Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Salvage Post-Operative Stereotatic Ablative Radiotherapy for Re-Current Squamous Cell Carcinoma of Head and Neck.

Background and Objectives: Patients with recurrent squamous cell carcinoma of the head and neck (rHNC) face an aggressive disease. Surgical resection is the gold standard treatment. Immediate adjuvant post-operative stereotactic ablative radiotherapy (PO-SABR) for rHNC is debatable. Materials and Methods: We retrospectively identified patients who were treated with PO-SABR at the AC Camargo Cancer Center, Brazil. Results: Eleven patients were treated between 2018 and 2021. The median time between salvage surgery and PO-SABR was 31 days (range, 25-42) and the median PO-SABR total dose was 40 Gy (range, 30-48 Gy). The 2-and 4-year actuarial DFS were 62.3% and 41.6%, while the 2-and 4-year OS probabilities were 80.0% and 53.3%, respectively. Eight (72.7%) patients were alive and six (54.5%) were without disease at the last follow-up. Two (18.1%) patients had local failure in the PO-SABR field. Three (27.3%) patients had distant metastasis, diagnosed in a median time of 9 months (range, 4-13) after completion of PO-SABR. On univariate analysis, predictive factors related to worse OS were: interval between previous radiotherapy and PO-SABR ≤ 24 months (p = 0.033) and location of the salvage target in the oral cavity (p = 0.013). The total dose of PO-SABR given in more than three fractions was marginally statistically significant, favoring the OS (p = 0.051). Conclusions: Our results encourage the use of a more aggressive approach in selected patients with rHNC by combining salvage surgery with immediate PO-SABRT, but this association needs to be further explored.

Cognitive changes in patients with epilepsy identified through the MoCA test during neurology outpatient consultation.

INTRODUCTION: Epilepsy is a chronic neurological disorder that may occur alongside cognitive changes, with effects on multiple cognitive domains. OBJECTIVE: To compare the cognitive performance of patients with epilepsy and healthy controls through Montreal Cognitive Assessment (MoCA) during outpatient consultation at a reference diagnostic center in Colombia and analyze and the influencing factors. MATERIALS AND METHODOLOGY: One-hundred and four patients during neurology outpatient consultation in the city of Cartagena, Colombia, were assessed with the (MoCA) test, i.e., 54 people who consulted for headache and have not been diagnosed with epilepsy (NEP) and 50 with a diagnosis of epilepsy (EPs) according to the diagnostic criteria of the International League Against Epilepsy (ILAE). RESULTS: Significant differences were found in the total mean scores of the (MoCA) between (EPs) and (NPE) groups (t = 4.72; p < 0.01), particularly in attention (t = 3.22; p < 0.02) and memory (t = 5.04; p < 0.01) dimensions. Additionally, a significant association was observed between years of schooling and (MoCA) scores (p = 0,019) but not between socioeconomic level (p = 0,510), age (p = 0,452) and the frequency of seizures (p = 0,471). DISCUSSION: Patients with epilepsy show lower scores in several cognitive domains in respect of the control group. The (MoCA) has proven its appropriateness for cognitive screening in the contexts of clinical neurology outpatient consultation.

Intraoperative breast radiotherapy: survival, local control and risk factors for recurrence.

BACKGROUND: Whole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients. AIM: To report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment. MATERIALS AND METHODS: 147 patients treated with a median follow up of 6.9 years (0.1â¿¿11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p â¿¤ 0.05 was considered statistically significant. RESULTS: Overall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016). CONCLUSIONS: IORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.

Trail making test - black & white (TMT B&W): Normative study for the Chilean population.

The trailmaking test (TMT) has an educational bias that makes it inapplicable to people with low levels of education due to its dependence on the alphabet. The TMT standardization is the only one available in Chile, and there is a need for alternative ways of using the TMT that do not depend on the level of education for its applicability. To determine the normative scores of the TMT - black & white (TMT B&W), considering sociodemographic factors in adult and elderly Chilean population. A total sample of 227 participants (133 healthy, 94 cognitively impaired) from the Ageing Mets cohort were recruited from three areas in Chile (Antofagasta, Santiago, and Puerto Montt). The TMT B&W was administered to all participants. A multiple regression model was used to generate normative data only in the cognitively healthy group, considering the effect of age, education and sex. A significant effect of age was found in the score of the TMT B&W Parts A and B. The level of education influenced the part B of the test; however, the completion rate of the TMT B&W parts A and B was over 90% in cognitively healthy people. Norms for the number of errors were obtained, and differences between groups were found after controlling for the effect of age and education. This study is the first to provide normative data for the Chilean version of the TMT B&W and will benefit clinical neuropsychologists by improving the procedures for more accurately assessing executive functions and its impairments.

Using a nonparametric item response theory model to identify patterns of cognitive decline: The Mokken scale analysis.

Cognitive decline, particularly in dementia, presents complex challenges in early detection and diagnosis. While Item Response Theory (IRT) has been instrumental in identifying patterns of cognitive impairment through psychometric tests, its parametric models often require large sample sizes and strict assumptions. This creates a need for more adaptable, less demanding analytical methods. This study aimed to evaluate the effectiveness of Mokken scale analysis (MSA), a nonparametric IRT model, in identifying hierarchical patterns of cognitive impairment from psychometric tests. Using data from 1164 adults over 60 years old, we applied MSA to the orientation subscale of ACE-III. Our analysis involved calculating scalability, monotone homogeneity, invariant item ordering (IIO) and response functions. The MSA effectively retrieved the hierarchical order of cognitive impairment patterns. Most items showed strong scalability and consistent patterns of cognitive performance. However, challenges with IIO were observed, particularly with items having adjacent difficulty parameters. The findings highlight MSA's potential as a practical alternative to parametric IRT models in cognitive impairment research. Its ability to provide valuable insights into patterns of cognitive deterioration, coupled with less stringent requirements, makes it a useful tool for clinicians and researchers.

Involved-Field Radiation Therapy for Patients With Unresectable Pancreatic Adenocarcinomas: Failure Pattern Analysis.

Introduction Unresectable pancreatic tumors are frequently diagnosed. Initial treatment is carried out with chemotherapy. Eventually, in selected cases, radiotherapy may be used to improve local control rates and relieve the symptoms. The volume of radiotherapy treatment fields is the subject of controversy in the literature. The use of involved fields with the gross tumor volume encompassing the primary tumor and lymph nodes considered clinically positive is associated with a lower rate of side effects, but can lead to a higher rate of regional loco failures, especially in regional lymph nodes. The purpose of this article is to analyze the failure pattern of chemotherapy and involved-field radiation therapy (IFRT) for treating patients with unresectable pancreatic adenocarcinomas. Methods Clinical records of thirty consecutive patients treated from March 2016 to June 2020 for unresectable pancreatic adenocarcinoma were analyzed. The patients were treated with initial systemic chemotherapy (median: 6 cycles) with regimens based on gemcitabine or oxaliplatin-irinotecan (folfirinox/folfox) followed by radiotherapy (total dose of 50-54 Gy/with fractionation of 2 Gy/day). The patients were treated with IFRT. Local failure (LF) was defined as an increase in radiographic abnormality within the planning target volume (PTV). Elective nodal failure (ENF) was defined as recurrence in any lymph node region outside the PTV. Any other failure was defined as distant failure (DF). Results The median age of the patients was 68 years (range: 44-80 years); 20 patients (66.7%) were men, and 11 (36.6%) and 19 (63.4%) patients presented with tumors of stage II and III, respectively. Most patients (63.3%) had tumors in the pancreatic head. The median survival was 17.2 months. Tumor recurrences were classified as LF, DF, LF and DF in 7 (23.3%), 17 (56.7%), and 5 (16.7%) patients, respectively. Only one patient (3.3%) had both LF and ENF. No severe side effects related to radiotherapy were reported. Conclusion The use of IFRT did not cause a significant amount of ENF, besides presenting low morbidity, which is of special importance for patients with locally advanced tumors or low performance status. The predominant failure pattern was distant metastases.

GAD-7 Generalised Anxiety Disorder scale in Colombian medical professionals during the COVID-19 pandemic: Construct validity and reliability.

INTRODUCTION: The detection of anxiety symptoms among health workers who care for patients infected with COVID-19 is a current priority. Fast and valid instruments are required for this population group. The objective is to establish the construct validity and reliability of the Generalised Anxiety Disorder (GAD-7) scale in Colombian doctors during the COVID-19 lockdown. METHODS: E-health study, in which cross-sectional data were collected online (n = 1030) from 610 COVID doctors and 420 non-COVID doctors, during the Colombian lockdown, between 20 April and 10 August 2020. Each subject was contacted, and they confirmed their participation, identity and professional role. RESULTS: A single factor factorial structure was found, made up of the 7 items of the instrument, which managed to explain 70% of the variance. The goodness of fit indices (RMSEA = 0.080; CFI = 0.995; SRMR = 0.053; p < 0.001) showed an "acceptable" unidimensionality and adequate factor loadings in each item of the GAD-7, >0.070. Finally, the internal consistency of the instrument was good, with a Cronbach's alpha of 0.920 (95%IC, 8.80-9.71). CONCLUSIONS: The GAD-7 is an instrument that presents adequate indicators of validity and reliability. It is an excellent tool that is reliable and easy and fast to use for the detection of generalised anxiety symptoms in medical personnel caring (or not) for patients infected with COVID-19.

Factors associated with cognitive impairment in Latin American older adults: A cross-sectional observational study of COVID-19 confinement.

INTRODUCTION: The effects of COVID-19 confinement have been severe, especially in older adults. Therefore, we analyzed the factors associated with cognitive impairment (CI) in Latin America (LA). METHODS: We conducted a cross-sectional observational study with a total of 5245 older adults from 10 countries in LA. Measurement: We used the Telephone Montreal Cognitive Assessment (T-MoCA) and the Eight-item Informant Interview to Differentiate Aging and Dementia (AD8) scale. RESULTS: We found that age, depressive symptomatology, bone fractures, being widowed, having a family member with dementia, and unemployment were associated with an increased risk of CI. In contrast, higher education, hypertension with continuous treatment, quarantine, and keeping stimulating cognitive and physical activities were associated with a lower probability of CI. No significant association was found between suffering from diabetes or being retired and CI. DISCUSSION: It is essential to conduct follow-up studies on these factors, considering their relationship with CI and the duration of confinement.

Education bias in typical brief cognitive tests used for the detection of dementia in elderly population with low educational level: a critical review.

Dementia is a significant decline in cognition that interfere with independent, daily functioning. Dementia is a syndrome caused by a myriad and include primary neurologic, neuropsychiatric, and medical conditions. It has been projected that the prevalence of dementia will triple in the elderly population by the year 2050. Despite the benefits of early diagnosis, there is an effective under-detection of around 62% of people with mild cognitive impairment (MCI) or dementia. One of the factors associated with this problem is that diagnostic techniques are affected by the educational level of those evaluated. This is an important aspect to consider in the use of brief cognitive tests for the detection of dementia. This review presents and critically analyzes the available evidence regarding the effect of educational level on the diagnostic utility of three of the most widely used tools in the clinical setting: the Mini-mental Test Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Addenbrooke's Cognitive Examination (ACE). Previous evidence shows that the tasks that require reading, writing, calculation, phonological fluency, and visuoconstruction are affected by educational level. These results lead to discourage the use of these tests in older people with less than 6 years of schooling. The development of brief cognitive tests appropriate for people with a low educational level is recommended. We posit that adequate cognitive tests should not consider tasks or items that resemble characteristics of academic contexts and should be more analogous to daily activities situations.

The cumulative effect of fibromyalgia symptoms on cognitive performance: The mediating role of pain.

Fibromyalgia (FMS) is a chronic condition that encompasses widespread pain associated with cognitive impairment and significant emotional distress related to functional disability. This study aimed to obtain evidence of the role of pain in the effect of time since FMS diagnosis and cognitive performance using a novel online protocol of neuropsychological evaluation since the COVID-19 pandemic has challenged traditional neuropsychology testing leading to the need for novel procedures transitioning to tele-neuropsychology. A sample of 70 adult women was evaluated (50 with FMS and 19 controls) using online questionnaires that evaluated pain and executive functioning (impulsivity, inhibition control, monitoring, and planning). Afterward, participants were evaluated by trained neuropsychologists in a 30 min online session using virtually adapted cognitive tests: the Hopkins Verbal Learning Test (memory), the Symbol-Digit Modalities Test (attention and speed processing), the F-A-S test (verbal fluency), and Digit Span tests (working memory). We found that the time of FMS diagnosis has an effect on cognitive functioning predominantly mediated by pain. Our results point out the role of pain as a mediator on cognitive performance, specifically in executive functions which are directly affected by the cumulative effect of the time of diagnosis. Furthermore, the importance of considering a broader perspective for assessment and treatment including novel procedures via tele-neuropsychology.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control.

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025-0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Postmastectomy Radiation Therapy Bolus Associated Complications in Patients Who Underwent 2-stage Breast Reconstruction.

Purpose: This study aimed to evaluate the association of bolus and 2-stage breast reconstruction complications, and whether the dosimetric advantage translates into improvements in local control. Methods and Materials: We retrospectively analyzed data from 2008 to 2019 of women who underwent a mastectomy and a planned 2-stage breast reconstruction, followed by adjuvant radiation therapy. We reviewed all data from medical records and radiation plans regarding patient characteristics, diagnoses, surgeries, complications, pathology, staging, systemic therapy, radiation therapy, and outcomes, and compared complication rates according to bolus usage. Results: A total of 288 women, age 25 to 71 years, were included in the study. Of these women, 6 were treated with daily bolus and 19 with alternate days bolus, totaling 25 of 288 patients (8.7%) in the bolus group. A total of 226 patients (78.5%) had the second stage performed. The median follow-up time was 61 months. The rates for 5-year overall survival and locoregional control were both 97%, and the metastasis-free rate was 83%. In the first stage, 6.25% of patients in the entire cohort had an infection and 4.2% had implant loss. Daily bolus significantly increased the risk of expander infection (hazard ratio [HR]: 10.3; 95% confidence interval [CI], 1.7-61.8) and loss (HR: 13.89; 95% CI, 2.24-85.98), but alternate-day bolus showed a nonsignificant increase for expander infection (HR: 1.14; 95% CI, 0.14-9.295) and loss (HR: 1.5; 95% CI, 0.19-12.87). Bolus was not associated with second-stage complications or local-regional failure. Local infection and implant loss were more frequent in the second than in the first stage (5.2% vs 10.2% and 4.2% vs 12.8%, respectively). Conclusions: Skin bolus significantly increased first-stage breast reconstruction complications (infection and reconstruction failure). Despite the small sample size and the need for future studies, these findings need to be taken into consideration when planning treatment and reconstruction, and recommendations should be individualized.

Clinical utility of Phototest via teleneuropsychology in Chilean rural older adults.

The COVID-19 pandemic has shown the need for neuropsychological care for older adults with memory complaints in different contexts, including rural areas or areas with difficult access. Objective: This study aimed to analyze the clinical utility of the Phototest, through telemedicine, to identify mild cognitive impairment in rural older adults with memory complaints, during the COVID-19 pandemic. Methods: We performed a cross-sectional, case-control, and clinical utility comparison of brief cognitive tests (BCTs). The sample included 111 rural elderly people with mild cognitive impairment (MCI) and 130 healthy controls from the Los Lagos region, Chile. The instruments adopted were modified Mini-Mental State Examination (MMSEm) and adapted version of the Phototest (PT) for Chile. Results: To identify mild cognitive impairment, using a cutoff score of 27-28 points, the Phototest showed a sensitivity of 96.6% and a specificity of 81.8%; indicators superior to those of the MMSEm. Conclusions: The Phototest is more accurate than the MMSEm in identifying cognitive alterations in rural older adults with cognitive memory complaints through telemedicine. Therefore, its use in primary care is recommended in order to perform early detection of preclinical cognitive alterations in mild cognitive impairment or neurodegenerative diseases.

A pandemia de COVID-19 mostrou a necessidade de cuidados neuropsicológicos para adultos idosos com queixas de memória em diferentes contextos, incluindo áreas rurais ou áreas de difícil acesso. Objetivo: Analisar a utilidade clínica do Phototest, por meio da telemedicina, para identificar uma leve deficiência cognitiva em adultos idosos rurais com queixas de memória, durante a pandemia de COVID-19. Métodos: Realizamos uma comparação transversal, caso-controle e utilidade clínica dos testes cognitivos breves. Amostra: Cento e onze idosos rurais com deficiência cognitiva leve (DCL) e 130 controles saudáveis da região de Los Lagos, Chile. Instrumentos: Minimental modificado (MMSEm) e versão do teste fotográfico (PT) adaptada para o Chile. Resultados: Para identificar a DCL, usando pontuação de corte de 27-28 pontos, o Phototest mostrou sensibilidade de 96,6% e especificidade de 81,8%; indicadores superiores aos do MMSEm. Conclusões: O Phototest é mais preciso que o MMSEm para identificar, por meio da telemedicina, alterações cognitivas em adultos idosos rurais com queixas de memória cognitiva. Sendo assim, seu uso na atenção primária é recomendado para realizar a detecção precoce de alterações cognitivas pré-clínicas em DCL ou doenças neurodegenerativas.

Impact of quarantine due to COVID-19 pandemic on health and lifestyle conditions in older adults from Centro American countries.

BACKGROUND: The impact of quarantine in older adults have been reported in several studies with contradictory results, reporting from negative effects to no significant outcomes or even beneficial consequences. Heterogeneity in aging plays a role in each region, the aim of this study is to analyze the impact of quarantine on health conditions (physical and mental) and lifestyle in older adults in five Centro American countries during COVID-19 pandemic. METHOD: In this cross-sectional study, n = 712 older adults 60 years and older from Mexico, Guatemala, El Salvador, Honduras and Costa Rica were assessed by telephone. Sociodemographic data, physical and mental health, lifestyle and quarantine conditions were asked previous informed consent. RESULTS: In general, mean of days in quarantine at the moment of the study was 142 days (approximately four months and three weeks). In the analysis of the impact of the days in quarantine effects were found on the frequency of falls, functional ability in Activities of Daily Living (ADL), general cognitive function, memory, orientation, language, frequency of drinking alcohol, having a balanced diet, and being active cognitively. Some differences were found between countries. CONCLUSIONS: Effects of quarantine on older adults in Centro America, requires attention of governments and healthcare to prevent long term morbidity and disability, and to promote healthy aging.

[Prevalence and factors associated with subjective cognitive complaints in Latin American health workers during the COVID-19 pandemic]. / Prevalencia y factores asociados con las quejas cognitivas subjetivas del personal sanitario latinoamericano durante la pandemia de COVID-19.

Background and objectives: An increase in emotional disturbances and complaints about cognitive performance has been observed in Latin American healthcare workers during the SARS-CoV-2 pandemic, which can affect attention capacity and increase the levels of stress and burnout of these professionals. The objective was to analyse subjective cognitive complaints (SCC) and associated factors in health personnel during the COVID-19 pandemic in five Latin American countries.Methods: Multicentre cross-sectional study, which included 3,738 professionals from Colombia, Chile, Argentina, Ecuador, Bolivia, and Peru. The Generalized Anxiety Disorder Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9) was used to assess depression, and the Mini-Z to assess Burnout. For the SCC, an item on cognitive concerns in attention and memory was used.Results: The prevalence of cognitive complaints was 69.2%. The factors associated with a higher risk of SCC were the scores in the GAD-7, PHQ and Mini-Z, in addition to being part of the Ecuadorian health personnel.Conclusions: There is a high prevalence of SCC in health personnel, which is modulated by emotional states and stress.

Executive functions and functional impairment in Latin seniors suffering from depression.

Functional impairment (FI) relates to the condition of executive functions (EFs). While EFs become affected by age and educational level (EL). Seniors suffering from depression (SSDs) on the other hand show EF-related deficiencies; however, there is hardly any literature available regarding their relationship with FI in Latin SSDs, who usually have low ELs. OBJECTIVE: To verify the relationship between EFs and FI in SSDs of Latin origins, by controlling the effects associated with age and educational level. METHODOLOGY: Cross-sectional study, of cases and controls, conducted on a nonprobability sample, made up of 102 self-sufficient SSDs and 142 control subjects over age 50, monolinguals of Latin origin (Chileans), all assessed by means of a battery of assessments such as: Geriatric Depression Scale, Addenbrook's Cognitive Assessment III, Trail making Tests A and B, STROOP word-color test, and semantic and phonological verbal fluency tests. A domain of composite EFs was established with standardized Chilean population scores, where age and educational levels were controlled. A simple linear regression analysis was conducted to determine the relationship between EFs and FI in SSDs. RESULTS: Upon controlling age and educational levels, EFs explained an FI variance of 3.9% in SSDs; depression explained an EF variance of 3.2%, and 3.7% of FI. CONCLUSION: The results of the present study highlight the importance of a timely intervention when it comes to geriatric depression, considering the negative effect it has over the executive functions and the functionality of seniors.

Clinical Prognostic Factors for Patients With Esophageal Cancer Treated With Definitive Chemoradiotherapy.

Background Treatment with definitive chemoradiotherapy (CRT) is the best option for patients with locally advanced esophageal tumors considered unresectable or for patients without clinical conditions to undergo surgical treatment. Technological advances in radiotherapy in the last decades have made treatment more accurate with less toxicity, and the association with more effective systemic treatment has been gradually improving survival rates. Aim Evaluate clinical prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with esophageal cancer treated with definitive radiotherapy (RT) and chemotherapy (ChT). Material and methods The clinical records of 60 patients treated from April 2011 until December 2019 with esophageal cancer considered unresectable and/or without clinical conditions for surgery, treated with definitive CRT, were analyzed. All patients had upper digestive endoscopy (UDE) with positive biopsy, neck, chest, and abdominal CT scan, and 18F-fluorodeoxyglucose positron-emission tomography (PET-CT). Patients were followed with physical examination and CTs every three months in the first and second years and every six months from the third year of follow-up. UDE was made every three to six months after the end of the treatment or in suspicion of tumor recurrence. PET-CT was also performed in the follow-up when clinically necessary. Local and regional failure (LRF) was defined as abnormalities in the image tests within the planning target volume (PTV) and/or positive biopsy on UDE. Any other failure was defined as a distant failure (DF). PFS was defined in the record of the first tumor recurrence site and OS in the death record from the date of the start of treatment. Results The median age of the patients was 66 years (range: 33 to 83 years) and 46 patients (76.7%) were male. Squamous cell carcinoma (SCC) was the most frequent histological type (85%). Most patients had tumors located in the mid-thoracic esophagus (53.3%) and stage III or IV (59.9%). All patients were treated using 3D (76.7%) or intensity-modulated radiotherapy (IMRT; 23.3%). The median total dose was 50.4Gy (41.4-50.4). All patients received platinum-based ChT concomitant with RT. The most common regimen used was carboplatin and paclitaxel, with a median of five cycles. With a median follow-up of 19 months, the median PFS and OS were 10 and 20 months, respectively. LRF and DF as the first site of failure were observed in 22 (36.6%) and 26 (43.3%) patients, respectively. In the univariate analysis, tumor length lower than 2.6 cm, gross tumor volume (GTV) volume lower than 28 cm3, clinical tumor stages T1 and T2, clinical node stage N0, clinical prognostic stage groups I and II, and complete response to treatment, were statistically significant factors for better PFS and OS. In the multivariate analysis, the presence of clinical nodal stage N0 was related to better PFS (p=0.02). Conclusion Node clinical status was the most important clinical factor for PFS. Despite all the technical progress observed in radiotherapy, treatments concomitant with platinum-based chemotherapy are associated with high levels of LRF and DF. New strategies in systemic therapy and radiotherapy are necessary for improving outcomes.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.