OBJECTIVE: There is no agreed-upon standard option for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) unfit for cisplatin-based regimens. Therefore, we performed a systematic review to explore alternative options for this population.
METHODS: We searched PubMed, Cochrane, and Embase databases for observational studies and clinical trials (CTs) assessing treatment options for LA HNSCC cisplatin-ineligible patients. This study was registered in PROSPERO under the number CRD42023483156.
RESULTS: This systematic review included 24 studies (18 observational studies and 6 CTs), comprising 4450 LA HNSCC cisplatin-ineligible patients. Most patients were treated with cetuximab-radiotherapy [RT] (50.3%), followed by carboplatin-RT (31.7%). In seven studies reporting median overall survival (OS) in patients treated with cetuximab-RT, it ranged from 12.8 to 46 months. The median OS was superior to 40 months in two studies assessing carboplatin-RT, and superior to 15 months in two studies assessing RT alone. For other regimens such as nimotuzumab-RT, docetaxel-RT, and carboplatin-RT plus paclitaxel the median OS was 21, 25.5, and 28 months, respectively.
CONCLUSIONS: Our systematic review supports the use of a variety of therapy combinations for LA HNSCC cisplatin-ineligible patients. We highlight the urgent need for clinical studies assessing treatment approaches in this population.

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There is increasing evidence regarding the role of various maintenance therapy (MT) strategies after initial induction to treat newly diagnosed transplant-ineligible patients with MM. We reviewed the literature on available regimens for patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). Lenalidomide (R)-based regimens are still the front-line therapy, but there is an increasing use of bortezomib-based regimens. The MT regimen is mainly based on the initial induction regimen. MT has shown survival benefits compared with patients without maintenance therapy. The most common adverse effects of MT include anemia, neutropenia, thrombocytopenia, infections, and peripheral neuropathy. In conclusion, induction followed by maintenance based on lenalidomide, bortezomib, ixazomib, or daratumumab-based regimens has shown promising results. Therefore, it is essential to conduct more clinical trials to better understand the role of MT in the treatment of NDMM patients who are not candidates for autologous stem cell transplantation.

OBJECTIVE: Intramyocardial autologous bone marrow-derived stem cells injection (IM-BMCs) has been used in patients with ischemic heart disease (IHD) who are ineligible for revascularization; however, the procedure has yielded mixed results. The objective of this meta-analysis was to evaluate the safety and therapeutic benefits of this treatment on a relatively large scale.
METHODS: PubMed, EMBASE, and Cochrane Library databases through September 2014 were searched for randomized clinical trials (RCTs) of IM-BMCs to treat IHD. Outcome measures were defined as mortality after treatment, change in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV). Weighted mean differences for the changes were estimated with a random-effects model.
RESULTS: Nine RCTs were eligible for inclusion. IM-BMCs significantly reduced the risk of mortality (RR, 0.33; 95% CI, 0.17-0.65; p = 0.001). IM-BMCs significantly improved LVEF by 2.57% (95% CI, 0.34-4.80%; p = 0.02) and reduced LVESV by 9.67 mL (95% CI, -16.43 mL to -2.91 mL; p = 0.005). No significant improvement in LVEDV (WMD = 4.73 mL; 95% CI, -7.22 mL to 16.68 mL; p = 0.44) was detected in patients who received IM-BMC therapy.
CONCLUSIONS: IM-BMC therapy showed clinical safety while being used as stand-alone treatment in IHD with no option of revascularization. The therapeutic efficacy requires further confirmation in large well-powered trials with long-term follow-up.

BACKGROUND: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown.
METHODS: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10(3)/uL, or neutrophil count <1500/mm(3).
RESULTS: Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378-1.751, P < 0.0001).
CONCLUSIONS: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.