Tolerance and Outcomes of Neoadjuvant Chemotherapy in Geriatric Breast Cancer Patients.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is an established treatment option for patients with human epidermal growth factor receptor 2-positive (Her2+) or triple-negative breast cancer (TNBC). However, the toxicities associated with NAC may lead to reduced tolerance in geriatric patients due to medical comorbidities. Our objective is to evaluate the tolerance and outcomes of NAC in geriatric patients with TNBC and Her2+ breast cancer. MATERIALS AND METHODS: An institutional review board approved, retrospective study of 43 geriatric (≥70 y) and 103 non-geriatric (<70 y) patients with TNBC and Her2+ breast cancer was conducted. Demographic, comorbidity, treatment, and toxicity variables were collected. Log-rank tests and Cox regression visualized survival outcomes evaluated associations with clinical and demographic variables. Descriptive statistics were performed. RESULTS: Following NAC, 30% geriatric patients had a pathologic complete response in the primary tumor, 54% had a partial response, and 16% had no response. Of the non-geriatric patients, 24% had a pathologic complete response, 64% had a partial response, and 12% showed no response. NAC-associated toxicities occurred in 81% of geriatric patients and 73% non-geriatric patients, with neutropenia occurring most frequently in both groups. Dose reduction and early discontinuation of NAC each occurred more frequently in the geriatric group (14%; 23%) than the non-geriatric group (7%; 6%). Higher post-treatment Eastern Cooperative Oncology Group scores were associated with worse overall survival and worse recurrence-free survival in both groups. CONCLUSIONS: NAC was associated with reduced tumor and nodal stage in most geriatric patients; however, NAC-associated toxicities were common and led some patients to reduce or stop their NAC regimen prematurely.

Oncogeriatric Developments.

Cancer is a disease of aging and is rapidly becoming the number one cause of mortality in older people. Over their lifetime, one in two men and one in three women will develop a cancer, with half of the risk being beyond the age of seventy. Therefore, cancer is a problem frequently encountered by geriatricians. In this article, we review a few recent progresses that will be of interest to the geriatric community. First, we now have robust evidence that a comprehensive geriatric assessment and management change outcomes in older cancer patients, notably allowing decreased treatment toxicity, better treatment completion, and increased functional outcomes. In gastrointestinal cancers and breast cancer, several recent studies have addressed when treatment intensity can be decreased, and when it cannot. New treatments for acute myeloid leukemia are finally beginning to improve outcomes for older patients and such patients should be referred to oncologists for management. In prostate cancer, new imaging techniques (e.g., PSMA scan) and treatment options can allow better treatment targeting and spare some hormonal and chemotherapy toxicity. Finally, we review recent public policy efforts to address the epidemiologic wave of cancer in older patients on a global scale.

Neoadjuvant systemic therapy in geriatric breast cancer patients: a National Cancer Database (NCDB) analysis.

PURPOSE: Neoadjuvant systemic therapy (NAST) can be an effective treatment option for patients with HER2 + or triple negative breast cancer (TNBC). However, its use in geriatric patients is largely understudied. Our aim is to investigate the effect of NAST in both septuagenarians and octogenarians with HER2 + or TNBC to better understand its role in the geriatric patient population. METHODS: We utilized the National Cancer Database (NCDB) to analyze female patients with HER2 + or TNBC between 70 and 89 years. We compared the baseline demographic and clinical characteristics of septuagenarians and octogenarians using mixed-effect modeling for continuous variables and conditional logistic regressions for categorical variables. Overall survival (OS) between several subgroups was compared based on a propensity score model. Kaplan-Meier method was used to calculate OS between the subgroups, and log-rank test was used to compare OS results. RESULTS: A total of 16,443 patients met inclusion/exclusion criteria, of which 92.9% had infiltrative ductal carcinoma and 73.5% were TNBC. Most patients received NAST as a first course of therapy (58.8%). Septuagenarians were more likely to receive NAST (65.9%), whereas octogenarians were more likely to receive upfront surgical resection (67.7%). Our analysis demonstrated OS benefit with NAST among patients who received surgical resection. However, in patients who received NAST, decline during therapy was associated with a significantly poorer OS outcomes in general. CONCLUSION: When combined with surgical resection, NAST is an effective treatment option in both septuagenarians and octogenarians. Nonetheless, careful selection of NAST recipients in this population remains critical to optimize patient outcome.

Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

Assessment of the external validity of the National Comprehensive Cancer Network (NCCN) guidelines for pancreatic ductal adenocarcinoma in a population of older patients aged 70 years and older.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) mainly occurs in older adults. Since randomized clinical trials (RCTs) provide the highest-quality evidence incorporated in NCCN recommendations, the underrepresentation of older patients in RCTs challenges guidelines' external validity and limits the solidity of evidence in this specific population. MATERIALS AND METHODS: The study aimed to investigate external validity of NCCN guidelines for PDCA and the impact of reference studies eligibility on overall survival (OS) in a real-world older population. We retrieved RCTs supporting NCCN recommendations for management of PDAC and identified ten topics. We matched a cohort of 707 PDAC patients aged ≥70 years from the Moffitt Cancer Center database with eligibility criteria of 96 reference RCTs to check the proportion of patients eligible for at least two RCTs. Eligibility >60% was rated full validity, 30%-60% partial validity and < 30% limited validity. We also performed log-rank test to assessed whether "eligibility" status affects OS, stratifying by age (70-74; 75-79; ≥80). RESULTS AND DISCUSSION: We found full validity for neoadjuvant (57/73 patients; 69.86%), locally advanced (28/39; 71.79%) and second line (88/110; 80%) treatment, while lowest validity was found for adjuvant chemotherapy (37/86; 43%). Eligible status was correlated with a significant OS benefit for adjuvant chemoradiation (p = 0.002) in all-comers and for first-line polychemotherapy in patients aged ≥80 (p = 0.01). Our analysis supports the limitation of guidelines' external validity in older patients, and hints at possible correlations with survival, although no definitive conclusions can be drawn at this stage. Renewing RCT design with broader eligibility criteria might help increase inclusion of older and thus strengthen the evidence.

Human papilloma virus infection prior to coitarche.

OBJECTIVE: The aim of our study was to determine the prevalence and the natural course of anogenital human papilloma virus (HPV) infections in girls prior to coitarche attending an outpatient gynecological unit. STUDY DESIGN: Specimens were taken from the anogenital region of 114 unselected 4-15 year old girls who were referred consecutively for various gynecological problems. RESULTS: Four girls were excluded because of sexual abuse. Low-risk HPV-deoxyribonucleic acid (DNA) was detected in 4 girls (3.6%) and high-risk HPV DNA in 15 children (13.6%). Two girls testing positive for HPV DNA had clinical apparent warts. After 1 year, 2 children had persistent high-risk HPV DNA, and in 1 case we found a switch from high-risk to low-risk HPV DNA. CONCLUSION: Subclinical genital low- and high-risk HPV infections are common in girls without any history of sexual abuse or sexual activity. We found persistence of genital HPV infection in children, which could be a reservoir for HPV-associated diseases later in life.

Identification of a novel mutation associated with familial adenomatous polyposis and colorectal cancer.

Colorectal cancer (CRC) is among the most fatal forms of solid tumor in men and women. While the majority of diagnosed CRC cases are sporadic, 15­25% of patients have a family history of adenomatous polyposis and CRC; however, the associated gene mutations remain largely unidentified. The aim of the present study was to investigate the genomes of a four­generational Chinese Han family with familial adenomatous polyposis and CRC to identify the potential genetic anomalies associated with the disease. Diagnoses were made by physical and enteroscopic examinations of all the family members. Mutational analyses of the potential CRC­associated genes were carried out by direct gene sequencing, and the statistically significant differences in polymorphisms between normal and diseased populations were determined. Multiple sequence alignment and protein modeling were conducted using the Vector NTI and DNAMAN software tools. Clinical and pathological features of all the examined patients were consistent with typical familial adenomatous polyposis (FAP) syndrome. From the genomes of these family members, a 131564T>C (p.1125Val>Ala) mutation was identified in exon 15 of the APC gene, and a 1126G>C (p.324Gln>His) mutation was identified in exon 12 of the MUTYH gene. The 131564T>C mutation co­segregated with the affected individuals in the family and was specifically associated with the incidence of CRC (P=0.018<0.05). The 1125Val residue was highly conserved in the APC protein, and the p.1125Val>Ala mutation led to changes in the secondary structure and hydrophilicity of the APC protein. In conclusion, the APC gene mutation 131564T>C is associated with FAP and the pathogenesis of CRC.

KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma.

INTRODUCTION: The aim of this study was to examine the effects of KRAS mutant subtypes on the outcome of patients with resected lung adenocarcinoma (AC). METHODS: Using clinical and sequencing data, we identified 179 patients with resected lung AC for whom KRAS mutational status was determined. A multivariate Cox model was used to identify factors associated with disease-free survival (DFS) and overall survival (OS). Publicly available mutation and gene-expression data from lung cancer cell lines and lung AC were used to assess whether distinct KRAS mutant variants have a different profile. RESULTS: Patients with KRAS mutation had a significantly shorter DFS compared with those with KRAS wild-type (p = 0.009). Patients with KRAS-G12C mutant tumors had significantly shorter DFS compared with other KRAS mutants and KRAS wild-type tumors (p < 0.001). In the multivariate Cox model, KRAS-G12C remained as an independent prognostic marker for DFS (Hazard ratio = 2.46, 95% confidence interval 1.51-4.00, p < 0.001) and for OS (Hazard ratio = 2.35, 95% confidence interval 1.35-4.10, p = 0.003). No genes were statistically significant when comparing the mutational or transcriptional profile of lung cancer cell lines and lung AC harboring KRAS-G12C with other KRAS mutant subtypes. Gene set enrichment analysis revealed that KRAS-G12C mutants overexpressed epithelial to mesenchymal transition genes and expressed lower levels of genes predicting KRAS dependency. CONCLUSIONS: KRAS-G12C mutation is associated with worse DFS and OS in resected lung AC. Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRAS-G12C mutants had an epithelial to mesenchymal transition and a KRAS-independent phenotype.

Psychiatric morbidity in gynecological and otorhinolaryngological outpatients: a comparative study.

OBJECTIVE: Assessment of the point prevalence of psychiatric disorders in a gynecological outpatient population compared to a control group consisting of otorhinolaryngological outpatients. METHODS: During an 11-month period of time, 150 unselected, consecutive gynecologic outpatients and 150 matched controls (otorhinolaryngological outpatients) were enrolled in the study. Patients were screened for psychiatric disorders using the Patient Health Questionnaire (PHQ). Sociodemographic data, psychiatric and medical history including inpatient treatments and outpatient contacts, and utilisation of the health care system were assessed. RESULTS: Within the gynecological group, 45.3% fulfilled the diagnostic criteria for at least one psychiatric diagnosis according to the PHQ, compared to 27.3% of the otorhinolaryngological control group (P=.002). With respect to distinct diagnoses, gynecological patients suffered significantly more often from somatoform disorders (P=.001) and depressive disorders (P=.003) than controls. Less than half of subjects of either group with any psychiatric diagnosis had ongoing psychiatric or psychotherapeutic treatment. CONCLUSIONS: We found a significant group difference in the number of psychiatric diagnoses between gynecological and otorhinolaryngological female outpatients. Psychiatric disorders may be frequent and unrecognised in women presenting in an outpatient setting, especially in those seeking medical care for gynecological problems. The PHQ may be a useful tool to detect psychiatric disorders even in busy clinical settings.

Preoperative orthostatic dysfunction is associated with an increased incidence of postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) occurs frequently after gynecologic surgery. Because hemodynamic condition seems to be influential, women presenting with preoperative orthostatic dysregulation may have an increased risk for PONV. The aim of the present study was to assess the relationship between preoperative orthostatic dysregulation and the incidence of PONV. METHODS: In a prospective observer-blinded clinical trial, 200 women who were scheduled for elective gynecologic surgery underwent an orthostatic test on the day before surgery. Based on the orthostatic test results, women were stratified into orthostatic dysregulation (OR; systolic blood pressure decrease > 20 mmHg on standing up) and nonorthostatic dysregulation (NOR; systolic blood pressure decrease < 20 mmHg) groups. RESULTS: Forty-nine women were stratified to the OR group and 151 to the NOR group. Frequencies of PONV and vomiting during the study period were higher in the OR group compared with the NOR group (77.6% vs. 31.1% and 55.1 vs. 18.5%, respectively; all P < 0.001). Women with hypotension in their history showed a significantly higher frequency of PONV within 24 h (P < 0.05). CONCLUSION: Women presenting with orthostatic dysregulation and arterial hypotension in their history exhibit an increased risk of PONV.