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.

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.

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.

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.

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.

Third dose of SARS-CoV-2 vaccine: A systematic review of 30 published studies.

We analyzed published studies on the efficacy and safety of the third dose of the COVID-19 vaccine in various general population settings. We conducted systematic searches of PubMed and EMBASE for series published in the English language through November 15, 2021, using the search terms "third" or "booster" or "three" and "dose" and "COVID-19" or "SARS-CoV-2." All articles were selected according to the MOOSE guidelines. The seroconversion risk after third doses was descriptively expressed as a pooled rate ratio ([seroconversion rate after the third dose]/[seroconversion rate after the second dose]). The search returned 30 studies that included a total of 2 734 437 vaccinated subjects. In more than 2 700 000 Israeli patients extracted from the general population, the reduction in the risk of infection ranged from 88% to 92%. Conversion rates for IgG anti-spike ranged from 95% to 100%. In cancer or immunocompromised patients, mean IgG seroconversion was 39.4% before and 66.6% after third doses. A third dose seems necessary to protect against all COVID-19 infection, severe disease, and death risk.

Preferred neoadjuvant therapy for gastric and gastroesophageal junction adenocarcinoma: a systematic review and network meta-analysis.

INTRODUCTION: Currently, the standard treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma, including distal esophagus, consists of perioperative chemotherapy (CT) according to FLOT schedule (5FU/leucovorin/oxaliplatin and docetaxel), or of concomitant chemoradiotherapy (CTRT) based on CROSS regimen. However, due to the relatively lack of direct comparisons between perioperative CT and neoadjuvant CTRT, the effectiveness of these new combinations is unknown. Therefore, we performed a network meta-analysis (NMA) to compare the efficacy of different neoadjuvant treatments for gastric and GEJ adenocarcinoma in terms of overall and disease-free survival (OS and DFS). MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane from database inception until February 1st 2022 for randomized clinical trials that enrolled adults with gastric and GEJ carcinomas and provided data about OS and/or DFS. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank (SUCRA) curve plots were produced. The primary outcome was OS, secondary endpoint DFS. RESULTS: A total of 1247 citations were screened; 14 randomized clinical trials were included. In Bayesian comparisons, FLOT-based CT ranked as one of the better regimens with a probability of 41%, both with induction CT followed by CTRT (P = 0.45). For DFS analysis, the FLOT regimen was the preferred option (P = 0.62). CONCLUSIONS: In conclusion, this NMA adds further evidence to the optimization of treatment strategies for gastric and GEJ adenocarcinomas and confirms that incorporation of perioperative triplet-based CT improved both OS and DFS compared to surgery alone and other preoperative strategies.

Immunotherapy in older patients with non-small cell lung cancer: Young International Society of Geriatric Oncology position paper.

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

Immunotherapy treatment: an issue for metabolic response.

Since the beginning of second decade of last century, when it was introduced in many oncologic scenarios, immunotherapy has become an important tool in the management of a growing number of cancers. Immunotherapy for cancer appears to be useful, improving not only progression free survival but also overall survival, thus achieving the goal that many advanced cancers, previously considered without effective treatment options, have now become successfully treatable. However, considering the relatively recent introduction of these drugs in clinical scenarios and the continuous release of new drugs, there is a lack of large validated clinical experiences and many issues are today debated amongst which the evaluation of the response to immune-therapy. Engaging the host immune system in fighting against cancer is an energy-consuming process, requiring T-cell recruiting; this process, named "pseudo-progression," sometimes produces an increase of both dimensional and metabolic ratio of the lesions, as well as the appearance of "new lesions." This behavior, always considered as undisputed progressive disease when traditional chemotherapy is employed, should be carefully considered in the field of immunotherapy, where the phenomenon of "flare" followed by regression of the disease can occur. In this paper, Authors analyzed the best available evidence in this field, reviewed the most important issues concerning the development of immunotherapy, and addressed evidence and concerns about the evaluation of response when using immunotherapy drugs, in terms of both radiological and nuclear medicine criteria.

Ceritinib compassionate use for patients with crizotinib-refractory, anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer.

AIM: Ceritinib was evaluated within a compassionate use program of Italian patients. PATIENTS & METHODS: 70 patients with anaplastic lymphoma kinase-positive crizotinib-refractory advanced non-small-cell lung cancer received ceritinib. RESULTS: Overall response was 40.6%, median progression-free survival was 8.2 months and median survival was 15.5 months. Dose reduction due to treatment-related adverse events occurred in 50.8% of patients starting at 750 mg/day. No significantly different progression-free survival was observed between patients who underwent any time dose reduction (n = 38) versus those who remained on the recommended dose of 750 mg/day (n = 32; p = 0.07). CONCLUSION: The efficacy of ceritinib compassionate use program resembled that of clinical trials. Dose reductions and adjustments did not appear to negatively affect clinical outcome.

Anti-epidermal growth factor receptor skin toxicity: a matter of topical hydration.

Skin toxicity is a frequent complication of anti-epidermal growth factor receptor therapy, which can be an obstacle in maintaining the dose intensity and may negatively impact on the clinical outcome of cancer patients. Skin lesions depend on the disruption of the keratinocyte development pathways and no treatment is clearly effective in resolving the cutaneous alterations frequently found during anti-epidermal growth factor receptor therapy. Among systemic treatments, oral tetracycline proved to be useful in preventing skin manifestations. We describe the case of a patient affected by metastatic colorectal cancer, for whom a combination of chemotherapy and cetuximab was used as second-line treatment. The patient developed a symptomatic papulopustular skin rash that disappeared completely after a twice-daily application of a hydrating and moisturizing cream, mainly consisting of a mixture of paraffin, silicone compounds, and macrogol. The marked cutaneous amelioration allowed the patient to continue cetuximab without any further symptoms and was associated with a partial radiological response.

Contrast enhanced chest-MDCT in oncologic patients. Prospective evaluation of the prevalence of incidental pulmonary embolism and added value of thin reconstructions.

OBJECTIVES: To prospectively assess prevalence/characteristics of clinically unsuspected pulmonary embolism (PE) in cancer patients undergoing follow-up chest MDCT and investigate MDCT protocol. METHODS: We evaluated 1013 oncologic patients. MDCT images at 5 and 1.25 mm thickness were independently evaluated. Pulmonary artery opacification degree was assessed. Presence, level, and site of PE were reported. Type of malignancy and metastases were reported for PE-positive patients. RESULTS: After excluding 1.4% (14/1013) of examinations due to inadequate vessel opacification, 999 patients (572 male; mean age:68 ± 12 years; range:26-93 years) entered the study. Prevalence of PE was 5%. There was significant improvement in the sensitivity for both readers in the evaluation of 1.25 mm compared to 5 mm images (46-50% to 82-92%). 30% (15/51) PE were not described by the radiologist in the prospectively issued report; 53 % (27/51) of PE were segmental, 72.5% (37/51) unilateral. The right lower lobe was the most involved (59%). 27% patients had colon cancer, 18% lung cancer. Among PE-positive patients (25 male; mean age 70 ± 10 years; range:44-87 years), 25% (13/51) had lung cancer, 15% (8/51) colon cancer. CONCLUSIONS: Thin reconstructions are essential for PE diagnosis, regardless of reader experience. Regarding oncologic patients, incidental PE diagnosis influences anticoagulation therapy. KEY POINTS: • CT pulmonary angiography is the gold standard for PE diagnosis. • Cancer and oncological treatments are risk factors for PE. • The prevalence of unsuspected PE was 5%. • Thin reconstructions are essential for PE diagnosis regardless of reader experience. • In oncologic patients, PE diagnosis influences anticoagulation therapy.

[Cancer treatment in elderly patients: evidence and clinical research]. / Il trattamento oncologico nel paziente anziano tra evidenze e ricerca clinica.

In 2020 the percentage of patients with a diagnosis of cancer in people with more than 65 years will exceed 70% and 28% in ethnic minorities. The treatment of cancer in these populations is challenging for the oncologists due to socio-economic issues such as poverty, reduced access to the hospital care, level of education. The clinical pathway "diagnosis-treatment-cure", typical of the care of young patients has to be integrated in elderly patients with a more individualized treatment by means of comprehensive geriatric assessment (CGA). IADL (Instrumental Activities of Daily Living) have the best predictive role in oncological setting and their impairment significantly correlate with overall survival, chemotherapy toxicities and thirty days postoperative morbidities. The CGA is universally accepted as the most appropriate instrument to analitically evaluate the age related problems of elderly patients. The role of CGA is crucial to identify geriatric issues not easily diagnosed, to predict treatment toxicities, functional or cognitive decline, post operative complications and to estimate life expectancy. The CGA items are predictive of severe toxicity, however it is not clearly established which are the best performers and the best cut-offs points. Today CGA is integrated with physical performance tests (the most widely used is the "time up and go" test) and laboratory assay of Interleukin 6 and D-Dimer that correlate with mortality and physical decline. There are few prospective studies that evaluated the role of CGA in treatment choice. The first is a phase II study in solid tumors, the second is a haematological trial on non Hodgkin lymphoma. The largest trial is a 571 patients observational series that confirmed the role of CGA in decision making. The administration of CGA is time consuming and consequently some screening tools were developed. VES-13 is a 13 items tool that explores prevalently the functional status and the self reported health status. VES-13 showed a good sensibility (87.3%) but a low specificity (62%) with respect to CGA for the diagnosis of patients with disabilities. Overcash et al. proposed an abbreviated form of CGA using a reduced number of items of ADL, IADL, MMSE and GDS. There was a good correlation between complete and reduced scales (coefficient of correlation 0.8). G8 is a screening tool composed of 8 questions that explore functional, cognitive and nutritional status. The score with the best equilibrium between sensibility and specificity was 14 (sensibility 85% and specificity 65%). In the first observational trial age, hystotype, chemotherapy dose, haemoglobin (man: 11 g/dL; women: 10 g/dL), creatinine clearance less than 34 mL/min (Jelliffe formula), earing problems, at least a fall in the last six months, walking problems, low social activity, were related to a major risk of toxicity; in another trial IADL, diastolic blood pressure, LDH and MAX2 index were predictive of haematological toxicity, while performance status, Mini-Mental Status score, Mini-Nutritional Assessment (MNA) score and MAX2 index were predictive of non haematological toxicity. Based on these parameters a 0-2 score was developed. A recent "position article" of EORTC (European organization for Research and Treatment of Cancer) and SIOG analyzed the pro and the contra of the use of some indicators in elderly patients. The overall survival (OS) frequently used in classical clinical trial could give wrong messages as there are some competitive risks of death in elderly patients. Another important indicator is the disease specific survival (DSS). Concerning the design of clinical trials, a possible strategy is to enrol elderly patients without upper age limit and to plan stratification. An interesting trial design is the so called "extended trial" that allow to re-open the arm of a trial in which a too low number of older patients was enrolled.

miR-296/Scribble axis is deregulated in human breast cancer and miR-296 restoration reduces tumour growth in vivo.

miR-296-5p is a central regulator of signalling pathways affecting development, stem cell differentiation and cancer. We hypothesized that miR-296-5p is involved in breast cancer onset and progression possibly through regulation of its target SCRIB (Scribble), a polarity protein recently implicated in the acquisition of cancer stem cell traits and in cell motility. We found that miR-296-5p levels were consistently reduced in human breast cancer tissues compared with non-neoplastic mammary parenchyma, and low expression of this miRNA predicted shorter disease-free survival independently of classic clinicopathological parameters. Further, reduced miR-296-5p levels were significantly correlated with an earlier spread of cancer in the overall series and with distant metastases in the subset. In contrast with its regulator, SCRIB was overexpressed and mislocalized in primary breast cancers or locoregional or distant metastatic lesions compared with normal parenchyma. Notably, SCRIB mislocalization was associated with overall survival, metastatic spread and organ tropism in patients with breast cancer. Finally, direct injection of a precursor miR-296-5p into tumours of a breast cancer xenograft model significantly decreased tumour growth. Our results show that the miR-296-5p/SCRIB axis plays a role in breast carcinogenesis and an miR-296-5p-based therapeutic approach hampers breast cancer tumour growth in vivo. Modulation of miR-296-5p may represent a new therapeutic option for patients with breast cancer.

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.

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).

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.

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.

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.

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.