Cholangiocarcinoma (CCA) is a rare malignancy with generally dismal prognosis. Immunotherapy has revolutionized the management of cancer patients during the last decade, offering durable responses ...
Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients with schizophrenia. Information on 39 variables was collected. Multiple component analysis was used to identify dimensions that explained the variance between patients. Three axes, accounting for 99% of the variance, were associated with disease severity (64%), socioeconomic status (27%) and patient autonomy (8%). These dimensions discriminated between six discrete patient subgroups, identified using ascending hierarchical classification analysis. The six subgroups differed regarding educational level, illness severity, autonomy, symptom presentation, addictive behaviors, comorbidities and cardiometabolic risk factors. Subgroup 1 patients had moderately severe physician-rated disease and addictive behaviours (23.2%); Subgroup 2 patients were well-integrated and autonomous with mild to moderate disease (6.7%); Subgroup 3 patients were less well-integrated with mild to moderate disease, living alone (11.2%); Subgroup 4 patients were women with low education levels (5.4%), Subgroup 5 patients were young men with severe disease (36.8%); and Subgroup 6 patients were poorly-integrated with moderately severe disease, needing caregiver support (16.7%). The presence of these subgroups, which require confirmation and extension regarding potentially identifiable biological markers, may help individualizing treatment in patients with schizophrenia.
Poly-ADP ribose polymerase (PARP) inhibitors are constantly increasing in their indications for use as anti-cancer treatment in various neoplasms, the majority of which are linked with BRCA deficiency. Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting “BRCAness” or homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. With the current report we present the case of a heavily pretreated 55-year-old male patient diagnosed with stage IV ATM-deficient CRC, who was effectively treated with an off-label olaparib-irinotecan combination after exhaustion of all available treatment choices; furthermore, we discuss the existing data providing evidence for the use of PARP inhibitors in ATM-deficient CRC and encourage the implementation of next-generation sequencing (NGS) in patients with no other available treatment options.
Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (Her2) – targeted antibody-drug conjugate that is approved for patients previously treated with trastuzumab and a taxane for Her2-positive advanced breast cancer and those who have progressed within 6 months of completion of adjuvant chemotherapy, as well as for patients with residual invasive Her2-positive disease after the completion of adjuvant chemotherapy. Peripheral neuropathy is a common adverse event; however, ocular events have also been described. With the current report we present the case of a 67-year old woman who developed transient grade 2–3 blurred vision after the first T-DM1 infusion, which was complicated with grade 2 diplopia causing vertigo after the second infusion. After extended investigation, this symptomatology was attributed to central neurotoxicity, and gradually resolved after T-DM1 discontinuation.
Cholangiocarcinoma consists of a heterogeneous group of malignancies with generally poor prognoses. Immunotherapy has emerged in the treatment landscape of many tumors, offering survival benefits, ... Plain language summary Cholangiocarcinomas are a group of rare tumors. Survival time is limited, due to late diagnosis and advanced symptoms. The small number of patients makes it difficult to carr...
Monoclonal antibodies against programmed cell death protein 1 (PD-1) and PD-1 ligand 1 (PD-L1) are the main representatives in the field of immunotherapy and their indications are constantly increasing in medical oncology and hematology during the last decade. They are associated with long-lasting responses and an acceptable toxicity profile, although they may infrequently cause life-threatening complications requiring prolonged hospitalization or urgent interventions. With the current report, we present the case of a 75-year-old woman diagnosed with stage IV lung adenocarcinoma, who developed acute abdominal pain without preceding symptomatology while on pembrolizumab-pemetrexed maintenance treatment. A contained rupture of the appendix was found, for which she was managed conservatively. Subsequent endoscopic as well as histopathological findings from biopsies obtained via colonoscopy associated the clinical and imaging findings with grade 4 immune-mediated colitis. Interestingly, high-grade colitis is more frequent with anti-CTLA-4 agents in comparison to anti-PD-1 agents; moreover, most cases of anti-PD-1-mediated colitis present with preceding symptomatology (like diarrhea or vomiting), while cases or colonic perforation are extremely rare if ever described.