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INTRODUCTION: Vestibular schwannomas (VSs) are rare, benign intracranial tumours that have prompted clinical practice guideline (CPG) creation given their complex management. Our aim was to utilize the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument to assess if such CPGs on the management of VSs with radiosurgery and radiotherapy are of acceptable quality. METHODS: Relevant CPGs were identified following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols. Experienced reviewers then extracted general CPG properties and rated their quality via the AGREE II instrument. Intraclass correlation coefficients (ICCs) were quantified to assess interrater reliability. RESULTS: Nine CPGs on the management of VSs with radiosurgery and radiotherapy were identified. All CPGs were created in the past six years and developed recommendations based on literature review and expert consensus. One guideline was deemed as high quality with seven others being moderate and one being low in quality. The clarity of the presentation domain had the highest mean scaled domain score of 96.0%. The domains of stakeholder involvement and applicability had the lowest means of 49.2% and 47.2%, respectively. ICCs were either good or excellent across all domains. CONCLUSION: Current CPGs on the management of VSs with radiosurgery and radiotherapy are of acceptable quality but would greatly benefit from improvements in applicability, stakeholder involvement, editorial independence and rigour of development. We recommend CPG authors reference the European Association of Neuro-Oncology (EANO) guideline as a developmental framework with the Congress of Neurological Surgeons/American Association of Neurological Surgeons (CNS/AANS) CPG being a valid alternative.
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Neuroma Acústico , Guias de Prática Clínica como Assunto , Radiocirurgia , Humanos , Radiocirurgia/normas , Radiocirurgia/métodos , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgiaRESUMO
Background and purpose: The ability to determine the risk and predictors of lymphedema is vital in improving the quality of life for head and neck (HN) cancer patients. However, selecting robust features is challenging due to the multicollinearity and high dimensionality of radiotherapy (RT) data. This study aims to overcome these challenges using an ensemble feature selection technique with machine learning (ML). Materials and methods: Thirty organs-at-risk, including bilateral cervical lymph node levels, were contoured, and dose-volume data were extracted from 76 HN treatment plans. Clinicopathologic data was collected. Ensemble feature selection was used to reduce the number of features. Using the reduced features as input to ML and competing risk models, internal and external lymphedema prediction capability was evaluated with the ML models, and time to lymphedema event and risk stratification were estimated using the risk models. Results: Two ML models, XGBoost and random forest, exhibited robust prediction performance. They achieved average F1-scores and AUCs of 84 ± 3.3 % and 79 ± 11.9 % (external lymphedema), and 64 ± 12 % and 78 ± 7.9 % (internal lymphedema). Predictive ML and risk models identified common predictors, including bulky node involvement, high dose to various lymph node levels, and lymph nodes removed during surgery. At 180 days, removing 0-25, 26-50, and > 50 lymph nodes increased external lymphedema risk to 72.1 %, 95.6 %, and 57.7 % respectively (p = 0.01). Conclusion: Our approach, involving the reduction of HN RT data dimensionality, resulted in effective ML models for HN lymphedema prediction. Predictive dosimetric features emerged from both predictive and competing risk models. Consistency with clinicopathologic features from other studies supports our methodology.
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Purpose: Head and neck lymphedema (HNL) following radiation therapy for head and neck cancer (HNC) causes patient morbidity. Predicting individual patients' risk of HNL after treatment is challenging. We aimed to identify the demographic, disease-related, and treatment-related factors associated with external and internal HNL following treatment of HNC with definitive or adjuvant radiation therapy. Methods and Materials: Relevant clinical, pathologic, and dosimetric data for 76 consecutive patients who received definitive or adjuvant radiation ± chemotherapy were retrospectively collected from a single institution. Multivariable models predictive of external and internal lymphedema using clinicopathologic variables alone and in combination with dosimetric variables were constructed and optimized using competing risk regression. Results: After median follow-up of 550 days, the incidence of external and internal HNL at 360 days was 70% and 34%, respectively. When evaluating clinical and treatment-related factors alone, number of lymph nodes removed and advanced adenopathy status were predictive of external lymphedema. With incorporation of dosimetric variables, the optimized model included the percentage volume of the contralateral lymph node level VII receiving 30Gy V30 ≥50%, number of lymph nodes removed, and advanced adenopathy status. For internal lymphedema, our clinicopathologic model identified both adjuvant radiation, as opposed to definitive radiation, and advanced adenopathy status. With inclusion of a dosimetric variable, the optimized model included larynx V45 ≥50% and advanced adenopathy. Conclusions: HNL following HNC treatment is common. For both external and internal lymphedema, nodal disease burden at diagnosis predicts increased risk. For external lymphedema, increasing extent of lymph node dissection prior to adjuvant therapy increases risk. The contralateral level VII lymph node region is also predictive of external lymphedema when radiation dose to V30 is ≥50%, meriting investigation. For internal lymphedema, we confirm that increasing radiation dose to the larynx is the most significant dosimetric predictor of mucosal edema when larynx V45 is ≥50%.
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Purpose: Our purpose was to report complications requiring surgical intervention among patients treated with postmastectomy proton radiation therapy (PMPRT) for breast cancer in the setting of breast reconstruction (BR). Methods and Materials: Patients enrolled on a prospective proton registry who underwent BR with immediate autologous flap, tissue expander (TE), or implant in place during PMPRT (50/50.4 Gy +/- chest wall boost) were eligible. Major reconstruction complication (MRC) was defined as a complication requiring surgical intervention. Absolute reconstruction failure was an MRC requiring surgical removal of BR. A routine revision (RR) was a plastic surgery refining cosmesis of the BR. Kaplan-Meier method was used to assess disease outcomes and MRC. Cox regression was used to assess predictors of MRC. Results: Seventy-three courses of PMPRT were delivered to 68 women with BR between 2013 and 2021. Median follow-up was 42.1 months. Median age was 47 years. Fifty-six (76.7%) courses used pencil beam scanning PMPRT. Of 73 BR, 29 were flaps (39.7%), 30 implants (41.1%), and 14 TE (19.2%) at time of irradiation. There were 20 (27.4%) RR. There were 9 (12.3%) MRC among 5 implants, 2 flaps, and 2 TE, occurring a median of 29 months from PMPRT start. Three-year freedom from MRC was 86.9%. Three (4.1%) of the MRC were absolute reconstruction failure. Complications leading to MRC included capsular contracture in 5, fat necrosis in 2, and infection in 2. On univariable analysis, BR type, boost, proton technique, age, and smoking status were not associated with MRC, whereas higher body mass index trended toward significance (hazard ratio, 1.07; 95% CI, 0.99-1.16; P = .10). Conclusions: Patients undergoing PMPRT to BR had a 12.3% incidence of major complications leading to surgical intervention, and total loss of BR was rare. MRC rates were similar among reconstruction types. Minor surgery for RR is common in our practice.
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Introduction: Proton radiation therapy (PBT) may reduce cardiac doses in breast cancer treatment. Limited availability of proton facilities could require significant travel distances. This study assessed factors associated with travel distances for breast PBT. Materials and Methods: Patients receiving breast PBT at the University of Pennsylvania from 2010 to 2021 were identified. Demographic, cancer, and treatment characteristics were summarized. Straight-line travel distances from the department to patients' addresses were calculated using BatchGeo. Median and mean travel distances were reported. Given non-normality of distribution of travel distances, Wilcoxon rank sum or Kruskal-Wallis test was used to determine whether travel distances differed by race, clinical trial participation, disease laterality, recurrence, and prior radiation. Results: Of 1 male and 284 female patients, 67.8% were White and 21.7% Black. Median travel distance was 13.5 miles with interquartile range of 6.1 to 24.8 miles, and mean travel distance was 13.5 miles with standard deviation of 261.4 miles. 81.1% of patients traveled less than 30 and 6.0% more than 100 miles. Black patients' travel distances were significantly shorter than White patients' and non-Black or non-White patients' travel distances (median = 4.5, 16.5, and 11.3 miles, respectively; P < .0001). Patients not on clinical trials traveled more those on clinical trials (median = 14.7 and 10.2 miles, respectively; P = .032). There was no difference found between travel distances of patients with left-sided versus right-sided versus bilateral disease (P = .175), with versus without recurrent disease (P = .057), or with versus without prior radiation (P = .23). Conclusion: This study described travel distances and demographic and clinicopathologic characteristics of patients receiving breast PBT at the University of Pennsylvania. Black patients traveled less than White and non-Black or non-White patients and comprised a small portion of the cohort, suggesting barriers to travel and PBT. Patients did not travel further to receive PBT for left-sided or recurrent disease.
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This study aimed to assess the incidental radiation exposure of the hippocampus (HC) in locoregionally-advanced oropharyngeal cancer patients undergoing volumetric modulated arc therapy and the feasibility of HC-sparing plan optimization. The initial plans were generated without dose-volume constraints to the HC and were compared with the HC-sparing plans. The incidental Dmean_median doses to the bilateral, ipsilateral and contralateral HC were 2.9, 3.1, and 2.5 Gy in the initial plans and 1.4, 1.6, and 1.3 Gy with HC-sparing. It was feasible to reduce the HC dose with HC-sparing plan optimization without compromising target coverage and/or dose constraints to other OARs.
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BACKGROUND: Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review. METHODS: Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS. RESULTS: Thirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9- and 12-month OS were 96% (75.1-99.8%), 86.6% (63.5-95.5%), respectively; 9- and 12-month PFS were 68% (47.5-82.5%), 48.7% (25.3-68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05). CONCLUSIONS: Among LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.
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Metabolite profiling using (1)H nuclear magnetic resonance (NMR) spectroscopy was used to investigate the metabolic changes associated with deletion of the gene for the transcriptional coactivator p300 in the human colon carcinoma cell line HCT116. Multivariate statistical methods were used to distinguish between metabolite patterns that were dependent on cell growth conditions and those that were specifically associated with loss of p300 function. In the absence of serum, wild-type cells showed slower growth, which was accompanied by a marked decrease in phosphocholine concentration, which was not observed in otherwise isogenic cell lines lacking p300. In the presence of serum, several metabolites were identified as being significantly different between the two cell types, including glutamate and glutamine, a nicotinamide-related compound and glycerophosphocholine (GPC). However, in the absence of serum, these metabolites, with the exception of GPC, were not significantly different, leading us to conclude that most of these changes were context dependent. Transcript profiling, using DNA microarrays, showed changes in the levels of transcripts for several enzymes involved in choline metabolism, which might explain the change in GPC concentration. Localized in vivo (1)H NMR measurements on the tumors formed following s.c. implantation of these cells into mice showed an increase in the intensity of the peak from choline-containing compounds in the p300(-) tumors. These data show that NMR-based metabolite profiling has sufficient sensitivity to identify the metabolic consequences of p300 gene deletion in tumor cells in vitro and in vivo.
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Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Fatores de Transcrição de p300-CBP/deficiência , Animais , Meios de Cultivo Condicionados , Deleção de Genes , Perfilação da Expressão Gênica , Células HCT116 , Humanos , Camundongos , Camundongos SCID , Ressonância Magnética Nuclear Biomolecular , Transplante Heterólogo , Fatores de Transcrição de p300-CBP/genéticaRESUMO
PURPOSE: Proton radiation therapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0%-16%) than most photon series (2.2%-8.6%). We report the incidence of brainstem injury and a risk factor analysis in pediatric patients with posterior fossa primary tumors treated with proton radiation therapy at our institution. METHODS AND MATERIALS: The study included 216 consecutive patients treated between 2000 and 2015. Dosimetry was available for all but 4 patients. Grade 2 to 5 late brainstem toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The histologies include medulloblastoma (n=154, 71.3%), ependymoma (n=56, 25.9%), and atypical teratoid rhabdoid tumor (n=6, 2.8%). The median age at irradiation was 6.6 years (range, 0.5-23.1 years); median dose, 54 gray relative biological effectiveness (Gy RBE) (range, 46.8-59.4 Gy RBE); and median follow-up period, 4.2 years (range, 0.1-15.3 years) among 198 survivors. Of the patients, 83.3% received chemotherapy; 70.4% achieved gross total resection. The crude rate of injury was 2.3% in all patients, 1.9% in those with medulloblastoma, 3.6% in those with ependymoma, and 0% in those with atypical teratoid rhabdoid tumor. The 5-year cumulative incidence of injury was 2.0% (95% confidence interval, 0.7%-4.8%). The median brainstem dose (minimum dose received by 50% of brainstem) in the whole cohort was 53.6 Gy RBE (range, 16.5-56.8 Gy RBE); maximum point dose within the brainstem (Dmax), 55.2 Gy RBE (range, 48.4-60.5 Gy RBE); and mean dose, 50.4 Gy RBE (range, 21.1-56.7 Gy RBE). In the 5 patients with injury, the median minimum dose received by 50% of the brainstem was 54.6 Gy RBE (range, 50.2-55.1 Gy RBE); Dmax, 56.2 Gy RBE (range, 55.0-57.1 Gy RBE); mean dose, 51.3 Gy RBE (range, 45.4-54.4 Gy RBE); and median volume of the brainstem receiving ≥55 Gy RBE (V55), 27.4% (range, 0%-59.4%). Of the 5 patients with injury, 4 had a brainstem Dmax in the highest quartile (≥55.8 Gy RBE, P = .016) and a V55 in the highest tertile (>6.0%) of the cohort distribution (P = .047). Of the 5 patients with injury, 3 were aged >6 years (age range, 4.1-22.8 years), and 4 of 5 patients received chemotherapy and achieved gross total resection. CONCLUSIONS: The incidence of injury in pediatric patients with posterior fossa tumors is consistent with previous reports in the photon setting. Our data suggest that when Dmax and V55 are kept <55.8 Gy RBE and ≤6.0%, respectively, the 5-year rate of radiation brainstem injury would be <2%.
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Tronco Encefálico/efeitos da radiação , Neoplasias Infratentoriais/radioterapia , Terapia com Prótons/efeitos adversos , Lesões por Radiação/epidemiologia , Adolescente , Criança , Pré-Escolar , Intervalos de Confiança , Ependimoma/tratamento farmacológico , Ependimoma/mortalidade , Ependimoma/radioterapia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Neoplasias Infratentoriais/tratamento farmacológico , Neoplasias Infratentoriais/mortalidade , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/mortalidade , Meduloblastoma/radioterapia , Intervalo Livre de Progressão , Lesões por Radiação/mortalidade , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Tumor Rabdoide/tratamento farmacológico , Tumor Rabdoide/mortalidade , Tumor Rabdoide/radioterapia , Medição de Risco , Teratoma/tratamento farmacológico , Teratoma/mortalidade , Teratoma/radioterapia , Adulto JovemRESUMO
OBJECTIVES: Management of unresectable adenocystic carcinoma (ACC) of the nasopharynx is challenging given the high dose required for tumor control while respecting dose constraints. We evaluated long-term outcomes and toxicity in patients with unresectable ACC of the nasopharynx treated with definitive proton beam therapy. METHODS: Between 2000 and 2013, 14 patients with ACC of the nasopharynx were treated. Ninety-three percent had T4 disease. All had involvement of the skull base. Seventy-nine percent and 21% of patients underwent biopsy and endoscopic debulking surgery, respectively. Median dose was 73.8Gy (RBE). Fifty percent of patients received concurrent chemotherapy. Locoregional control and overall survival probabilities were estimated by the Kaplan-Meier method. Treatment toxicity was scored by the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Median follow-up of surviving patients was 69months. There were 3 local, 1 regional, and 4 distant failures. Median time of local failures was 69months (range: 63-161). All local recurrences were within previous high-dose regions. Four patients developed metastatic disease at a median of 30months (range: 4-64). Five-year overall survival was 59%. The most common cause of death was due to metastatic disease. There was one acute grade 3 toxicity. No patient required gastrostomy tube or hospitalization. Three patients developed grade 3 or higher late toxicity. Two of these patients received combined modality treatment. With 176months follow-up, no second cancer was observed. CONCLUSION: Proton beam therapy results in promising local control with acceptable toxicity in patients with unresectable ACC of the nasopharynx. As late recurrence is common, longer follow-up is necessary to confirm our findings.
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Carcinoma Adenoide Cístico/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Terapia com Prótons , Base do Crânio/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
Purpose This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. Methods In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. Results A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow-up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47-168). The 3- and 5-year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3- and 5-year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. Conclusion This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.
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PURPOSE: To review and report the long-term treatment-induced adverse events (AEs) and outcomes of concomitant chemoradiotherapy boosted by low-dose-rate (LDR) conventional brachytherapy (BT) planning in patients with locoregionally advanced cervical cancer. PATIENTS AND METHODS: After obtaining institutional review board approval, we reviewed the records of patients with stage IB1 to IVA, intact cervical cancer who were treated at our institution between 1983 and 2009. Eligible patients underwent definitive radiotherapy with external-beam radiation concomitant with cisplatin-based chemotherapy and boosted by LDR BT. Patient, tumor, and treatment characteristics; treatment-induced AEs, namely, gastrointestinal and genitourinary toxicities, as well as treatment outcomes; locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were reviewed and reported. RESULTS: The study included 129 eligible cervical cancer patients; the median age was 46 years (mean, 47 ± 11 y; range, 28 to 81 y), consisting of stages I, II, III, and IV (29.5%, 48.1%, 17.8%, and 4.6%, respectively). The median follow-up was 37 months (mean, 58 ± 59 mo; range, 3 to 275 mo). The 3-year OS, PFS, LRC, and DC were 75.9%, 71.6%, 84.7%, and 80.2%, respectively. The 5-year OS, PFS, LRC, and DC were 70.7%, 68.7%, 84.7%, and 78.3%, respectively. The 10-year OS, PFS, LRC, and DC were 68.7%, 62.3%, 82.5%, and 73.2%, respectively. Gastrointestinal and genitourinary grade 3 and 4 acute AEs were reported in 3.9% and 0%, and chronic grade 3 and 4 AEs were reported in 20.9% and 12.4% of all patients, respectively. CONCLUSIONS: Definitive chemoradiotherapy followed by conventional LDR BT boost is effective, feasible, and tolerable treatment modality for cervical cancer. A comparison with MRI image-guided BT shows comparable treatment outcomes with superior OS in favor of LDR BT but inferior LC with a relatively worse toxicity profile.
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Braquiterapia/efeitos adversos , Carcinoma/radioterapia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Braquiterapia/métodos , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidadeRESUMO
PURPOSE: The purpose of this study was to identify the axillary lymph nodes on pretreatment diagnostic computed tomography (CT) of the chest to determine their position relative to the anatomic axillary borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. METHODS AND MATERIALS: Pretreatment diagnostic CT chest scans available for 30 breast cancer patients with clinically involved lymph nodes were fused with simulation CT. Contouring of axillary levels I, II, and III according to the RTOG guidelines was performed. Measurements were made from the area of distal tumor to the anatomic borders in 6 dimensions for each level. RESULTS: Of the 30 patients, 100%, 93%, and 37% had clinical involvement of levels I, II, and III, respectively. The mean number of lymph nodes dissected was 13.6. The mean size of the largest lymph node was 2.4 cm. Extracapsular extension was seen in 23% of patients. In 97% of patients, an aspect of the involved lymph node lay outside of the anatomic border of a level. In 80% and 83% of patients, tumor extension was seen outside the cranial (1.78 ± 1.0 cm; range, 0.28-3.58 cm) and anterior (1.27 ± 0.92 cm; range, 0.24-3.58 cm) borders of level I, respectively. In 80% of patients, tumor extension was seen outside the caudal border of level II (1.36 ± 1.0 cm, range, 0.27-3.86 cm), and 0% to 33% of patients had tumor extension outside the remaining borders of all levels. CONCLUSIONS: To cover 95% of lymph nodes at the cranial and anterior borders of level I, an additional clinical target volume margin of 3.78 cm and 3.11 cm, respectively, is necessary. The RTOG guidelines may be insufficient for coverage of axillary disease in patients with clinical nodal involvement who are undergoing neoadjuvant chemotherapy, incomplete axillary dissection, or treatment with intensity modulated radiation therapy. In patients with pretreatment diagnostic CT chest scans, fusion with simulation CT should be considered for tumor delineation.
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Linfonodos/diagnóstico por imagem , Ilustração Médica , Planejamento da Radioterapia Assistida por Computador , Neoplasias Unilaterais da Mama/diagnóstico por imagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila , Quimioterapia Adjuvante , Feminino , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Irradiação Linfática/métodos , Mastectomia Radical/estatística & dados numéricos , Mastectomia Segmentar/estatística & dados numéricos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X , Carga Tumoral , Neoplasias Unilaterais da Mama/tratamento farmacológico , Neoplasias Unilaterais da Mama/patologia , Neoplasias Unilaterais da Mama/radioterapiaRESUMO
OBJECTIVES: CD30(+) lymphoproliferative disorder is a rare variant of cutaneous T-cell lymphoma. Sustained complete response following first-line treatments is rare. This retrospective review evaluates the response of refractory or recurrent lesions to palliative radiation therapy. METHODS: The records of 6 patients with 12 lesions, treated with radiation therapy, were reviewed. All patients received previous first-line treatments. Patients with clinical and pathological evidence of symptomatic CD30(+) lymphoproliferative disorder, with no history of other cutaneous T-cell lymphoma variants, and with no prior radiation therapy to the index site were included. RESULTS: The median age of patients was 50.5 years (range, 15-83 years). Median size of the treated lesions was 2.5 cm (range, 2-7 cm). Four sites were treated with a single fraction of 750-800 cGy (n = 3) and 8 sites were treated with 4000-4500 cGy in 200-250 cGy fractions (n = 3). Radiation therapy was administered with electrons and bolus. Median follow-up was 113 months (range, 16-147 months). For all sites, there was 100% complete response with acute grade 1-2 dermatitis. CONCLUSIONS: For recurrent and symptomatic radiation-naïve CD30(+) lymphoproliferative disorder lesions, palliative radiation therapy shows excellent response. A single fraction of 750-800 cGy is as effective as a multifractionated course and more convenient.
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Antígeno Ki-1/metabolismo , Transtornos Linfoproliferativos/radioterapia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Transtornos Linfoproliferativos/metabolismo , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/química , Pele/citologia , Pele/patologiaRESUMO
OBJECTIVES: The objective of this study was to compare outcomes for patients with cervical cancer treated with radiation concurrently with cisplatin, cisplatin/5-fluorouracil (5-FU), or without chemotherapy. MATERIALS AND METHODS: We reviewed the records of eligible patients with locoregionally confined, stage IB1 through IVA, intact cervical cancer who were treated at Northwestern Memorial Hospital. All patients underwent definitive radiotherapy with combined external beam radiation-the majority with extended-field (62%)-and received low-dose rate brachytherapy. RESULTS: A total of 236 patients were included: 99 had no concurrent chemotherapy, 95 were treated with concurrent cisplatin, and 42 were treated with cisplatin/5-FU. For all patients treated with or without chemotherapy, overall survival at 5 and 10 years was 64% and 59%, respectively. Patients treated with chemotherapy had a superior recurrence-free survival rate of 69% at 5 years versus 49% in patients who did not receive chemotherapy (P=0.09). Twenty-six percent of patients treated with cisplatin alone, 31% of patients treated with cisplatin/5-FU, and 45% of patients who did not receive chemotherapy experienced a disease recurrence. Adenosquamous histology conferred a higher rate of recurrence as compared with adenocarcinoma and squamous cell histologies (54% vs. 34%, respectively; P=0.05). CONCLUSIONS: Cisplatin-based concurrent chemoradiotherapy showed a trend toward improved recurrence-free survival survival in the definitive treatment of nonmetastatic cervical cancer. The addition of 5-FU to cisplatin did not appear to significantly impact survival or recurrence-free survival. Adenosquamous histology was associated with a higher risk of recurrence as compared with other histologic subtypes.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
We have shown that genistein, a major component of soy, has anti-colon cancer effects in vitro. These effects are attainable at high concentrations that are difficult to achieve in the serum. The purpose of this study was to enhance the activity of genistein against colon cancer cells by coupling it to 17.1A. The monoclonal antibody 17.1A recognizes an epithelial membrane antigen that is overexpressed in colon cancer. Synthesis of Gen-17.1A was achieved by photochemical conjugation using sulfa-SANPAH. Its purity was evaluated by SDS-PAGE. Binding of Gen-17.1A to SW-620 and HT-29 cells was shown using flow cytometry. Internalization was demonstrated by FITC-labeling. Gen-17.1A induced apoptosis in colon cancer cells as evidenced by the acridine orange/ethidium bromide staining method. Gen-17.1A significantly inhibited colon cancer cell growth in vitro and in vivo. Our findings suggest that conjugating genistein to 17.1A monoclonal antibody enhances its effects against colon cancer cells.