RESUMO
The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast cancer. A Markov model was developed to compare 18 hypothetical cohorts of 45-year-old women with newly diagnosed unilateral, sporadic breast cancer treated with or without CPM. The probability of developing distant metastases by American Joint Committee on Cancer stage and molecular subtype was derived from British Columbia Cancer Agency data. Additional model parameters were identified from the medical literature. Sensitivity analyses were performed to examine the impact of plausible variations in key model parameters on results. CPM improved LE in all cohorts (range 0.06-0.54 years). Stage had more effect on LE than subtype (stage I mean, 0.44 years, stage III mean, 0.11 years). However, after adjusting for quality-of-life, No CPM was favored in all cohorts. Univariate sensitivity analysis demonstrated that the most influential model parameter was the post-CPM health state utility. The preferred strategy shifted from No CPM to CPM when the post-CPM utility exceeded 0.83 (base case value 0.81). PSA indicated that LE gains and QALE decreases were stable in all cohorts. The primary determinant of survival after unilateral breast cancer is stage at diagnosis. Our results suggest that routine CPM would not improve quality-adjusted survival for the majority of women with unilateral sporadic breast cancer.
Assuntos
Mastectomia , Medição de Risco , Neoplasias Unilaterais da Mama/prevenção & controle , Neoplasias Unilaterais da Mama/cirurgia , Colúmbia Britânica/epidemiologia , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Feminino , Humanos , Incidência , Expectativa de Vida , Cadeias de Markov , Mastectomia/métodos , Metástase Neoplásica , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Sensibilidade e Especificidade , Neoplasias Unilaterais da Mama/epidemiologiaRESUMO
Breast cancer is commonly diagnosed in postmenopausal women, the majority of whom express 1 or more cardiovascular disease risk factors. Cardiovascular disease poses a significant competing risk for morbidity and mortality among nonmetastatic breast cancer survivors. Adjuvant systemic therapies may result in late-cardiac toxicity decades after treatment completion. The cumulative incidence of treatment-related cardiotoxic outcomes may be as high as 33% after some adjuvant breast cancer therapies. Breast cancer treatment-induced cardiotoxicity may manifest as cardiomyopathy, coronary ischemia, thromboembolism, arrhythmias and conduction abnormalities, and valvular and pericardial disease. Evidence indicates that preexisting cardiovascular conditions such as hypertension or left ventricular dysfunction may compound the adverse effects of cardiotoxic treatments. There are currently no published clinical practice guidelines that address ongoing cardiac surveillance for cardiotoxicity after breast cancer, and existing guidelines for monitoring and promoting cardiovascular health in older women are often not followed. The multidisciplinary prospective surveillance system proposed elsewhere in this supplement would allow for earlier detection of cardiotoxicity from treatment and may improve monitoring of cardiovascular health in the growing population of breast cancer survivors.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/terapia , Doenças Cardiovasculares/terapia , Coração/efeitos dos fármacos , Coração/efeitos da radiação , Saúde da Mulher , Adulto , Idoso , American Cancer Society , Neoplasias da Mama/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Adjuvante , Terapia Combinada , Congressos como Assunto , Feminino , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Prevenção Primária/métodos , Prognóstico , Estudos Prospectivos , Radioterapia Adjuvante , Medição de Risco , Índice de Gravidade de Doença , Sobreviventes , Resultado do TratamentoRESUMO
The purpose of this paper is to review the incidence of upper-body morbidity (arm and breast symptoms, impairments, and lymphedema), methods for diagnosis, and prevention and treatment strategies. It was also the purpose to highlight the evidence base for integration of prospective surveillance for upper-body morbidity within standard clinical care of women with breast cancer. Between 10% and 64% of women report upper-body symptoms between 6 months and 3 years after breast cancer, and approximately 20% develop lymphedema. Symptoms remain common into longer-term survivorship, and although lymphedema may be transient for some, those who present with mild lymphedema are at increased risk of developing moderate to severe lymphedema. The etiology of morbidity seems to be multifactorial, with the most consistent risk factors being those associated with extent of treatment. However, known risk factors cannot reliably distinguish between those who will and will not develop upper-body morbidity. Upper-body morbidity may be treatable with physical therapy. There is also evidence in support of integrating regular surveillance for upper-body morbidity into the routine care provided to women with breast cancer, with early diagnosis potentially contributing to more effective management and prevention of progression of these conditions.
Assuntos
Neoplasias da Mama/cirurgia , Prestação Integrada de Cuidados de Saúde/organização & administração , Linfedema/epidemiologia , Dor/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Adulto , Idoso , American Cancer Society , Neoplasias da Mama/mortalidade , Neoplasias da Mama/reabilitação , Congressos como Assunto , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Linfedema/etiologia , Linfedema/reabilitação , Mastectomia/efeitos adversos , Mastectomia/métodos , Mastectomia/reabilitação , Pessoa de Meia-Idade , Modelos Organizacionais , Debilidade Muscular/epidemiologia , Debilidade Muscular/etiologia , Debilidade Muscular/reabilitação , Dor/etiologia , Dor/reabilitação , Prevenção Primária/métodos , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologia , Índice de Gravidade de Doença , Fatores de Tempo , Extremidade Superior/fisiopatologiaRESUMO
BACKGROUND: The current model of care for individuals with breast cancer focuses on treatment of the disease, followed by ongoing surveillance to detect recurrence. This approach lacks attention to patients' physical and functional well-being. Breast cancer treatment sequelae can lead to physical impairments and functional limitations. Common impairments include pain, fatigue, upper-extremity dysfunction, lymphedema, weakness, joint arthralgia, neuropathy, weight gain, cardiovascular effects, and osteoporosis. Evidence supports prospective surveillance for early identification and treatment as a means to prevent or mitigate many of these concerns. This article proposes a prospective surveillance model for physical rehabilitation and exercise that can be integrated with disease treatment to create a more comprehensive approach to survivorship health care. The goals of the model are to promote surveillance for common physical impairments and functional limitations associated with breast cancer treatment; to provide education to facilitate early identification of impairments; to introduce rehabilitation and exercise intervention when physical impairments are identified; and to promote and support physical activity and exercise behaviors through the trajectory of disease treatment and survivorship. METHODS: The model is the result of a multidisciplinary meeting of research and clinical experts in breast cancer survivorship and representatives of relevant professional and advocacy organizations. RESULTS/CONCLUSIONS: The proposed model identifies time points during breast cancer care for assessment of and education about physical impairments. Ultimately, implementation of the model may influence incidence and severity of breast cancer treatment-related physical impairments. As such, the model seeks to optimize function during and after treatment and positively influence a growing survivorship community.
Assuntos
Neoplasias da Mama/reabilitação , Prestação Integrada de Cuidados de Saúde/organização & administração , Exercício Físico/fisiologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Qualidade de Vida , Adulto , Idoso , American Cancer Society , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Congressos como Assunto , Intervalo Livre de Doença , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos Organizacionais , Avaliação das Necessidades , Educação de Pacientes como Assunto , Modalidades de Fisioterapia , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: On-board cone-beam computed tomography (CBCT) provides soft tissue information that may improve setup accuracy in patients undergoing accelerated partial breast irradiation (APBI). We used CBCT to assess the residual error in soft tissue after two-dimensional kV/MV alignment based on bony anatomy. We also assessed the dosimetric impact of this error. METHODS AND MATERIALS: Ten patients undergoing APBI were studied as part of an institutional review board-approved prospective trial. Patients were aligned based on skin/cradle marks plus orthogonal kV/MV images registered based on bony landmarks to digitally reconstructed radiographs from the planning CT. A subsequent CBCT was registered to the planning CT using soft tissue information. This "residual error" and its dosimetric impact was measured. RESULTS: The root-mean-square of the residual error was 3, 4, and 4 mm, in the right-left, anterior-posterior, and superior-inferior directions, respectively. The average vector sum was 6+/-2 mm. Average reductions in mean dose to the lumpectomy cavity, clinical target volume (CTV), and planning target volume were 0.1%, 0.4%, and 1%, respectively. The mean difference in the clinical target and planning target volumes that received 95% of the prescribed dose (V95) were 1% and 4%. CONCLUSIONS: In this initial study with a modest number of patients, the residual error in soft tissue was typically <5 mm, and with the field margins used, the resultant dosimetric consequences were modest. In patients immobilized in a customized cradle, setup using orthogonal kV images thus appears accurate and reproducible. The CBCT technique may have particular utility in patients with larger breast volumes or breast deformations. Further studies involving larger numbers of patients are needed to further assess the utility of CBCT.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Mamografia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias da Mama/radioterapia , Calibragem , Feminino , Humanos , Aceleradores de Partículas , Estudos Prospectivos , Dosagem Radioterapêutica , Reprodutibilidade dos TestesRESUMO
RATIONALE, AIMS AND OBJECTIVES: The burden of illness from colorectal cancer (CRC) can be reduced by improving the quality of care. Identifying appropriate quality measures is the first step in this direction. We identified process measures currently available to assess the quality of diagnosis and management of CRC. We also evaluated the extent to which these measures are ready to be implemented in clinical practice, and identified areas for future research. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, and relevant grey literature. We identified 3771 abstracts and reviewed 74 articles that included quality measures for diagnosis or management of CRC. Measures from traditional quality improvement literature, and from epidemiological and other studies that included quality measures as part of their research agenda, were considered. In addition, we devised a summary rating scale (IST) to appraise the extent of a measure's importance and usability, scientific acceptability and extent of testing. RESULTS: The coverage of general process measures in CRC is extensive. Most measures are important, but need to be developed and field-tested. The best available measures relate to pathology and chemotherapy. No measures are available for assessing quality of management of stage IV rectal cancer and hepatic metastasis; chemotherapy for stage II colon cancer; and procedure notes. CONCLUSIONS: There is an urgent need to refine existing measures and to develop scientifically accurate quality measures for a comprehensive assessment of the quality of CRC care. The role of the federal government and professional societies is critical in pursuing this goal.
Assuntos
Neoplasias do Colo/terapia , Garantia da Qualidade dos Cuidados de Saúde/normas , Neoplasias Retais/terapia , Neoplasias do Colo/diagnóstico , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde , Indicadores de Qualidade em Assistência à Saúde , Neoplasias Retais/diagnósticoRESUMO
IMPORTANCE: The use of a radiotherapy (RT) boost to the tumor bed after whole-breast RT (WBRT) for ductal carcinoma in situ (DCIS) is largely extrapolated from invasive cancer data, but robust evidence specific to DCIS is lacking. OBJECTIVE: To compare ipsilateral breast tumor recurrence (IBTR) in women with DCIS treated with vs without the RT boost after breast-conserving surgery and WBRT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis pooled deidentified patient-level data from 10 academic institutions in the United States, Canada, and France from January 1, 1980, through December 31, 2010. All patients had newly diagnosed pure DCIS (no microinvasion), underwent breast-conserving surgery, and received WBRT with or without the boost with a minimum of 5 years of follow-up required for inclusion in the analysis. Given the limited events after WBRT, an a priori power analysis was conducted to estimate the DCIS sample size needed to detect the anticipated benefit of the boost. Data were uniformly recoded at the host institution and underwent primary and secondary reviews before analysis. Sample size calculations (ratio of patients who received the boost dose to those who did not, 2:1; α = .05; power = 80%) estimated that 2982 cases were needed to detect a difference of at least 3%. The final analysis included 4131 patients (2661 in the boost group and 1470 in the no-boost group) with a median follow-up of 9 years and media boost dose of 14 Gy. Data were collected from July 2011 through February 2014 and analyzed from March 2014 through August 2015. INTERVENTIONS: Radiotherapy boost vs no boost. MAIN OUTCOMES AND MEASURES: Ipsilateral breast tumor recurrence. RESULTS: The analysis included 4131 patients (median [SD] age, 56.1 [10.9] years; range, 24-88 years). Patients with positive margins, unknown estrogen receptor status, and comedo necrosis were more likely to have received an RT boost. For the entire cohort, the boost was significantly associated with lower IBTR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) and with IBTR-free survival (boost vs no-boost groups) of 97.1% (95% CI, 0.96-0.98) vs 96.3% (95% CI, 0.95-0.97) at 5 years, 94.1% (95% CI, 0.93-0.95) vs 92.5% (95% CI, 0.91-0.94) at 10 years, and 91.6% (95% CI, 0.90-0.93) vs 88.0% (95% CI, 0.85-0.91) at 15 years. On multivariable analysis accounting for confounding factors, the boost remained significantly associated with reduced IBTR (HR compared with no boost, 0.68; 95% CI, 0.50-0.91; P = .01) independent of age and tamoxifen citrate use. CONCLUSIONS AND RELEVANCE: This patient-level analysis suggests that the RT boost confers a statistically significant benefit in decreasing IBTR across all DCIS age groups, similar to that seen in patients with invasive breast cancer. These findings suggest that a DCIS RT boost to the tumor bed could be considered to provide an added incremental benefit in decreasing IBTR after a shared discussion between the patient and her radiation oncologist.
Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/radioterapia , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Radioterapia Adjuvante , Adulto JovemRESUMO
While the data regarding radiotherapy (RT)-induced cardiovascular disease in lung cancer patients is limited, the cardiotoxic effects of RT have been thoroughly documented in long-term survivors of breast cancer and Hodgkin's disease. Herein we review data illustrating the cardiotoxic effects of thoracic RT in lung and breast cancer patients. Older RT techniques for treating the breast/chest wall and draining lymph nodes resulted in a relatively high dose being delivered to a substantial volume of heart, and convincing evidence exists of excess cardiovascular morbidity and mortality in patients treated with these techniques. While modern RT techniques have reduced radiation exposure to the heart, they have not eliminated it. In patients treated with modern techniques, there are conflicting data regarding the impact of radiation on late cardiovascular morbidity and mortality. Thus, it is prudent to reduce cardiac exposure as much as possible. Techniques to reduce further cardiac exposure (eg, respiratory gating, intensity modulated radiation therapy) are currently under investigation. Further work is needed to quantify the frequency and severity of cardiac injury and develop preventative methods.
Assuntos
Neoplasias da Mama/radioterapia , Cardiopatias/etiologia , Coração/efeitos da radiação , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/epidemiologia , Sobreviventes , Cardiopatias/epidemiologia , Humanos , Infarto do Miocárdio/epidemiologia , Radioterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de RegistrosRESUMO
PURPOSE: To compare the location and extent of the tumor bed as defined by surgical clips and computed tomography (CT) scans, after lumpectomy, for electron boost planning as part of breast radiotherapy. METHODS AND MATERIALS: Planning CT images of 31 operated breasts in 30 patients who underwent lumpectomy were reviewed. One or more clips were placed in the lumpectomy cavity. Serial CT images were used to measure the depth and transverse and longitudinal dimensions. The area and geometric center of the tumor bed were defined by the clips and CT. RESULTS: The CT and clip measurements were identical for the maximal tumor depth in 27 of 30 patients. The CT bed extended beyond the clips by 0-7 mm medially in the transverse/longitudinal extent (multiclip patients). The median distance between the geometric centers in the coronal plane for the tumor bed center was larger for patients with single clips than for those with multiple clips (p < 0.025). Tumor bed areas in the coronal plane defined by both methods correlated strongly. However, the CT-defined area was larger by 13.9 mm2. The CT bed was more readily visible in patients with a shorter interval between surgery and radiotherapy. CONCLUSION: The maximal depth of the tumor bed was similar using the two methods. The extent and centers of the clip-and CT-determined beds differed significantly. This may indicate an underestimation of the tumor bed as defined by clips only and justifies integration of CT information in boost field planning.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma in Situ/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Instrumentos Cirúrgicos , Adulto , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma in Situ/radioterapia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Elétrons/uso terapêutico , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Radioterapia Adjuvante , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Pretreatment anemia is an adverse prognostic variable in squamous cell head-and-neck cancer (HNC) patients treated with radiotherapy (RT) alone. Tumor hypoxia is an adverse parameter for treatment with RT alone or with RT and concurrent chemotherapy (CCT). Tumor hypoxia is more prevalent in patients who present with pretreatment hemoglobin (Hgb) concentrations less than 13 g/dL. RT/CCT improves survival over RT alone in advanced HNC, and its use is becoming more widespread. This study was performed to evaluate whether pretreatment Hgb less than 13 g/dL was correlated with treatment outcome in patients with advanced HNC treated with a uniform regimen of RT/CCT. METHODS AND MATERIALS: The study population consisted of patients with AJCC Stage III or IV, M0 HNC who were treated with 70 to 72.5 Gy accelerated hyperfractionated RT (1.25 Gy b.i.d.) and CCT consisting of 2 cycles of CDDP (12-20 mg/m(2)/d x 5 days) and continuous infusion 5-FU (600 mg/m(2)/d x 5 days) during Week 1 and Week 6. A planned break in RT occurred during Week 4. These patients were enrolled on the experimental arm of a prospective randomized trial that compared this regimen to hyperfractionated irradiation alone from 1990 to 1996. RT/CCT was delivered as standard therapy from 1996 to 2000. The primary endpoint was failure-free survival (FFS). Secondary endpoints included local-regional control and overall survival. RESULTS: One hundred and fifty-nine patients were treated from 1990 to 2000. The median (25-75%) pretreatment Hgb was 13.6 (12.2-13.5) g/dL. Hgb was 13 g/dL or higher in 105 patients and less than 13 g/dL in 54 patients. Primary tumor sites included oropharynx (43%), hypopharynx/larynx (36%), oral cavity (9%), and nasopharynx (6%). Seventy-eight percent of the patients with Hgb 13 g/dL or higher and 92% of the patients with Hgb less than 13 g/dL had a primary tumor stage of T3 or T4 (p = 0.01). Node-positive disease was present in 74 of 105 (70%) of patients with Hgb 13 g/dL or higher patients and in 36/54 (67%) of patients with Hgb less than 13 g/dL patients. Median follow-up of surviving patients was 42 months (range, 4-128 months). Five-year FFS was 75% for patients with Hgb 13 g/dL or higher vs. 50% for patients with Hgb less than 13 g/dL had a (p < 0.01). A total of 49 failures occurred in both patient cohorts. The median (25-75%) decrease in Hgb during RT/CCT was 2.2 (1.3-3.1) g/dL, both in patients who failed and in those who remained disease-free. CONCLUSION: Pretreatment Hgb less than 13 g/dL is correlated with adverse outcomes in advanced HNC patients treated with RT/CCT. Whether anemia actually causes poor outcomes remains unknown. The therapeutic effect of anemia correction is being evaluated in prospective trials.
Assuntos
Anemia/complicações , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Hemoglobinas/metabolismo , Adulto , Idoso , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/sangue , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Falha de TratamentoRESUMO
PURPOSE: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. METHODS: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. RESULTS: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. CONCLUSIONS: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects.
Assuntos
Neoplasias da Mama/radioterapia , Coração/efeitos da radiação , Contração Miocárdica/efeitos da radiação , Lesões por Radiação/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Circulação Coronária/fisiologia , Circulação Coronária/efeitos da radiação , Feminino , Coração/diagnóstico por imagem , Coração/fisiopatologia , Humanos , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Estudos Prospectivos , Doses de Radiação , Lesões por Radiação/diagnóstico por imagem , Volume Sistólico/fisiologia , Volume Sistólico/efeitos da radiação , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Radiotherapy (RT) to the breast or chest wall of young women is associated with long-term cardiotoxicity and an increased risk of secondary breast cancers. As many patients with early stage breast cancer and Hodgkin's disease are cured of their disease, there is significant concern regarding the long term risks of therapy. Older RT techniques for treating the breast/chest wall and draining lymph nodes for breast cancer resulted in a relatively high dose being delivered to a substantial volume of heart, and convincing evidence exists of excess cardiovascular morbidity and mortality in patients treated with these techniques. While modern RT techniques have reduced radiation exposure to the heart, they have not eliminated it. Many large studies of Hodgkin's disease survivors have demonstrated a clear risk of secondary breast cancer development after mantle RT for Hodgkin's disease. The risk of developing breast cancer after mantle RT appears to be related to age at time of irradiation, dose delivered to the breast tissue, and whether or not chemotherapy is incorporated into the overall treatment plan. In this article we review late cardiac complications associated with tangential breast RT and the risk of developing a secondary breast cancer after mantle RT for Hodgkin's disease.
Assuntos
Neoplasias da Mama/radioterapia , Coração/efeitos da radiação , Adolescente , Adulto , Fatores Etários , Neoplasias da Mama/etiologia , Doenças Cardiovasculares/etiologia , Criança , Feminino , Coração/diagnóstico por imagem , Doença de Hodgkin/radioterapia , Humanos , Metanálise como Assunto , Segunda Neoplasia Primária/etiologia , Radiografia , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Neck dissection has traditionally played an important role in the treatment of patients with squamous cell carcinoma of the head and neck who present with regionally advanced neck disease (N2-N3). Radiotherapy and concurrent chemotherapy improves overall survival in advanced head-and-neck cancer compared with radiotherapy alone. The necessity for postchemoradiation neck dissection is controversial. The intent of this report was to define the value of neck dissection in this patient population better. METHODS AND MATERIALS: Patients with locally advanced squamous carcinoma of the head and neck who also presented with nodal disease and underwent hyperfractionated radiotherapy and concurrent cisplatin/5-fluorouracil chemotherapy constituted the study population. Adjuvant modified neck dissection (MND) was planned 6 to 8 weeks after completion of chemoradiation in those patients who had a biopsy-proven pathologically complete response at the primary tumor site, irrespective of the clinical/radiographic neck response. A cohort of patients underwent electrode assessment of tumor oxygenation. Pathologic findings from the MND were used to compute the negative and positive predictive values and overall accuracy of the clinical/radiographic response (cCR). Regional control, failure-free survival, and survival were compared according to whether patients actually underwent MND. RESULTS: A total of 154 patients received concurrent chemoradiation. Of these, 108 presented with nodal disease: N1, n = 30; and N2-N3, n = 78. MND was performed in 65 (60%) of 108 patients, including 13 (43%) of 30 with Stage N1 and 52 (66%) of 78 with Stage N2-N3. For N1 patients, the negative predictive value of a cCR, positive predictive value of less than a cCR, and the overall accuracy for clinical response was 92%, 100%, and 92%, respectively. For N2-N3 patients, the corresponding values were 74%, 44%, and 60%. Patients with poorly oxygenated tumors were more likely to have residual disease at MND. The median follow-up was 4 years. The 4-year disease-free survival rate was 70% for N1 patients, irrespective of the clinical response or whether MND was performed. The 4-year disease-free survival rate was 75% for N2-N3 patients who had a cCR and underwent MND vs. 53% for patients who had a cCR but did not undergo MND (p = 0.08). The 4-year overall survival rate was 77% vs. 50% for these two groups of patients (p = 0.04). CONCLUSION: The clinical and pathologic responses in the neck correlated poorly with one another for patients with N2-N3 neck disease undergoing concurrent chemoradiation for advanced head-and-neck cancer. MND still appears to confer a disease-free survival and overall survival advantage with acceptably low morbidity. Tumor oxygenation assessment may be useful in selecting patients who are especially prone to have residual disease. Better tools need to be developed to determine prospectively whether this procedure is required for individual patients.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Esvaziamento Cervical , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Taxa de SobrevidaRESUMO
Our group has demonstrated that tangential radiation therapy (RT) to the left breast or chest wall can cause perfusion changes in the anterior myocardium. We assess if RT-induced perfusion changes are associated with the development of symptoms consistent with cardiac dysfunction. Between 1998 and 2001, 114 patients were enrolled into an institutional review board-approved prospective study and had pre-RT and serial post-RT (range, 6-24 months) single photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion. Thirty-one patients were excluded. The incidence of cardiac symptoms in patients with and without RT-induced perfusion defects was compared using a 2-tailed Fisher's exact test. With a median follow-up of 16 months (range, 6-24 months), 10 of 83 evaluable patients had > or = 1 episode of transient chest pain, occurring 0-14 months after RT (median, 6 months). The rates of chest pain in the patients with and without new perfusion defects were 9 of 31 and 1 of 52, respectively (P = 0.0004). A similar result was found when patients were segregated based on the use of chemotherapy. Two of these 10 cases were diagnosed as pericarditis. No patient had myocardial infarction or congestive heart failure. Cardiac symptoms occur more frequently in patients with perfusion abnormalities by SPECT after RT than in patients with normal SPECT scans, suggesting that such perfusion defects may be clinically significant. One confounding factor is that women who know they have RT-induced perfusion defects may be more likely to report episode of chest pain. Long-term follow-up will be necessary to better assess the clinical significance of RT-induced perfusion defects.
Assuntos
Neoplasias da Mama/radioterapia , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária/efeitos da radiação , Lesões por Radiação/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/diagnóstico por imagem , Radioterapia/efeitos adversos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
To assess if there has been increased sectioning of pathologic specimens with ductal carcinoma in situ (DCIS), identify sources of this change, and consider the clinical consequences, pathologic data from patients who underwent initial excisional biopsies at our institution and were referred to the radiation oncology department with DCIS from 1992-2002 were retrospectively reviewed. One hundred forty-four of 480 patients with DCIS were eligible for review. Specimen size was recorded as length, to the nearest 0.1 cm, in 3 dimensions. Specimen volume was approximated by the product of the 3 dimensions of the specimen. The primary endpoint was the number of microscopic sections taken from gross specimens, corrected for specimen size. Other analysis included margin status, use of a previous stereotactic needle biopsy, and whether a subsequent repeat excision was performed. Over time, there was an increase in size of the excisional biopsy specimens (mean of 49 cm3 from 1992 to 1994 and 90 cm3 from 2001 to 2002; P = 0.045). Mean numbers of slides per centimeter of specimen were 2.5, 2.7, 3.9, and 5.8 for the intervals 1992-1994, 1995-1997, 1998-2000, and 2001-2002, respectively (P < 0.001 for 1992-1997 vs. 1998-2002). Adjusting for volume, the increase over time in the number of slides per specimen was statistically significant (parameter significance, P < 0.001). For a given volume, the number of slides increased approximately 9.1% per year, on average, during the study period. The positive margin rates were 52%, 46%, 23%, and 25% from 1992 to 1994, from 1995 to 1997, from 1998 to 2000, and from 2001 to 2002, respectively. The degree of sectioning, corrected for specimen length and volume, increased over time.
Assuntos
Biópsia/estatística & dados numéricos , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Recidiva Local de Neoplasia/patologia , Avaliação de Resultados em Cuidados de Saúde , Manejo de Espécimes/métodos , Feminino , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , North Carolina , Reoperação , Estudos RetrospectivosRESUMO
Rituximab in combination with chlorambucil or radiation therapy may be an effective and less-toxic therapeutic alternative for patients with lymphocyte predominance Hodgkin's disease (LPHD). We treated 6 patients with LPHD with weekly rituximab at 375 mg/m2 for 4 weeks, followed by either radiation therapy or chlorambucil. Four patients had previously untreated disease and 2 had relapsed LPHD. All patients had no evidence of disease progression at a median follow-up time of 12.5 months after receiving rituximab therapy (range, 6-39 months) and a median follow-up time of 6.5 months after completion of chlorambucil or radiation therapy (range, 3-25 months). Further follow-up is warranted to evaluate response duration and late toxicity of this novel treatment strategy
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Linfócitos/patologia , Adolescente , Adulto , Anticorpos Monoclonais Murinos , Antígenos CD20/análise , Antineoplásicos Alquilantes/uso terapêutico , Clorambucila/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , RituximabRESUMO
PURPOSE: Postexcision preirradiation mammography (PPM) is frequently performed in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy (BCT) to evaluate for residual suspicious calcifications; but no clear evidence supports this practice. The current study was undertaken to investigate the value of PPM in the management of patients with DCIS. METHODS AND MATERIALS: We conducted a retrospective review of patients treated for DCIS with BCT at the University of Pennsylvania. The impact of PPM on surgical management and on local recurrence was evaluated. Factors associated with the use of PPM, the results of PPM, and the likelihood of finding residual malignancy at the time of re-excision in patients with PPM were also examined. RESULTS: One hundred forty-four of 281 patients (51%) underwent PPM. Of the 144 patients who received PPM, 34 (24%; 95% confidence interval, 17%-31%) had residual suspicious calcifications (a "positive PPM"). Of the 34 patients with a positive PPM, all underwent a re-excision and 19 (56%; 95% confidence interval, 35%-70%) were found to have residual malignancy. Ten of 34 patients with a positive PPM had negative margins, of which 6 had a residual malignancy. Assuming all patients with close, positive, or indeterminate surgical margins would have undergone re-excision regardless of the findings of PPM, PPM resulted in a change in surgical management in 7% (10/144) of patients and removal of residual DCIS in 4% (6/144). With a median follow-up of 9.5 years, the use of PPM was not associated with an improvement in 10-year local recurrence-free survival (94.8% vs 91.5%, P = .368). CONCLUSIONS: In this study, PPM affected surgical management in only a small percentage of patients and had no impact on local recurrence. The routine use of PPM in women undergoing BCT for DCIS may not be warranted.
RESUMO
PURPOSE: In women with unfavorable thoracic anatomy undergoing left breast radiation therapy (RT) after breast-conserving surgery, a significant volume of the heart may receive high-dose radiation, which has been shown previously to be associated with increased late cardiac morbidity and mortality. Use of intensity modulated radiation therapy (IMRT) has been proposed to reduce cardiac dose in these patients. We compared cardiac exposure from IMRT delivered from 2 opposed fields and 3-dimensional conformal radiation therapy (3DCRT) plans employing simple heart blocks. METHODS AND MATERIALS: Fourteen patients with left-sided breast cancer treated with breast-conserving surgery and RT were identified to have unfavorable cardiac anatomy, defined as maximum heart depth (MHD) ≥1.0 cm within the unblocked opposed tangential fields. 3DCRT plans utilized dynamic wedges, segments, and custom heart blocks designed by the treating physician. Tangent IMRT plans were optimized to reduce cardiac dose while maintaining planning target volume (PTV) coverage equal to that achieved with the 3DCRT plan. We generated tangential field plans with complete heart block (CHB) or no heart block (NHB) for comparison. Plans were normalized to deliver 46 Gy to the PTV. Dose to the heart, PTV, and lumpectomy cavity were compared. RESULTS: Mean MHD was 1.44 cm (1.0-1.86 cm). There was no significant difference in PTV receiving >95% of the prescription dose between 3DCRT and IMRT, as intended. Mean V30 to the heart was 0% for CHB plans, 1.7% for 3DCRT plans, 1.8% for IMRT plans, and 3.3% for NHB plans, respectively. There was no significant difference in heart V30 for 3DCRT and IMRT plans (P = .8). IMRT plans delivered 256 total monitor units compared with 201 in 3DCRT plans (P < .01). CONCLUSIONS: Inverse-planned tangent IMRT does not reduce high-dose radiation to the heart compared with 3DCRT, incorporating a simple heart block in women with left-sided cancer and unfavorable cardiac anatomy when PTV coverage was equalized for both plans. In select patients with early-stage breast cancer and unfavorable thoracic anatomy, 3DCRT with heart block may be sufficient to adequately protect the heart from high-dose radiation.
RESUMO
PURPOSE: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. METHODS AND MATERIALS: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34(+) selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. RESULTS: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. CONCLUSIONS: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.