Oncologist最新文献

Invasive lobular carcinoma of the breast demonstrates a distinct infiltrative growth pattern and a predilection for metastasis to the gastrointestinal tract, often without forming discrete masses. We report a 64-year-old woman with a history of estrogen receptor-positive, HER2-negative invasive lobular carcinoma who presented with progressive nausea, vomiting, and diarrhea. Recent surveillance imaging had shown no evidence of metastatic disease. Computed tomography revealed nonspecific findings, despite extensive mucosal involvement that was later identified on endoscopy. Upper endoscopy and colonoscopy demonstrated diffuse nodular and congested mucosa throughout the duodenum and colon without focal lesions. Histologic evaluation revealed poorly cohesive tumor cells infiltrating the lamina propria, and immunohistochemistry was positive for cytokeratin 7, GATA3, and estrogen receptor, confirming metastatic breast carcinoma. Diffuse gastrointestinal involvement by invasive lobular carcinoma is uncommon and may mimic inflammatory, infectious, ischemic, or medication-related conditions, contributing to delayed diagnosis. This case highlights an important diagnostic pitfall and underscores the need to consider metastatic disease in patients with a history of lobular breast carcinoma who present with unexplained gastrointestinal symptoms, even in the absence of radiographically apparent disease.

The global incidence of cancer is on the rise, with Africa experiencing a particularly steep increase in both cancer incidence and mortality. This upward trend is driven by a combination of factors, including population growth, poverty, aging, urbanization, and the adoption of lifestyles that increase the risk of cancer. It is projected that from 2022 to 2045, the incidence of cancer in Africa will increase by 106.8%, while cancer mortality will rise by 111.7% if no action is taken. In contrast, Europe is expected to see increases of only 22.5% in incidence and 32.2% in mortality. Despite global advancements in cancer care, Africa continues to grapple with significant inequities in access to cancer prevention, diagnosis, and treatment. These disparities are primarily driven by financial barriers, inadequate healthcare infrastructure, and imbalances in the global pharmaceutical market. As a result, we are witnessing a troubling rise in premature deaths and their associated consequences. This paper delves into the escalating public health crisis of cancer in Africa. The authors highlight the urgent need to improve access to essential cancer medicines for all affected individuals. Additionally, the paper calls for policy reforms and a coordinated, collaborative effort among stakeholders-including governments, international organizations, and pharmaceutical companies-to ensure equitable access to treatments and improve outcomes for cancer patients in Africa. Addressing this crisis requires alignment with the Sustainable Development Goals (SDGs) to prevent avoidable deaths.

Background: the homologous recombination deficiency signature (HRDsig) is emerging as a novel potential predictor of PARP-inhibitor (PARPi) response. We compared genomic alterations (GA) across BRCA2-loss, BRCA2 short variant-mutated (svmut), and BRCA2-wild type (wt) clinically advanced prostate carcinoma (CAPC) samples, combined with an assessment of HRDsig status to gain a better understanding of these biomarkers.

Methods: Comprehensive genomic profiling (CGP) was performed on 22,061 CAPC cases to evaluate all classes of GA. Microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic ancestry, were derived from sequencing data. HRDsig status was calculated using genome-wide copy number features. PD-L1 expression was assessed by IHC. Comparisons were performed using Fisher's exact test with Benjamini-Hochberg correction for false discovery.

Results: Among 22,061 CAPC cases, 10.2% were HRDsig+. HRDsig+ and were enriched for BRCA2, RB1, MYC, RAD21, and AR alterations, while SPOP, MSI-high, high TMB, and MMR signatures were more frequent in HRDsig- cases. Across BRCA2-defined subgroups, 597(2.7%) were BRCA2-loss, 1,085(4.9%) BRCA2-svmut, and 20,379(92.4%) BRCA2-wt. Both BRCA2-loss and BRCA2-svmut were associated with higher GA burden and enrichment for RB1 alterations. BRCA2-loss cases displayed lower TMB-high incidence, while BRCA2-svmut showed higher MSI-high and TMB-high incidence. Most BRCA2 alterations were bi-allelic, with concurrent alterations in other HRR genes being rare.

Conclusions: BRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.

Background: The first-generation Bruton's tyrosine kinase inhibitor (BTKi), ibrutinib, is associated with significant cardiotoxicity. Second-generation agents were developed to mitigate this risk and offer an improved safety profile. This systematic review and meta-analysis of six direct comparator studies compares the cardiac safety profiles of first- and second-generation BTKi.

Methods: We systematically searched Medline, Embase, and Cochrane for studies directly comparing first- and second-generation BTKi. Data from 6 studies, encompassing 14,455 patients (12,816 in the first-generation arm and 1,639 in the second-generation arm), were included. The primary outcomes were the incidence of atrial fibrillation (AF) and cardiac events, defined by the Medical Dictionary for Regulatory Activities (MedDRA) system organ class. All pooled analyses were conducted using a random-effects model. Publication bias was evaluated visually using a funnel plot, quantitatively with Egger's regression test, and corrected using the Duval and Tweedie trim-and-fill method.

Results: Compared to second-generation agents, ibrutinib was associated with a significantly higher risk of AF (OR 2.50, 95% CI 1.97 to 3.17), total cardiac events (OR 1.53, 95% CI 1.18 to 1.99), and heart failure (OR 2.08, 95% CI 1.13 to 3.83). This translated to a threefold higher rate of treatment discontinuation for a cardiac cause (OR 3.32, 95% CI 1.46 to 7.55). No significant difference in all-cause mortality was found.

Conclusion: Second-generation BTKi may provide a more favorable cardiovascular safety profile than ibrutinib, resulting in fewer key cardiac events and less treatment-limiting toxicity. These findings should inform clinical decision-making, especially for patients with increased risk for cardiovascular disease.

Background: Cytogenetic abnormalities (CAs) in multiple myeloma (MM) are traditionally assessed statically at diagnosis, but longitudinal monitoring reveals dynamic clonal evolution, particularly during relapse. In Asian populations, data on CA dynamics and their prognostic impact remain scarce.

Patients and methods: This retrospective study included 106 MM patients (2014-2024) in whom CAs were evaluated at diagnosis and relapse via cIg-FISH. The prognostic impact of clonal burden, copy number alterations, and longitudinal evolution of cytogenetic complexity was comprehensively assessed.

Results: At first relapse, 33.0% of patients acquired new CAs, with 1q21+ and del(17p13) incidences significantly increasing (P = .032, P = .003). Longitudinal analysis showed 1q21 amplification (≥4 copies) expanded (27.4% to 40.6%), while gain (3 copies) remained stable. Baseline 1q21 amplification predicted shorter 1st PFS (P = .002), whereas 1q21 gain at relapse correlated with inferior 2nd PFS (P = .023), often co-occurring with del(17p13) (28.1%). Persistent 1q21+ and de novo del(17p13) both predicted inferior OS (P ＜ .05). Based on clonal dynamics, patients with >20% expansion exhibited significantly shorter 1st PFS (P = .045) compared to the stable (unchanged) CAs subgroup. Similarly, those acquiring new CAs had shorter 2nd PFS (P = .039) and a trend toward worse OS (P = .056).

Conclusion: Both acquisition of new CAs and expansion of existing clones at relapse are key prognostic indicators, highlighting the importance of dynamic CA monitoring in MM management.

Background: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the largest SBA cohort to date.

Methods: We retrospectively reviewed SBA patients treated with taxane-based chemotherapy at MD Anderson Cancer Center from 1994-2024. Eligible patients had pathologic confirmation, received >1 treatment cycle, and had tumor response evaluation. Survival analyses were analyzed using Kaplan-Meier and Cox proportional hazard models.

Results: Seventy patients were identified. Median age was 57, and 59% were male. Primary sites were duodenum (44%), jejunum (34%), and Ileum (16%). Metastatic sites included peritoneum (39%) and liver (31%). Common mutations were TP53 (63%), KRAS (47%), SMAD4 (24%), and APC (15%). Taxanes were administered as single agents (29%) or in combination (71%), most often in second-(40%) or third-line (33%) settings. Overall response rate was 24%. Median time to progression (mTTP) was 3.1 months (95% CI: 2.0-4.2) and median overall survival (mOS) was 8.7 months (95% CI: 7.4-10.1). Efficacy did not differ by treatment line, regimen type, or tumor site, but was significantly associated with TP53 status; response rate was 20% in TP53-mutated vs 45% in wild-type (P = 0.009), with mTTP 2.5 vs 4.9 months (P = 0.009) and mOS 7.3 vs 10.6 months (P = 0.002). On multivariable analysis, TP53 mutation predicted worse outcomes.

Conclusion: Taxane-based therapy demonstrated activity in metastatic SBA, with 24% response and 3.1-month mTTP. TP53 mutation may be a negative predictive marker for taxane efficacy. These findings support prospective investigation in metastatic SBA.

Background: Exocrine pancreatic insufficiency (EPI), a common complication of pancreatic cancer (PC), reduces quality of life and may shorten survival. While pancreatic enzyme replacement therapy (PERT) improves symptoms and outcomes, real-world patterns of EPI workup and PERT use across PC subtypes remain poorly described in the US.

Patients and methods: We retrospectively analyzed 250 patients with resectable or metastatic PC from a single institution's prospectively maintained registry (2013-2018), collecting data on clinical characteristics, EPI symptoms, fecal elastase testing, and PERT prescriptions. In addition to the retrospective analysis, a quality improvement intervention for EPI management was implemented (1/2021-1/2023) and outcomes were analyzed.

Results: Among 250 patients, 97 underwent surgery for resectable disease and 153 received non-surgical management for metastatic PC. EPI symptoms occurred in 58% of metastatic and 68% of surgical patients. Fecal elastase testing was rarely performed (2% vs. 9%, respectively). PERT was prescribed to 46.5% of metastatic and 84% of surgical patients, but average doses were suboptimal (18,500 vs. 20,000 USP units per meal; recommended: ≥40,000). Among those on PERT, symptom resolution was reported in 33% of metastatic and 44% of surgical patients. Contrasting with results from the retrospective analysis, the quality improvement intervention led to 90% of 41 participants being prescribed PERT at an average dose of 44,700 USP units per meal. 74.1% of treated patients experienced complete resolution of EPI symptoms.

Conclusion: Despite prevalent EPI symptoms in PC patients, fecal elastase testing was infrequently utilized, and PERT was often underdosed. Educational initiatives are needed to improve guideline adherence and optimize outcomes.

Background: To investigate the outcomes of combined lenvatinib plus immune checkpoint inhibitors (ICIs) in patients with unresectable, recurrent, or metastatic hepatocellular carcinoma (HCC) in a real-world setting.

Material and methods: This retrospective study included patients with unresectable, recurrent, or metastatic HCC who received lenvatinib combined with ICIs at the Fifth Medical Center of the Chinese PLA General Hospital between May 2018 and November 2022. The study outcomes were overall survival (OS), progression-free survival (PFS), and treatment response.

Results: This study included 117 patients. The objective response rate (comprising both complete and partial responses) was 53.2%. Among those with first-line lenvatinib plus ICI (n = 109), the disease control rate (complete response, partial response, and stable disease) was 89.9%. In all patients, the median OS and PFS were 26.0 (95% CI: 22.0-30.4) and 15.3 (95% CI: 13.2-17.5) months, respectively. In first-line patients, the median OS and PFS were 27.6 (95% CI: 23.4-34.6) and 15.4 (95% CI: 13.4-18.2) months, respectively. Among the 117 patients, treatment was discontinued in 58 (50%) because of AE (n = 9, 16%), PD (n = 43, 74%), or an unknown reason (n = 6, 10%). Among the 117 patients, treatment was interrupted in 26 (22%), and the dose was adjusted in 24 (21%).

Conclusion: This real-world study supports the possibility of using lenvatinib combined with ICI for the management of patients with unresectable, recurrent, or metastatic HCC, including first-line treatment. Confirmation through a formal clinical trial would provide firmer conclusions.

Background: Symptom trajectories vary among patients during cancer treatment. The National Institutes of Health resilience model, which defines resilience as the ability to resist, recover, or grow from stressors, may be useful in understanding these variations. This study examined variations in symptom trajectories through the lens of resilience among older adults with advanced cancer.

Methods: This longitudinal quantitative study included patients aged 70 and older with advanced cancer who were receiving treatment regimens associated with a high risk of treatment-related toxicities, using data from the GAP70+ study (NCT02054741). A summary severity score of 24 symptoms from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events and functional status (measured by instrumental activities of daily living) were assessed prior to the treatment regimen initiation, at 4-6 weeks, 3 months, and 6 months later. Symptom trajectories were estimated using growth mixture models. Resilience was indicated by trajectories of resisting, recovering, or growing (i.e., improving from moderate/severe to none/mild severity). Its association with functional status was examined using longitudinal linear mixed models.

Results: The study included 710 patients (average age 77.2, 43.2% female, 88.0% receiving chemotherapy). Overall, 17.7% of patients showed resilience in symptom response, which was associated with higher baseline functional status (13.2 vs 12.0, p < 0.001) and stable functioning over six months. In contrast, non-resilience in symptom response was associated with a functional decline of 0.7-0.9 points without recovery by six months (p < 0.001).

Conclusion: Resilience in symptom response provides a novel perspective on symptom trajectory variations. Future research should explore underlying contributing factors to inform interventions that promote resilient symptom responses.