RESUMO
BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Assuntos
Antagonistas de Androgênios , Anilidas , Nitrilas , Prostatectomia , Neoplasias da Próstata , Compostos de Tosil , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/administração & dosagem , Idoso , Compostos de Tosil/uso terapêutico , Compostos de Tosil/administração & dosagem , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Nitrilas/administração & dosagem , Oligopeptídeos/uso terapêutico , Oligopeptídeos/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Terapia Combinada , Antígeno Prostático Específico/sangueRESUMO
BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
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Antagonistas de Androgênios , Anilidas , Nitrilas , Prostatectomia , Neoplasias da Próstata , Compostos de Tosil , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/cirurgia , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/administração & dosagem , Idoso , Compostos de Tosil/uso terapêutico , Compostos de Tosil/administração & dosagem , Pessoa de Meia-Idade , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Nitrilas/uso terapêutico , Nitrilas/administração & dosagem , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Antígeno Prostático Específico/sangue , Terapia Combinada , Esquema de MedicaçãoRESUMO
BACKGROUND: Compared with other soft tissue sarcomas, myxoid liposarcoma (MLS) occurs in younger patients, has a propensity for intermuscular locations and is highly radiosensitive. With pre-operative radiotherapy, intermuscular MLS demonstrates substantial volume reduction and can be easily separated from surrounding tissues during resection. However, it is unclear whether marginal excision of MLS is oncologically safe. This study aimed to assess the association between margins and survival in irradiated, intermuscular MLS. METHODS: The study identified 198 patients from seven sarcoma centres with a first presentation of localized, extremity, intermuscular MLS that received pre-operative radiotherapy and was diagnosed between 1990 and 2017. Patient and treatment characteristics, radiological and histological responses to neoadjuvant treatment and clinical surveillance were recorded. RESULTS: Margins were microscopically positive in 11% (n = 22), <1.0 mm in 15% (n = 29) and ≥1.0 mm in 72% (n = 143). There was no association between margin status and local recurrence-free, metastasis-free or overall survival. This finding held true even in patients at higher risk of worse overall survival based on multivariable analysis (% round cell≥5%, percentage ellipsoid tumour volume change ≤ -60.1%). CONCLUSION: Irradiated, extremity, intermuscular myxoid liposarcoma can safely undergo marginal resection without compromising oncologic control.
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Lipossarcoma Mixoide , Lipossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Lipossarcoma Mixoide/patologia , Terapia Neoadjuvante , Resultado do Tratamento , Extremidades/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgiaRESUMO
Purpose: Variations in dosimetric outcomes among patients treated with low-dose-rate brachytherapy for prostate cancer exist, even when implants are within dose constraints. Here, we used control charts to investigate reasons for intra-patient dosimetric variability. Material and methods: Univariate and multivariate control charts for prostate V100 (percentage of prostate volume that received 100% of prescribed radiation dose), D90 (radiation dose to 90% of prostate volume), and RV100 (rectal wall volume that received 100% of prescribed radiation dose) were generated for 212 consecutive prostate cancer patients implanted with iodine-125 (125I) radioactive seeds at the Princess Margaret Cancer Centre. Control limits were calculated based on the first fifty implants. Data points that were out of control were identified, and their pre-treatment and post-treatment dosimetric and clinical parameters were compared to data points that were in-control, using Student's t-test. Results: All implants were clinically acceptable. Twelve data points exceeded multivariate control limits. Ten of those points fell below the lower control limit of V100 control chart. Average prostate edema in the 10 out-of-control patients on both multivariate and V100 charts was 8.3%, as compared to 0.4% for in-control patients (p < 0.04). Two patients were observed to be out-of-control on multivariate control chart, but not on V100 control chart, and were found to have a reduction in prostate volume of 19.1% and 20.1% at one month after seed implant, compared to prostate volumes of pre-implantation evaluations. Conclusions: Control charts helped in identifying cases with out-of-control variability in post-plan prostate dosimetry. Post-treatment prostatic edema and contraction are important factors predicting variability in patients treated with 125I permanent seed brachytherapy.
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The University of Toronto - Department of Radiation Oncology (UTDRO) has had a well-established Fellowship Program for over 20 years. An assessment of its graduates was conducted to evaluate training experience and perceived impact on professional development. Graduates of the UTDRO Fellowship Program between 1991 and 2015 were the focus of our review. Current employment status was collected using online tools. A study-specific web-based questionnaire was distributed to 263/293 graduates for whom active e-mails were identified; questions focused on training experience, and impact on career progression and academic productivity. As a surrogate measure for the impact of UTDRO Fellowship training, a comparison of current employment and scholarly activities of individuals who obtained their Fellow of the Royal College of Physicians of Canada (FRCPC) designation in Radiation Oncology between 2000 and 2012, with (n = 57) or without (n = 230) UTDRO Fellowship training, was conducted. Almost all UTDRO Fellowship graduates were employed as staff radiation oncologists (291/293), and most of those employed were associated with additional academic (130/293), research (53/293), or leadership (68/293) appointments. Thirty-eight percent (101/263) of alumni responded to the online survey. The top two reasons for completing the Fellowship were to gain specific clinical expertise and exposure to research opportunities. Respondents were very satisfied with their training experience, and the vast majority (99%) would recommend the program to others. Most (96%) felt that completing the Fellowship was beneficial to their career development. University of Toronto, Department of Radiation Oncology Fellowship alumni were more likely to hold university, research, and leadership appointments, and author significantly more publications than those with FRCPC designation without fellowship training from UTDRO. The UTDRO Fellowship Program has been successful since its inception, with the majority of graduates reporting positive training experiences, benefits to scholarly output, and professional development for their post-fellowship careers. Key features that would optimize the fellowship experience and its long-term impact on trainees were also identified.
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Internato e Residência , Radioterapia (Especialidade) , Escolha da Profissão , Bolsas de Estudo , Humanos , Liderança , Radio-Oncologistas , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) before cystectomy improves survival in muscle-invasive urothelial bladder cancer (MIBC). The use of NAC before chemoradiation (CRT) has been limited, as these patients are often elderly, frail, and ineligible for cisplatin. However, the role of NAC in fit, cisplatin-eligible patients who opt for bladder preservation warrants further evaluation. PATIENTS AND METHODS: Patients with MIBC treated with NAC followed by CRT at the Princess Margaret and Durham Regional cancer centers from 2008 to 2017 were retrospectively reviewed. Gemcitabine-cisplatin NAC was given for 2 to 4 cycles, followed by reassessment for CRT. External-beam radiotherapy (60-66 Gy) over 6 weeks was given with concurrent weekly cisplatin at 40 mg/m2. Kaplan-Meier method was used for survival analyses. RESULTS: We identified 57 consecutive patients. Median age was 72 (range 45-87), and all had an Eastern Cooperative Oncology Group performance status of 0 (60%) or 1 (40%). Stage II disease (65%), stage III disease (25%), and regional nodal metastases (11%) were included. Most completed planned NAC (95%). All patients completed external-beam radiotherapy, and 84% completed at least 60% of the planned concurrent weekly cisplatin doses. Median (range) follow-up was 19.3 (4.8-96.1) months. Median overall survival (OS) was not reached. Two-year OS and disease-specific survival rates were 74% (95% confidence interval, 57.7-84.9) and 88% (95% confidence interval, 78.5-98.1), respectively. Two-year bladder-intact disease-free survival was 64%. Salvage cystectomy was performed in 14%. Distant relapse occurred in 11%, and 9% died of metastatic disease. OS was associated with baseline hydronephrosis and with bladder-intact disease-free survival with residual disease on cystoscopy. CONCLUSION: NAC followed by CRT can result in encouraging outcomes and tolerability in cisplatin-eligible patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Cistectomia/mortalidade , Neoplasias Musculares/mortalidade , Terapia Neoadjuvante/mortalidade , Tratamentos com Preservação do Órgão/mortalidade , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Neoplasias Musculares/terapia , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
Purpose Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32). Results Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.
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Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to determine the relationship of the time interval between completion of preoperative radiation therapy (RT) and surgical resection on wound complications (WCs) in extremity soft tissue sarcoma (STS). METHODS: Overall, 798 extremity STS patients were managed with preoperative RT and surgery from 1989 to 2013. WCs were defined as requiring secondary operations/invasive procedures for wound care, use of vacuum-assisted closure, prolonged dressing changes, or infection within 120 days of surgery. RESULTS: Mean tumor size was 8.8 cm. A total of 743 (93 %) tumors were primary presentations, 565 (71 %) patients had lower extremity tumors, and 238 patients (30 %) had a prior unplanned excision. Of 242 patients (30 %) who developed a WC, 206 (37 %) had lower extremity tumors and 36 (15 %) had upper extremity tumors. Mean time from RT completion to surgery was 41.3 (range 4-470) days; 42.0 (range 4-470) days for upper extremity cases, and 41.1 (range 4-109) days for lower extremity cases. Similarly, mean time interval for patients who developed a WC was 40.9 (range 4-100) days, and 41.5 (range 4-470) days for those who did not develop a WC (p = 0.69). Thirty-nine cases (5 %) had surgery within 3 weeks of RT; 15 (38 %) patients developed WCs versus 227 (30 %) patients who had their tumors excised after 3 weeks (p = 0.28). One hundred and twenty-nine (16 %) patients had surgery within 4 weeks, and 39 (30 %) patients developed WCs versus 203 (30 %) patients who had their tumors excised after 4 weeks (p = 1.0). A trend towards a higher rate of WCs was seen for those patients who had surgery after 6 weeks (28 % prior vs. 34 % after; p = 0.08). There was no difference in WCs with intensity-modulated RT (IMRT) versus non-IMRT cases (p = 0.6). CONCLUSION: The time interval between preoperative RT and surgical excision in extremity STS had minimal influence on the development of WCs. Four- or 5-week intervals showed equivalent complication rates between the two groups, suggesting an optimal interval to reduce potential WCs.
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Extremidade Inferior/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Sarcoma/complicações , Infecção da Ferida Cirúrgica/etiologia , Extremidade Superior/cirurgia , Cicatrização , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Extremidade Inferior/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Prognóstico , Estudos Prospectivos , Radioterapia Adjuvante , Sarcoma/patologia , Sarcoma/radioterapia , Sarcoma/cirurgia , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/epidemiologia , Fatores de Tempo , Extremidade Superior/efeitos da radiação , Adulto JovemRESUMO
PURPOSE: Cisplatin-based chemotherapy, a mainstay of treatment for disseminated germ cell tumors (GCTs), is associated with venous thromboembolism (VTE). Many patients with disseminated GCTs have large retroperitoneal lymph node (RPLN) metastases that may cause venous stasis and increase the risk of VTE development. We hypothesized that there was an association between large RPLN and chemotherapy-associated VTE risk. PATIENTS AND METHODS: The training cohort was composed of patients with disseminated GCT receiving first-line chemotherapy at Princess Margaret Cancer Centre between January 2000 and December 2010. Large RPLN was defined as more than 5 cm in maximal axial diameter. The predictive and discriminatory accuracies of a model using large RPLN in predicting VTE were compared with high-risk Khorana score (≥ 3) using logistic regression and area under receiver operator characteristic curves (AUROCs). The model was externally validated in a cohort of patients treated at the London Health Sciences Centre. RESULTS: The training cohort comprised 216 patients, 21 (10%) of whom developed VTE during chemotherapy. VTE was associated with large RPLN (odds ratio [OR], 5.26; P = .001), high-risk Khorana score (OR, 11.8; P < .001), intermediate-/poor-risk disease (OR, 3.76; P = .005), and hospitalization during chemotherapy (OR, 4.24; P = .002). Large RPLN showed higher discriminatory accuracy than high-risk Khorana score (AUROC, 0.71 v 0.67, respectively). Superior discriminatory accuracy of large RPLN over high-risk Khorana score was validated in the London cohort (AUROC, 0.61 v 0.57, respectively). CONCLUSION: Large RPLN is associated with VTE in patients with disseminated GCT and provides higher discriminatory accuracy than high-risk Khorana score. Results should be validated in larger, prospective studies. Prophylactic anticoagulation may be considered in high-risk patients.
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Doenças Linfáticas/sangue , Doenças Linfáticas/patologia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Estudos de Coortes , Humanos , Modelos Biológicos , Neoplasias Embrionárias de Células Germinativas/sangue , Tromboembolia Venosa/induzido quimicamenteRESUMO
BACKGROUND: This study sought to determine if preoperative image-guided intensity-modulated radiotherapy (IG-IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma. METHODS: The primary endpoint was the development of an acute wound complication (WC). IG-IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high-grade and 58 (98%) were deep to fascia. RESULTS: Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow-up of 49 months. CONCLUSIONS: The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG-IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained.
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Extremidade Inferior , Terapia Neoadjuvante/métodos , Radioterapia de Intensidade Modulada/métodos , Sarcoma/radioterapia , Sarcoma/cirurgia , Retalhos Cirúrgicos , Infecção da Ferida Cirúrgica/prevenção & controle , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Intervalo Livre de Doença , Feminino , Fibrossarcoma/radioterapia , Fibrossarcoma/cirurgia , Hemangiossarcoma/radioterapia , Hemangiossarcoma/cirurgia , Humanos , Imageamento Tridimensional , Incidência , Estimativa de Kaplan-Meier , Leiomiossarcoma/radioterapia , Leiomiossarcoma/cirurgia , Lipossarcoma/radioterapia , Lipossarcoma/cirurgia , Extremidade Inferior/patologia , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Morbidade , Análise Multivariada , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Sarcoma Sinovial/radioterapia , Sarcoma Sinovial/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: To analyze the location of metastatic lymph nodes in seminoma patients relative to vascular and bony anatomy and conventional radiation fields. MATERIALS AND METHODS: Cross-sectional scans of 90 seminoma patients with infradiaphragmatic adenopathy were analyzed. The position of each node respective to vascular anatomy was transferred to a standardized template. Conventional radiation fields were overlaid on the template and locations of metastatic nodes were assessed. RESULTS: One hundred and forty-five nodes were radiographically positive. Eighty-four percent, 9%, and 7% of nodes were located in the para-aortic, common iliac, and pelvic regions, respectively. Ninety-nine percent of nodes were within a 2.5 cm lateral and 2.1cm anterior expansion of the aorta inferior to T12/L1. No radiographically positive nodes were identified within the renal hilum or superior to L1 in left-sided seminomas. For right-sided seminomas, no radiographically positive nodes were superior to L2. Three percent of all radiographically positive nodes would have been located outside of conventional and modified fields. CONCLUSIONS: Infradiaphragmatic nodal metastases from a contemporary cohort of seminoma patients localized to a smaller area than is targeted by conventional radiation fields. Modified treatment fields based on vascular, rather than bony, anatomy are smaller and may allow for a significant decrease in normal tissue irradiation and toxicity.
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Seminoma/radioterapia , Neoplasias Testiculares/radioterapia , Humanos , Metástase Linfática , Masculino , Planejamento da Radioterapia Assistida por Computador , Seminoma/patologia , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: The treatment of diffuse tenosynovial giant cell tumor (TGCT) requires extensive surgical resection of the hypertrophic synovium and multiple soft tissue masses yet still may result in high rates of local failure. The authors of this report examined their experience in treating patients with advanced/multiply recurrent TGCT with a combination of surgery and external-beam radiotherapy. METHODS: Fifty patients who were treated for TGCT with radiotherapy and surgery from 1972 to 2006 were identified. Patient demographics, radiotherapy treatment parameters, surgical treatment, and oncologic and functional outcomes were evaluated. All patients had pathologic review at presentation and required at least 1 year follow-up. RESULTS: Forty-nine patients had diffuse TGCT with both intra-articular and extra-articular disease (1 had malignant TGCT). Twenty-eight patients (56%) were referred after at least 1 local recurrence. Thirty patients (60%) underwent at least 2 operations before radiotherapy. The mean dose of radiation delivered was 39.8 gray. At a mean follow-up of 94 months (range, 19-330 months), 47 patients (94%) had not developed a recurrence or had stable disease/signal characteristics on serial cross-sectional imaging (for those patients who had gross residual disease at the time of radiotherapy). Two patients required subsequent total hip arthroplasty because of progressive osteoarthritis, and there were 4 cases of avascular necrosis (only 1 post-treatment). Forty-one patients had good/excellent function. CONCLUSIONS: For patients with extensive or multiple local relapses or when surgery alone would result in a large burden of residual disease or major functional loss, the addition of moderate-dose adjuvant radiotherapy provided excellent local control while maintaining good function with low treatment-related morbidity.
Assuntos
Tumores de Células Gigantes/radioterapia , Tumores de Células Gigantes/cirurgia , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Sinovite Pigmentada Vilonodular/radioterapia , Sinovite Pigmentada Vilonodular/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: To examine the geometric relationship between local recurrence (LR) and external beam radiotherapy (RT) volumes for soft-tissue sarcoma (STS) patients treated with function-preserving surgery and RT. METHODS AND MATERIALS: Sixty of 768 (7.8%) STS patients treated with combined therapy within our institution from 1990 through 2006 developed an LR. Thirty-two received preoperative RT, 16 postoperative RT, and 12 preoperative RT plus a postoperative boost. Treatment records, RT simulation images, and diagnostic MRI/CT data sets of the original and LR disease were retrospectively compared. For LR location analysis, three RT target volumes were defined according to the International Commission on Radiation Units and Measurements 29 as follows: (1) the gross tumor or operative bed; (2) the treatment volume (TV) extending 5 cm longitudinally beyond the tumor or operative bed unless protected by intact barriers to spread and at least 1-2 cm axially (the TV was enclosed by the isodose curve representing the prescribed target absorbed dose [TAD] and accounted for target/patient setup uncertainty and beam characteristics), and (3) the irradiated volume (IRV) that received at least 50% of the TAD, including the TV. LRs were categorized as developing in field within the TV, marginal (on the edge of the IRV), and out of field (occurring outside of the IRV). RESULTS: Forty-nine tumors relapsed in field (6.4% overall). Nine were out of field (1.1% overall), and 2 were marginal (0.3% overall). CONCLUSIONS: The majority of STS tumors recur in field, indicating that the incidence of LR may be affected more by differences in biologic and molecular characteristics rather than aberrations in RT dose or target volume coverage. In contrast, only two patients relapsed at the IRV boundary, suggesting that the risk of a marginal relapse is low when the TV is appropriately defined. These data support the accurate delivery of optimal RT volumes in the most precise way using advanced technology and image guidance.
Assuntos
Recidiva Local de Neoplasia , Sarcoma/radioterapia , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Tratamentos com Preservação do Órgão/métodos , Radiografia , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Carga Tumoral , Adulto JovemRESUMO
Although a rare presentation for testicular germ cell tumors, the optimal management for stage II disease generates considerable debate, which is, in large part, because of the potential curative role of single-modality treatment in many patients and overall excellent survival in those who require salvage treatment. Individualizing the treatment of each patient to ensure cure with minimal toxicity is challenging, given the rudimentary tools available for predicting disease relapse after initial therapy. Long-term toxicity and patient choice should be taken into account when selecting the management options.
Assuntos
Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Seminoma/cirurgia , Neoplasias Testiculares/cirurgia , Quimioterapia Adjuvante , Humanos , Excisão de Linfonodo , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Radioterapia Adjuvante , Seminoma/patologia , Seminoma/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapiaRESUMO
PURPOSE: To evaluate inter- and intrafractional motion and rotational error for lower extremity soft tissue sarcoma patients by using cone beam computed tomography (CBCT) and an optical localization system. METHODS AND MATERIALS: Thirty-one immobilized patients received CBCT image-guided intensity-modulated radiation therapy. Setup deviations of >3 mm from the planned isocenter were corrected. A second CBCT acquired before treatment delivery was registered to the planning CT to estimate interfractional setup error retrospectively. Interfractional error and rotational error were calculated in the left-right (LR), superoinferior (SI), and anteroposterior (AP) dimensions. Intrafractional motion was assessed by calculating the maximum relative displacement of optical localization system reflective markers placed on the patient's surface, combined with pre- and postfraction CBCT performed for 17 of the 31 patients once per week. The overall systematic error (SE) and random error (RE) were calculated for the interfractional and intrafractional motion for planning target volume margin calculation. RESULTS: The standard deviation (SD) of the interfractional RE was 1.9 mm LR, 2.1 mm SI, and 1.8 mm AP, and the SE SD was 0.6 mm, 1.2 mm, and 0.7 mm in each dimension, respectively. The overall rotation (inter- and intrafractional) had an RE SD of 0.8° LR, 1.7° SI, and 0.7° AP and an SE SD of 1.1° LR, 1.3° SI, and 0.3° AP. The SD of the overall intrafractional RE was 1.6 mm LR, 1.6 mm SI, and 1.4 mm AP, and the SE SD was 0.7 mm AP, 0.6 mm SI, and 0.6 mm AP. CONCLUSIONS: A uniform 5-mm planning target volume margin was quantified for lower extremity soft tissue sarcoma patients and has been implemented clinically for image-guided intensity-modulated radiation therapy.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Extremidade Inferior/diagnóstico por imagem , Movimento , Radioterapia de Intensidade Modulada/métodos , Sarcoma/diagnóstico por imagem , Sarcoma/radioterapia , Humanos , Extremidade Inferior/cirurgia , Masculino , Cuidados Pré-Operatórios , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Rotação , Sarcoma/cirurgiaRESUMO
PURPOSE: For patients with an extremity soft tissue sarcoma (STS) treated with preoperative radiotherapy and surgically excised with positive margins, we retrospectively reviewed whether a postoperative radiation boost reduced the risk of local recurrence (LR). METHODS AND MATERIALS: A total of 216 patients with positive margins after resection of an extremity STS treated between 1986 and 2003 were identified from our institution's prospectively collected database. Patient demographics, radiation therapy parameters including timing and dose, classification of positive margin status, reasons for not administering a postoperative boost, and oncologic outcome were collected and evaluated. RESULTS: Of the 216 patients with a positive surgical margin, 52 patients were treated with preoperative radiation therapy alone (50 Gy), whereas 41 received preoperative radiation therapy plus a postoperative boost (80% received 16 Gy postoperatively for a total of 66 Gy). There was no difference in baseline tumor characteristics between the two groups. Six of 52 patients in the group receiving preoperative radiation alone developed a LR compared with 9 of 41 in the boost group. Five-year estimated LR-free survivals were 90.4% and 73.8%, respectively (p = 0.13). CONCLUSIONS: We found that including the postoperative radiation boost after preoperative radiation and a margin-positive excision did not provide an advantage in preventing LR for patients treated with external beam radiotherapy. Given that higher radiation doses placed patients at greater risk for late complications such as fracture, fibrosis, edema, and joint stiffness, judicious avoidance of the postoperative boost while maintaining an equivalent rate of local control can reduce the risk of these difficult-to-treat morbidities.
Assuntos
Sarcoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Feminino , Histiocitoma Fibroso Benigno/patologia , Histiocitoma Fibroso Benigno/prevenção & controle , Histiocitoma Fibroso Benigno/radioterapia , Histiocitoma Fibroso Benigno/cirurgia , Humanos , Leiomiossarcoma/patologia , Leiomiossarcoma/prevenção & controle , Leiomiossarcoma/radioterapia , Leiomiossarcoma/cirurgia , Salvamento de Membro , Lipossarcoma/patologia , Lipossarcoma/prevenção & controle , Lipossarcoma/radioterapia , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual , Cuidados Pós-Operatórios , Dosagem Radioterapêutica , Retratamento , Sarcoma/patologia , Sarcoma/prevenção & controle , Sarcoma/cirurgia , Adulto JovemRESUMO
BACKGROUND: The objective of the current study was to formulate a scoring system to enable decision making for prophylactic stabilization of the femur after surgical resection of a soft tissue sarcoma (STS) of the thigh. METHODS: A logistic regression model was developed using patient variables collected from a prospectively collected database. The study group included 22 patients who developed a radiation-related pathological fracture of the femur after surgery and radiotherapy for an STS of the thigh. The control group of 79 patients received similar treatment but did not sustain a fracture. No patients received chemotherapy. The mean follow-up was 8.6 years. The variables examined were age, gender, tumor size, radiation dose (low [50 grays (Gy)] vs high [> or = 60 Gy]), extent of periosteal stripping (<10 cm, 10-20 cm, and >20 cm), and thigh compartment involvement (posterior, adductor, anterior or other [ie, abductors and groin]). RESULTS: On the basis of an optimal regression model, the ability to predict radiation-associated fracture risk was 91% sensitive and 81% specific. The area under the receiver operating characteristic curve was 0.9, which supports this model as a very accurate predictor of fracture risk. CONCLUSIONS: Radiation-related fractures of the femur after combined surgery and radiotherapy for STS are uncommon, but are difficult to manage and their nonunion rate is extremely high. The results of the current study suggest that it is possible to predict radiation-associated pathological fracture risk using patient and treatment variables with high sensitivity and specificity. This would allow for the identification of high-risk patients and treatment with either close follow-up or prophylactic intramedullary nail stabilization. The presentation of this model as a nomogram will facilitate its clinical use.
Assuntos
Terapia Combinada/efeitos adversos , Fêmur , Fraturas Espontâneas/complicações , Sarcoma/complicações , Coxa da Perna , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Dosagem Radioterapêutica , Medição de Risco , Sarcoma/radioterapia , Sarcoma/cirurgia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: After orchidectomy, the standard management options available for stage I seminoma are surveillance, adjuvant radiotherapy, or adjuvant chemotherapy. The optimal follow-up protocol for surveillance is yet to be determined but includes frequent chest radiography (CXR) and computed tomography (CT) scan of the abdomen and pelvis (CT-AP). OBJECTIVE: The purpose of this study was to identify the modality that first detected relapse and to assess the value of the CXR in this setting. DESIGN, SETTING, AND PARTICIPANTS: Five hundred twenty-seven patients with histologically confirmed stage I testicular seminoma were managed with surveillance at our institution between 1982 and 2005. Routine CXRs were performed with each CT-AP and were done every 4-6 mo for 7 yr and annually thereafter. The median follow-up was 72 mo (range: 1-193). MEASUREMENTS: Measurements included the 5-yr relapse rate, overall survival, and disease-free survival to determine the modality that first detected relapse disease. RESULTS AND LIMITATIONS: The 5-yr actuarial relapse rate for the 527 patients was 14%. The 5-yr disease-free survival and overall survival were 85.7% and 98.6%, respectively. Seventy-three patients (97.3%) had an abnormal CT-AP and a normal CXR at relapse. One patient (1.3%) had an abnormal CT-AP with pulmonary metastasis on CXR and CT chest scan, and one patient (1.3%) had a biopsy-proven inguinal node metastasis with a normal CXR. No patient had a normal CT-AP or physical examination with an abnormal CXR at relapse. This is a single-center retrospective study based on a relatively small number of relapses and may be subject to bias. Confirmation of these results from other studies would be useful for wider clinical applicability. CONCLUSIONS: All except one relapse were detected by CT-AP with no relapses detected on CXR alone; therefore, CXR may be omitted as routine imaging in surveillance protocols.
Assuntos
Radiografia Torácica , Seminoma/cirurgia , Neoplasias Testiculares/cirurgia , Humanos , Masculino , Vigilância da População , Seminoma/secundário , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: Myxoid liposarcoma has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The authors report the results of multidisciplinary treatment of extremity myxoid liposarcoma compared with a contemporary cohort of other STS subtypes with an emphasis on the role of radiotherapy (RT) in improving local control. METHODS: Between 1989 and 2004, 691 patients were identified from a prospective STS database who underwent combined management for localized extremity STS and were followed for a minimum of 12 months or until death. All patients underwent surgery together with pre or postoperative RT, depending on their presenting characteristics and resection margins. Demographics and outcomes were compared between patients with myxoid liposarcoma and other STS subtypes (other-STS). RESULTS: Of 691 patients, 88 patients had myxoid liposarcoma and 603 had other STS subtypes (other-STS). Median age was 48 and 60 years for the myxoid liposarcoma and other-STS groups, respectively. Median follow-up was 86 and 61 months, respectively. For myxoid liposarcoma and other-STS groups, preoperative RT was used in 57% versus 61% of patients and postoperative RT in 43% versus 39%, respectively. The 5-year local recurrence-free survival was 97.7% for patients with myxoid liposarcoma compared with 89.6% for patients with other-STS tumors (P = .008). High-grade tumors were present in 7% and 59% of myxoid liposarcoma and other-STS patients, respectively (P = .0003). Two myxoid liposarcoma patients with local recurrence had positive resection margins, whereas only 33% of patients in the other-STS group who developed a local recurrence had positive resection margins. No patients with myxoid liposarcoma required amputation as primary management, whereas 8 (1.3%) required amputation as primary management in the other-STS group. Systemic disease control was superior in myxoid liposarcoma compared with other-STS patients, with 5-year overall and metastasis-free survival rates of 93.9% versus 76.4% (P = .0008) and 89.1% versus 66.0% (P = .0001) respectively. Of 12 myxoid liposarcoma patients with distant metastases, 7 appeared in nonpulmonary sites. In comparison, 205 (34%) patients with other-STS tumors developed systemic disease but 78% had pulmonary metastases. CONCLUSIONS: Multidisciplinary management of extremity STS achieves high rates of local control. Myxoid liposarcoma is associated with higher rates of local control compared with other STS subtypes, after combined surgery and radiation, suggesting a particular radiosensitivity that can be exploited to improve oncologic outcome in appropriate cases.
Assuntos
Extremidades , Lipossarcoma Mixoide/radioterapia , Sarcoma/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Lipossarcoma Mixoide/mortalidade , Lipossarcoma Mixoide/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/cirurgia , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). METHODS AND MATERIALS: Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. RESULTS: For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. CONCLUSIONS: The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.