in cancer patients, no significant relationship was found between MN induction, either in fibroblasts or keratinocytes, and acute and late effects.Conclusion: Since the MN assay showed no predictive value, it is rather impossible that the severe late complication observed in one of the six HRS-like positive patients reflects her low-dose chromosomal hypersensitivity in vitro.

Antimalarial lichenoid tissue reactions in patients with pre-existing lupus erythematosus

Recently a number of cases of drug induction or exacerbation of lupus erythematosus (LE) specific skin disease have been described in the literature. Many of the responsible medications are also known for their ability to induce a lichenoid tissue reaction. Aminoquinoline antimalarials are currently the first line of therapy in cutaneous LE specific skin disease. Lichenoid tissue reactions are among the most common cutaneous side effects of aminoquinolone antimalarials. We report three cases of aminoquinolone antimalarial induced or exacerbated LE specific skin disease. We also review the pathophysiology of LE specific skin disease and propose a mechanism by which induction of the lichenoid tissue reaction may result in Koebnerization of LE specific skin lesions.

A randomized clinical trial on continuous 7-day-a-week postoperative radiotherapy in high-risk squamous cell head-and-neck cancer: a preliminary report on acute normal tissue reactions

Purpose/Objective: To evaluate acute normal tissue reactions in patients treated with continuous accelerated postoperative irradiation (p-CAIR) vs. conventionally fractionated postoperative radiotherapy (p-CF). Materials/Methods: Between October 2001 and December 2002 100 patients with squamous cell cancer of the larynx, oral cavity, oropharynx or hypopharynx, after major surgical intervention, with high-risk pathologic features, and no gross residual disease were recruited for this trial. The patients were randomly assigned to receive 63 Gy in 1.8 Gy 7-day-a-week fractions over a period of 5 weeks (n=48), or 63 Gy in 1.8 Gy fractions given Monday to Friday over 7 weeks (n=52). Acute mucosal reactions were scored using Dische system. The supportive anti-inflammatory treatment was given when the severity score exceeded 10. Results: Ninety five patients complied to the assigned treatment. Two patients in the p-CAIR and 1 in the p-CF arm received <60 Gy because of deteriorating general performance and/or tumor progression; one patient died before radiotherapy was started, and one terminated radiotherapy due to psychosis. The average maximum Dische score in both arms of the trial was 11.9 (range 2–21) and was significantly higher in patients treated with p-CAIR, compared to p-CF (10.8 vs. 13.3, p<0.05). Patients with cancer of the oral cavity and oropharynx had higher average maximum Dische scores (p-CAIR:16.4 vs. p-CF:12.3) compared to cancer of the larynx or hypopharynx (p-CAIR:11.8 vs. p-CF:9.6). The average body weight loss during radiotherapy was the same in both arms of the trial (3.3%), but it varied depending on primary tumor site (2.7% larynx/hypoharynx vs. 4.4% other). The hematological toxicity was mild and similar in both arms of the trial. No consequential side toxicity of radiotherapy was observed. Conclusions: The acute normal tissue morbidity in the initial group of 48 patients randomly assigned to the p-CAIR schedule appears acceptable, and allows further recruitment into the trial. In both trial arms patients with cancer of the larynx or hypopharynx tolerated postoperative radiotherapy better than patients with cancer of the oral cavity or oropharynx.

Describing patients' normal tissue reactions: concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Steering Committee of the BioMed2 European Union Concerted Action Programme on the Development of Predictive Tests of Normal Tissue Response to Radiation Therapy.

Clinical radiotherapeutic doses are limited by the tolerance of normal tissues. Patients given a standard treatment exhibit a range of normal tissue reactions, and a better understanding of this individual variation might allow for individualisation of radiotherapeutic prescriptions, with consequent improvement in the therapeutic ratio. At present, there is no simple way to describe normal tissue reactions, which hampers communication between clinic and laboratory and between groups from different centres. There is also no method for comparing the severity of reactions in different normal tissues. This arises largely because there is no definition of a "normal" reaction, an "extreme" reaction or the particular term "over-reactor" (OR). This report proposes definitions for these terms, as well as a simple terminology for describing normal tissue reactions in patients having radiotherapy. The "normal" range represents the individual variation in normal tissue reactions amongst large numbers of patients treated in the same way which is within clinically acceptable limits. The term "OR" is applied to an individual whose reaction is more severe than the normal range but also implies that this forced a major change in the radiotherapeutic prescription or that the reactions were very severe or fatal. A "severe OR" would develop serious problems with a typical radical dose, while an "extreme OR" would have such difficulties at a much lower dose. To describe the normal range, a numerical scale is suggested, from 1 to 5, resistant to sensitive. The term "highly radiosensitive" (HR) is suggested for category 5. An "informal" relative scale, as suggested here, is quick and simple. It should allow comparison between different hospitals, compensate for differences in radiotherapeutic dose and technique and allow comparison of reactions between different anatomical sites. It should be adequate for discriminating patients at the extremes of the normal range from those at the centre. It is hoped that the definitions and terminology proposed here will aid communication in the field of predictive testing of normal tissue radiosensitivity.

Late normal tissue reactions in patients with breast carcinoma

I was interested to read the paper by Bates (1988) dealing with the late normal tissue reactions experienced by patients with breast carcinoma treatedby mastectomy and post-operative radiotherapy given in either two or three fractions per week (a comparison of six fractions in 18 days with 12 fractions in 28 days). I would, however, suggest that the negative α/βratio obtained indicates that the treatment of 51 Gy in 12 fractions is notequivalent to that of 35 Gy in six fractions.