High mortality risk among women with acromegaly still persists

IntroductionThe mortality ratio in patients with acromegaly has improved over the last few decades. We aimed to determine the mortality rate and correlated factors in patients with acromegaly before and after the introduction of national protocols for treatment. In addition, we determined whether there are sex-related differences in mortality of patients with acromegaly.MethodsThis observational retrospective study included 399 consecutive patients with acromegaly between January 2001–December 2022. Paraclinical data included random growth hormone (GH) and insulin-like growth factor-I (IGF1) levels, maximal pituitary tumor diameter at diagnosis, first visit, and last evaluation. Standardized mortality ratio (SMR) was calculated by dividing the observed and expected mortality rates. Cox regression analysis revealed the independent factors associated with mortality.ResultsAt the last visit, 31.07% (124) of patients were cured, 22.05% (88) had controlled acromegaly with medication, and 45.31% (181) had not controlled acromegaly. During follow-up (13.03 ± 5.65 years, 5216.62 person-years), 89 patients died (0.017%), resulting in an SMR of 1.18 [95% CI 0.95–1.45]. The independent factors associated with mortality were the last IGF1 level/last random GH level, absence of surgery, gonadotropin deficiency, and age. Patients with normal IGF1 after treatment showed an SMR of 0.71, whereas patients with IGF1 ratio > 1 showed SMR=1.51. Patients diagnosed between 1975–2007 and 2008–2022 had SMR = 1.25 [95% CI 0.97–1.58] and SMR = 1.09 [95% CI 0.68–1.65], respectively. In females with acromegaly, SMR was 1.63 [95% CI 1.24–2.11]; 1.76 [95% CI 1.30–2.34] in women diagnosed before 2008 and 1.33 [95% CI 0.69–2.33] in those diagnosed after 2008. Males with acromegaly had a mortality ratio similar to males from the general population (SMR = 0.99, [95% CI 0.66–1.41]).ConclusionPatients diagnosed with acromegaly in the last 15 years had lower mortality rates than those diagnosed before 2008, due to the availability of new medications, primarily somatostatin receptor analogs and to a higher proportion of patients undergoing surgery. Females still have a high mortality ratio owing to older age at diagnosis and higher risk of metabolic complications. Therefore, efforts should be made for early diagnosis of acromegaly in women

Upstaging and Downstaging in Gliomas—Clinical Implications for the Fifth Edition of the World Health Organization Classification of Tumors of the Central Nervous System

In 2021, the 5th edition of the WHO Classification of Tumors of the Central Nervous System (WHO-CNS5) was published as the sixth volume of the international standard for brain and spinal cord tumor classification. The most remarkable practical change in the current classification involves grading gliomas according to molecular characterization. IDH mutant (10%) and IDH wild-type tumors (90%) are two different entities that possess unique biological features and various clinical outcomes regarding treatment response and overall survival. This article presents two comparative cases that highlight the clinical importance of these new classification standards. The first clinical case aimed to provide a comprehensive argument for determining the IDH status in tumors initially appearing as low-grade astrocytoma upon histologic examination, thus underlining the importance of the WHO-CNS5. The second case showed the implications of the histologic overdiagnosis of glioblastoma using the previous classification system with a treatment span of 7 years that proceeded through full-dose re-irradiation up to metronomic therapy. The new WHO-CNS5 classification significantly impacted complex neurooncological cases, thus changing the initial approach to a more precise therapeutic management

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer

Leptomeningeal metastases (LM) are a rare but rapidly fatal complication defined by the spread of tumor cells within the leptomeninges and the subarachnoid space, found in approximately 10% of patients with HER2-positive breast cancers. This pilot study evaluated the efficacy of local treatment with intrathecal Trastuzumab (IT) added to systemic treatment. The oncologic outcome of 14 patients with HER2-positive LM is reported. Seven received IT, and seven received standard of care (SOC). The mean number of IT cycles administered was 12.14 ± 4.00. The response rate to CNS after IT treatment + SOC was 71.4%, and three patients (42.8%) obtained durable responses lasting more than 12 months. The median progression-free survival (mPFS) after LM diagnosis was six months, and the median overall survival (mOS) was ten months. The mean values of the PFS in favor of IT therapy (10.6 mo vs. 6.6 mo) and OS (13.7 vs. 9.3 mo) suggest a non-negligible investigation direction in the sense of exploiting intrathecal administration as a possible treatment modality in these patients. Adverse events reported were local pain related to intrathecal administration and one case of arachnoiditis, hematoma, and CSF fistulae. Intrathecal administration of Trastuzumab, alongside systemic treatment and radiotherapy, might improve oncologic outcomes in LM HER2-positive breast cancer with manageable toxicity