RESUMO
PURPOSE: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/radioterapia , Mastectomia Segmentar/métodos , Trastuzumab/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trastuzumab/farmacologiaRESUMO
BACKGROUND: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. METHODS: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. FINDINGS: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. INTERPRETATION: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. FUNDING: National Cancer Institute, US Department of Health and Human Services.
Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Humanos , Metástase Linfática , Mamografia , Mastectomia Segmentar , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Taxa de SobrevidaRESUMO
PURPOSE: The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. PATIENTS AND METHODS: Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). RESULTS: From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). CONCLUSION: Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.
Assuntos
Canal Anal , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/métodos , Tratamentos com Preservação do Órgão , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Adulto , Idoso , Canal Anal/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Radioterapia Adjuvante , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Resultado do TratamentoRESUMO
PURPOSE: To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative (125)I Vicryl mesh brachytherapy. METHODS AND MATERIALS: Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of (125)I seeds along the resection line. The (125)I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. RESULTS: The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm(2) (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. CONCLUSION: (125)I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.
Assuntos
Braquiterapia/métodos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Proteínas de Arabidopsis , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada/métodos , Feminino , Ferredoxina-NADP Redutase , Seguimentos , Humanos , Tempo de Internação , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pennsylvania , Pneumonectomia/métodos , Poliglactina 910 , Dosagem Radioterapêutica , Telas Cirúrgicas , Análise de SobrevidaAssuntos
Neoplasias da Mama/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Fracionamento da Dose de Radiação , Estética , Feminino , Fibrose/patologia , Humanos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração , Gordura Subcutânea/patologia , Gordura Subcutânea/efeitos da radiaçãoRESUMO
Techniques for generating simplified IMRT treatment plans for treating non-small cell lung cancer (NSCLC) patients with respiratory motion were investigated. To estimate and account for respiratory motion, 4-dimensional computed tomography (4DCT) datasets from 5 patients were used to design 5-field 6-MV ungated step-and-shoot intensity modulated radiotherapy (IMRT) plans delivering a dose of 66 Gy to the planning target volume (PTV). For each patient, 2 plans were generated using the mean intensity and the maximum intensity of 10 CT datasets from different breathing phases. The plans also utilized different margins around the clinical target volume/internal target volume (CTV/ITV) to account for tumor motion. To reduce the treatment time and ensure accurate dose delivery to moving targets, the number of intensity levels was minimized while maintaining dose coverage to PTV and minimizing dose to organs at risk (OARs). Dose-volume histograms (DVHs), dosimetric metrics, and outcome probabilities were evaluated for all plans. Plans using the averaged CT image dataset were inferior, requiring larger margins around the PTV, with a maximum of 1.5 cm, to ensure coverage of the tumor, and therefore increased the dose to OARs located in proximity of the tumor. The plans based on superimposed CT image datasets achieved full coverage of the tumor, while allowing tight margins around the PTV and minimizing the dose to OARs. A small number of intensity-levels (3 to 5), resulting in IMRT plans with a total of 13 to 30 segments, were sufficient for homogeneous PTV coverage, without affecting the sparing of OARs. In conclusion, a technique involving treatment planning with the superimposed CT scans of all respiratory phases, and the application of IMRT with only a small number of segments was feasible despite significant tumor motion; however, greater patient numbers are needed to support the statistical significance of the results presented in this work.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Tomografia Computadorizada por Raios X/métodos , Artefatos , Humanos , Imageamento Tridimensional/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Mecânica Respiratória , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. METHODS AND MATERIALS: A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV_EVAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV_EVAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. RESULTS: The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% +/- 1.6% and -0.1 +/- 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm(3)) to Fraction 1 (0.8 cm(3)). The PTV_EVAL volume change was insignificant. The average variation for the %PTV_EVAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% +/- 2.4%, -0.35 +/- 2.4%, and -0.34 +/- 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 +/- 0.47 and -0.16 +/- 0.29 Gy, respectively. CONCLUSION: The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant.
Assuntos
Braquiterapia/instrumentação , Neoplasias da Mama/radioterapia , Cateterismo/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Ar , Braquiterapia/métodos , Neoplasias da Mama/diagnóstico por imagem , Fracionamento da Dose de Radiação , Feminino , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
PURPOSE: A retrospective review to assess the efficacy and morbidity of surgical resection and (125)I interstitial lung brachytherapy placed in approximation to the aorta. METHODS AND MATERIALS: The records and postoperative films of 278 patients who had undergone intrathoracic (125)I brachytherapy at our institution were reviewed. All patients had undergone a gross total resection of a non-small-cell lung cancer using segmental resection, wedge resection, or sublobar resection. Frozen section margins of resection were required to be negative before the intraoperative delivery of the implant. Of those reviewed, 29 patients were implanted with (125)I impregnated Vicryl mesh that contacted greater than 50% with the aorta. Implants consisted of (125)I seeds sewn into a nomographically guided geometric array. Only implants where 50% or greater of the implant volume directly approximated the aorta were selected for inclusion into this study. The mean aortic volume receiving the entire prescribed dose was 17.2cc (mean surface area=34.4cm(2)) and the mean prescribed dose was 114Gy (range, 85-120) over the permanent life of the implant calculated by isodose curve distribution at a depth of 0.5cm from the plane of the implant. Five patients have received postoperative mediastinal dose supplementation with external beam irradiation to further address occult mediastinal nodal disease not revealed during the intraoperative frozen section analysis. RESULTS: All patients tolerated the surgery and brachytherapy well with no perioperative mortality. With a median followup of 45.3 months (range, 1-117), 1 of the 29 patients suffered a fatal hemorrhage from suspected great vessel rupture. A review of this case demonstrated that the interstitial therapy had been supplemented with 4500cGy of external irradiation, which overlapped a small portion of the implant volume overlying the aorta. No other patients suffered even minor events referable to the implant and have continued to do well without symptomatic evidence of chronic sequelae as of the publication of this article or the time of their death. Local control has been achieved in all patients still living and had been achieved in all patients who died from subsequent progression of metastatic disease or other cause. CONCLUSIONS: Interstitial (125)I intrathoracic brachytherapy is a safe and effective method when used with sublobar resection in high-risk stage I non-small-cell lung cancer patients and may be used even in situations that require placement of the sources in close approximation to the aorta. The tolerance of the aorta seems to be greater than previously thought, and may well exceed 12,000cGy over the permanent life of the interstitial implant. Interstitial (125)I brachytherapy can safely be used to deliver significant radiation dose in direct contact with the aorta but supplemental, overlapping external beam irradiation should be avoided.
Assuntos
Aorta/efeitos da radiação , Braquiterapia/métodos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Idoso , Braquiterapia/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Humanos , Radioisótopos do Iodo/efeitos adversos , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos , Procedimentos Cirúrgicos TorácicosRESUMO
Accurate daily patient localization is becoming increasingly important in external-beam radiotherapy (RT). Mega-voltage cone-beam computed tomography (MV-CBCT) utilizing a therapy beam and an on-board electronic portal imager can be used to localize tumor volumes and verify the patient's position prior to treatment. MV-CBCT produces a static volumetric image and therefore can only account for inter-fractional changes. In this work, the feasibility of using the MV-CBCT raw data as a fluoroscopic series of portal images to monitor tumor changes due to e.g. respiratory motion was investigated. A method was developed to read and convert the CB raw data into a cine. To improve the contrast-to-noise ratio on the MV-CB projection data, image post-processing with filtering techniques was investigated. Volumes of interest from the planning CT were projected onto the MV-cine. Because of the small exposure and the varying thickness of the patient depending on the projection angle, soft-tissue contrast was limited. Tumor visibility as a function of tumor size and projection angle was studied. The method was well suited in the upper chest, where motion of the tumor as well as of the diaphragm could be clearly seen. In the cases of patients with non-small cell lung cancer with medium or large tumor masses, we verified that the tumor mass was always located within the PTV despite respiratory motion. However for small tumors the method is less applicable, because the visibility of those targets becomes marginal. Evaluation of motion in non-superior-inferior directions might also be limited for small tumor masses. Viewing MV-CBCT data in a cine mode adds to the utility of MV-CBCT for verification of tumor motion and for deriving individualized treatment margins.
Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Movimento , Neoplasias/diagnóstico por imagem , Neoplasias/fisiopatologia , Sistemas On-Line , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias/radioterapia , Doses de Radiação , Radioterapia Conformacional , Reprodutibilidade dos Testes , RespiraçãoRESUMO
A given outcome of radiotherapy treatment can be modeled by analyzing its correlation with a combination of dosimetric, physiological, biological, and clinical factors, through a logistic regression fit of a large patient population. The quality of the fit is measured by the combination of the predictive power of this particular set of factors and the statistical significance of the individual factors in the model. We developed a genetic algorithm (GA), in which a small sample of all the possible combinations of variables are fitted to the patient data. New models are derived from the best models, through crossover and mutation operations, and are in turn fitted. The process is repeated until the sample converges to the combination of factors that best predicts the outcome. The GA was tested on a data set that investigated the incidence of lung injury in NSCLC patients treated with 3DCRT. The GA identified a model with two variables as the best predictor of radiation pneumonitis: the V30 (p=0.048) and the ongoing use of tobacco at the time of referral (p=0.074). This two-variable model was confirmed as the best model by analyzing all possible combinations of factors. In conclusion, genetic algorithms provide a reliable and fast way to select significant factors in logistic regression analysis of large clinical studies.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Neoplasias/radioterapia , Radioterapia/métodos , Análise de Regressão , Algoritmos , Área Sob a Curva , Humanos , Modelos Genéticos , Modelos Estatísticos , Modelos Teóricos , Curva ROC , Radiometria , Planejamento da Radioterapia Assistida por Computador , Resultado do TratamentoRESUMO
The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 degrees gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6 +/- 1.0 Gy for the bladder and comparable for the rectum (-0.3 +/- 1.4 Gy). In addition, an average mean dose increase of 1.9 +/- 0.8 Gy in the femoral heads and 1.7 +/- 0.6 Gy in irradiated tissue was observed. However, the V65 and V70 values for bladder and rectum were lower by 2.3 +/- 1.5% and 2.4 +/- 2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It allows for daily treatment modifications where other volumetric tomographic imaging techniques may not be feasible and/or available and where accurate patient localization with a high degree of precision is required.
Assuntos
Adenoma/radioterapia , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Hipofisárias/radioterapia , Neoplasias da Próstata/radioterapia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Masculino , Aceleradores de Partículas , Fótons , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos TestesRESUMO
Treatment management decisions in three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) are usually made based on the dose distributions in the target and surrounding normal tissue. These decisions may include, for example, the choice of one treatment over another and the level of tumour dose escalation. Furthermore, biological predictors such as tumour control probability (TCP) and normal tissue complication probability (NTCP), whose parameters available in the literature are only population-based estimates, are often used to assess and compare plans. However, a number of other clinical, biological and physiological factors also affect the outcome of radiotherapy treatment and are often not considered in the treatment planning and evaluation process. A statistical outcome analysis tool, EUCLID, for direct use by radiation oncologists and medical physicists was developed. The tool builds a mathematical model to predict an outcome probability based on a large number of clinical, biological, physiological and dosimetric factors. EUCLID can first analyse a large set of patients, such as from a clinical trial, to derive regression correlation coefficients between these factors and a given outcome. It can then apply such a model to an individual patient at the time of treatment to derive the probability of that outcome, allowing the physician to individualize the treatment based on medical evidence that encompasses a wide range of factors. The software's flexibility allows the clinicians to explore several avenues to select the best predictors of a given outcome. Its link to record-and-verify systems and data spreadsheets allows for a rapid and practical data collection and manipulation. A wide range of statistical information about the study population, including demographics and correlations between different factors, is available. A large number of one- and two-dimensional plots, histograms and survival curves allow for an easy visual analysis of the population. Several visual and analytical methods are available to quantify the predictive power of the multivariate regression model. The EUCLID tool can be readily integrated with treatment planning and record-and-verify systems.
Assuntos
Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Software , Algoritmos , Humanos , Modelos Logísticos , Oncologia/métodos , Modelos Estatísticos , Modelos Teóricos , Análise Multivariada , Probabilidade , Radioterapia (Especialidade)/métodos , Dosagem Radioterapêutica , Análise de Regressão , Resultado do TratamentoRESUMO
The evolution of ever more conformal radiation delivery techniques makes the subject of accurate localization of increasing importance in radiotherapy. Several systems can be utilized including kilo-voltage and mega-voltage cone-beam computed tomography (MV-CBCT), CT on rail or helical tomography. One of the attractive aspects of mega-voltage cone-beam CT is that it uses the therapy beam along with an electronic portal imaging device to image the patient prior to the delivery of treatment. However, the use of a photon beam energy in the mega-voltage range for volumetric imaging degrades the image quality and increases the patient radiation dose. To optimize image quality and patient dose in MV-CBCT imaging procedures, a series of dose measurements in cylindrical and anthropomorphic phantoms using an ionization chamber, radiographic films, and thermoluminescent dosimeters was performed. Furthermore, the dependence of the contrast to noise ratio and spatial resolution of the image upon the dose delivered for a 20-cm-diam cylindrical phantom was evaluated. Depending on the anatomical site and patient thickness, we found that the minimum dose deposited in the irradiated volume was 5-9 cGy and the maximum dose was between 9 and 17 cGy for our clinical MV-CBCT imaging protocols. Results also demonstrated that for high contrast areas such as bony anatomy, low doses are sufficient for image registration and visualization of the three-dimensional boundaries between soft tissue and bony structures. However, as the difference in tissue density decreased, the dose required to identify soft tissue boundaries increased. Finally, the dose delivered by MV-CBCT was simulated using a treatment planning system (TPS), thereby allowing the incorporation of MV-CBCT dose in the treatment planning process. The TPS-calculated doses agreed well with measurements for a wide range of imaging protocols.
Assuntos
Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada Espiral/métodos , Carga Corporal (Radioterapia) , Relação Dose-Resposta à Radiação , Humanos , Imagens de Fantasmas , Doses de Radiação , Eficiência Biológica Relativa , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A dosimetric comparison was performed on external-beam three-dimensional conformal partial breast irradiation (PBI) and whole breast irradiation (WBI) plans for patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol at our institution. Twenty-four consecutive patients were treated with either PBI (12 patients) or WBI (12 patients). In the PBI arm, the lumpectomy cavity was treated to a total dose of 38.5 Gy at 3.85 Gy per fraction twice daily using a four-field noncoplanar beam setup. A minimum 6 h interval was required between fractions. In the WBI arm, the whole breast including the entirety of the lumpectomy cavity was treated to a total dose of 50.4 Gy at 1.8 Gy per fraction daily using opposed tangential beams. The lumpectomy cavity volume, planning target volume for evaluation (PTV_EVAL), and critical structure volumes were contoured for both the PBI and WBI patients. Dosimetric parameters, dose volume histograms (DVHs), and generalized equivalent uniform dose (gEUD) for target and critical structures were compared. Dosimetric results show the PBI plans, compared to the WBI plans, have smaller hot spots in the PTV_EVAL (maximum dose: 104.2% versus 110.9%) and reduced dose to the ipsilateral breast (V50: 48.6% versus 92.1% and V100: 10.2% versus 50.5%), contralateral breast (V3: 0.16% versus 2.04%), ipsilateral lung (V30: 5.8% versus 12.7%), and thyroid (maximum dose: 0.5% versus 2.0%) with p values < or = 0.01. However, similar dose coverage of the PTV_EVAL (98% for PBI and 99% for WBI, on average) was observed and the dose difference for other critical structures was clinically insignificant in both arms. The gEUD data analysis showed the reduction of dose to the ipsilateral breast and lung, contralateral breast and thyroid. In addition, preliminary dermatologic adverse event assessment data suggested reduced skin toxicity for patients treated with the PBI technique.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Mama/patologia , Mama/efeitos da radiação , Doses de Radiação , Neoplasias da Mama/diagnóstico por imagem , Dermatologia , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Mastectomia Segmentar , Estadiamento de Neoplasias , Radiometria , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Lymph node (LN) -negative breast cancer tumors > or = 5 cm occur infrequently, and their optimal management is not well defined. In this study, we assess patterns of locoregional failure (LRF) in LN-negative patients who underwent mastectomy, either with or without adjuvant chemotherapy or hormonal therapy and without postmastectomy radiation therapy (PMRT). PATIENTS AND METHODS: Of 8,878 breast cancer patients enrolled onto National Surgical Adjuvant Breast and Bowel Project B-13, B-14, B-19, B-20, and B-23 node-negative trials, 313 had tumors that were 5 cm or larger (median, 5.5 cm; range, 5.0 to 15.5 cm) at pathology and were treated by mastectomy. Median follow-up time was 15.1 years. Therapy included adjuvant chemotherapy in 34.2% of patients; tamoxifen in 21.1%; chemotherapy plus tamoxifen in 19.2%; and no systemic therapy in 25.5%. RESULTS: Twenty-eight patients experienced LRF. The overall 10-year cumulative incidences of isolated LRF, LRF with and without distant failure (DF), and DF alone as first event were 7.1%, 10.0%, and 23.6%, respectively. Cumulative incidences for isolated LRF as first event for patients with tumors of 5 cm or more than 5 cm were 7.0% and 7.2%, respectively (P = .9). For patients who underwent no systemic treatment, chemotherapy alone, tamoxifen alone, or chemotherapy plus tamoxifen, the incidences were 12.6%, 5.6%, 4.6%, and 5.3%, respectively (P = .2). The majority of failures occurred on the chest wall (24 of 28 patients). Multivariate analysis did not identify significant prognostic factors for LRF. CONCLUSION: In patients with LN-negative tumors > or = 5 cm who are treated by mastectomy with or without adjuvant systemic therapy and no PMRT, LRF as first event remains low. PMRT should not be routinely used for these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Mastectomia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/prevenção & controle , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: A 58-year-old Caucasian man with a history of irritable bowel syndrome and occasional rectal bleeding presented with a 4-week history of progressive, bright red blood per rectum. A digital rectal examination revealed a 3 cm distal, midrectal mass. Laboratory tests showed an elevated serum prostate-specific antigen of 32 ng/ml but other physical and medical examinations were unremarkable. INVESTIGATIONS: Digital rectal examination, colonoscopy, rectal mass biopsy, endorectal ultrasound, transrectal ultrasound-guided prostate biopsy, CT scan and MRI. DIAGNOSIS: Clinical stage III (T3N1M0), moderately differentiated adenocarcinoma of the rectum and clinical stage II (T1cN0M0) adenocarcinoma of the prostate. MANAGEMENT: Intensity-modulated radiation therapy, chemoradiation, chemotherapy, hormone therapy and surgery.