RESUMO
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.
Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Estudos Prospectivos , Vagina/patologia , Comportamento Sexual , MorbidadeRESUMO
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.
Assuntos
Líquen Escleroso e Atrófico , Neoplasias Vulvares , Feminino , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/patologiaRESUMO
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.
Assuntos
Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Quimiorradioterapia/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Biópsia , Braquiterapia , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Fracionamento da Dose de Radiação , Feminino , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Linfonodos/cirurgia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/estatística & dados numéricos , Estudos Observacionais como Assunto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapiaRESUMO
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: 105â¯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, PIBSâ¯+â¯2â¯cm, PIBSâ¯-â¯2â¯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 EBRTâ¯+â¯BT equivalent dose in 2â¯Gy fractions using α/ßâ¯=â¯3 and T1/2â¯=â¯1.5â¯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 (R2â¯=â¯0.492), as well as D0.1cm3 (R2â¯=â¯0.356). Bladder neck D0.1cm3 was always lower than trigone D0.1cm3 and higher than IUO. Correlation between PIBSâ¯+â¯2â¯cm and IUO was poor (R2â¯=â¯0.273), while PIBS and PIBS-U were almost equal (R2â¯=â¯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.
Assuntos
Braquiterapia/efeitos adversos , Doses de Radiação , Sistema Urinário/efeitos da radiação , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia , Feminino , Humanos , Órgãos em Risco/fisiopatologia , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Análise de Sobrevida , Sistema Urinário/fisiopatologia , Neoplasias do Colo do Útero/fisiopatologiaRESUMO
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.
Assuntos
Complicações Pós-Operatórias , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Disfunções Sexuais Fisiológicas/etiologia , Transtornos Urinários/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dinamarca , Dispareunia/etiologia , Incontinência Fecal/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Comportamento Sexual , Inquéritos e Questionários , Incontinência Urinária/etiologia , Vagina/efeitos da radiaçãoRESUMO
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.
Assuntos
Recidiva Local de Neoplasia/cirurgia , Exenteração Pélvica , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Adulto , Idoso , Fístula Anastomótica/epidemiologia , Feminino , Hérnia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Exenteração Pélvica/mortalidade , Pneumonia/epidemiologia , Estudos Prospectivos , Sepse/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
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.
Assuntos
Colectomia , Cuidados Pré-Operatórios/métodos , Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Prospectivos , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Adenocarcinoma/radioterapia , Colectomia , Neoplasias Colorretais/radioterapia , Vigilância da População , Cuidados Pré-Operatórios/métodos , Adenocarcinoma/epidemiologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/cirurgia , Períneo/cirurgia , Procedimentos de Cirurgia Plástica , Reto do Abdome/transplante , Retalhos Cirúrgicos , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/complicações , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Terapia de Salvação , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Carcinoma/fisiopatologia , Hipóxia Celular , Oxigênio/análise , Neoplasias do Colo do Útero/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/química , Carcinoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Nitroimidazóis/metabolismo , Pressão Parcial , Radiossensibilizantes/metabolismo , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/patologiaRESUMO
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.
Assuntos
Amifostina/administração & dosagem , Protetores contra Radiação/administração & dosagem , Xerostomia/prevenção & controle , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Cães , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Camundongos , Doses de Radiação , Lesões por Radiação/prevenção & controle , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Neoplasias do Colo do Útero/radioterapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Feminino , Humanos , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radioterapia de Alta Energia , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
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.
Assuntos
Fator de Crescimento Epidérmico/uso terapêutico , Intestinos/efeitos da radiação , Lesões Experimentais por Radiação/prevenção & controle , Pele/efeitos da radiação , Análise Atuarial , Animais , Fator de Crescimento Epidérmico/administração & dosagem , Feminino , Membro Posterior/efeitos da radiação , Humanos , Injeções Subcutâneas , Dose Letal Mediana , Modelos Lineares , Camundongos , Camundongos Endogâmicos , Doses de Radiação , Proteínas Recombinantes , Cloreto de Sódio , Taxa de Sobrevida , Irradiação Corporal TotalRESUMO
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.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Penianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
The success of radiotherapy in eradicating the primary tumor in patients with locally advanced cervical cancer is limited by normal tissue tolerance. Systematic recording of morbidity and treatment parameters is therefore very important for radiobiologic treatment optimization and clinical decision making. There is substantial evidence that fractionation schedules employing large doses per fraction lead to a loss of therapeutic ratio. A similar argument could be used for high-dose-rate (HDR) brachytherapy that should also be administered in small dose fractions. However, HDR brachytherapy might convey some advantage to physical dose distribution that should be weighed against the radiobiologic advantages of low-dose-rate (LDR) continuous irradiation. Increasing overall treatment time reduces local control probability, whereas a shorter overall treatment time by accelerated fractionation may improve the therapeutic ratio, at least in fast-growing tumors. Hypoxia and reduced oxygen delivery are associated with poor radiation response. Anemia should be compensated, if necessary. The role of hypoxic modification needs to be further explored. In the future, the therapeutic ratio may also be improved by the use of chemical and biologic response modifiers. Tumors are heterogeneous with respect to intrinsic radiosensitivity, proliferation parameters, and extent of hypoxia. Until a detailed prognostic profile can be obtained for each patient, optimal curative radiotherapy must aim for a sufficient dose, short overall treatment time, hypoxic modification, and LDR or low dose per fraction.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Tolerância a Radiação , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/métodos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estadiamento de Neoplasias , Dosagem RadioterapêuticaRESUMO
In Denmark about 40 new cases of cancer of the penis are diagnosed each year. Several studies have retrospectively investigated the treatment results in this rare disease. However, most of these studies include few patients and are difficult to compare because several classification systems have been used. Treatment of the primary tumour consists of local excision, laser surgery, partial/total penectomy or irradiation. The prognosis for early stage disease is apparently independent of the mode of treatment and the specific five-year survival rate is 80-90%. Several centres advise prophylactic treatment of the groin in node negative patients, claiming that the survival thereby is increased. However, the morbidity is considerable and randomized studies are not available. The treatment for metastatic inguinal nodes consists of adenectomy or irradiation. The specific five-year survival rate is 40-50%. Chemotherapy has been used for advanced disease. The response rates are low and the responses are of short duration.
Assuntos
Neoplasias Penianas/terapia , Terapia Combinada , Humanos , Masculino , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/mortalidade , PrognósticoRESUMO
The effects of step-down (SDH) and step-up heating (SUH) on the development of thermotolerance were investigated in a C3H mammary carcinoma in vivo. The endpoint was tumour growth time, i.e. the time for a tumour to reach a volume five times that of the first treatment day. SDH consisted of 44.5 degrees C/5 min followed immediately by 41.0 degrees C/120 min. SUH consisted of the same heat treatments but in reverse sequence. Thermotolerance was detected by subsequent heating at 43.5 degrees C at variable intervals following the primary SDH or SUH. The degree of thermotolerance was quantified by the thermotolerance ratio (TTR) calculated as a ratio between the slope of the dose-response curve for tumours heated at 43.5 degrees C and tumours preheated with either SDH or SUH followed by 43.5 degrees C. Both SDH and SUH induced thermotolerance. However, the maximal degree of thermotolerance and the time interval to reach maximum thermotolerance were different. For SUH maximal thermotolerance was observed at 8 h with a TTR of 3.6. For SUH, thermotolerance peaked at 24-28 h with a TTR of 7.3. In both cases thermotolerance had decayed with a 120 h interval. The SDH priming induced about 2.5 times more heat damage than SUH. The results are therefore in agreement with previous data obtained in the same tumour model by single heating showing that both the degree and the time to reach maximal thermotolerance increases with pretreatment heat damage. In addition, the results indicate that thermotolerance and thermosensitization are independent phenomena.
Assuntos
Hipertermia Induzida , Neoplasias Mamárias Experimentais/fisiopatologia , Animais , Feminino , Cinética , Neoplasias Mamárias Experimentais/terapia , Camundongos , Camundongos Endogâmicos C3H , TemperaturaRESUMO
A preclinical evaluation of the 'movable applicator phased array hyperthermia system' was performed. The system employs four coherent applicators enabling power steering by amplitude and phase control. This concept has already been used in other systems, but the combination with a compact applicator design and easy movement of applicators has not been used before. The paper contains a description of the system and a verification of its performance using quality assurance tests with scanned E-field measurements. A clinical simulation was performed in pig to address the clinical feasibility of the system. The target volume was the left kidney. Two heating sessions, with and without occluded blood-flow to the kidney, were performed. In the low-flow experiments a temperature of 48 degrees C and 46 degrees C was obtained in the upper and lower pole of the kidney respectively. For the high-flow experiment the temperature in the upper pole was 48 degrees C.
Assuntos
Hipertermia Induzida/métodos , Animais , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Hipertermia Induzida/instrumentação , Rim/irrigação sanguínea , Fluxo Sanguíneo Regional , Suínos , TemperaturaRESUMO
The effect of tetrahydraindazolone dicarboxylic acid (HIDA) on tumour response and mouse lethality after treatment with cisplatin given either alone or combined with hyperthermia (43.5 degrees C/60 min) with or without radiation, was studied in the CDF1 mouse bearing a foot transplanted C3H mouse mammary carcinoma. The tumour response to a combined heat, cisplatin and HIDA treatment was assessed by tumour growth time, while local tumour control was used when irradiation was added to that treatment scheme. Toxicity was estimated as lethality within 14 days. Cisplatin and heat exerted the highest antitumour effect when given simultaneously, but at the same time there was a substantial increase in lethality. No sensitization of the tumour response or enhanced toxicity to cisplatin was observed if heat was given sequentially (i.e. 4 h) after cisplatin. The effect of this sequential schedule being only additive. When HIDA (100 mg/kg) was given 150 min before cisplatin and tumours heated 15 min later, the lethal toxicity was significantly reduced. HIDA did not, however, influence tumour growth time results. In tumour control studies combining radiation, drug and heat, cisplatin (6 mg/kg) and heat (43.5 degrees C/60 min) were given simultaneously 4 h after local irradiating the leg of tumour-bearing mice. The lethality of this regime was more than 55%, but when HIDA was added to the protocol, the toxicity fell to 5% without affecting local tumour control. In conclusion, HIDA administered before cisplatin protects against drug-induced toxicity without reducing the drug's antitumour activity when used alone or in combination with hyperthermia and/or radiation, and thus results in a significantly improved therapeutic benefit.
Assuntos
Cisplatino/administração & dosagem , Hipertermia Induzida , Indazóis/administração & dosagem , Neoplasias Mamárias Experimentais/terapia , Animais , Cisplatino/antagonistas & inibidores , Cisplatino/toxicidade , Terapia Combinada , Estudos de Avaliação como Assunto , Feminino , Masculino , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/radioterapia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos DBARESUMO
Jung (1986) has proposed a mathematical model for cell killing by hyperthermia which assumes that heat killing involves two steps: the production (p) of non-lethal lesions at random and a subsequent conversion (c) into lethal lesions. The p & c model has been shown to predict the survival of CHO cells heated in vitro even when complicated biological phenomena such as thermotolerance and step-down heating (SDH) are involved (Jung 1986, 1991). In the present study the objective was to test the p & c model's ability to describe the effect of single heating and SDH in an experimental tumour in vivo. The endpoint was tumour growth delay (GD). The doubling times (DT) for untreated and heated tumours were similar, and the surviving fraction (SF) could therefore be estimated using: SF = -in(2).GD/DT. SF was fitted to the model by non-linear regression. The p & c model adequately described the GD obtained by SDH (39-44.5 degrees C) and single heating above 42.5 degrees C. Multiple linear regression showed that the residuals for single heating and SDH were independent of both heating time and temperature. However, the residuals for single heating (41-44.5 degrees C) were significantly correlated to heating time when analysed separately. The GD obtained by the use of extended single heating times at or below 42.5 degrees C was therefore overestimated by the model. Development of chronic thermotolerance during heating may account for the observed divergence. The Arrhenius plots for both p and c were log-linear with activation energies of 678 and 311 kJ/mol, respectively. Jung (1986) has previously reported similar p and c activation energies above 42.5 degrees C for CHO cells in vitro.