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BACKGROUND/PURPOSE: To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal cancer (NPC). METHODS: A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival. RESULTS: Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p = 0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p = 0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p = 0.017). CONCLUSION: The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.
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Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/terapia , Estudos Retrospectivos , Carcinoma Nasofaríngeo/terapia , Prognóstico , InflamaçãoRESUMO
BACKGROUND: The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self-expandable metal stents (SEMS) for the treatment of locally advanced esophageal cancer. MATERIALS AND METHODS: Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty-eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed. RESULTS: The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio [HR], 72.30; 95% confidence interval [CI], 8.62-606.12; p < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15-15.21; p < .001). CONCLUSION: CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life-threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations. IMPLICATIONS FOR PRACTICE: Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent.
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Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Stents/normas , Idoso , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: With the increasing popularity of CT screening, more cases of early-stage lung cancer are being diagnosed. However, 24.5% of stage I non-small-cell lung cancer (NSCLC) patients still experience treatment failure post-surgery. Biomarkers to predict lung cancer patients at high risk of recurrence are needed. MATERIALS AND METHODS: We collected protein mass spectrometry data from the Taiwan Lung Cancer Moonshot Project and performed bioinformatics analysis on proteins with differential expressions between tumor and adjacent normal tissues in 74 stage I lung adenocarcinoma (LUAD) cases, aiming to explore the tumor microenvironment related prognostic biomarkers. Findings were further validated in 6 external cohorts. RESULTS: The analysis of differentially expressed proteins revealed that the most enriched categories of diseases and biological functions were cellular movement, immune cell trafficking, and cancer. Utilizing proteomic profiling of the tumor microenvironment, we identified five prognostic biomarkers (ADAM10, MIF, TEK, THBS2, MAOA). We then developed a risk score model, which independently predicted recurrence-free survival and overall survival in stage I LUAD. Patients with high risk scores experienced worse recurrence-free survival (adjusted hazard ratio = 8.28, p < 0.001) and overall survival (adjusted hazard ratio = 6.88, p = 0.013). Findings had been also validated in the external cohorts. CONCLUSION: The risk score model derived from proteomic profiling of tumor microenvironment can be used to predict recurrence risk and prognosis of stage I LUAD.
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Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Neoplasias Pulmonares , Estadiamento de Neoplasias , Proteômica , Microambiente Tumoral , Humanos , Prognóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Feminino , Biomarcadores Tumorais/metabolismo , Masculino , Proteômica/métodos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/diagnóstico , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Taiwan/epidemiologia , Biologia Computacional/métodosRESUMO
Purpose: The present longitudinal study aimed to evaluate the potential impact of modern radiotherapy (RT) techniques on quality of life (QOL) in patients with head and neck (HNC) cancer. Materials and methods: In this single-center prospective study, participants were asked to complete QOL questionnaires that included the EORTC QLQ-C30, QLQ-H&N 35 and utility score by time trade-off (TTO) at three time points (2 weeks, 3 months and 6 months) after completion of RT. All patients were treated by modern RT techniques [volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT)]. Patients who developed recurrence or died before the 6-month follow-up were excluded. Linear mixed models with random intercepts for participants and restricted maximum likelihood estimates were used to assess the effect of our study variables (age, sex, primary site, cancer stage, treatment, radiation dose and radiation method). Overall changes in QOL, utility scores and symptom burdens at different time points were tested using paired t tests. Results: A total of 45 patients were recruited from 2022 to 2023. Those who completed the surveys at 2 weeks with at least 1 follow-up (30 patients, 67%) were enrolled in the final analysis. The majority of these 30 patients were men (76.7%), had oral cancer (40%), had stage III or IV disease (60%), received surgical intervention (63%) and were treated with chemoradiation (80%). A curative total dose of 66 to 70 Gy was delivered to 23 (76.7%) patients, half of whom received HT. Patients who received chemotherapy had significantly lower global QoL scales (mean difference, 27.94; 95% CI, 9.33-46.55; p=0.005). Global QOL, physical function, symptoms of sticky saliva, cough, feelings of illness and weight loss improved significantly between 2 weeks and 3 months. There was no significant difference between 3 and 6 months. Interestingly, improvements in social function, social contact, pain and nutrition reached significance at 6 months. Subgroup analysis revealed greater pain relief over time for patients who underwent HT (p=0.030). Moreover, patients who participated in swallowing rehabilitation programs had a greater decrease in nausea and vomiting (p=0.036). Conclusion: HNC patients treated with modern RT techniques experience improved QOL and physical function over time. The most significant improvement occurs between 2 weeks and 3 months, after which the improvement plateaus. However, social function, social contact, pain and nutrition may require longer recovery intervals after treatment. HT with daily image guidance could provide a therapeutic opportunity for improving pain relief in patients with HNC.
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BACKGROUND: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. Traditionally, the RT chest wall (CW) volume encompasses the entire implant. For patients with retropectoral implants, the deep lymphatic plexus dorsal part of the implant is no longer considered high risk and can be omitted. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different CW delineation according to ESTRO ACROP guideline for patients who have undergone implant-based reconstruction. METHODS: We conducted a retrospective review of breast cancer patients who underwent a mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. RESULTS: The study included 26 patients, with 15 in the prepectoral group and 11 in the whole expander group. No significant differences were observed in normal organ exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p = 0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. CONCLUSIONS: For patients undergoing two-stage expander/implant retropectoral breast reconstruction and PMRT, our data provided comparable outcomes and normal organ exposure for those omitting the deep lymphatic plexus.
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BACKGROUND: Protecting cardiac function in patients with advanced left-breast cancer receiving radiation therapy (RT) with regional nodal irradiation (RNI) is an important issue. Modern RT techniques can limit cardiac exposure. The aim of this study was to explore the association be-tween cardiac dose and cardiac function. METHODS: Between 2017 and 2020, we retrospectively reviewed left-breast cancer patients who received adjuvant RT, including RNI with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT). Left ventricular ejection fraction (LVEF) was assessed by echocardiography before RT and 1 year after RT to detect any early deterioration in cardiac systolic function. RESULTS: A total of 30 eligible patients were enrolled. The median follow-up time from the initiation of RT was 3.9 years (range 0.6-5 years). Seventeen patients received VMAT, and the other 13 patients received HT. The median RT dose was 55 Gray (Gy), and the mean heart dose was 3.73 Gy (range 1.95-9.36 Gy). The median LVEF before and after RT was 68% and 68.5%, respectively. No obvious deterioration was found. There was no association between cardiac dose (mean heart dose, V5-V30) and LVEF (change in values or post-RT). CONCLUSIONS: For left-breast cancer patients undergoing RT with RNI, VMAT, or HT can be used to limit cardiac exposure. Cardiac function as evaluated by LVEF revealed no obvious deterioration after RT in our patients, and no association was found between cardiac dose and LVEF in those treated with either VMAT or HT in early cardiac surveillance.
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BACKGROUND: For advanced breast cancer with lymph node involvement, adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) has been indicated to reduce cancer recurrence and mortality. However, an extensive RT volume is associated with normal organ exposure, which increases the toxicity and affects patient outcomes. Modern arc RT techniques can improve normal organ sparing compared with conventional techniques. The aim of this study was to explore the optimal technique for left-breast RT with RNI. METHODS: We retrospectively reviewed patients receiving RT with RNI for left-breast cancer. We used modern arc RT techniques with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT) with a novel block technique, and compared differences in dosimetry parameters between the two groups. Subgroup analysis of RNI with or without internal mammary node (IMN) volume was also performed. RESULTS: A total of 108 eligible patients were enrolled between 2017 and 2020, of whom 70 received VMAT and 38 received HT. The median RT dose was 55 Gy. No significant differences were found regarding the surgery, RT dose, number of fractions, target volume, and RNI volume between the VMAT and HT groups. VMAT reduced the heart mean dose more than HT (3.82 vs. 5.13 Gy, p < 0.001), as well as the cardiac parameters of V5-V20, whole-lung mean dose, lung parameters of V5-V20, and contralateral-breast and esophagus mean dose. In the subgroup analysis of RNI with IMNs, the advantage of VMAT persisted in protecting the heart, lung, contralateral breast, and esophagus. HT was beneficial for lowering the thyroid mean dose. For RNI without IMN, VMAT improved the low-dose exposure of the heart and lung, but HT was similar to VMAT in terms of heart, whole-lung, and contralateral-breast mean dose. CONCLUSIONS: For patients with left-breast cancer receiving adjuvant RT with RNI, VMAT reduced the exposure dose to the heart, lung, contralateral breast, and esophagus compared with HT. VMAT was superior to HT in terms of normal organ sparing in the patients who underwent RNI with IMN irradiation. Considering the reduction in normal organ exposure and potential toxicity, VMAT is the optimal technique for patients receiving RNI when deep inspiration breath-hold is not available.
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BACKGROUND: Helical irradiation of the total skin (HITS) was modified as simultaneous integrated boost (SIB)-helical arc radiotherapy of total skin (HEARTS) technique and applied to an acute myeloid leukemia (AML) patient with disseminated leukemia cutis. METHODS: The original HITS plan was revised for different regimens, i.e. HEARTS, low-dose HEARTS and SIB-HEARTS. The uniformity index (UI), conformity index (CI), and dose of organs at risk (OARs) were used to evaluate the plans. Additionally, the SIB-HEART (21/15 Gy) was delivered to the total skin and chloromas. RESULTS: No significant differences were observed for the CI and UI between HITS and HEARTS regimens. Compared with HITS, the reduced mean doses to various bone marrows ranged from 17 to 88%. The mean OARs doses for the head, chest and abdomen of a patient with AML treated with SIB-HEARTS (21/15 Gy) were 2.1 to 21.9 Gy, 1.8 to 7.8 Gy and 1.7 to 3.3 Gy, respectively. No severe adverse effects were noted except for grade 4 leukocytopenia and thrombocytopenia. CONCLUSION: HEARTS and different regimens reduced the dose to OARs and bone marrow while maintaining the uniformity and conformity. SIB-HEARTS deliveries different doses to the total skin and enlarged tumors simultaneously. TRIAL REGISTRATION: Retrospectively registered and approved by the Institutional Review Board of our hospital ( FEMH-106151-C ).
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Leucemia/radioterapia , Linfoma/radioterapia , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Cutâneas/radioterapia , Adulto , Seguimentos , Humanos , Leucemia/patologia , Linfoma/patologia , Masculino , Prognóstico , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Neoplasias Cutâneas/patologiaRESUMO
This study estimates the prevalence of depressed mood in caregivers of individuals with mild cognitive impairment (MCI) and assesses whether demographics, stressors, intrapsychic strain, and gain are associated with depressed mood. A secondary analysis of baseline data from the Alzheimer's Disease Cooperative Study MCI trial was conducted using a cross-sectional, correlational design. Descriptive statistics to estimate the prevalence of caregiver depressed mood and univariate and block-wise logistic regression analyses were used. The prevalence of depressed mood in 769 caregivers was 24.6% (95% confidence interval, 21.5-27.7). The odds of being depressed were significantly higher in younger, nonspousal caregivers with less education, who cared for MCI patients with lower activities of daily living functioning, and who perceived greater relational deprivation, higher levels of self-loss, and personal gain. Controlling for relevant variables, relational deprivation and caregiver education continued to be significantly associated with depressed mood. Relational deprivation may be important for future interventions.
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Doença de Alzheimer , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Transtornos Cognitivos , Depressão/epidemiologia , Depressão/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Depressão/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Índice de Gravidade de DoençaRESUMO
The specific aims of this study were to (a) identify relationships among care-giving stress, caregivers' functional ability, and number of self-care behavior responses to physical and psychological symptoms in caregivers of persons with dementia and (b) examine the mediating function of functional ability in the relationship between caregiving stress and self-care behavior response to symptoms. A correlational, cross-sectional design was used, and a survey was mailed to 99 caregivers. The survey questionnaire contained items about demographics, caregiving stress, functional ability, and self-care behavior. The results indicate that caregivers who reported higher levels of caregiving stress had poorer self-rated health, poorer physical function, more symptoms, high levels of depressed mood, and more self-care behaviors. Caregiving stress was indirectly related to self-care behavior response to symptoms through functional ability, which suggests a need for developing early interventions to enhance the functional ability and self-care behaviors in response to some caregivers' symptoms.
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Cuidadores/psicologia , Autocuidado , Estresse Psicológico , Doença de Alzheimer/enfermagem , Estudos Transversais , HumanosRESUMO
RATIONALE: Leptomeningeal metastasis from cervical adenosquamous carcinoma is extremely rare especially after radiotherapy for vertebral metastasis. PATIENT CONCERNS: A 52-year-old woman with International Federation of Gynecology and Obstetrics (FIGO) stage IIB adenosquamous carcinoma of cervix presented with bilateral lower limbs weakening after 2 courses radiotherapy to thoracic vertebral metastases. DIAGNOSES: Initial spine magnetic resonance imaging (MRI) showed no obvious nerve compression, and radiation myelopathy was suspected by the clinician. Progressive multifocal neurological signs developed one month after completion of spine re-irradiation. She was diagnosed with leptomeningeal metastasis by MRI and cerebrospinal fluid (CSF) study. INTERVENTIONS: She received whole brain irradiation with a dose of 30 Gy in 10 fractions. Systemic chemotherapy with cisplatin (50âmg/m) and topotecan (0.75âmg/m) was administered sequentially. OUTCOMES: She died with progressive disease two months after the diagnosis of leptomeningeal metastases. LESSONS: Poorly differentiated advanced-stage cervical adenosquamous carcinoma is an aggressive neoplasm with a worse outcome. Leptomeningeal metastasis should be included in the differential diagnosis for patients with multifocal craniospinal neurological signs. A combination of detailed neurological examinations, MRI and CSF study allowed us to establish a correct diagnosis of leptomeningeal metastasis and initiate treatment in a timely manner.
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Carcinoma Adenoescamoso/secundário , Neoplasias Meníngeas/secundário , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Neoplasias do Colo do Útero/patologia , Carcinoma Adenoescamoso/diagnóstico por imagem , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/radioterapia , Evolução Fatal , Feminino , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/terapia , Pessoa de Meia-Idade , Reirradiação , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapiaRESUMO
Sorafenib followed by fractionated radiotherapy (RT) has been shown to decrease the phagocytic and candidacidal activities of antifungal agents due to radiosensitization. Moreover, sorafenib has been shown to suppress the immune system, thereby increasing the risk for candida colonization and infection. In this study, we present the 2 hepatocellular carcinoma (HCC) patients suffered from epigastric distress caused by esophageal candidiasis who received sorafenib plus RT. Two patients who had received sorafenib and RT for HCC with bone metastasis presented with hiccups, gastric ulcer, epigastric distress, anorexia, heart burn, and fatigue. Empiric antiemetic agents, antacids, and pain killers were ineffective at relieving symptoms. Panendoscopy revealed diffuse white lesions in the esophagus. Candida esophagitis was suspected. Results of periodic acid-Schiff staining were diagnostic of candidiasis. Oral fluconazole (150âmg) twice daily and proton-pump inhibitors were prescribed. At 2-weak follow-up, esophagitis had resolved and both patients were free of gastrointestinal symptoms. Physicians should be aware that sorafenib combined with RT may induce an immunosuppressive state in patients with HCC, thereby increasing their risk of developing esophagitis due to candida species.
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Antineoplásicos/efeitos adversos , Candidíase/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Esofagite/microbiologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Candidíase/induzido quimicamente , Carcinoma Hepatocelular/radioterapia , Fracionamento da Dose de Radiação , Esofagite/tratamento farmacológico , Fluconazol/uso terapêutico , Azia/microbiologia , Soluço/microbiologia , Humanos , Neoplasias Hepáticas/radioterapia , Masculino , Niacinamida/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Sorafenibe , Úlcera Gástrica/microbiologiaRESUMO
Treatment for bilateral breast cancer with chest wall and abdominal skin invasion normally involves conventional radiotherapy (RT); however, conventional RT provides inadequate target volume coverage and excessive treatment of large volumes of normal tissue. Helical tomotherapy (HT) has the ability to deliver continuous craniocaudal irradiation that suppresses junction problems and provides good conformity of dose distribution. A 47-year-old female with stage IV bilateral breast cancer with chest wall and pectoralis major muscle invasion, lymphadenopathy, bilateral pleural effusion, and multiple bone metastases received chemotherapy and target therapy beginning in January 2014; 4 months after the initiation of chemotherapy, computed tomography revealed progression of chest and abdominal wall invasion. A total dose of 70.2 Gy was delivered to both breasts, the chest wall, the abdominal wall, and the bilateral supraclavicular nodal areas in 39 fractions via HT. The total planning target volume was 4,533.29 cm(3). The percent of lung volume receiving at least 20 Gy (V20) was 28%, 22%, and 25% for the right lung, left lung, and whole lung, respectively. The mean dose to the heart was 8.6 Gy. Follow-up computed tomography revealed complete response after the RT course. Grade 1 dysphagia, weight loss, grade 2 neutropenia, and grade 3 dermatitis were noted during the RT course. Pain score decreased from 6 to 1. No cardiac, pulmonary, liver, or intestinal toxicity developed during treatment or follow-up. Concurrent HT with or without systemic treatment could be a safe salvage therapy for chemorefractory locally advanced breast cancer patients with extensive cutaneous metastasis.
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The primary purpose of this study was to compare knowledge of use of and need for community services between older (60 years of age and older) African-American men and women. A secondary purpose was to determine whether predisposing, enabling, and health-status factors could predict knowledge of need for, and use of specific community services among African-American women and men, 60 years of age and older Data were gleaned from a community-based random telephone survey of African-Americans (77 female and 23 male), 60 years of age and older, living in northeastern Ohio. Data generated from this study were analyzed using chi-square, and independent samples t-test, and multiple regression. Findings from this study suggested that women had higher levels of knowledge of use of and need for community-specific services than their male counterparts. Another finding from this study suggested that none of the identified predisposing, enabling, and health-status factors found in this study could plausibly explain knowledge of need for, or use of community-specific services.
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Negro ou Afro-Americano , Conhecimentos, Atitudes e Prática em Saúde , Necessidades e Demandas de Serviços de Saúde , Serviços de Saúde para Idosos/estatística & dados numéricos , Negro ou Afro-Americano/educação , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Ohio , Análise de Regressão , Fatores Sexuais , Fatores SocioeconômicosRESUMO
The purpose of this paper is to describe commonalities of the lived experience of being a spouse caregiver of a person with mild cognitive impairment (MCI). The Colaizzi method of empirical phenomenology was used for inter-viewing and analyzing data obtained from 10 spouse caregivers of persons with MCI. Four major themes were found and labeled: (a) Putting the Puzzle Pieces Together-There Really is Something Wrong; (b) A Downward Spiral into a World of Silence; (c) Consequences to Caregivers of Living in a World of Silence; (d) Taking Charge of Care. The findings of this study provided rich data to guide interventions to help caregivers to improve their awareness of MCI, gain new information and skills to deal more effectively with and adjust to the caregiving of their spouse with MCI over the long-term.