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BACKGROUND: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase II como Assunto , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Compostos Organoplatínicos/administração & dosagem , Intervalo Livre de Progressão , Estudos Prospectivos , Adulto JovemRESUMO
Introduction: Objective: several dietary and non-dietary factors and genetic predisposition may play an important role in gastric carcinogenesis. The findings about associations between micronutrients and gastric cancer (GC) is still inconsistent. This study aimed to investigate the effect of dietary micronutrients on gastric cancer risk. Methods: a case-control study comprised of 173 GC (107 males: 66 females) patients and 313 (190 males: 123 females) population-based controls matched for age, occupation, and marital status. Demographics, medical history, physical activity, and nutrient intake information were collected using reliable interview-based questionnaires. Information on dietary micronutrient intake was collected from the participants using a validated food frequency questionnaire (FFQ). Multinomial logistic regression was used to calculate Odds ratios (ORs) and their corresponding 95 % confidence intervals (CIs) and evaluate associations between dietary micronutrients and GC risk. Results: GC was inversely associated with the consumption of vitamin A, beta-carotene, vitamins D, E, K, B2, B3, B6, B12, and C, folate, chromium, iodine, and selenium. Additionally, a protective effect was observed for consumption of calcium, copper, iron, magnesium, phosphate, sodium, and zinc. In almost all the micronutrients, the second tertile showed a more pronounced reduction in GC risk as compared to the first tertile. Conclusions: our data support favorable effects of dietary consumption of some vitamins and minerals against GC risk.
Introducción: Objetivo: varios factores dietéticos y no dietéticos y predisposiciones genéticas pueden jugar un papel importante en la carcinogénesis gástrica. Los hallazgos sobre las asociaciones entre los micronutrientes y el cáncer gástrico (CG) aún son inconsistentes. Métodos: este estudio tuvo como objetivo investigar el efecto de los micronutrientes sobre el riesgo de cáncer gástrico. Métodos: Un estudio de casos y controles comprendió 173 pacientes con GC (107 hombres: 66 mujeres) y 313 (190 hombres: 123 mujeres) controles basados en la población emparejados por edad, ocupación y estado civil. La información demográfica, el historial médico, la actividad física y la ingesta de nutrientes se recopilaron mediante cuestionarios confiables basados en entrevistas. La información sobre la ingesta de micronutrientes en la dieta se recopiló de los participantes mediante un cuestionario de frecuencia de alimentos (FFQ) validado. Se utilizó la regresión logística multinomial para calcular las razones de probabilidad (OR) y sus correspondientes intervalos de confianza (IC) del 95 % y evaluar las asociaciones entre los micronutrientes de la dieta y el riesgo de GC. Resultados: la GC se asoció inversamente con el consumo de vitamina A, betacaroteno, vitaminas D, E, K, B2, B3, B6, B12 y C, folatos, cromo, yodo y selenio. Adicionalmente, se observó un efecto protector para el consumo de calcio, cobre, hierro, magnesio, fosfato, sodio y zinc. En casi todos los micronutrientes, el tercer tercil mostró una reducción más pronunciada del riesgo de CG en comparación con el primer tercil en hombres. Por el contrario, el segundo tercil exhibió un nivel de protección significativamente marcado en comparación con el primer tercil en mujeres. Conclusiones: nuestros datos respaldan los efectos favorables del consumo dietético de algunas vitaminas y minerales para el riesgo de desarrollar cáncer gástrico.
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Selênio , Neoplasias Gástricas , Masculino , Feminino , Humanos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Estudos de Casos e Controles , Jordânia , Vitaminas , MicronutrientesRESUMO
Countries experiencing a significant shift toward Western lifestyle are facing an increased risk of gastric cancer (GC). While many studies have explored the link between diet and GC, the role of meat and dairy consumption remains uncertain. To delve deeper into this association, we conducted a case-control study in Jordan involving 173 GC cases and 314 controls, matched by age and marital status. Using a validated food frequency questionnaire, we assessed the intake of different dairy and meat products. The adjusted odds ratios and corresponding 95% confidence intervals indicated a strong correlation between high intake of red meat, milk, and buttermilk and GC. Our multinomial logistic regression analysis revealed that daily consumption of red meat (≥1 serving/day; OR, 3.34 [95% CI 1.85-6.03, p value of trend <.001], ≥1 serving/day) and weekly intake of milk (2-3 servings/week; OR, 2.04 [95% CI 1.14-3.64, p value of trend = .041]) and buttermilk (2-3 servings/week; OR, 2.07 [95% CI 1.12-3.83, p value of trend = .018], per 2-3 servings/week) were significantly associated with an increased risk of GC. Furthermore, consuming cooked eggs daily (OR = 2.44, 95% CI 1.24-4.79, p trend <.001) or weekly (OR, 3.34, 95% CI 1.58-7.10, p value of trend <.001) was also associated with an increased risk of GC. These findings highlight the potential health risks associated with excessive meat and some dairy products consumption and suggest that a balanced intake of these products, along with eggs, may help prevent GC.
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OBJECTIVES: Patterns and predictors of relapse in primary gastric diffuse large B cell lymphoma (DLBCL) were variably reported. Our study aims to evaluate the patterns and predictors of relapse in early-stage gastric DLBCL treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (RCHOP). METHODS: From 2005 to 2019, the medical records of 72 patients with stage I or stage II gastric DLBCL treated with six cycles of RCHOP without radiotherapy were reviewed. Different variables were correlated with progression free survival (PFS), overall survival (OS), and local relapse free survival (LRFS). RESULTS: 64 (88.1%) patients achieved a complete response (CR), while 8 (11.9%) had refractory disease. After CR, 9 (14%) patients relapsed; 7 (78%) relapses were loco-regional. Abnormal LDH (p = 0.028), H. pylori negative (p = 0.032) and, stage adjusted international prognostic index (sa-IPI) > 1 (p = 0.013) correlated with loco-regional failure. The 5-year PFS, OS, and LRFS were 74.8%, 75.3%, and 87.5%, respectively, after a median follow-up of 58 (range: 6-185) months. The median time to progression or relapse was 9 months (range: 5-54 months). In multivariate analysis, a sa-IPI >1 (HR: 3.56, CI: 1.35-8.8, p = 0.01) was associated with PFS while low albumin (HR: 8.85, CI: 1.09-71.4, p = 0.041) was associated with worse OS. None of the variables were associated with LRFS. CONCLUSION: Treatment of primary gastric DLBCL with RCHOP results in a high CR rate. The majority of treatment failures were loco-regional. Sa-IPI and H. pylori status may be used to identify patients who may benefit from combined modality treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Humanos , Intervalo Livre de Doença , Prednisona , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rituximab/uso terapêutico , Ciclofosfamida , Vincristina , Doxorrubicina , Estudos RetrospectivosRESUMO
OBJECTIVES: Pancreatic cancer (PC) has been related directly to many risk factors; however, diet is considered one of the most modifiable risk factors. This study is designed to observe the associations between the intake of macromicronutrients and the risk of pancreatic cancer in a Jordanian population. METHODS: A case-control study included 100 patients with the incident and histologically confirmed PC and 309 control subjects frequency-matched on age, educational level, occupation, and marital status. Face-to-face interview was used to collect the study's sociodemographic, physical activity, and dietary information. Intakes of macronutrients and micronutrients were assessed by a validated food-frequency questionnaire. Multinomial logistic regression was used to calculate odds ratios and confidence intervals. RESULTS: The patients reported higher consumption of almost all the macromicronutrients and micronutrients as compared with control subjects. The highest tertile of dietary intake of carbohydrates, sugars, fats, saturated fats, monounsaturated fats, trans fats, cholesterol, and vitamin B3 was positively associated with PC risk (Ptrend < 0.05). However, dietary intakes of polyunsaturated fats, omega-3, and some vitamins and minerals were not associated (Ptrend > 0.05) with the risk of PC. CONCLUSIONS: Our findings support the positive role of proteins, carbohydrates, sugars, fats, saturated fats, monounsaturated fats, trans fats, and cholesterol on pancreatic carcinogenesis.
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Micronutrientes , Neoplasias Pancreáticas , Humanos , Gorduras na Dieta/efeitos adversos , Ingestão de Energia , Estudos de Casos e Controles , Jordânia/epidemiologia , Carboidratos da Dieta , Ácidos Graxos , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , AçúcaresRESUMO
Diet is an important modifiable lifestyle factor, but epidemiological studies evaluating the association between dietary patterns and pancreatic cancer (PC) have reported inconsistent findings. This study aimed to evaluate the impact of several dietary choices on the risk of PC among newly diagnosed Jordanian patients. A case-control study was conducted at major teaching and general hospitals, including a Jordanian oncology center. The study included 101 patients with incident pancreatic cancer and 314 controls. Data was collected using interview-based questionnaires. Dietary intake was estimated using a validated Arabic and reproducible food-frequency questionnaire. Dietary patterns were derived using Principal Component Analysis. Multinomial logistic regression was used to estimate the association between dietary patterns and PC. Four dietary patterns were identified. The "Traditional" dietary pattern, which presented a diet rich in fresh fruits, vegetables, milk, yogurt, and lentils, was associated with a significant decrease in the odds of PC (OR = 0.42, 95% CI = 0.21-0.84) for the third quartile compared to first one. The "High-fruit" dietary pattern, which was loaded with strawberry, melon, watermelon, and other fruits, significantly reduced the odds of PC (OR = 0.38, 95% CI = 0.19-0.75) for the second quartile compared to the first one. The "Soup" dietary pattern was mainly composed of vermicelli soup, vegetable soup, lentil soup, and mushroom soup, which decreased the odds of PC (OR = 0.18, 95% CI = 0.07-0.38). There was no relation between PC and the "Western" dietary pattern, loaded with beer, wine, roasted lamb, meat, chicken sandwich, beefsteak, and fried fish. The "Traditional," "High-fruit," and "Soup" dietary patterns were associated with reduced risk of PC among Jordanians.
Assuntos
Neoplasias Pancreáticas , Vinho , Ovinos , Animais , Estudos de Casos e Controles , Pesquisa , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/prevenção & controleRESUMO
Studies on the association between gastric cancer (GC) and the intake of nutrients in Jordan are very limited, while findings from other reports on the intake of energy and macronutrients are controversial. This study aimed to examine the associations between intake of energy and macronutrients and the risk of GC in a Jordanian population. A case-control study was carried out between March 2015 and August 2018 in four major hospitals, including an oncology center in Jordan. Study participants were 173 cases with incident and histologically confirmed GC and 314 frequency-matched controls. Interview-based questionnaires were used to obtain the study's information. Data on nutrient intake were collected using a validated Arabic food-frequency questionnaire (FFQ). Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated through multinomial logistic regression and adjusted for potential confounders, including age, marital status, education, body mass index (BMI), smoking, period of smoking, family history of gastric cancer, history of gastric ulcer, and physical activity. Intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, trans-fat, and omega-6 fatty acids were significantly associated with increased risk of GC. The ORs for the highest versus the lowest tertiles were 6.47 (95% Cl: 3.29-12.77), 2.97 (95% CI: 1.58-5.58), 6.84 (95% CI: 3.46-13.52), 6.19 (95% CI: 3.15-12.17), 3.05 (95% CI: 1.58-5.88), 8.11 (95% CI: 4.20-15.69), and 2.74 (95% CI: 1.47-5.09), respectively. No significant association was found for energy, protein, carbohydrate, sugar, fibers, and omega-3 fatty acids. The findings of this study suggest that high intake of selected types of fats was associated with an increased risk of GC.
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Neoplasias Gástricas , Estudos de Casos e Controles , Gorduras na Dieta/efeitos adversos , Ingestão de Alimentos , Humanos , Nutrientes , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologiaRESUMO
Background: Diet pattern is an important modifiable lifestyle factor. However, epidemiological studies show that the association between dietary patterns and gastric cancer (GC) is conflicting. This study aims to assess the impact of several dietary choices on the risk of GC among newly diagnosed Jordanian patients. Methods: A case-control study was conducted at major oncology centers and hospitals in Jordan. Study participants included 172 patients with incident gastric cancer and 314 controls. Data was collected using interview-based questionnaires. Dietary intake was estimated using a validated Arabic and reproducible food-frequency questionnaire (FFQ). Dietary patterns were derived using Principal Component Analysis (PCA). Multinomial logistic regression was used to estimate the association between dietary patterns and GC. Results: Four dietary patterns were itemized; "Mediterranean", "Prudent", "Unhealthy" and "High-fruit" dietary patterns. The "Mediterranean" dietary pattern, which includes a diet rich in fresh fruits, vegetables, milk, yogurt, lentils, and olive oil was associated with a significant decrease in the odds ratio (OR) of GC for the third and fourth quartiles (OR, 0.394 (confidence interval (CI): 0.211-0.736); 0.212 (CI: 0.107-0.419), respectively) after adjusting for age, gender, body mass index, smoking, marital status, total energy intake, education level, and physical activity. While the "Unhealthy" and "Prudent" dietary patterns enhance the risk of developing GC, this risk was insignificant at any quartile. Additionally, the "High-Fruit" dietary pattern shows an insignificant protective effect against the risk of GC. Conclusion: The "Mediterranean" dietary pattern was associated with a reduced risk of GC among Jordanians. However, the other three identified dietary patterns were not significantly associated with the risk of GC.
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Gastric cancer (GC) and pancreatic cancer (PC) are the third and seventh most likely cancers to cause death worldwide. We aimed to determine the dietary and lifestyle factors of patients with GC or PC and their associated risk among Jordanians. This case-control study enrolled 587 adults (patients with PC, 101; patients with GC, 172; healthy controls, 314) between March 2015 and August 2018, who were assessed using interview-based personal and physical activity questionnaires. Multivariable logistic regression models were taken as measures for predictors of GC and PC risk. We showed that GC and PC patients had higher pre-diagnosis body-mass indexes, a greater proportion smoked and had a family history of cancer than controls. Furthermore, consumption of two snacks [odds ratios (OR)=0.44, 95% confidence intervals (CI): 0.23~0.85], three snacks (OR=0.04, 95% CI: 0.01~0.23) and no meals eaten outside (OR=0.31, 95% CI: 0.09~0.99) showed a protective effect against GC, and consumption of three snacks (OR=0.08, 95% CI: 0.02~0.40) reduced significantly the risk of PC. These results suggest that bodyweight, physical activity, smoking, and family history of cancer are among factors that affect GC and PC risk among Jordanians.
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BACKGROUND: Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC). METHODS: This study is prospective single-arm, multicenter phase II trial adopting Simon's two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3-4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit. RESULTS: 13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33-73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported. CONCLUSION: In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1 .
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Quimiorradioterapia Adjuvante , Feminino , Fluoruracila/uso terapêutico , Humanos , Imunoterapia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/uso terapêutico , Estudos Prospectivos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
Objective: several dietary and non-dietary factors and genetic predisposition may play an important role in gastric carcinogenesis. The findingsabout associations between micronutrients and gastric cancer (GC) is still inconsistent. This study aimed to investigate the effect of dietarymicronutrients on gastric cancer risk.Methods: a case-control study comprised of 173 GC (107 males: 66 females) patients and 313 (190 males: 123 females) population-basedcontrols matched for age, occupation, and marital status. Demographics, medical history, physical activity, and nutrient intake information werecollected using reliable interview-based questionnaires. Information on dietary micronutrient intake was collected from the participants using avalidated food frequency questionnaire (FFQ). Multinomial logistic regression was used to calculate Odds ratios (ORs) and their corresponding95 % confidence intervals (CIs) and evaluate associations between dietary micronutrients and GC risk.Results: GC was inversely associated with the consumption of vitamin A, beta-carotene, vitamins D, E, K, B2, B3, B6, B12, and C, folate, chromium,iodine, and selenium. Additionally, a protective effect was observed for consumption of calcium, copper, iron, magnesium, phosphate, sodium,and zinc. In almost all the micronutrients, the second tertile showed a more pronounced reduction in GC risk as compared to the first tertile.Conclusions: our data support favorable effects of dietary consumption of some vitamins and minerals against GC ris.(AU)
Objetivo: varios factores dietéticos y no dietéticos y predisposiciones genéticas pueden jugar un papel importante en la carcinogénesis gástrica.Los hallazgos sobre las asociaciones entre los micronutrientes y el cáncer gástrico (CG) aún son inconsistentes.Métodos: este estudio tuvo como objetivo investigar el efecto de los micronutrientes sobre el riesgo de cáncer gástrico. Métodos: Un estudio de casos ycontroles comprendió 173 pacientes con GC (107 hombres: 66 mujeres) y 313 (190 hombres: 123 mujeres) controles basados en la población empa-rejados por edad, ocupación y estado civil. La información demográfica, el historial médico, la actividad física y la ingesta de nutrientes se recopilaronmediante cuestionarios confiables basados en entrevistas. La información sobre la ingesta de micronutrientes en la dieta se recopiló de los participantesmediante un cuestionario de frecuencia de alimentos (FFQ) validado. Se utilizó la regresión logística multinomial para calcular las razones de probabilidad(OR) y sus correspondientes intervalos de confianza (IC) del 95 % y evaluar las asociaciones entre los micronutrientes de la dieta y el riesgo de GC.Resultados: la GC se asoció inversamente con el consumo de vitamina A, betacaroteno, vitaminas D, E, K, B2, B3, B6, B12 y C, folatos, cromo,yodo y selenio. Adicionalmente, se observó un efecto protector para el consumo de calcio, cobre, hierro, magnesio, fosfato, sodio y zinc. En casitodos los micronutrientes, el tercer tercil mostró una reducción más pronunciada del riesgo de CG en comparación con el primer tercil en hombres.Por el contrario, el segundo tercil exhibió un nivel de protección significativamente marcado en comparación con el primer tercil en mujeres.Conclusiones: nuestros datos respaldan los efectos favorables del consumo dietético de algunas vitaminas y minerales para el riesgo dedesarrollar cáncer gástrico.(AU)