RESUMO
BACKGROUND: Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. METHODS: We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (± SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3 ± 1.8% vs. 64.7 ± 2.3%; hazard ratio for recurrence or metastasis, 0.76; P=0.01), and those with thick melanomas, defined as >3.50 mm (50.7 ± 4.0% vs. 40.5 ± 4.7%; hazard ratio, 0.70; P=0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1 ± 4.8% among those with metastasis versus 85.1 ± 1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0 ± 7.0% and 64.6 ± 4.9% (hazard ratio, 1.75; P=0.03). Biopsy-based management improved the 10-year rate of distant disease-free survival (hazard ratio for distant metastasis, 0.62; P=0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P=0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted. CONCLUSIONS: Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease-free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. (Funded by the National Cancer Institute, National Institutes of Health, and the Australia and New Zealand Melanoma Trials Group; ClinicalTrials.gov number, NCT00275496.).
Assuntos
Excisão de Linfonodo , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/cirurgia , Pessoa de Meia-Idade , Observação , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Taxa de SobrevidaRESUMO
Sarcomas are malignant heterogenous tumors of mesenchymal derivation. Emerging data suggest that miRNA might have a causal role in sarcomagenesis. Herein, we used a selective miRNA screening platform to study the comparative global miRNA expression signatures in a cohort of human sarcomas with the caveat that comparisons between tumor and non-tumor cells were performed from the same patients using formalin-fixed paraffin-embedded tissue. Five histologic types were examined that included: myxoid liposarcoma, well-differentiated liposarcoma, dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, and synovial sarcoma. In addition, soft-tissue lipomas and normal fat were included as a separate set of controls for the lipogenic tumors. Clustering analysis showed a distinct global difference in expression patterns between the normal and sarcoma tissues. Expression signatures in an unsupervised hierarchical clustering analysis revealed tight clustering in synovial and myxoid liposarcomas, and the least clustering was observed in the pleomorphic rhabdomyosarcoma subtype. MiR-145 showed underexpression in pleomorphic rhabdomyosarcoma, well-differentiated liposarcoma, and synovial sarcoma. Unexpectedly, we found that a set of muscle-specific microRNAs (miRNAs; myomiRs): miR-133, miR-1, and miR-206 was significantly underexpressed in well-differentiated liposarcoma and synovial sarcoma, suggesting that they may function as tumor suppressors as described in muscle-relevant rhabdomyosarcomas. In addition, a tight linear progression of miRNA expression was identified from normal fat to dedifferentiated liposarcoma. These results suggest that miRNA expression profiles could elucidate classes of miRNAs that may elicit tumor-relevant activities in specific sarcoma subtypes.
Assuntos
Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Sarcoma/genética , Adulto , Idoso , Análise por Conglomerados , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Lipossarcoma/diagnóstico , Lipossarcoma/genética , Lipossarcoma Mixoide/diagnóstico , Lipossarcoma Mixoide/genética , Masculino , MicroRNAs/classificação , Pessoa de Meia-Idade , Músculos/metabolismo , Especificidade de Órgãos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/genética , Sarcoma/diagnóstico , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/genética , Adulto JovemRESUMO
Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this malignancy.
Assuntos
Antígenos de Neoplasias/metabolismo , Lipossarcoma/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Testiculares/metabolismo , Testículo/metabolismo , Antígenos de Neoplasias/genética , Humanos , Lipossarcoma/genética , Lipossarcoma/patologia , Masculino , Proteínas de Membrana/genética , Estudos Retrospectivos , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Testículo/patologiaRESUMO
Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. Design, Setting, and Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. Intervention: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Main Outcomes and Measures: Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. Results: Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). Conclusions and Relevance: This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. Trial Registration: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).
Assuntos
Terapia Neoadjuvante , Sarcoma , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Feminino , Sarcoma/mortalidade , Prognóstico , Intervalo Livre de Progressão , Intervalo Livre de DoençaRESUMO
BACKGROUND: For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery with or without SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial. METHODS: Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation. We evaluated recurrence site, therapy (selected by treating clinician), and survival after stage IV diagnosis. RESULTS: Of 291 patients with complete data for stage IV recurrence, 161 (55 %) underwent surgery with or without SMT. Median survival was 15.8 versus 6.9 months, and 4-year survival was 20.8 versus 7.0 % for patients receiving surgery with or without SMT versus SMT alone (p < 0.0001; hazard ratio 0.406). Surgery with or without SMT conferred a survival advantage for patients with M1a (median > 60 months vs. 12.4 months; 4-year survival 69.3 % vs. 0; p = 0.0106), M1b (median 17.9 vs. 9.1 months; 4-year survival 24.1 vs. 14.3 %; p = 0.1143), and M1c (median 15.0 vs. 6.3 months; 4-year survival 10.5 vs. 4.6 %; p = 0.0001) disease. Patients with multiple metastases treated surgically had a survival advantage, and number of operations did not reduce survival in the 67 patients (42 %) who had multiple surgeries for distant melanoma. CONCLUSIONS: Our findings suggest that over half of stage IV patients are candidates for resection and exhibit improved survival over patients receiving SMT alone, regardless of site and number of metastases. We have begun a multicenter randomized phase III trial comparing surgery versus SMT as initial treatment for resectable distant melanoma.
Assuntos
Excisão de Linfonodo/mortalidade , Melanoma/cirurgia , Metastasectomia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Cutâneas/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de SobrevidaRESUMO
The optimal strategy for follow-up of extremity soft tissue sarcoma patients after primary treatment with curative intent is not known. The 1592 members of the Society of Surgical Oncology (SSO) were sent a survey to determine their practices. Office visits and chest X-rays were the most frequently performed items for all years. Complete blood count and liver function tests were the most commonly ordered blood tests, but many respondents did not order any blood tests routinely. Imaging studies of the extremities were recommended for most patients during the first postoperative year. Postoperative surveillance strategies after sarcoma treatment vary appreciably among surgeons. Surgeon age, tumor size, tumor grade, and geographic location of the surgeon account for only a modest amount of the variation, suggesting that lack of evidence supporting any particular strategy is the factor responsible for most of the variation. Efforts to provide high-quality evidence on this topic are warranted.
Assuntos
Sarcoma/terapia , Extremidades , Humanos , Prática Profissional , Sarcoma/diagnóstico , Sociedades Médicas , Fatores de TempoRESUMO
Soft-tissue sarcoma is an uncommon cancer with the potential for high rates of recurrence after initial therapy. Multiple surveillance strategies have been developed to follow patients after primary treatment. The purpose of this study was to quantify the costs associated with various published post-treatment surveillance strategies. A literature review covering the years 1982-2003 was performed to find all modern published surveillance methods for extremity soft-tissue sarcoma. Only articles describing an explicit 5-year follow-up strategy were included. Total costs of 5-year follow-up were calculated for each strategy using Medicare-allowed charges as a proxy. Thirty-four articles depicting 54 strategies were identified. Total Medicare-allowed charges in year 2003 dollars ranged from 485 dollars for follow-up of low-grade sarcoma to 21,235 dollars for follow-up of high-grade sarcoma, a 42.8-fold cost differential. The average charge for these 54 strategies was 6,401 dollars. Physical examination and chest x-ray were the most commonly used screening modalities. Several guidelines have been proposed for extremity soft-tissue sarcoma patient follow-up, most prominently those of the National Comprehensive Cancer Network. The literature has yet to reflect the consensus these guidelines suggest. This study shows wide disparity in the costs of 54 specific methods of following soft-tissue sarcoma patients. Clinical trials are needed to identify an optimal surveillance strategy, one balancing gains in survival, quality of life, costs, and societal willingness to expend resources. Such trials have not been conducted due to the rarity of extremity soft-tissue sarcomas and the costs associated with conducting long-term trials. Alternatively, prospective evaluation of imaging modalities used in follow-up should be assessed as part of other trials. Computer simulation analysis also holds great promise as an assessment tool for surveillance strategies because patient participation is not required.
Assuntos
Extremidades , Sarcoma/economia , Sarcoma/terapia , Neoplasias de Tecidos Moles/economia , Neoplasias de Tecidos Moles/terapia , Extremidades/patologia , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , MasculinoRESUMO
A large recent survey disclosed considerable variation in the intensity of follow-up after potentially curative surgery for extremity soft tissue sarcoma among highly credentialed clinicians. The source of the variation is not known. The survey was reanalyzed to investigate whether tumor grade and size account for the variation. The 1,592 members of the Society of Surgical Oncology were surveyed to measure their follow-up practices for 10 years after initial therapy for extremity sarcoma. Repeated-measures analysis of variance was used to measure the relationship among follow-up practice patterns and tumor grade, tumor size, and years after surgery. The 318 respondents who performed surgery and also carried out long-term follow-up for their patients with extremity soft tissue sarcoma were considered evaluable; 94% were general surgeons and 5% were orthopedic surgeons. Office visit, complete blood count, liver function tests, chest X-ray, chest computed tomography, extremity computed tomography, and extremity magnetic resonance imaging were ordered significantly more frequently with increasing tumor grade and size. Tumor grade and size significantly impacted physician practice patterns in post-treatment follow-up, although the degree of variation attributable to these variables was modest. These data permit rational design of a randomized clinical trial of two alternative follow-up plans.
Assuntos
Sarcoma/patologia , Sarcoma/cirurgia , Atenção à Saúde/normas , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Soft tissue sarcomas are a challenging disease entity with a variety of histologic subtypes that can arise anywhere on the body. Much effort has been put forward to advance the care of patients with soft tissue sarcomas. Radical amputations have largely given way to limb-sparing procedures. With multimodality treatment, there has been progress in local control rates as well. As knowledge of the basic biology of this disease grows, there likely will be new strategies to treat soft tissue sarcomas. The development of STI-571, and its demonstrated effectiveness in GIST, represents an important advance in the treatment of these tumors and potentially a new paradigm for the development of therapeutic intervention in other sarcomas. Developing collaboration among ACOSOG other cooperative groups in the United States, Canada, and Europe may provide physicians with new venues for asking important clinical questions about these low-incidence tumors. The importance of collaboration in enrolling patients in clinical trials to evaluate these future therapies cannot be overstated.
Assuntos
Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologiaRESUMO
Despite an increasing trend towards early diagnosis of breast cancer,patients still present with locally advanced disease. Also, in some patients chemotherapy will fail, and local and regional recurrence will occur. This article outlines options for palliative care for such patients.
Assuntos
Cuidados Paliativos/métodos , Neoplasias Peritoneais/cirurgia , Qualidade de Vida , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Amputação Cirúrgica/métodos , Feminino , Humanos , Masculino , Dor Intratável/diagnóstico , Dor Intratável/terapia , Seleção de Pacientes , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Sarcoma/mortalidade , Sarcoma/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Análise de Sobrevida , Doente Terminal , Resultado do TratamentoRESUMO
About 1% of all cancers are soft tissue sarcomas (STS); about 60% of these occur in the extremities. Post-treatment surveillance programs are designed to identify recurrence, new primary cancers, and complications of therapy early enough to increase survival duration and quality of life. The intensity of surveillance varies among surgeons. We hypothesized that geographic factors would account for much of this variation. The 1,592 members of the Society of Surgical Oncology were surveyed regarding their personal postoperative STS surveillance strategy using standardized clinical vignettes and a questionnaire based on the vignettes. Practice patterns were analyzed by US Census Region, Metropolitan Statistical Area (MSA), and managed care organization (MCO) penetration rate, using repeated measures analysis of variance. The study end-point was surveillance intensity. Mean follow-up intensity for the 12 surveillance modalities on the questionnaire was highly correlated with tumor size, grade, and year post surgery. Controlling for tumor stage, grade, and year post surgery, the practice location of the surgeon infrequently impacted surveillance intensity. MSA was a significant (p<0.05) predictor only of office visit frequency. MCO penetration rate significantly predicted only the frequency of urinalysis and tumor-site MRI. US Census Region significantly predicted only the frequency of LFTs. Geographic factors do not generally predict self-reported surveillance practice patterns for patients after curative-intent STS surgery. The overall variation in follow-up intensity appears to reflect factors not evaluated, such as the absence of high-quality evidence supporting any particular strategy and the quality of patients' insurance.
Assuntos
Padrões de Prática Médica , Sarcoma/terapia , Coleta de Dados , Humanos , Oncologia , Sarcoma/cirurgia , Inquéritos e QuestionáriosAssuntos
Reação a Corpo Estranho/diagnóstico , Neoplasias Gastrointestinais/diagnóstico , Laparotomia/efeitos adversos , Linfoma/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Sarcoma/diagnóstico , Tampões de Gaze Cirúrgicos/efeitos adversos , Diagnóstico Diferencial , Feminino , Fibrose/etiologia , Reação a Corpo Estranho/patologia , Neoplasias Gastrointestinais/patologia , Humanos , Histerectomia , Linfoma/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios XAssuntos
Sarcoma/cirurgia , Amputação Cirúrgica/história , Braço , Membros Artificiais , Terapia Combinada , Hemipelvectomia/história , História do Século XIX , História do Século XX , Humanos , Perna (Membro) , Salvamento de Membro , Procedimentos de Cirurgia Plástica , Reimplante , Neoplasias da Coluna Vertebral/cirurgiaRESUMO
OBJECTIVES: Dermatofibrosarcoma protuberans (DFSP) is a spindle cell tumor with a high local recurrence rate. Wide excision (WE) has been the standard treatment, but ideal margin width is poorly defined and Mohs micrographic surgery (MMS) has emerged as an alternative procedure. This study examines the use of WE versus MMS for the treatment of primary DFSP at a single institution. METHODS: Retrospective review of 48 primary DFSP cases treated from 1971 to 2006. Patient demographics, tumor features, surgical modality (WE vs. MMS), final pathology, and clinical outcome were evaluated. RESULTS: Twenty-eight patients underwent WE versus 20 patients for MMS. Median age was 40 years. Median WE margin width was 2 cm. For MMS, the median number of layers required to clear the tumor was 2. Median maximal defect size was 10 cm for WE versus 9.4 cm for MMS. Advanced closure techniques were required for 18% WE versus 65% MMS (P = 0.001). Median operative time was significantly lower for WE at 77 minutes versus 257 minutes for MMS (P < 0.001). Positive margins were present in 21.4% (6/28) WE versus 0% MMS (P = 0.01). At a median follow-up of 49.9 months for WE and 40.4 months for MMS, local recurrence rates were 3.6% (1/28) and 0%, respectively (P = 1.0). CONCLUSIONS: From a surgical standpoint, WE was faster than MMS and resulted in a less complex defect/closure. Although positive margin resection was more common with WE, local control was ultimately similar for the 2 surgical modalities. The choice of WE versus MMS should be based on individualized patients/tumor characteristics and institutional expertise in these modalities.
Assuntos
Dermatofibrossarcoma/cirurgia , Cirurgia de Mohs , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Idoso , Dermatofibrossarcoma/patologia , Feminino , Secções Congeladas/estatística & dados numéricos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
BACKGROUND: The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long-term (≥5 years) follow-up in patients with high-grade, high-risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy. METHODS: Patients with high-grade soft tissue sarcoma≥8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine). RESULTS: Sixty-four of 66 patients were analyzed. After chemotherapy and RT, 61 patients had surgery; 58 had R0 resections (5 amputations), and 3 had R1 resections. Ninety-seven percent experienced grade 3 or higher toxicity, including 3 deaths. These toxicities were short term. With a median follow-up of 7.7 years in surviving patients, the 5-year rates of locoregional failure (including amputation), and distant metastasis were 22.2% (95% confidence interval [CI], 11.8-32.6) and 28.1% (95% CI, 17.0-39.2). The most common site of metastasis was lung. Estimated 5-year rates of disease-free survival, distant disease-free survival, and overall survival were 56.1% (95% CI, 43.9-68.3), 64.1% (95% CI, 52.3-75.8), and 71.2% (95% CI, 60.0-82.5), respectively. CONCLUSIONS: Although the toxicity was significant, it was limited in its course and for the most part resolved by 1 year. The long-term outcome was better than might be expected in such high-risk tumors.
Assuntos
Parede Abdominal , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Extremidades , Terapia Neoadjuvante , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/radioterapia , Parede Torácica , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Radioterapia Adjuvante , Risco , Neoplasias de Tecidos Moles/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The objective of this study was to evaluate the impact of adjuvant radiation therapy (RT) on regional recurrence and survival after therapeutic lymphadenectomy (TL) for clinically advanced, lymph node-metastatic melanoma. METHODS: Six hundred fifteen patients who had clinically advanced, regional lymph node-metastatic disease underwent TL. All patients were appropriate potential candidates for adjuvant RT (enlarged or multiple positive lymph nodes, extracapsular extension) because of a high risk for regional recurrence regardless of whether or not they received RT. Patient-related, tumor-related, and treatment-related variables that were associated with recurrence, survival, and treatment-related morbidity with and without RT were analyzed. RESULTS: The median follow-up was 5 years. The actuarial 5-year regional lymph node basin control rate was 81%. On multivariate analysis, the number of positive lymph nodes, the number of lymph nodes removed, and the use of adjuvant RT were associated with improved regional control. Treatment-related morbidity, particularly lymphedema, was increased with the use of adjuvant RT and an inguinal site of lymph node metastases. At last follow-up, 268 patients were alive with actuarial 5-year distant metastasis-free survival (DMFS) and disease-specific survival (DSS) rates of 40% and 48%, respectively. On multivariate analysis, DMFS and DSS both were influenced by the number of positive lymph nodes and the number of lymph nodes removed. In addition, DSS was influenced by primary tumor thickness and the receipt of adjuvant RT. CONCLUSIONS: Adjuvant RT was associated with improved regional lymph node basin control compared with TL alone in patients with high-risk, clinically advanced, lymph node-metastatic melanoma. Although it is a regional therapy, adjuvant RT also may have an impact on DSS.
Assuntos
Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Risco , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Taxa de SobrevidaRESUMO
PURPOSE: Two major questions were addressed: (1) Can fever-range whole body hyperthermia (FR-WBH) affect the number of perfused tumor blood vessels? (2) Can pre-treatment with FR-WBH improve accumulation or anti-tumor efficacy of doxorubicin or DOXIL (liposomal doxorubicin)? MATERIALS AND METHODS: Perfused blood vessels were visualized by intravenous injection of the fluorescent dye (DiOC7(3)) and the number of labeled vessels in tumors and normal organs of unheated mice and those previously heated to 39.5 degrees C for 6 hours were compared. Using three animal tumor models (one syngeneic murine model and two human tumor xenografts in SCID mice) we also compared tumor growth and amount of intratumoral doxorubicin (given as free drug or as DOXIL) in control mice or those given pre-treatment with FR-WBH. RESULTS: FR-WBH had no effect on the number of CD-31 labeled blood vessels. However, in tumors, but not in normal organs of the same animals, FR-WBH resulted in a significant increase in those blood vessels which could take up dye over a prolonged period of time after heating. There was also an increase in DOXIL uptake in the tumors of mice given FR-WBH prior to drug injection as well as enhanced therapeutic efficacy in all three tumor models. CONCLUSIONS: FR-WBH increases the number of perfused blood vessels in tumors over a prolonged period following FR-WBH and thus may be useful for improving tumor targeting of cancer therapeutics. We discuss these data in relation to long-conserved thermoregulatory features in normal vasculature, which may be deficient in tumor vasculature.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/uso terapêutico , Hipertermia Induzida/métodos , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral/transplante , Terapia Combinada , Modelos Animais de Doenças , Feminino , Febre , Humanos , Camundongos , Camundongos SCID , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológicoRESUMO
Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy. Surgery is the primary treatment for patients with no evidence of metastatic disease, and for small low-grade superficial tumors in which adequate margins can be obtained, it may be the only therapy indicated. For large, deep tumors or tumors that are close to important neurovascular structures or bone, the addition of radiotherapy to resection has improved local control and increased limb salvage without affecting overall survival. Adjuvant chemotherapy has been an issue of considerable debate. Because 50% of patients with high-risk tumors will develop metastatic disease, effective systemic treatment with chemotherapy is needed. Unfortunately, studies have shown minimal improvement in overall survival when chemotherapy is added to the local treatment of high-risk extremity STS. More recently, a few trials of neoadjuvant chemotherapy consisting of mesna, doxorubicin, ifosfamide, and dacarbazine and high-dose doxorubicin and ifosfamide have shown some early promising results, but at the price of increased toxicity. Targeted therapy has shown some of its best results with gastrointestinal stromal tumors, but so far there has been little success in treating extremity STS. At this time, high-dose adjuvant or neoadjuvant chemotherapy should be given in the setting of a clinical trial to patients with high-risk tumors who can tolerate a potentially toxic chemotherapeutic regimen. The goal of these trials should be to assess new combination therapies, possibly including targeted therapies, for the management of large high-grade, high-risk soft tissue sarcomas.
Assuntos
Sarcoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Extremidades , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Radioterapia Adjuvante , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Sarcoma/radioterapia , Sarcoma/cirurgiaRESUMO
BACKGROUND: A significant proportion of newly diagnosed melanomas are thin lesions (< or = 1.00 mm). Because tumor thickness correlates with the risk for nodal metastases, sentinel lymph node (SLN) biopsy in this subset is controversial. Incorporating other prognostic factors (Clark level and ulceration), we evaluated the 6th edition American Joint Committee on Cancer (AJCC) clinical stage as a simple and widely applicable guideline for offering SLN biopsy for thin melanoma. METHODS: This study was a review of a prospective melanoma SLN database from 1993 to 2003 with emphasis on SLN positivity rates based on the 6th edition AJCC primary tumor thickness intervals and clinical stage. RESULTS: Three hundred five patients underwent SLN biopsy, with an overall positivity rate of 17.7%. By the 6th edition AJCC, lesions < or = 1.00 mm had an SLN positivity rate of 6.6%. By 6th edition clinical stage, SLN positivity rates were 4.9% for stage IA and 10.4% for stage IB. By using stage IA as the criterion for not offering SLN biopsy, this procedure would have been avoided in 46% (39 of 85) of < or = 1.00-mm melanoma patients with a negative SLN. CONCLUSIONS: Sixth edition AJCC clinical stage IB as a selection criterion for performing SLN biopsy in thin melanoma identifies most patients with a positive SLN while also avoiding a negative SLN biopsy in many patients. Until additional widely accepted and validated selection criteria are available, SLN biopsy for clinical stage IB, but not stage IA, thin melanomas is a reasonable approach.