Vaginal changes, sexual functioning and distress of women with locally advanced cervical cancer treated in the EMBRACE vaginal morbidity substudy.

OBJECTIVE: The EMBRACE-vaginal morbidity substudy prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems and distress in the first 2-years after image-guided radio(chemo)therapy and brachytherapy for locally advanced cervical cancer. METHODS: Eligible patients had stage IB1-IIIB cervical cancer with ≤5 mm vaginal involvement. Assessment of vaginal changes was graded using CTCAE. PRO were assessed using validated Quality-of-Life and sexual questionnaires. Statistical analysis included Generalized-Linear-Mixed-Models and Spearman's rho-correlation coefficients. RESULTS: 113 eligible patients were included. Mostly mild (grade 1) vaginal changes were reported over time in about 20% (range 11-37%). At 2-years, 47% was not sexually active. Approximately 50% of the sexually active women reported any vaginal and sexual functioning problems and distress over time; more substantial vaginal and sexual problems and distress were reported by up to 14%, 20% and 8%, respectively. Physician-assessed vaginal changes and PRO sexual satisfaction differed significantly (p ≤ .05) between baseline and first follow-up, without further significant changes over time. No or only small associations between physician-assessed vaginal changes and PRO vaginal functioning problems and sexual distress were found. CONCLUSIONS: Mild vaginal changes were reported after image-guided radio(chemo)therapy and brachytherapy, potentially due to the combination of tumors with limited vaginal involvement, EMBRACE-specific treatment optimization and rehabilitation recommendations. Although vaginal and sexual functioning problems and sexual distress were frequently reported, the rate of substantial problems and distress was low. The lack of association between vaginal changes, vaginal functioning problems and sexual distress shows that sexual functioning is more complex than vaginal morbidity alone.

Lichen Sclerosis is Associated With a High Rate of Local Failure After Radio(chemo)therapy for Vulvar Cancer.

AIMS: Radio(chemo)therapy plays an important role in the treatment of vulvar cancer, either as postoperative treatment or as definitive treatment in patients who present with inoperable disease. Only limited data are available regarding outcome after modern state of the art radio(chemo)therapy and more information regarding prognostic factors are warranted. The aim of this study was to evaluate disease outcomes after radio(chemo)therapy in patients with vulvar cancer with special emphasis on the impact of lichen sclerosis on local control. MATERIALS AND METHODS: All consecutive patients (n = 109) from the western half of Denmark who were treated with definitive (n = 52) or postoperative (n = 57) radio(chemo)therapy between January 2013 and January 2020 were included. Local control, cause-specific survival and overall survival, as well as morbidity, were analysed using Kaplan-Meier statistics. Prognostic factors for local control were analysed in univariate and multivariate analysis. RESULTS: At a median follow-up of 35 (4-95) months, 46 (42.0%) patients were diagnosed with recurrence. Eighty per cent of the recurrences were located to the vulva region, leading to a 5-year local control of 58.9% (confidence interval 47.9-69.9). Cause-specific survival was 62.9% (confidence interval 53.1-72.7), whereas overall survival was 58.0% (confidence interval 47.6-68.5). Grade 3-4 morbidity was diagnosed in 10 (9%) patients. Lichen sclerosis (hazard ratio 3.89; confidence interval 1.93-7.79) was an independent risk factors for local recurrence. Patients without lichen sclerosis had a 5-year local control rate of 83.6% (confidence interval 67.2-99.0) and 62.6% (confidence interval 43.2-82.0) after postoperative and definitive radio(chemo)therapy, respectively. In patients with lichen sclerosis, the local control rate was 44.0% (confidence interval 19.3-69.0) and 17.6% (confidence interval 0-30.0) after postoperative and definitive radio(chemo)therapy, respectively. CONCLUSION: Radio(chemo)therapy plays an important role in the treatment of vulvar cancer. However, despite dose escalation, a substantial proportion of patients experienced local relapse. Pre-existing lichen sclerosis seems to have a significant impact on the risk of recurrence. This should influence surveillance programmes for these patients.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Assessment of dose to functional sub-structures in the lower urinary tract in locally advanced cervical cancer radiotherapy.

PURPOSE: To provide an analysis of dose distribution in sub-structures that could be responsible for urinary toxicity after Image-Guided Adaptive BrachyTherapy (IGABT) in Locally Advanced Cervical Cancer (LACC). METHODS: 105 LACC patients treated with radiochemotherapy and IGABT were selected. Sub-structures (bladder wall, trigone, bladder neck, urethra) were contoured on IGABT-planning MRIs. D2cm3 and D0.1cm3, ICRU Bladder-Point (ICRU BP) and Posterior-Inferior Border of Symphysis points (PIBS, PIBS + 2 cm, PIBS - 2 cm) doses were extracted. Internal-Urethral-Ostium (IUO) and PIBS-Urethra (PIBS-U) points were defined as urethral dose surrogates. Finally, the Vaginal Reference Length (VRL) was extracted. Values were converted into total EBRT + BT equivalent dose in 2 Gy fractions using α/ß = 3 and T1/2 = 1.5 h. RESULTS: Median D2cm3 for bladder and trigone were 71.7[interquartile-range:66.5;74.1]Gy and 57.8[53.3;63.6]Gy, respectively, while median D0.1cm3 were 82.2[77.6;89.1]Gy and 70.7[62.0;76.7]Gy, respectively. Median ICRU BP dose was 63.7[56.5;70.5]Gy and correlated with trigone D2cm3 and D0.1cm3, while bladder and trigone D2cm3 had poor correlation (R2 = 0.492), as well as D0.1cm3 (R2 = 0.356). Bladder neck D0.1cm3 was always lower than trigone D0.1cm3 and higher than IUO. Correlation between PIBS + 2 cm and IUO was poor (R2 = 0.273), while PIBS and PIBS-U were almost equal (R2 = 0.990). VRL correlated with dose to bladder base. CONCLUSIONS: The study confirmed that ICRU BP and trigone doses correlate. Bladder D2cm3 is not representative of trigone dose because hotspots are often placed in the bladder dome. VRL is a good indicator for bladder base sparing. In addition to D2cm3 and D0.1cm3 for whole bladder, ICRU BP, trigone D2cm3 and D0.1cm3, IUO and PIBS are useful for lower urinary tract reporting.

Urinary and sexual dysfunction in women after resection with and without preoperative radiotherapy for rectal cancer: a population-based cross-sectional study.

AIM: Knowledge of urinary and sexual dysfunction in women after rectal cancer treatment is limited. This study addresses this in relation to the use of preoperative radiotherapy, type of surgery and the presence of bowel dysfunction. METHOD: All living female patients who underwent abdominoperineal excision (APE) or low anterior resection (LAR) for rectal cancer in Denmark between 2001 and 2007 were identified. Validated questionnaires (the ICIQ-FLUTS and the SVQ) on urinary and sexual function were completed by 516 (75%) and 482 (72%) recurrence-free patients in 2009. RESULTS: Urgency and incontinence were reported by 77 and 63% of respondents, respectively. Vaginal dryness, dyspareunia and reduced vaginal dimensions occurred in 72, 53 and 29%, respectively, and 69% reported that they had little/no sexual desire. Preoperative radiotherapy was associated with voiding difficulties (OR = 1.63, 95% CI 1.09-2.44), reduced vaginal dimensions (OR = 4.77, 95% CI 1.97-11.55), dyspareunia (OR = 2.76, 95% CI 1.12-6.79), lack of desire (OR = 2.22, 95% CI 1.09-4.53) and reduced sexual activity (OR = 0.55, 95% CI 0.30-0.98). Patients undergoing APE had a higher risk of dyspareunia (OR = 2.61, 95% CI 1.00-6.85). Bowel dysfunction after LAR was associated with bladder storage difficulties (OR = 1.64, 95% CI 1.01-2.65), symptoms of incontinence (OR = 2.17, 95% CI 1.35-3.50), lack of sexual desire (OR = 2.69, 95% CI 1.21-5.98), sexual inactivity (OR = 0.48, 95% CI 0.24-0.96) and sexual dissatisfaction (OR = 0.40, 95% CI 0.20-0.82). CONCLUSION: Urinary and sexual problems are common in women after treatment for rectal cancer. Preoperative radiotherapy interferes with several aspects of urinary and sexual functioning. Bowel dysfunction after LAR is associated with urinary dysfunction and a reduction in sexual desire, activity and satisfaction.

Do clinicians and patients agree regarding symptoms? A comparison after definitive radiochemotherapy in 223 uterine cervical cancer patients.

BACKGROUND: In clinical cancer research of morbidity, low associations between clinician-assessed toxicity/morbidity and patient-reported symptoms are consistently described in the literature. While morbidity grading systems are supposed to follow more or less objective criteria, patient reported symptoms inherently are based on a subjective self-evaluation of the impact on quality of life. The aim of this study was to focus on major discrepancies with high clinical relevance and to evaluate its impact with regard to underreporting of morbidity. MATERIAL AND METHODS: Early morbidity assessed by clinicians with CTCAEv.3 and patient reported quality of life (EORTC-QLQ-C30/CX24) were compared regarding 12 overlapping symptoms in 223 patients with uterine cervical cancer 3 months after definitive radio(chemo)therapy in the ongoing EMBRACE study. Mismatches showing discrepancies between both grading systems were classified, if patients reported substantial symptoms (quite a bit/very much) and CTCAE grading was rated G0. RESULTS: In total, 360 substantial symptoms were reported by patients by EORTC-QLQ; 159 (44%) of those were not recognized by CTCAE. Symptoms with the highest occurrence of mismatches overall are urinary frequency, fatigue, and insomnia. Large institutional differences were found, showing two centers with 4 vs. 71% of patients with at least one mismatch. CONCLUSION: Analysis of mismatches indicated a high risk of underestimation of early morbidity. Thus, nearly half of the patient-reported substantial symptoms were not recognized by CTCAE scoring (G0) 3 months after treatment. Prospective assessment of morbidity in clinical studies should, therefore, integrate patient reported symptoms to receive a complete and comprehensive picture.

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

A 10-year experience of total pelvic exenteration for primary advanced and locally recurrent rectal cancer based on a prospective database.

AIM: The study was conducted in a dedicated centre treating the majority of Danish patients with intended curative total pelvic exenteration for primary advanced (PARC) or locally recurrent (LRRC) rectal cancer. We compared PARC and LRRC and analysed postoperative morbidity and mortality, and long-term outcome. METHOD: There were 90 consecutive patients (PARC/LRRC 50/40) treated between January 2001 and October 2010, recorded on a prospectively maintained database. RESULTS: The median age was 63 (32-75) years with a gender ratio of 7 women to 83 men. All patients were American Society of Anesthesiologists level I or II. Sacral resection was performed in five patients with PARC and 15 with LRRC (P=0.002). R0 resection was achieved in 33 (66%) patients with PARC and in 15 (38%) with LRRC, R1 resection in 17 (34%) with PARC and 20 (50%) with LRRC and R2 resection in five (13%) with LRRC. R0 resection was more frequent in PARC (P=0.007). Forty-four (49%) patients had no postoperative complications. Fifty-five major complications were registered. Two (2.2%) patients died within 30 days, and the total in-hospital mortality was 5.6%. The median follow-up was 12 (0.4-91) months. The 5-year survival was 46% for PARC and 17% for LRRC (P=0.16). CONCLUSION: Pelvic exenteration is associated with considerable morbidity but low mortality in an experienced centre. Pelvic exenteration can improve long-term survival, especially for patients with PARC. However, pelvic exenteration is also justified for patients with LRRC.

Clinical outcome in 520 consecutive Danish rectal cancer patients treated with short course preoperative radiotherapy.

AIM: The purpose of this study was to analyse the results of preoperative short course radiotherapy in a consecutive, national cohort of patients with rectal cancer. METHODS: Through a validated, prospective national database we identified 520 Danish patients who presented with high-risk mobile tumours in the lower two thirds of the rectum and were referred for preoperative radiotherapy with 5 x 5 Gy. The inclusion period was 56 months. Radiotherapy data was retrospectively collected. RESULTS: Of the 520 patients, 514 completed radiotherapy and 506 had surgery. Surgery was considered curative in 439 patients. The 3-year local recurrence rate was 4.0% (95% CI 2.5-6.5%) and the distant recurrence rate at 3 years was 18.7% (95% CI 15.4-22.5%). The 5-year disease free survival rate was 40.2% (95% CI 27.0-53.1%) and overall survival 50.4% (95% CI 36.1-63.1%). Most tumours (61%) were classified as T3 or T4 and 41% of the local recurrences occurred in patients with a fixed tumour at surgery. CONCLUSION: This study confirms data from randomised studies that the short course 5 x 5 Gy regime is a feasible treatment for locally advanced rectal cancer even when applied in a population outside clinical trials.

A national cohort study of long-course preoperative radiotherapy in primary fixed rectal cancer in Denmark.

OBJECTIVE: Preoperative radiotherapy has been shown to enable a fixed rectal cancer to become resectable which in turn may result in long-time survival. In this study, we analysed the outcome of long-course preoperative radiotherapy in fixed rectal cancer in a national cohort including all Danish patients registered with primary inoperable rectal cancer and treated in the period May 2001 to December 2005. METHOD: The study was based on surgical and demographic data from a continuously updated and validated national database. In addition, retrospective data were retrieved from all departments of radiotherapy concerning technique of radiotherapy, dose and fractionation and use of concomitant chemotherapy. Outcome was determined by actuarial analysis of local control, disease-free survival and overall survival. RESULTS: A total of 258 patients with fixed rectal cancer received long-course radiotherapy (> 45 Gy). The median age at diagnosis was 66 years (range: 32-85) and 185 (72%) patients were male. The resectability rate was 80%, and a R0 resection was obtained in 148 patients (57% of all patients and 61% of those operated). The 5-year local recurrence rate for all patients was 5% (95% CI: 3-7%), and the actuarial distant recurrence rate was 41% (95% CI: 35-47%). The cumulative 5-year disease-free survival was 27% (95% CI: 22-32%) and overall 5-year survival was 34% (95% CI: 29-39%). CONCLUSIONS: This study is the first population-based report on outcome of preoperative long-course radiotherapy in a large unselected patient group with clinically fixed rectal cancer. Most patients could be resected with the intention of cure and one in three was alive after 5 years.

Perineal healing and survival after anal cancer salvage surgery: 10-year experience with primary perineal reconstruction using the vertical rectus abdominis myocutaneous (VRAM) flap.

Salvage surgery of recurrent or persistent anal cancer following radiotherapy is often followed by perineal wound complications. We examined survival and perineal wound complications in anal cancer salvage surgery during a 10-year period with primary perineal reconstruction predominantly performed using vertical rectus abdominis myocutaneous (VRAM) flap. Between 1997 and 2006, 49 patients underwent anal cancer salvage surgery. Of these, 48 had primary reconstruction with VRAM. Overall survival was computed by the Kaplan-Meier method and mortality rate ratios (MRRs) by Cox regression. One patient (2%) died within 30 days postoperatively. Postoperative complications necessitated reoperation in eight (16%) patients. We found no major perineal wound infections. Major perineal wound breakdown occurred in the only patient in whom VRAM was not used. Five-year survival was 61% [95% confidence interval (CI) 43-75%]. Free resection margins (R0) were obtained in 78% of patients, with 5-year survival of 75% (95% CI 53-87%). Involved margins, microscopically only (R1) or macroscopically (R2), strongly predicted an adverse outcome [age-adjusted 2-year MRRs (95% CI) R1 vs. R0 = 4.1 (0.7-23.6), R2 vs. R0 = 10.9 (2.2-54.2)]. We conclude that anal cancer salvage surgery can yield long-time survival but obtaining free margins is critical. A low rate of perineal complications is achievable by primary perineal reconstruction using VRAM flap.

CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation.

AIM: To characterise uveal melanoma that has metastasised to the central nervous system (CNS). METHODS: Review of 2365 patients constituting all patients diagnosed as having primary uveal melanoma in Denmark during the period 1943-1997. All patients with malignant uveal melanoma and metastasis to the CNS were identified. For each patient, clinical and histopathological data were gathered. RESULTS: Sixteen patients with CNS metastasis were identified. The median age was 58 years. The majority of CNS metastases were located in the frontal and parietal lobes. Eleven patients had widespread metastases. Five patients had exclusively metastasis to the CNS. The average time from diagnosis of primary tumour to symptoms of CNS metastasis was 91 months. The average time from the initial CNS symptoms to death was 20 months. All tumours were composed of either mixed or spindle cells. The average largest basal diameter of the primary tumours was 12 mm. One tumour was a ring melanoma. The majority of tumours had a ruptured Bruch membrane. Retinal invasion was observed in 36% of tumours. No specimen had optic nerve invasion. Scleral invasion was pronounced in 36% of cases, and extrascleral extension was observed in two cases (14%). The amount of tumour infiltrating lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had multiple organ metastases, and the average time from the initial CNS symptoms to death was 8 months. Five patients had metastasis to the CNS solely, and the average time from the initial CNS symptoms to death was 57 months.

Whither papillon? Future directions for contact radiotherapy in rectal cancer.

Although contact radiotherapy was developed 70 years ago, and is highly effective with cure rates of over 90% for early rectal cancer, there are few centres that offer this treatment today. One reason is the lack of replacement of ageing contact X-ray machines, many of which are now over 30 years old. To address this problem, the International Contact Radiotherapy Evaluation (ICONE) group was formed at a meeting in Liverpool in 2005 with the aim of developing a new contact X-ray unit and to establish clinical protocols that would enable the new machine to safely engage in the treatment of rectal cancer. As a result of these efforts, a European company is starting production of the new Papillon RT-50 machine, which will be available shortly. In addition, the ICONE group is planning an observational study on contact X-ray and transanal endoscopic microsurgery (CONTEM) for curative treatment of rectal cancer. This protocol will ensure standardised diagnostic procedures, patient selection and treatment in centres across the world and the data will be collected prospectively for analysis and audit. It is hoped that the CONTEM trial will provide the scientific evidence that is needed to obtain a broader acceptance of local contact radiotherapy as a treatment option for selected cases with early stage rectal cancer.

Uveal and conjunctival malignant melanoma in Denmark, 1943-97: incidence and validation study.

PURPOSE: To study the incidence of malignant melanoma in the ocular region in Denmark during the period 1943-97. METHODS: The patients were mainly identified through the Danish Cancer Registry. Age-period-cohort modelling of the incidence rates was done based on age at diagnosis, calendar period and birth cohort in 5-year groups and for each gender. RESULTS: The age-standardized incidence of malignant melanoma in the ocular region was 0.78 for men (N = 1327) and 0.65 for women (N = 1242) per 100,000 person-years. Calendar period and birth cohort had no effect on the incidence in the ocular region or in the topography subgroups choroid/ciliary body and conjunctiva. However, the incidence increased with birth cohort for iris melanomas. CONCLUSIONS: The incidence of malignant melanoma in the ocular region was stable in contrast to a major increase in cutaneous melanoma in Denmark during the period 1943-97. The incidence of iris melanomas increased substantially, whereas the rate was stable for choroid/ciliary body and conjunctival melanomas.

Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma.

PURPOSE: This study was designed to compare tumor hypoxia assessed by invasive O2 sensitive electrodes and pimonidazole labeling in primary human cervix carcinomas. METHODS AND MATERIALS: Twenty-eight patients with primary cervix carcinomas (FIGO Stage Ib-IVa) were investigated. Both invasive pO2 measurements and pimonidazole labeling were obtained in all patients. Before treatment, patients were given pimonidazole as a single injection (0.5 g/m2 i.v.). Ten to 24 h later, oxygenation measurements were done by Eppendorf histography, and after this procedure biopsies were taken for pimonidazole-binding analysis. Tumor oxygen partial pressure (pO2) was evaluated as the median tumor pO2 and the fraction of pO2 values < or = 10 mmHg (HF10). Biopsies were formalin fixed and paraffin embedded, and hypoxia was detected by immunohistochemistry using monoclonal antibodies directed against reductively activated pimonidazole. Pimonidazole binding was evaluated by a semiquantitative scoring system. RESULTS: Both Eppendorf measurements and pimonidazole binding showed large intra-and intertumor variability. A comparison between pimonidazole binding expressed as the fraction of fields at the highest score and HF10 showed a trend for the most well-oxygenated tumors having a low fraction of fields; however, the correlation did not reach statistical significance (p = 0.43, r = 0.165; Spearman's rank correlation test). CONCLUSION: Hypoxia measured in human uterine cervix carcinomas is heterogeneously expressed both within and between tumors when assessed by either invasive pO2 measurements or pimonidazole binding. Despite a trend that tumors with high pO2 values expressed less pimonidazole binding, no correlation was seen between the two assays in this preliminary report.

Has the outlook improved for amifostine as a clinical radioprotector?

UNLABELLED: Amifostine has recently been approved for clinical radiotherapy as a protector against irradiation-induced xerostomia. It is our aim to review the outlook for using amifostine as a general clinical radioprotector. Protection against X-rays is mainly obtained by the scavenging of free radicals. The degree of protection is therefore highly dependent on oxygen tension, with protection factors ranging from 1 to 3. Maximal protection is observed at physiological levels of oxygenation. A great variability in protection has also been observed between different normal tissues. Some tissue, like brain, is not protected while salivary glands and bone marrow may exhibit a three-fold increase in radiation tolerance. Amifostine is dephosphorylized to its active metabolite by a process involving alkaline phosphatase. Due to lower levels of alkaline phosphatase in tumor vessels, amifostine is marketed as a selective protector of normal tissue and not tumors. However, the preclinical investigations concerning the selectivity of amifostine are controversial and the clinical studies are sparse and do not have the power to evaluate the influence of amifostine on the therapeutic index. CONCLUSION: based on the present knowledge amifostine should only be used in experimental protocols and not in routine practice.

Radiotherapy in the management of cervical cancer in elderly patients.

PURPOSE: To report treatment results and complications experienced by elderly patients treated with curatively intended radiotherapy for cancer of the uterine cervix. PATIENTS AND METHODS: One hundred and fourteen elderly patients (median 75.5 years, range 70.0-85.9) consecutively referred for curative radiotherapy in the period 1987-1996 were prospectively followed with regard to tumour control and complications. The importance of age, stage (FIGO), tumour size, histology, tumour fixation, haemoglobin, concurrent disease, performance status (WHO) and type of radiotherapy were assessed using univariate and multivariate analyses. RESULTS: Treatment was completed as planned in 68%, delayed in 29% and stopped prematurely in 3%. The frequency of grade 3 late complications was 11% and the actuarial probability at 5 years was 20%. Overall 5-year survival according to FIGO was 61% (I), 34% (II) and 25% (III). Cox multivariate analysis identified tumour size as independent prognostic factor for tumour control, disease-free survival and overall survival. FIGO stage was predictive for late grade 2 complications. We were unable to identify significant factors with respect to grade 3 complications. Age was not a significant parameter for any of the investigated endpoints. CONCLUSION: Elderly patients in good performance status with advanced cancer of the uterine may tolerate radical radiotherapy with acceptable morbidity and reasonable survival. Radiotherapy may also be a good alternative in early stage disease for surgically unfit elderly patients.

Epidermal growth factor and acute radiation damage in CDF1 mice in vivo.

The aim was to investigate if extent and time course of acute radiation damage to epidermis and intestine could be moderated by epidermal growth factor (EGF). Twelve-to-sixteen weeks old female CDF1 mice were treated either by single dose local irradiation to the right hind leg or total body irradiation (TBI). The endpoints were skin score and lethality, respectively. Human recombinant EGF was given s.c. or i.p. at a dose of 5-10 microg/day either before or after irradiation. Body weight was significantly higher for EGF treated animals compared with controls treated with saline. However, EGF did not reduce the median skin score following local irradiation and did not increase LD50 (days 1-6) following TBI. Further studies using more specific assays are necessary to determine if radiation damage to less toxic levels can be ameliorated by EGF.

A retrospective analysis of 82 cases of cancer of the penis.

OBJECTIVE: To identify prognostic factors for penile cancer and to evaluate the treatment strategy for early-stage disease, proposed recently by the European Board of Urology (EBU). PATIENT AND METHODS: The records of 82 patients consecutively referred to the uro-oncological centre at Aarhus University Hospital between 1965 and 1993 were reviewed. The importance of tumour stage, differentiation, patient age, local control and regional lymph node control were assessed using univariate and multivariate analyses. RESULTS: Cox multivariate analysis identified differentiation (odds ratio [OR] = 6.04), UJCC-1978 T-stage (OR = 1.88) and age (OR = 1.04) as independent prognostic variables for survival. Penile amputation in tumours < 4 cm in diameter improved local control but not survival. Regional control and survival were not significantly improved by prophylactic adenectomy. CONCLUSION: Differentiation, T-stage and age were prognostic factors for survival. The results support the EBU treatment strategy involving penis-conserving therapy and watchful waiting for early-stage disease.