Osimertinib in a patient with end-stage kidney disease not on hemodialysis.

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) effective in non- small cell lung cancer (NSCLC) with EGFR mutations. Since the drug is primally eliminated by the fecal route no dose adjustment is needed in patient with chronic-kidney disease (CKD); despite this there is limited data about its safety in cancer patients with end-stage renal disease (ESRD). Herein, we reported a case report of a 77-year-old woman, diagnosed in 2018 with lung adenocarcinoma EGFR mutated with lymph nodal and cerebral metastasis, who started Osimertinib 80 mg/day. She under- went 41 cycles of therapy with no Osimertinib interruptions, no severe toxicities and obtaining complete radiological response. We conclude that Osimertinib has an acceptable safety profile also in cancer patients with ESRD not undergoing hemodialysis (HD).

Effectiveness and Safety of Argon Plasma Coagulation in Patients with Haemoptysis Caused by an Endobronchial Malignancy.

INTRODUCTION: Patients with central neoplasms and haemoptysis show low survival rates. Symptom control without recurrence 48 h after bronchoscopic interventions may improve the prognosis of these patients. Bronchoscopic argon plasma coagulation (APC) is a useful technique for endobronchial management of haemoptysis in patients with central malignancies. Nevertheless, limited data are available in the literature on its efficacy and safety and the main predictors of success are still unclear. METHODS: An observational, prospective, single-centre cohort study was carried out to assess the efficacy (i.e., immediate bleeding cessation without recurrence during the following 48 h) of bronchoscopic APC in the treatment of patients with haemoptysis caused by endobronchial malignancies and the main predictors of success. RESULTS: A total of 76 patients with median age 75 years (interquartile range: 65-79) were enrolled. 67 (88.2%) patients had bleeding cessation without recurrence 48 h after bronchoscopic APC. A low rate of non-serious adverse events (5.3%) was recorded and a low (7.6%) recurrence rate of haemoptysis at 3.5 months after the procedure was also shown. No clinical, demographic and endoscopic variables related to a successful procedure at 48 h were found. CONCLUSION: This study demonstrates that bronchoscopic APC is an effective procedure in the treatment of patients with haemoptysis caused by endobronchial malignancies, regardless of the clinical characteristics of the patients, the endoscopic and histological features of the neoplasm and the severity of the symptom. Furthermore, it shows a low rate of complications and long-term efficacy in bleeding control.

Localized prostate cancer in older patients: Radical prostatectomy or radiotherapy versus observation.

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.

Platinum dose in neoadjuvant therapy for triple-negative breast cancer: A systematic review and network meta-analysis.

INTRODUCTION: There are multiple neoadjuvant regimens, including platinum agents for triple-negative breast cancer (TNBC), each with a different safety profile, outcome, and pathologic complete response rate (pCR%). We performed a systematic review and network meta-analysis to compare the efficacy and safety of different platinum-based neoadjuvant CT treatments for TNBC. METHODS: Bibliographic databases (PubMed, Embase, and Cochrane Library) were searched from their inception to October 31, 2022. Eligible studies were randomized clinical trials that evaluated the addition of carboplatin or cisplatin to standard neoadjuvant CT for TNBC. The primary endpoints were pCR rates and DFS/EFS, while the secondary endpoints were grade (G)3-4 hematological toxicity and OS. RESULTS: Thirteen trials involving 3154 patients comparing six treatments (carboplatin AUC 5, carboplatin AUC 6, carboplatin AUC 2, carboplatin AUC 1.5, cisplatin 75 mg/m2, and standard anthracycline-and/or taxane-based CT) were identified. Based on the most effective treatments added to neoadjuvant CT, carboplatin AUC 2 was associated with the least improvement in pCR% (RR, 1.49; 95%CI, 1.23, 1.8), carboplatin AUC 6 was associated with similar improvement in pCR% (RR 1.58, 95%CI, 1.35, 1.84) and carboplatin AUC 5 with the highest improvement in pCR% (RR 2.23, 95%CI, 1.6,32). The treatment associated with the most considerable improvement in DFS when added to neoadjuvant CT was carboplatin AUC 5 (HR 0.36, 95%CI 0.18, 0.73). It was also better than AUC 6 and AUC 2 (HR= 0.45, 95%CI 0.21-0.96 and HR=0.48, 95%CI 0.23-0.98). All schedules exhibited similar outcomes in terms of OS; however, only AUC 2 demonstrated a significant improvement compared to the no-platinum arms. Neutropenia, thrombocytopenia, and anemia G3-4 were significantly increased by carboplatin AUC 6. CONCLUSIONS: Based on this network meta-analysis, carboplatin AUC 5 added to standard neoadjuvant CT may provide substantial pCR and DFS benefits with a low toxicity risk compared to other carboplatin doses.

Adjuvant and neoadjuvant chemotherapy for MSI early gastric cancer: a systematic review and meta-analysis.

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.

Immune checkpoint inhibitor doublets: Are they beneficial for older patients? A systematic review and meta-analysis.

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.

Network meta-analysis of first-line systemic regimens for older patients with advanced NSCLC.

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.

Prognostic relevance of sidedness in older patients with colon cancer: A review and pooled analysis of 227,218 patients.

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.

Prognostic Value of HER2-low Status in ER+ Early Breast Cancer: A Systematic Review and Meta-Analysis.

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.

The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis.

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.

Treatments for relapsed, BRCA-wild type, platinum-sensitive ovarian cancer: A systematic review and network meta-analysis.

INTRODUCTION: Although platinum-based chemotherapy (CT) is considered the standard treatment for relapsed platinum-sensitive ovarian cancer, there is currently no standard treatment for these patients. We compared the effectiveness of modern and older therapies in relapsed platinum-sensitive, BRCA-wild type, and ovarian cancers using a network meta-analysis (NMA). METHODS: A systematic search of PubMed, EMBASE, and Cochrane Library was performed up to October 31, 2022. Randomized controlled trials (RCT) that compared different second-line approaches were included. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). RESULTS: In total, 17 RCTs (n = 9405) comparing various strategies were included. The risk of death was significantly decreased with carboplatin + pegylated liposomal doxorubicin + bevacizumab compared to platinum-based doublet CT (hazard ratio [HR] = 0.59, 95%CI 0.35, 1). Various strategies, including secondary cytoreduction followed by platinum-based CT, carboplatin + pegylated liposomal doxorubicin + bevacizumab, and platinum-based CT with bevacizumab or cediranib, were better than platinum-based doublets alone for PFS. CONCLUSIONS: This NMA showed that carboplatin + pegylated liposomal doxorubicin + bevacizumab seems to increase the efficacy of standard second-line CT. These strategies can be considered when treating patients with relapsed platinum-sensitive ovarian cancer without BRCA mutations. This study provides systematic comparative evidence for the efficacy of different second-line therapies for relapsed ovarian cancer.

Human papillomavirus infection and non-oropharyngeal head and neck cancers: an umbrella review of meta-analysis.

OBJECTIVE: The causative and prognostic roles of human papillomavirus (HPV) in non-oropharyngeal squamous cell carcinoma of the head and neck are uncertain. This umbrella review assessed the strength and quality of evidence and graded the evidence derived from published meta-analyses on this subject. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched. Meta-analyses of observational studies and randomized trials were included. REVIEW METHODS: Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. RESULTS: 15 meta-analyses were evaluated. The association with HPV was highly suggestive of oral (OR = 2.40, [1.87-3.07], P < 0.00001) and nasopharyngeal cancers (OR = 17.82 [11.20-28.35], P < 0.00001). Improved survival emerged only in hypopharyngeal carcinoma and was confirmed in studies in which only p16 + cancers were considered. CONCLUSION: HPV infection may increase the risk of oral cavity and nasopharyngeal cancer. However, the prognosis was not influenced, except in hypopharyngeal carcinoma.

Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses.

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.

Duration of androgen deprivation with radiotherapy for high-risk or locally advanced prostate cancer: A network meta-analysis.

OBJECTIVE: To evaluate various outcomes of different lengths of androgen deprivation therapy in high- and very-high-risk prostate cancer, we conducted a network meta-analysis of randomized trials. The treatment of high-risk PC comprises the use of radical radiotherapy associated with various durations of androgen deprivation therapy, with luteinizing hormone releasing hormone analogues initiated during or immediately before the beginning of radiation. METHODS AND MATERIALS: This study followed the PRISMA extension statement to report network meta-analyses. We systematically searched online databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, for all randomized trials published up to April 2022. The primary outcomes were overall survival, prostate cancer-specific mortality, and metastasis-free survival. Network meta-analyses were performed under a Bayesian framework using the "gemtc" package (https://gemtc.drugis.org). RESULTS: The network meta-analysis included 12 studies (10 treatments) on overall survival outcomes. None of the arms showed superiority to radiotherapy alone with respect to overall deaths. Nine studies and 10 treatment arms had prostate cancer-specific mortality data. Overall, 36 months of adjuvant androgen deprivation therapy resulted in a better outcome than radiotherapy alone, three months of neoadjuvant androgen deprivation therapy, or 12 or 24 months of adjuvant androgen reprivation therapy, and it was the better treatment (73%) in terms of cancer mortality. Treatment involving luteinizing hormone releasing hormone analogues for 6 months before and during radiotherapy ranked the highest in reducing distant metastases (42%). CONCLUSIONS: We found that 36 months of adjuvant androgen deprivation therapy after radiotherapy was the optimal duration of endocrine treatment with regard to cancer mortality for high-risk and locally advanced prostate cancer.

Chemotherapy Duration for Various Indications in Colorectal Cancer: a Review.

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.

Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis.

The current standard of care for resected early-stage triple negative breast cancer (TNBC) patients who did not receive systemic preoperative therapy is adjuvant anthracycline- and taxane-based chemotherapy (CT). A network meta-analysis (NMA) of randomized controlled trials (phase III) enrolling patients with resected stage I-III TNBC comparing adjuvant regimens was performed. Overall survival (OS) and disease-free survival (DFS) data were extracted. A total of 27 phase III clinical trials were selected including 15,242 TNBC patients. This NMA showed an OS benefit from the incorporation of capecitabine into classic anthracycline/taxane-based combinations compared to anthracyclines with or without taxanes alone.

Comparison of different treatments for HPV+ oropharyngeal carcinoma: a network meta-analysis.

INTRODUCTION: Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma. MATERIAL AND METHODS: Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS. RESULTS: A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III-IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29-65 and 0.3; 95% CrIs 0.03-2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19-12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34). CONCLUSIONS: This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS.

Outcome of non-small-cell lung cancer with driven mutations treated with anti-PD-(L)1 agents: A systematic review.

Patients whose tumours harbour epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) driver mutations can benefit most from treatment with tyrosine kinase inhibitors (TKIs). Most trials with immune checkpoint inhibitors (ICIs) included few patients whose tumour had oncogenic driver alterations. We therefore performed a meta-analysis of studies reporting the activity of ICIs in oncogene addicted NSCLC. A comprehensive search of MEDLINE, The Cochrane Library and EMBASE was conducted to identify relevant studies published up to 31 January 2021. The primary outcomes were median overall survival (OS); the secondary endpoints were progression-free survival and overall response rate (PFS and ORR). Overall, 46 studies were screened and selected for final analysis. The pooled ORR was 14.5% (95% CI 9.6-21.2%). The median pooled PFS in EGFR/ALK mutated cases was 3.9 months (95% CI 3-5.2 months). Median pooled OS was 10.7 months (95% CI 9.2-12.5 months). All registration trials in second line did not show any benefit of immunotherapy for the subgroup of patients with EGFR-mutated or ALK-rearranged tumours. The unsatisfied benefit of immunotherapy in oncogene-addicted tumours has been debated and is mainly due to the lower mutation burden of these neoplasms. Our data do not support the use of immunotherapy in the setting of oncogene actionable tumours. More data are needed to confirm or reject the benefit of the combination of TKIs with ICIs.

COVID-19 and Lung Cancer Survival: An Updated Systematic Review and Meta-Analysis.

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.