RESUMO
OPINION STATEMENT: Esophageal cancer is a global health problem, which is 7th most common and 6th most deadly cancer. It has been the era of immuno-oncology for esophageal cancer management. Radiation therapy has been one of the key local therapeutic approaches for esophageal cancer treatment, while its role in advanced disease is challenging and debatable. There have been emerging clinical and translational studies of radiation therapy in recurrent or metastatic esophageal cancer. Immunotherapy has been established the standard care of 1st and 2nd line systemic therapies of advanced esophageal cancer, and the development of tumor immunity has opened a new chapter for the esophageal cancer radiation therapy. The current review will summarize the classic radiation therapy research in advanced esophageal cancer, as well as the most recent key findings. The subtitles will cover palliative radiotherapy for dysphagia, re-radiation for recurrent disease, oligo-focal disease management and stereotactic radiation therapy, and radiotherapy with immunotherapy. Radiotherapy plays vital role in multidisciplinary management of advanced EC. External or intratumoral irradiation has been used for palliation of dysphagia and improving QOL in esophageal cancer patients traditionally, while recent clinical and technical advance enables radiotherapy to be considered in recurrent or metastatic disease for curation attention. Novel clinical and translational investigation is opening a new chapter of radiotherapy with immunotherapy for benefiting advanced EC patients.
Assuntos
Transtornos de Deglutição , Neoplasias Esofágicas , Humanos , Transtornos de Deglutição/terapia , Qualidade de Vida , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/tratamento farmacológico , Cuidados PaliativosRESUMO
Background and Objectives: The morbidity and mortality associated with COVID-19 have burdened worldwide healthcare systems beyond their capacities, forcing them to promptly investigate the virus characteristics and its associated outcomes. This clinical analysis aimed to explore the key factors related to the fatal outcome of severe COVID-19 cases. Materials and Methods: Thirty-five adult severe COVID-19 patients were enrolled from two COVID-19 hospitals in Dhaka, Bangladesh. Clinical manifestation, comorbid conditions, medications, SARS-CoV-2 RT-PCR related cycle threshold (CT) value, hematology, biochemical parameters with SARS-CoV-2 specific IgG and IgM responses at enrollment were compared between the survivors and deceased participants. Results: Total 27 patients survived and 8 patients died within 3 months of disease onset. Deceased patients suffered longer from shortness of breath than the survived (p = 0.049). Among the severe cases, 62% of the deceased patients had multiple comorbid condition compared to 48% of those who survived. Interestingly, the anti-viral was initiated earlier among the deceased patients [median day of 1 (IQR: 0, 1.5) versus 6.5 (IQR: 6.25, 6.75)]. Most of the survivors (55%) received a combination of anticoagulant (p = 0.034). Liver enzymes, creatinine kinase, and procalcitonin were higher among the deceased patients during enrollment. The median CT value among the deceased was significantly lower than the survivors (p = 0.025). A significant difference for initial IgG (p = 0.013) and IgM (p = 0.030) responses was found between the survivor and the deceased groups. Conclusions: The factors including older age, male gender, early onset of respiratory distress, multiple comorbidities, low CT value, and poor antibody response may contribute to the fatal outcome in severe COVID-19 patients. Early initiation of anti-viral and a combination of anticoagulant treatment may prevent or lower the fatality among severe COVID-19 cases.
Assuntos
COVID-19 , Adulto , Humanos , Masculino , SARS-CoV-2 , Estudos Prospectivos , Bangladesh/epidemiologia , Antivirais , Anticoagulantes , Imunoglobulina G , Imunoglobulina MRESUMO
To investigate the feasibility of volumetric modulated arc therapy (VMAT) delivery for whole breast irradiation with a 5-fraction regimen according to the FAST-Forward trial. Recently, we treated 10 patients with carcinoma of the left breast after breast conserving surgery. The dose prescription to the PTV was 26 Gy in 5 fractions. Treatment plans were produced using a VMAT technique with the Eclipse treatment planning system for 6 MV flattening filter (FF) and FF free (FFF) beams. Dose volume histograms (DVHs) for the PTV and the organs at risk (OARs), the ipsilateral lung and heart, were compared with the dose constraints specified in the FAST-Forward trial (PTV, D95 > 95%, D5 < 105%, D2 < 107% and Dmax < 110%; ipsilateral lung, D15 < 8Gy; Heart, D30 < 1.5Gy and D5 < 7Gy). Furthermore, conformity index (CI), homogeneity index (HI) and dose to the heart, contralateral lung, contralateral breast, and left anterior descending artery (LAD), were also assessed. Mean ± SD D95(%), D5(%), D2(%), and Dmax (%) for PTV were 97.75 ± 1.12, 105.2 ± 0.82, 105.90 ± 0.89, 109.36 ± 1.00 (FF) and 96.46 ± 0.75, 103.97 ± 0.97, 104.70 ± 1.09, 108.58 ± 1.33 (FFF) respectively. The mean ± SD CI was 1.07 ± 0.05 (FF), 1.048 ± 0.06 (FFF) and HI was 0.11 ± 0.02 (FF), 0.10 ± 0.02 (FFF). Dose constraints for OARs were met for both treatment techniques. However, D15 (Gy) for ipsilateral lung was 3.0% lower with FFF beams. In contrast, D5 (Gy) for heart was 9.0% higher with FFF beams. The dose difference between FF and FFF beams for other OARs such as contralateral lung-D10 (Gy) contralateral breast-D5 (Gy) and LAD was up to 6.0%. Both FF and FFF methods met the acceptable criteria. However, the treatment plans with FFF mode were more conformal and provided greater target homogeneity.
Assuntos
Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , PulmãoRESUMO
BACKGROUND: From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant. METHODS: A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days' duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose. RESULTS: In total, 313 cases were matched to 1196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: -21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines. CONCLUSIONS: Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries.
RESUMO
The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets.
Assuntos
COVID-19 , Humanos , Bangladesh/epidemiologia , Células B de Memória , SARS-CoV-2 , Imunoglobulina G , Anticorpos Antivirais , Gravidade do Paciente , Células Th17RESUMO
Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM+ (both OX40+CD137+ and OX40+CD40L+) CD4+ T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIMs (CD137+CD69+), which indicates the exhaustion of CD8+ T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2.
Assuntos
COVID-19 , Bangladesh/epidemiologia , Ligante de CD40 , Linfócitos T CD8-Positivos , Humanos , Imunidade Humoral , Estudos Longitudinais , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
BACKGROUND: COVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients. METHODOLOGY/PRINCIPAL FINDINGS: This longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases. Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases. CONCLUSION/SIGNIFICANCE: We report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.
Assuntos
Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , COVID-19/imunologia , Índice de Gravidade de Doença , Adulto , Formação de Anticorpos , Bangladesh , Teste para COVID-19 , Estudos de Coortes , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Imunoglobulina G , Estudos Longitudinais , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Fatores de Risco , SARS-CoV-2 , Carga ViralRESUMO
AIM: To define safety and efficacy of a palliative, short-course accelerated radiation therapy for symptomatic locally advanced primary pelvic cancer. MATERIALS AND METHODS: A phase II trial was planned based on the minimax Simon's two-stage design. A total of 18 Gy in 4.5 Gy/fraction administered twice a day was delivered (SHARON). Pain and quality of life were recorded according to the Visual Analogue self-assessment and the cancer linear analog scales (CLAS), respectively. RESULTS: Twenty-five patients were enrolled in the study. The most frequent baseline symptoms were pain (48%), bleeding (40%), bleeding/pain (8%), and intestinal sub-occlusion (4%). The overall palliative response rate was 96.0%, with a median palliative duration of 6 months. An improvement of quality-of-life indices (well-being, fatigue, and ability to perform daily activities) was noted in 64.0%, 36.0%, and 48.0% of patients, respectively. CONCLUSION: The SHARON regimen was well tolerated and effective in the palliative treatment of patients with locally advanced pelvic cancer. Based on these results, a multicentric prospective phase III trial is ongoing to compare this regimen with traditional 2-week radiotherapy treatment.
Assuntos
Cuidados Paliativos , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/patologia , Radioterapia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pélvicas/patologia , Pelve/patologia , Pelve/efeitos da radiação , Qualidade de Vida , Dosagem RadioterapêuticaRESUMO
The main clinical goal for patients with advanced or metastatic thoracic cancer is palliation of tumor-related symptoms and improvement of quality of life. The aim of this phase I-II trial was to define the maximum tolerated dose (MTD) of a short-course of palliative radiotherapy (RT) and to evaluate its efficacy in terms of palliative response. A phase I trial was planned with escalating dose increments. Total doses ranged from 16 to 20 Gy delivered (BID) in two consecutive days. Dose limiting toxicity was defined as any acute grade ≥ 3 toxicity based on the RTOG scale. MTD was used in the phase II trial to evaluate the efficacy of this regimen using a two stage Simon's design. Fifty-four patients were enrolled. The upper dose level of 20 Gy was defined as the MTD. In patients treated with this dose, the overall palliative response rate was 96.5% (CI 0.95: 81.3-99.9%). Complete pain relief rate was 50.0%. Median survival without symptomatic progression was 3 months. The tested short course accelerated regimen was well tolerated and effective in the palliative setting of metastatic or locally advanced chest cancer. A phase III trial is ongoing to validate this RT schedule.Trial registration: NCT03465553.
Assuntos
Neoplasias Pulmonares/radioterapia , Cuidados Paliativos/métodos , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-IdadeRESUMO
AIM: To determine the maximum tolerated dose (MTD) of a short-course accelerated radiotherapy and its feasibility for symptomatic palliation of advanced head and neck cancer or head and neck metastases from any primary site. PATIENTS AND METHODS: A phase I trial in four dose-escalation steps was planned: total dose ranged between 14 and 20 Gy in a total of four fractions administered twice a day. The dose-limiting toxicity (DLT) was determined as grade 3 or more toxicity occurring during treatment. The MTD obtained was used to plan a phase II trial. RESULTS: A total of 48 patients were treated. In the phase I trial, the 20 Gy dose level was determined to be the MTD. In the phase II trial, the palliative response rate was 82.7%, with a median duration of palliation of 3 months. CONCLUSION: Short-course accelerated radiotherapy was well tolerated and effective for palliation. These findings may help design future prospective randomized studies.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Cuidados Paliativos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Fracionamento da Dose de Radiação , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Qualidade de Vida , Dosagem Radioterapêutica , Fatores de TempoRESUMO
OBJECTIVES: To evaluate the efficacy and safety of a conformal Short Course Accelerated Radiation therapy (SHARON) for symptomatic palliation of locally advanced or metastatic cancers in older patients. MATERIALS AND METHODS: This is a pooled analysis on patients aged ≥80 years selected between subjects enrolled in 3 phase I-II studies on a short course palliative treatment of advanced or metastatic cancer. The primary endpoint was to evaluate the symptoms response rate produced by accelerated radiotherapy delivered in 4 total fractions in twice a day. Total dose ranged between 14 Gy and 20 Gy while dose/fraction between 3.5 and 5 Gy. RESULTS: A total of 48 patients were included in this analysis. Twenty-six patients (54.2%) had advanced primary or metastatic head and neck tumors, 11 (22.9%) locally advanced or metastatic thoracic cancers, 11 (22.9%) complicated bone metastases. The majority of patients presented pain (60.4%). With a median follow-up time of 5.5 months, no G4 acute and late toxicities were recorded. The overall palliative response rate was 91.7% with a median duration of palliation of 4 months. CONCLUSION: Short course accelerated radiotherapy in locally advanced or metastatic cancers is effective in terms of symptom relief and well tolerated even in older patients.