Chinese clinical oncology最新文献

Background: Real-world data on afatinib for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) G719X + S768I co-mutations remains limited. This study aims to evaluate the efficacy and safety of afatinib in a relatively large cohort of NSCLC patients with these uncommon mutations in Xuanwei and Fuyuan counties, China.

Methods: A retrospective study was conducted on 96 NSCLC patients from Xuanwei and Fuyuan, China, between August 2019 and March 2024. Patients with advanced-stage NSCLC harboring EGFR G719X + S768I co-mutations or single EGFR G719X/S768I mutations who received first-line afatinib treatment were included in the study. The parameters analyzed included the progression-free survival (PFS), and overall survival (OS). While treatment-related adverse events (AEs) were assessed for the safety of afatinib.

Results: All of the 96 patients, 59 were female and 37 were male, with a median age was 59.2±9.0 years. The mutations were classified as single EGFR G719X/S768I mutations (n=34; 35.4%) and G719X + S768I co-mutations (n=62; 64.6%). The median progression-free survival (mPFS) for all patients was 12 months (95% CI: 9.5-14.5), and median overall survival (mOS) was 29 months (95% CI: 18.0-40.0). Patients with the G719X + S768I co-mutations exhibited significantly longer mPFS (17 vs. 8 months, P<0.001) and mOS (33 vs. 15 months, P=0.04) compared to those with and single EGFR G719X/S768I mutation. Common treatment-related AEs included diarrhea (n=80; 83.3%), skin rash/acne (n=77; 80.2%), paronychia (n=53; 55.2%), and stomatitis (n=33; 34.4%), all of which were manageable. There was no significant difference in AEs between the two mutation groups.

Conclusions: This study represents the largest cohort of NSCLC patients with EGFR G719X + S768I co-mutations treated with first-line afatinib. Our findings confirmed the effectiveness and safety of afatinib in this patient population. Furthermore, the presence of the G719X + S768I co-mutations serves as an independent predictor of favorable PFS for NSCLC patients. This study will provide new clinical evidence supporting afatinib therapy for patients with EGFR G719X + S768I co-mutations, both in China and globally. This study fills an important gap in the existing literature by providing robust, large-scale clinical data, offering new insights for the treatment of NSCLC patients with these uncommon mutations.

Background: Endometrial cancer, the sixth most common malignancy in women, is frequently treated with carboplatin-paclitaxel chemotherapy. While myelosuppression is a common adverse effect, drug-induced pure red cell aplasia (PRCA) is exceedingly rare. This report presents a case of refractory PRCA induced by this regimen, which was successfully reversed with low-dose corticosteroids, underscoring its clinical significance.

Case description: A postmenopausal patient with endometrial cancer (stage IA, high p53 expression) received adjuvant paclitaxel and carboplatin chemotherapy. She subsequently developed severe anemia (reticulocytes 0.001×1012/L). Bone marrow examination revealed an absence of erythroid precursor cells. PRCA was diagnosed after excluding hemolysis, hematologic malignancies, infections, and autoimmune disorders. Given normal pre-chemotherapy hemoglobin (Hb) levels, drug-induced PRCA was suspected. Chemotherapy was discontinued, and stanozolol was initiated; however, Hb remained stable at 60 g/L without improvement. Low-dose corticosteroids (0.5 mg/kg) were added one week later, resulting in Hb increasing to 82 g/L within 2 weeks. Levels normalized within four weeks and remained stable after corticosteroid taper.

Conclusions: This case highlights PRCA as a potential complication of carboplatin-paclitaxel therapy, emphasizing the importance of obtaining reticulocyte counts and bone marrow studies in cases of refractory chemotherapy-induced anemia. Early low-dose corticosteroid intervention proved effective and safe. Clinicians should include PRCA in the differential diagnosis during chemotherapy toxicity surveillance to optimize supportive care in cancer patients.

Background: Small cell carcinoma is a highly aggressive neoplasm that commonly arises in the lungs. The occurrence of this tumor in the salivary gland, particularly the parotid gland, is extremely rare, accounting for less than 1% of all cases of malignant parotid gland tumors, and is associated with poor prognosis. Owing to its rarity, there remains no consensus on standardized therapeutic protocols.

Case description: A 58-year-old woman presented with a 4-month history of a progressively enlarging left preauricular mass and was ultimately diagnosed with small cell neuroendocrine carcinoma (SCNC) of the parotid gland. Evaluations including ultrasound, contrast-enhanced computed tomography (CT), and biopsy revealed a left parotid mass with cervical lymph node involvement, no metastases, specific histopathological and immunohistochemical features. Molecular testing showed TP53 and HRAS mutations, a programmed death ligand-1 (PD-L1) expression level of 30%, and the clinical staging was IVA (cT3N2bM0). A novel therapeutic strategy of induction chemotherapy in combination with sequential radiotherapy exhibited substantial therapeutic efficacy for this rare malignancy. We conducted a narrative review spanning 2000-2024 to elucidate the epidemiologic characteristics, diagnostic challenges, therapeutic paradigms, and prognostic determinants associated with parotid gland SCNC.

Conclusions: These findings yield valuable insights into the biological and clinical behaviors of this rare parotid gland neoplasm. Furthermore, this work enhances the understanding of the epidemiological characteristics and optimal management strategies for parotid gland SCNC.

Background and objective: Cancer is a public health problem and is considered the leading cause of death around the globe. Despite the advances in cancer therapies, many patients suffer from adverse side effects and drug resistance. Among the cancer hallmarks, metabolic reprogramming is essential for supporting the higher energy demand of cancer cells. Due to the Warburg effect, a misconception that oxidative phosphorylation (OXPHOS) and other mitochondrial-related metabolic pathways are dispensable for tumor cells was created. Nowadays, many studies have been demonstrating the importance of mitochondria and their metabolism to cancer bioenergetics and progression. Through this review, we aim to show natural compounds that regulate mitochondrial metabolism to exert their anticancer activity.

Methods: In this literature review, studies found in PubMed, in English and published between 1925-2025 were considered.

Key content and findings: Throughout this review, we discussed the importance of mitochondrial metabolism for carcinogenesis, updated and brought new natural products as potential therapies to target mitochondrial metabolism to counteract cancer progression. Furthermore, we discussed the future directions to overcome the limitations of the use of natural products as anticancer compounds.

Conclusions: Natural compounds can act in different pathways of mitochondrial metabolism to exert their antitumoral effects, however, some limitations need to be overcome. Developing natural product-based hybrids through the conjugation of natural compounds with bioactive molecules has gained interest to surpass these limitations, representing a good strategy to enhance the anticancer treatment effectiveness of natural products.

Background: Water-clear cell carcinoma of the parathyroid gland is an exceedingly rare malignancy, with the majority of published cases focusing on adenomas that are typically large and associated with mild elevations in parathyroid hormone (PTH) levels.

Case description: We present the case of a 43-year-old woman who presented with a pelvic pathological fracture and very high serum calcium of 15.5 mg/dL, along with a severely elevated PTH level (>2,500 pg/mL). Imaging studies, including ultrasound, computed tomography (CT), and technetium-99m sestamibi (99mTc-MIBI) subtraction scintigraphy, revealed a mass in the inferior parathyroid gland on the left side of the thyroid gland. The patient underwent surgical resection, and the excised tumor measured 3 cm × 2.5 cm × 1.5 cm and weighed 10.7 grams. Histopathological examination confirmed the diagnosis of water-clear cell carcinoma of the parathyroid gland, with prominent vascular invasion.

Conclusions: This case is particularly significant as it represents the largest water-clear cell carcinoma of the parathyroid gland reported in the literature to date. The patient was closely monitored postoperatively, and at 1-year follow-up, there were no signs of distant metastases or recurrence of hyperparathyroidism. This case underscores the aggressive nature of water-clear cell carcinoma, highlighting the need for early detection and prompt surgical intervention in such rare and potentially life-threatening tumors.

Background: Breast cancer (BC) is a leading cause of cancer-related deaths worldwide. Obesity, an established risk factor for BC in postmenopausal women, may also affect prognosis. This study evaluated the impact of obesity on the survival of BC patients treated at a public reference center in Brazil.

Methods: A retrospective cohort study was conducted with 7,424 BC patients treated at Hospital da Mulher (São Paulo, Brazil) from January 2011 to June 2021. Patients were categorized into four groups based on body mass index (BMI): underweight, healthy weight, overweight, and obese. Clinical, pathological, staging, and immunohistochemistry data were analyzed. Survival outcomes (overall and progression-free) were assessed using Kaplan-Meier estimates, with comparisons via logistic and Cox regression.

Results: Among the patients, 67.81% were overweight or obese, and 64.82% were postmenopausal (assumed ≥50 years old). A total of 6,992 patients were included in the survival analysis, with 3.79% succumbing to BC. No statistically significant differences in overall or progression-free survival were observed across BMI categories.

Conclusions: While obesity is highly prevalent among Brazilian women with BC, it did not significantly impact survival outcomes in this study. These findings underscore the need for prospective studies to explore potential confounding factors and long-term effects, as well as to inform tailored interventions in similar healthcare settings.

Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have revolutionized non-small cell lung cancer (NSCLC) treatment. Atezolizumab, a promising PD-L1 inhibitor, has unknown effectiveness and safety in patients with different PD-L1 expression statuses. This study aimed to evaluate the effectiveness and safety of atezolizumab compared with docetaxel in patients with NSCLC.

Methods: We conducted a systematic review and meta-analysis of double-blind randomized controlled trials (RCTs) comparing atezolizumab with docetaxel in NSCLC patients. PubMed, EMBASE, CNKI, Web of Science, Wanfang, and Cochrane Library databases were searched from January 2013 to December 2024. Two reviewers independently extracted data and assessed bias using the Cochrane Risk of Bias Tool. Meta-analysis was performed with Revman 5.3, pooling hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for adverse events (AEs), with subgroup analyses by PD-L1 expression status (positive/negative). PD-L1-positive was defined as either tumor cell (TC) PD-L1 expression ≥1% or immune cell (IC) PD-L1 expression ≥1%, while PD-L1-negative was defined as both TC <1% and IC <1%. The I2 statistic was used to evaluate heterogeneity between summary data.

Results: A total of 10 articles were included, involving 3,445 patients in the atezolizumab group and 3,018 patients in the docetaxel group. The results showed that atezolizumab had better efficacy than docetaxel for overall survival (OS) [hazard ratio (HR): 0.77, 95% confidence interval (CI): 0.73 to 0.81], OS (PD-L1-positive) (HR: 0.72, 95% CI: 0.65 to 0.79), OS (PD-L1-negative) (HR: 0.78, 95% CI: 0.71 to 0.85), progression-free survival (PFS) (HR: 0.93, 95% CI: 0.88 to 0.99), and PFS (PD-L1-positive) (HR: 0.89, 95% CI: 0.80 to 0.98). There was no obvious benefit in terms of objective response rate (ORR) and PFS (PD-L1-negative). Meanwhile, atezolizumab was well tolerated, with a lower incidence of grade 3-5 AEs (OR: 0.21, 95% CI: 0.15 to 0.28) and a lower discontinuation rate (OR: 0.35, 95% CI: 0.20 to 0.61) compared with docetaxel.

Conclusions: Atezolizumab showed OS improvement and great safety in NSCLC. There was no direct relationship between the effectiveness of atezolizumab and PD-L1 expression status. The safety and maintenance of efficacy remain undetermined, and further research is needed to explore the long-term effectiveness of atezolizumab.