Cancer Medicine最新文献

Aim: Although Japanese expert consensus introduced the borderline resectable (BR) criteria, additional classification is considered necessary for clinical practice. This study aimed to evaluate the prognostic predictive value of the modified BR (mBR) criteria.

Methods: From 2009 to 2024, 1056 treatment-naïve patients with hepatocellular carcinoma (HCC) and Child-Pugh A were enrolled (median age: 73 years). To obtain the mBR criteria, the original BR classification was modified by separately considering patients with extrahepatic metastasis (EHM, termed "boldly BR") (n = 42) while categorizing the rest into resectable (n = 790), mBR1 (n = 95), and mBR2 (n = 129) groups. Treatments were classified as Cur (curative: surgical resection or radiofrequency ablation), NC (non-curative: other treatment), or BSC (best supportive care). Clinical features and prognosis according to mBR criteria were analyzed retrospectively.

Results: Overall survival (OS) was stratified according to the mBR criteria (resectable/mBR1/mBR2/BBR = 113.3/49.4/30.1/10.3 months). Albumin-bilirubin scores worsened progressively, according to the criteria (-2.70/-2.54/-2.40/-2.37), and elevated tumor marker levels (alpha-fetoprotein [AFP] levels ≥ 100 ng/mL: 18.5%/35.8%/46.5%/59.5%; AFP-L3 ≥ 10%: 19.8%/40.9%/54.7%/66.7%; and des-gamma-carboxy prothrombin levels ≥ 100 mAU/mL: 35.8%/67.4%/81.4%/90.5%, each p < 0.001) occurred more frequently in advanced groups. The Cur group in the resectable category showed significantly better OS compared with the NC and BSC groups (121.3/48.1/35.3 months, p < 0.001). Similar trends occurred in mBR1 (66.5/34.2/5.2 months) and mBR2 (57.3/22.4/7.5 months). Conversely, although some patients in the curative group had long-term survival, treatment modality and baseline characteristics showed no prognostic impact on BBR (15.0/10.3/9.0 months).

Conclusion: Other than for patients with EHM, aggressive surgical resection may be considered a potential initial therapeutic option for advanced HCC; however, direct comparisons with other treatment modalities were not performed in this study.

Background: While receipt of surgery at regional referral centers is associated with improved perioperative outcomes, many vulnerable patients may experience barriers in accessing these hospitals. When these patients do manage to undergo surgery at referral centers, it remains unclear where they are readmitted to receive care when complications arise. Patients may be readmitted to the hospital where surgery was performed (index readmission) or to a different hospital (non-index readmission). This study examined whether factors associated with readmission to index versus non-index hospitals differ for patients undergoing surgery at referral centers compared to non-referral centers.

Methods: We used data from the Pennsylvania Cancer Registry and the Pennsylvania Health Care Cost Containment Council (PHC4) to identify patients who had major cancer surgery and were subsequently readmitted within 90 days. We fit a multivariable logistic regression model to identify factors associated with 90 day readmission to an index versus non-index hospital. We included an interaction term between referral center status and cancer type in this model.

Results: A total of 8215 patients were readmitted within 90 days of cancer surgery, of whom 78% (N = 6388) were readmitted to the index hospital. On multivariable analysis, factors associated with lower odds of index versus non-index readmission included older age, high Elixhauser comorbidity scores, and longer travel times. There was no significant difference in odds of index readmission when patients were treated at referral versus non-referral centers (OR = 0.77; 95% CI, 0.50-1.20). When assessing interactions, patients with lung cancer had lower odds of index readmission when treated at referral versus non-referral centers, relative to other cancers (OR = 0.59; 95% CI, 0.41-0.84).

Conclusions: Higher clinical complexity and greater travel burdens were associated with lower odds of index readmission. Relative to other cancers, patients with lung cancer may be more likely to experience care fragmentation after undergoing surgery at a referral center.

Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, accounting for approximately 80% of all skin cancers. Although more prevalent among Caucasians, BCC affects individuals of all racial and ethnic groups and may present atypically in skin of color, contributing to delayed diagnosis.

Aims: This review aims to examine the causes, clinical presentations, prevention strategies, and treatment options for BCC, with an emphasis on recent advancements and ongoing challenges in management.

Materials and methods: This review integrates current peer-reviewed literature with clinical insights derived from dermatologic practice, including the evaluation of representative, deidentified patient cases. Observations from clinical experience were incorporated to contextualize diagnostic approaches, management strategies, and treatment outcomes across diverse patient populations. All patient information was anonymized, and no identifiable data were included.

Results: Ultraviolet (UV) radiation remains the leading cause of BCC in fair-skinned populations, whereas genetic predispositions and environmental factors play a larger role in darker-skinned individuals. Diagnostic advances, including dermoscopy and reflectance confocal microscopy, have improved detection, particularly for pigmented lesions that may mimic benign conditions. Preventative strategies include broad-spectrum physical sunscreens, protective clothing, lifestyle modifications, and supplementation such as nicotinamide, which has demonstrated potential in reducing UV-induced skin damage. Treatment options range from Mohs micrographic surgery, considered the gold standard for high-risk and cosmetically sensitive areas, to simple excision, electrodessication and curettage, radiation therapy, and advanced systemic therapies including sonic hedgehog and PD-1 inhibitors for locally advanced or metastatic disease.

Discussion: Emerging diagnostic tools and expanding therapeutic modalities have enhanced the ability to tailor BCC management to individual patient risk profiles and tumor characteristics. Non-surgical and combination approaches continue to evolve, offering effective alternatives for select cases.

Conclusion: By integrating prevention, early diagnosis, and personalized treatment strategies, modern approaches to BCC management are improving patient outcomes and addressing the complexities of care across diverse populations, underscoring the importance of multidisciplinary and individualized management.

Purpose: In non-small cell lung cancer (NSCLC) patients resistant to first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), only half develop the T790M mutation and thus qualify for the treatment using third-generation EGFR-TKIs. For T790M-negative patients, chemotherapy is the recommended second-line treatment. We compared the efficacy between third-generation EGFR-TKIs and chemotherapy with or without first/second-generation EGFR-TKIs in T790M-negative patients.

Patients: This study included T790M-negative patients with EGFR-mutated advanced NSCLC and progressing after first-line treatment with first- or second-generation EGFR-TKIs. Data on clinical characteristics, disease features, and survival were collected, including general conditions, medical history, imaging, histology, and molecular profiling.

Results: Of 82 patients progressing after first- or second-generation EGFR-TKIs without acquiring T790M, 45 received third-generation EGFR-TKIs and 37 received chemotherapy and/or first/second-generation EGFR-TKIs. We found that third-generation EGFR-TKIs led to significantly longer median progression-free survival (mPFS) than other treatments [10.20 months vs. 5.70 months, p = 0.017]. Subgroup analyses indicated that third-generation EGFR-TKIs had similar mPFS to the chemotherapy group but were significantly superior to first/second-generation EGFR-TKIs with or without chemotherapy (10.20 months vs. 4.80 months, p < 0.001; 10.20 months vs. 3.30 months, p = 0.004). The median overall survival (mOS) for patients treated with third-generation EGFR-TKIs and with non-third-generation therapy was 39.80 months (95% CI 23.14 to 56.46) and 32.40 months (95% CI 18.71 to 46.09), p = 0.408, respectively.

Conclusions: Third-generation EGFR-TKIs significantly improved mPFS in T790M-negative patients with EGFR-mutated advanced NSCLC and resistant to first-line treatment with first- or second-generation EGFR-TKIs.

Trial registration: ChiCTR2500096109.

Introduction: BI 891065, a second mitochondria-derived activator of caspases mimetic targets the inhibitor of apoptosis (IAP) family member cIAP1. We describe two first-in-human phase 1 trials assessing BI 891065 ± the anti-programmed cell death protein-1 (PD1) antibody, ezabenlimab, in advanced solid tumors.

Methods: Trials were conducted in the USA (NCT03166631) and Japan (NCT04138823). Dose escalation of BI 891065 monotherapy (part A) and combined with ezabenlimab (part B) was guided by a Bayesian Logistic Regression Model with overdose control. Primary endpoints were maximum tolerated dose (MTD) and number of patients with dose-limiting toxicities (DLTs) in Cycle 1. Other endpoints included objective response (RECIST v 1.1), pharmacokinetics, and changes in peripheral blood mononuclear cell (PBMC) and tumor cIAP1 levels.

Results: Twenty-five patients (USA study) received 5-400 mg daily BI 891065 monotherapy; 12 patients (Japan study) received 100 mg daily, 200 mg daily, or 200 mg twice-daily BI 891065 monotherapy. No DLTs occurred in the USA study; three occurred in the Japan study: grade 3 increased bilirubin (n = 2) and maculopapular rash (n = 1). Neither study reached MTD for monotherapy. Treatment-related adverse events (TRAEs) occurred in 52% and 75% of patients, respectively. BI 891065 plus ezabenlimab combination (USA study part B only) was received by 37 patients (50-400 mg daily, 200 mg twice-daily) plus ezabenlimab (240 mg fixed-dose, Day 1 of 21-day cycles). One DLT occurred (grade 2 pneumonitis). MTD was not reached. TRAEs occurred in 81% of patients. Neither study reported objective responses; 25%-40% and 35% of patients achieved stable disease with BI 891065 monotherapy and the combination, respectively. cIAP1 levels were reduced in PBMCs and biopsies.

Conclusions: BI 891065 was tolerable in patients with advanced solid tumors, demonstrating target engagement as monotherapy and combined with ezabenlimab. Both studies ended early due to efficacy data that were insufficiently promising to justify continuation.

Trial registration: NCT03166631, NCT04138823.

Background: This study aimed to evaluate the long-term oncologic outcomes of robotic-assisted versus laparoscopic surgery in non-metastatic patients with locally advanced rectal cancer and to identify prognostic factors influencing overall survival (OS) and disease-free survival (DFS).

Material and methods: In this retrospective cohort study, 74 patients with mid or low rectal cancer underwent either laparoscopic (Gr. 1) (n = 28) or robotic-assisted (Gr. 2) (n = 46) surgery over 10 years. Baseline characteristics, surgical details, postoperative complications, and survival outcomes were analyzed. Multivariate Cox regression was used to identify independent predictors of OS and DFS.

Results: Both groups had no significant difference in hospital stay, conversion rates, or postoperative complications. Multivariate analysis revealed that robotic surgery was independently associated with improved OS (HR: 2.651; p = 0.019). Other significant predictors of poor OS included tumor grade G3, perineural invasion, and postoperative complications. For DFS, perineural invasion, postoperative complications, conversion to open surgery, and tumor recurrence were associated with worse outcomes. Restoration of bowel continuity via end-to-end anastomosis was linked to improved survival.

Conclusions: Robotic-assisted surgery offers comparable, and in some aspects superior, long-term oncologic outcomes to laparoscopic surgery for locally advanced rectal cancer. Independent predictors of poor survival included high-grade tumors, perineural invasion, conversion to open surgery, and postoperative complications. Surgical technique, selection criteria, and perioperative care remain crucial for optimizing outcomes.