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INTRODUCTION: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells and potentially cancer cells via the metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3), impacting their proliferation, differentiation, and apoptosis. An umbrella review was conducted to evaluate the potential protective effect of vitamin D3 intake and serum levels on the incidence and mortality of cancer. MATERIAL AND METHODS: A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE databases from their inception to October 1, 2023. We included meta-analyses of observational or randomized clinical trials that compared interventions (vitamin D3 intake) or blood levels in a healthy population, with cancer incidence or mortality as outcomes. The grading of evidence certainty followed established criteria, including strong, highly suggestive, suggestive, weak, or not significant. RESULTS: A total of 71 systematic reviews were included. Strong evidence indicated that vitamin D3 supplementation reduced total cancer mortality (odds ratio [OR], 0.9 [95% CI, 0.87-0.92]; P<.01). In the context of site-specific cancers, there exists highly suggestive evidence pointing towards the potential prevention of head and neck, breast, colorectal, lung, and renal cell cancers through the intake of vitamin D3. Furthermore, strong evidence suggests that maintaining sufficient levels of vitamin D3 may effectively lower the risk of renal cell and thyroid cancer (OR=0.76 [95%CI 0.64-0.88]). CONCLUSIONS: There is significant evidence that vitamin D3 intake may reduce the incidence of some cancers. Routine assessments to ensure sufficient levels of vitamin D3 and administering supplements to address deficiencies may serve as crucial preventive measures for healthcare systems.
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INTRODUCTION: There is a significant gap in the literature concerning the effective management of second-line therapy for patients with metastatic renal cell carcinoma (RCC) who have received immune checkpoint inhibitors (ICIs). Most of the published articles were small multicenter series or phase 2 studies. To our knowledge, a systematic review that comprehensively outlines the range of treatment options available for patients with metastatic RCC who do not respond to first-line ICIs has not yet been conducted. Our aim was to synthesize evidence on second-line therapies for patients with metastatic RCC after initial treatment with ICIs and to offer recommendations on the best treatment regimens based on the current literature. MATERIAL AND METHODS: We conducted a search in PubMed, Embase, and the Cochrane Library on 29 February 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We selected articles that met the predetermined inclusion criteria (written in English, retrospective observational studies, prospective series, and randomized trials reporting second-line therapy for metastatic RCC after failure of ICI-based therapy). Relevant articles were identified in the reference lists. The main endpoint was the overall response rate (ORR), with the median progression-free survival (PFS) and overall survival (OS) as secondary endpoints. RESULTS: We included 27 studies reporting the outcomes of 1970 patients. Salvage therapies were classified as targeted therapy (VEGFR TKIs) in 18 studies and ICIs in 8 studies. In studies where TKIs were the second line of choice, the pooled ORR was 34% (95% CI: 30.2-38%). In studies where ICIs, alone or in combination with TKIs, were used as second-line therapies, the ORR was 25.7% (95% CI: 15.7-39.2%). In studies where TKIs and ICIs were the second-line choices, the pooled median PFS values were 11.4 months (95% CI: 9.5-13.6 months) and 9.8 months (95% CI: 7.5-12.7 months), respectively. CONCLUSIONS: This systematic review shows that VEGFR TKIs and ICIs are effective second-line therapies following an initial treatment with anti-PD(L)1 alone or in combination. The treatment choice should be personalized, taking into account the patient's response to first-line ICIs, the site of the disease, the type of first-line combination (with or without VEGFR TKIs), and the patient's overall condition.
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BACKGROUND: There is an ongoing debate in the medical community about the association between the laterality of breast cancer (BC: whether it arises in the left or right breast) and its outcome. This study aims to assess the disparities in overall survival (OS), cardiac mortality, and cancer-specific survival (CSS) between BC affecting the left side and BC affecting the right side. MATERIALS AND METHODS: We conducted a thorough search of databases, such as PubMed, EMBASE, and the Cochrane Library, starting from their inception up until December 1, 2023. The primary outcome was OS. Additional endpoints included cardiac mortality and CSS. RESULTS: The meta-analysis included 50 publications (nâ¯=â¯7,527,156 patients) with similar rates of left and right BCs. Patients with left-sided BC showed a marginally decreased OS (HRâ¯=â¯1.03, 95â¯%CI 1.01-1.04; Pâ¯<â¯.01) and a 10% increase in cardiac mortality (HRâ¯=â¯1.1, 95â¯%CI 1.04-1.16; Pâ¯<â¯.01). Cancer-specific survival was similar for both groups (HRâ¯=â¯1.01, 95â¯%CI 0.98-1.03; Pâ¯=â¯.32). CONCLUSIONS: According to this study, there is a slight increase in mortality and a 10â¯% rise in cardiac-related deaths associated with left-sided breast cancer compared to right-sided breast cancer.
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Neoplasias Unilaterais da Mama , Feminino , Humanos , Prognóstico , Taxa de Sobrevida , Neoplasias Unilaterais da Mama/mortalidade , Neoplasias Unilaterais da Mama/patologiaRESUMO
INTRODUCTION: This study evaluates the effects of radical prostatectomy (RP) or irradiation on overall survival (OS) and prostate cancer-specific mortality (PCSM) in older patients with localized prostate cancer (PC). MATERIALS AND METHODS: We conducted a comprehensive literature review across PubMed, EMBASE, and the Cochrane Library from inception up to December 2023 to identify studies comparing the outcomes of surgery or radiotherapy (RT) versus observation in patients aged 65 and older with localized PC. We pooled hazard ratios (HRs) for OS and PCSM using random-effects models. RESULTS: Thirteen studies involving 284,066 patients were analyzed. Three were large randomized trials (RCTs) and 10 were retrospective studies. Overall survival with surgery was greater in observational studies (HR = 0.52, 95% confidence interval [CI] 0.47-0.59; P < 0.001) than in RCTs (HR = 0.84, 95%CI 0.72-0.98; P = 0.03). Data on PCSM from seven studies also indicated a significant benefit for RP in RCTs (HR = 0.47; 95% CI: 0.3-0.73; P < 0.001) and observational studies (HR = 0.41, 95%CI 0.27-0.62; P < 0.001). Both analyses presented high heterogeneity (I2 = 90%, P < 0.001 and I2 = 65%, P = 0.01). An analysis of patients receiving RT indicated a significant, albeit smaller, OS (n = 7 studies) and PCSM (n = 5 studies) advantage (HR = 0.69; 95% CI: 0.59-0.79; P < 0.001; and HR = 0.60; 95% CI 0.44-0.82; P = 0.001) compared to observation (1 RCT and 8 observational studies). DISCUSSION: The evidence suggests that patients with PC might consider opting for surgery as the main treatment option or, alternatively, for RT, as an alternative to observation, based on their individual medical history, life expectancy, and preferences.
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Prostatectomia , Neoplasias da Próstata , Idoso , Humanos , Masculino , Estudos Observacionais como Assunto , Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Conduta ExpectanteRESUMO
Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone's prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients' quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations.
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Various immunotherapy treatments have received approval for the treatment of advanced non-small cell lung cancer (NSCLC), either as standalone or in conjunction with chemotherapy, contingent upon the extent of PD-L1 expression. These treatments are commonly utilized in clinical practice. However, a specific gap exists in direct comparisons of these regimens in elderly patients. The aim of this network meta-analysis (NMA) was to examine the effectiveness of PD-1/PD-L1 inhibitors, either alone or in conjunction with chemotherapy, as the initial treatment for elderly patients diagnosed with advanced NSCLC. We extensively searched PubMed, EMBASE and the Cochrane Library to gather randomized clinical trials that utilized PD-1/PD-L1 inhibitors as the first-line therapy for advanced NSCLC. By means of Bayesian NMA, we conducted an analysis on hazard ratios (HRs) related to overall survival (OS). A total of 5240 patients were included in the 21 trials. Across all studies, cemiplimab exhibited a noteworthy superiority to chemotherapy in terms of OS [HR = 0.48, 95% confidence interval (CI): 0.3-0.77]. In the subgroup analysis, it was observed that patients with PD-L1 expression of 50% or higher experienced the greatest OS benefit from cemiplimab (HR = 0.48, 95% CI: 0.3-0.77). Conversely, the cohort with unselected PD-L1 scores (>1 or any score) exhibited the greatest OS benefit when treated with pembrolizumab combined with chemotherapy, as indicated by a HR of 0.69 (95% CI: 0.52-0.9). Chemotherapy combined with pembrolizumab and cemiplimab monotherapy may represent the reference regimens for older patients with NSCLC with unselected and >50% PD-L1 expression, respectively.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metanálise em Rede , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Idoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Imunoterapia/métodosRESUMO
INTRODUCTION: The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. MATERIALS AND METHODS: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. RESULTS: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). DISCUSSION: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.
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Inibidores de Checkpoint Imunológico , Neoplasias , Idoso , Humanos , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/antagonistas & inibidoresRESUMO
Background: Perioperative chemotherapy (CT) is an established therapeutic approach for patients diagnosed with stage IB-III gastric cancer (GC). Objectives: This study aimed to investigate the efficacy of this approach in individuals with GC exhibiting high microsatellite instability (MSI-H). Design: A systematic review was conducted, including studies that provided data on (neo)adjuvant CT outcomes in patients with MSI-H GC. Methods: Systematic searches were conducted in PubMed, Cochrane Central of Controlled Trials, and Embase databases. Data were aggregated using hazard ratios (HRs) to compare overall survival between CT and surgery. Results: Data analysis from 23 studies, including 22,011 patients, revealed that the prevalence of MSI-H is 9.8%. Administration of adjuvant or perioperative CT did not significantly reduce the risk of death or relapse in patients with MSI-H GC (HR = 0.8, 95% CI 0.54-1.16; p = 0.24 and HR = 0.84, 95% CI 0.59-1.18; p = 0.31, respectively). Conclusion: Chemotherapy did not benefit patients diagnosed with MSI-H nonmetastatic GC but rather will be integrated with immune checkpoint inhibitors in the near future.
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Age is a major risk factor for sporadic colon cancer (CC). In the general population, the side of the tumor (right versus left) shows a possible significant prognostic effect, with right tumors displaying the worst outcome due to biological differences. However, little is known about the role of sidedness in the older population. We conducted a pooled analysis of observational and prospective studies to confirm or reject the hypothesis that side is a prognostic variable, even in older patients with CC. Using the terms ("colorectal" or "colon") and ("cancer" or "carcinoma") and ("elderly" or "older" or "65 years" or "70 years" or "75 years") and ("side" or "site" or "right" or "left"), we searched PubMed, Embase, and the Cochrane Library through January 2023. We selected studies in the English language to compare the prognosis of left versus right CC in older patients (with a lower age limit of 65 years). The primary endpoint was overall survival (OS). Hazard ratios (HRs) for OS with relative 95% confidence intervals (CIs) were extracted from each study. Summary HRs were calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. The review process led to the inclusion of 13 articles. The studies reported the OS data for a total of 227,218 patients with CC. The CC side was not independently associated with mortality risk in older CC patients (HR 0.97; 95% CI 0.9-1.04; p = 0.34). High heterogeneity was observed in the main analysis (P < 0.01; I2 = 85%). In conclusion, our analysis shows that the tumor being on the left or right side in older patients with CC has no significant role in the risk of overall death. These data support the use of other parameters, such as stage, biology, comorbidities, and life expectancy, to decide on treatment and the prolongation of screenings until a patient's latest years.
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Neoplasias do Colo , Humanos , Idoso , Prognóstico , Estudos Prospectivos , Estadiamento de Neoplasias , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND/AIM: Low human epidermal growth factor receptor 2 expression (HER2-low: 1+/2+ by immunohistochemistry without HER2 amplification) is emerging as defining a specific breast cancer (BC) subgroup owing to its distinct biological features. However, its prognostic role has not been confirmed in clinical practice. We conducted a systematic review and meta-analysis to determine the prognostic role of HER2-low status in patients with estrogen receptor-positive (ER+) early BC. MATERIALS AND METHODS: We searched PubMed, EMBASE, and the Cochrane Library for prospective or retrospective studies that reported data on overall (OS) or disease-free (DFS) survival for HER2-low compared to HER2-negative BC. Data were pooled using hazard ratios (HR) with confidence intervals (CI) for OS/DFS of HER2-low vs. HER2-negative subgroups according to the random-effects model. OS was the primary outcome measure, and DFS and pathological complete response were the secondary endpoints. RESULTS: An analysis was made of 25 studies collected, including 34,965 patients with HER2-low BC. A HER2-low status was associated with an HR for OS of 0.83 (95% CI=0.76-0.9, p<0.0.01). Similarly, a pooled HR of 0.89 (95% CI=0.840.94, p<0.0.01) showed that patients with HER2-low BC had an increased DFS. Pathological complete response was significantly lower in HER2-low BC in 13 studies (OR=0.72, 95% CI=0.58-0.91; p<0.01). CONCLUSION: Based on these data, HER2-low status should be identified as a potential prognostic factor in early stage ER+ BC. This should be taken into account when considering treatment in (neo)adjuvant settings, and it should be a potential stratification factor in future investigations.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Estudos Retrospectivos , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Modelos de Riscos Proporcionais , Intervalo Livre de DoençaRESUMO
INTRODUCTION: Adjuvant hormonal therapy, with or without prior chemotherapy, has been widely recognised as the preferred treatment strategy for resected breast cancer (BC) for a minimum duration of 5 years. If the effectiveness of therapy beyond a 5-year period has been established, there is still ongoing debate regarding the optimal duration for this prolonged period. A network meta-analysis (NMA) was conducted to ascertain the optimal duration of extended therapy for resected BC in postmenopausal women. MATERIAL AND METHODS: A comprehensive search was conducted on online databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, to identify all randomised trials on extended duration of endocrine therapy. The search was limited to trials that had been published before 30th April 2023. The study focused on evaluating disease-free survival (DFS) as the primary outcome, with overall survival (OS) as the secondary endpoint. Under the Bayesian framework, NMA was performed using the GeMTC package. The relative rankings of the treatments were determined by utilising surface under the cumulative ranking curve (SUCRA) p scores. A network meta-regression analysis was employed to ascertain the impact of the baseline characteristics of the disease and the initial treatments administered. RESULTS: In the overall population, increasing the duration by 5 years did not result in a significantly better DFS compared to durations of 2-3 and 3-4 more years (hazard ratio [HR] = 0.97, 95% confidence interval [CI] [0.88-1.08] and HR = 0.87, 95% CI [0.72-1.06]). This effect was independent of adjuvant chemotherapy and nodal status. However, the effect of 5 more years of AI was significantly better in node-positive BC and in those who received some years of tamoxifen instead of aromatase inhibitors (AIs) as initial adjuvant therapy. OS was not affected by the administration of extended endocrine therapy. CONCLUSIONS: We conclude that an extended course of AI lasting 2-3 years, following an initial 5-year treatment, may be considered an appropriate regimen for achieving DFS benefits. In node-positive BC cases, it has been observed that a duration of 10 years provides a greater advantage compared to shorter durations, especially when tamoxifen is administered initially. Therefore, it is suggested that a longer duration is a potential standard of care in these cases.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Pós-Menopausa , Teorema de Bayes , Metanálise em Rede , Tamoxifeno/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Quimioterapia Adjuvante , Adjuvantes Imunológicos/uso terapêuticoRESUMO
INTRODUCTION: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC. METHODS: We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS. RESULTS: The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years. CONCLUSION: This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.
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Neoplasias da Mama , Idoso , Humanos , Feminino , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina , Receptor ErbB-2 , Quinase 6 Dependente de Ciclina , Fulvestranto , Inibidores de Proteínas Quinases , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to appraise the proof provided by published meta-analyses. METHODS: MEDLINE, Embase, and the Cochrane Library were searched from database inception to 31 May 2022. Meta-analyses of prospective or retrospective observational studies and randomized trials were included. Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. RESULTS: From 74 publications, 27 meta-analyses described five associations between vitamin D3 levels and supplementation and COVID-19 outcomes. Low levels of vitamin D3 were significantly associated with severity (highly suggestive evidence; OR = 1.97 [95% CI, 1.55-2.51], p < 0.01; I2 = 77%, p < 0.01) and mortality risk due to COVID-19 disease (OR = 1.83 [95% CI, 1.55-2.16], p < 0.01; I2 = 50%, p < 0.01). Vitamin D3 supplementation, after a diagnosis of COVID-19 infection, was associated with significantly reduced infection severity (e.g., ICU admission) and mortality. CONCLUSIONS: This umbrella review of the available evidence suggests that insufficient vitamin D3 may increase COVID-19 infection risk, severity, and mortality, in addition to showing a highly suggestive association between vitamin D3 supplementation and reduced severity and mortality among infected patients.
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PURPOSE OF REVIEW: The treatment of colorectal cancer (CRC) has evolved and become more personalized during the past several years. For example, depotentiation/reduced duration of systemic therapies has proven to be beneficial in both advanced and early stages of the disease. RECENT FINDINGS: In particular, recent randomized studies of stage III and high-risk stage II CRC showed that a shorter duration (3 months), when compared to the historical 6-month comparator, provides nearly similar overall survival (OS) and disease-free survival (DFS). In the setting of advanced, inoperable CRC, a relatively short induction phase (six to eight cycles) followed by biological agents is the current standard of care in RAS wild-type (wt). versus RAS mutated cases. With regard to potentially operable stage IV disease (with the aim of converting liver metastases to operability), a relatively short number of cycles (four to six cycles) should be offered with re-staging and re-evaluation for surgery as soon as possible in most cases. For inoperable liver metastases, a relatively intensive triplet or doublet plus targeted therapy may attain conversion in some cases and may even result in cure. Rectal cancer treatment continues to be a complex disease in terms of treatment and oncological results. Recent data seem to showcase the benefits of more prolonged sequential strategies (total neoadjuvant therapy, all treatment delivered before surgery, to reduce the risk of distant metastases and local control). In recent years, different strategies regarding treatment intensity have been employed in CRC in adjuvant and metastatic setting. Introduction of triplets as first-line therapy for colon cancer and as induction phase for rectal cancer are now therapeutic options. Conversely in stage II disease or low-risk stage III resected CRC, a reduced chemotherapy length is a new standard of care.
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Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Humanos , Fluoruracila/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Retais/tratamento farmacológico , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/secundárioRESUMO
Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio [HR] =2.73 [95%CI 0.84, 8.94], p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic.
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BACKGROUND: Over recent years, immune checkpoint inhibitors (ICIs) have changed the clinical management and prognosis for most cancers. However, data on older patients in clinical trials are scarce. OBJECTIVE: We performed a systematic review and pooled analysis of real-life studies to explore the efficacy and toxicity of ICIs in unselected older individuals in multiple tumor settings treated outside of clinical trials. PATIENTS AND METHODS: We searched articles, including prospective cohort studies, observational or retrospective series, or expanded access programs, published in English from 2010 to October 2020 in PubMed, MEDLINE, the Cochrane Library, and EMBASE. We excluded hematological malignancies. RESULTS: Forty-eight studies met the predefined criteria and were eligible for inclusion in the systematic review. We included 5524 patients. The pooled median overall survival was 8.9 (95% CI 7.3-10.5) and 14.3 (95% CI 11.3-17) months for non-small cell lung cancer (NSCLC: n = 17 studies; 95% in pretreated setting) and melanoma, respectively (n = 3). Median progression-free survival was 3.2 (95% CI 2.7-3.8) and 7.9 (95% CI 6.05-9.78) months for NSCLC and melanoma cohorts. Pooled rates of Grade 1-5 hepatitis, pneumonitis, hypothyroidism, and diarrhea were 5.3% (95% CI 3.7-7.6), 6% (95% CI 3.8-9.4), 8.3% (95% CI 5.4-12.5) and 7.6% (95% CI 5.7-10), respectively. CONCLUSIONS: Our findings suggest that ICIs could be safely administered in older individuals with comparable survival outcomes with respect to younger individuals. Future studies should include some form of geriatric assessment to improve patient stratification.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Importance: Obesity, defined as a body mass index (BMI) greater than 30, is associated with a significant increase in the risk of many cancers and in overall mortality. However, various studies have suggested that patients with cancer and no obesity (ie, BMI 20-25) have worse outcomes than patients with obesity. Objective: To assess the association between obesity and outcomes after a diagnosis of cancer. Data Sources: PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020. Study Selection: Studies reporting prognosis of patients with obesity using standard BMI categories and cancer were included. Studies that used nonstandard BMI categories, that were limited to children, or that were limited to patients with hematological malignant neoplasms were excluded. Screening was performed independently by multiple reviewers. Among 1892 retrieved studies, 203 (17%) met inclusion criteria for initial evaluation. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were reporting guideline was followed. Data were extracted by multiple independent reviewers. Risk of death, cancer-specific mortality, and recurrence were pooled to provide an adjusted hazard ratio (HR) with a 95% CI . A random-effects model was used for the retrospective nature of studies. Main Outcomes and Measures: The primary outcome of the study was overall survival (OS) in patients with cancer, with and without obesity. Secondary end points were cancer-specific survival (CSS) and progression-free survival (PFS) or disease-free survival (DFS). The risk of events was reported as HRs with 95% CIs, with an HR greater than 1 associated with a worse outcome among patients with obesity vs those without. Results: A total of 203 studies with 6â¯320â¯365 participants evaluated the association of OS, CSS, and/or PFS or DFS with obesity in patients with cancer. Overall, obesity was associated with a reduced OS (HR, 1.14; 95% CI, 1.09-1.19; P < .001) and CSS (HR, 1.17; 95% CI, 1.12-1.23; P < .001). Patients were also at increased risk of recurrence (HR, 1.13; 95% CI, 1.07-1.19; P < .001). Conversely, patients with obesity and lung cancer, renal cell carcinoma, or melanoma had better survival outcomes compared with patients without obesity and the same cancer (lung: HR, 0.86; 95% CI, 0.76-0.98; P = .02; renal cell: HR, 0.74; 95% CI, 0.53-0.89; P = .02; melanoma: HR, 0.74; 95% CI, 0.57-0.96; P < .001). Conclusions and Relevance: In this study, obesity was associated with greater mortality overall in patients with cancer. However, patients with obesity and lung cancer, renal cell carcinoma, and melanoma had a lower risk of death than patients with the same cancers without obesity. Weight-reducing strategies may represent effective measures for reducing mortality in these patients.
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Neoplasias/mortalidade , Obesidade/epidemiologia , Saúde Global , Humanos , Incidência , Neoplasias/etiologia , Obesidade/complicações , Taxa de Sobrevida/tendênciasRESUMO
INTRODUCTION: Steroids are commonly used for managing brain edema in patients with glioblastoma multiforme (GBM), treated with surgery and concomitant temozolomide-based chemoradiotherapy (CTRT). The adverse effects of glucocorticoids include lymphopenia, hyperglycemia, and risk of infection. We report the results of a meta-analysis evaluating the effects of steroids on outcome when associated with the treatment of GBM. METHODS: PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with GBM and treated or not treated with steroids. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR > 1 associated with the worst outcome in steroid users compared to non-users. RESULTS: Twenty-two publications were retrieved from studies selected for a total of 8,752 patients. In the primary analysis (n = 22 studies reporting data), OS was reduced in GBM patients taking steroids during treatment (HR = 1.54, 95% CI 1.37-1.75; p < 0.01). Similarly, PFS was inferior in steroid users in n = 9 studies with data available (HR = 1.28, 95% CI 1.1-1.49; p < 0.01). CONCLUSIONS: In patients with GBM and treated with RT and/or CT, association with steroids significantly reduces survival and PFS. Use of the lowest dose of glucocorticoids for the shortest period needed to achieve the treatment goals and prevention of steroid-associated complications are essential aims of treatment of this disease.