“Restlessness” After Cancer Diagnosis and Treatment

A 76-year-old woman sought care for unintentional weight loss, hematuria, and fatigue. She was diagnosed with plurimetastatic renal cell carcinoma. After resection of the primary tumor and metastases, she was treated with pembrolizumab, an immune checkpoint inhibitor. The patient experienced involuntary tongue and face movements with dysphagia and weight loss. She was also described as “restless.” At that point, the patient was in cancer remission with ongoing immune checkpoint inhibitor treatment. Blood testing was unremarkable. Brain magnetic resonance imaging showed basal ganglia T2/fluid-attenuated inversion recovery hyperintensities without gadolinium enhancement. Cerebrospinal fluid testing showed slightly increased protein concentration and 8 cerebrospinal fluid-restricted oligoclonal bands. Serum and cerebrospinal fluid testing for neural autoantibodies showed immunoglobulin G immunoreactivity in a mouse tissue indirect immunofluorescence assay, predominantly staining the basal ganglia. The immunoglobulin G was subsequently identified to bind to phosphodiesterase 10A. The patient was diagnosed with paraneoplastic phosphodiesterase 10A-immunoglobulin G autoimmunity manifesting as hyperkinetic movement disorder triggered by immune checkpoint inhibitor treatment. Given the patient’s cancer remission, the immune checkpoint inhibitor treatment was discontinued. She was treated with high-dose intravenous corticosteroids, with improvement of her hyperkinetic movement disorder but persistence of some dystonic movements. Further treatment with oral prednisone did not produce further improvement. The patient was treated symptomatically with onabotulinumtoxinA injections and tetrabenazine, which ameliorated her dystonic movements. Three years after her cancer diagnosis, she was alive and in cancer remission with minimal residual movements. Immune checkpoint inhibitors are monoclonal antibodies targeting “stop signs” of the immune response, which lead to enhanced endogenous responses, including those against cancer. Autoimmune complications are consequences of the enhanced immunity and can affect all organs, including the nervous system.

The quality and meaning of life of cancer patients in remission: socio-psychological aspects

The sense of the meaning of life is a subjectively felt, positive mental state. Suffering in chronic illness intensifies in a human being the sense of isolation and gives rise to emotions with that an individual often cannot cope. Such experiences are characteristic of the process of cancer remission. The sense of coherence strengthens the sense of coping with disease, which increases prospects of recovery. The article presents the results of the authors' research (103 respondents) on the quality and meaning of life of cancer patients in remission: socio-psychological aspects, indicators of the categories of «meaning of life», «responsibility», «consistency», and the latter is dominant at the stage of cancer remission in the studied cohorts. The survey was conducted on the basis of the methodology developed by the authors using the «Goal in Life» test (PIL) by J. K. Crumbaugh and J.J. Smith. Maholicka, as well as «The sense of coherence» by A. Antonovsky (SOC-29). The study showed that the group under survey had a fairly high level of indicators of the categories «meaning of life», «responsibility», «consistency», which did not depend on when the respondents were diagnosed with cancer, as well as the fact that the studied indicators reached higher values in women than in men. Interpersonal factors «meaning of life» and «responsibility» were identified as dominant in the study of the quality and meaning of life in relation to other socio-psychological factors.

Modeling Cancer Remission Time Data by Means of the Max Erlang Binomial Distribution

In this paper, a statistical simulation algorithm for the power series distribution, called the Max Erlang Binomial distribution, is proposed, analyzed, and tested for bladder cancer remission time data. In order to present the simulation technique, the EM algorithm for statistical estimation aimed at estimating the model parameters is described.

Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. TRAIL has been widely studied as a novel strategy for tumor elimination, as cancer cells overexpress TRAIL death receptors, inducing apoptosis and inhibiting blood vessel formation. However, cancer stem cells (CSCs), which are the main culprits responsible for therapy resistance and cancer remission, can easily develop evasion mechanisms for TRAIL apoptosis. By further modifying their properties, they take advantage of this molecule to improve survival and angiogenesis. The molecular mechanisms that CSCs use for TRAIL resistance and angiogenesis development are not well elucidated. Recent research has shown that proteins and transcription factors from the cell cycle, survival, and invasion pathways are involved. This review summarizes the main mechanism of cell adaption by TRAIL to promote response angiogenic or pro-angiogenic intermediates that facilitate TRAIL resistance regulation and cancer progression by CSCs and novel strategies to induce apoptosis.

Anti-Tr/DNER antibody paraneoplastic cerebellar degeneration preceding a very late relapse of Hodgkin Lymphoma after 12 years

Background Paraneoplastic cerebellar degeneration (PCD) is a classic neurological syndrome where the presence of Anti-Tr/DNER antibodies is strongly associated with Hodgkin Lymphoma (HL). Awareness of the syndrome is important because with prompt treatment the prognosis of HL is good. The diagnosis can be a challenge in some patients. The importance of PCD in the detection of a cancer relapse is not clarified. We report the case of a 76-year-old man where a PCD, initially misdiagnosed as a stroke led to a diagnosis of a very late relapse of HL after 12 years. Case presentation A 76-year-old male with a 3-week history of unstable walking, slow speech and dizziness was admitted to our stroke unit apparently because the symptoms started acutely. With a diagnostic delay of 3–4 weeks a correct diagnosis of relapse HL was made based on cerebrospinal fluid changes with a strong positive reaction to anti-Tr/DNER antibodies, FDG-PET/CT scan, and biopsy findings. The medical history revealed that the patient had been diagnosed with HL previously, but has been in complete remission for 12 years. The patient was treated with intravenous immunoglobulin, chemo- and radiation therapy. Over the following 6–8 weeks he improved. Conclusions Late relapse in HL is very rare. If it occurs it presents as a symptomatic lymphadenopathy. Our case shows, that PCD can be the only presenting symptom of a very late relapse of HL. Paraneoplastic neurological syndromes (PNS) should be considered even in patients with very long cancer remission. PCD can in rare cases mimic a stroke within the posterior circulation. If MR imaging in severe acute/subacute cerebellar syndrome is normal further investigation is mandatory to rule out a PNS, particular in patients with a previous cancer.

Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer

Immune checkpoint blockade (ICB) therapy has revolutionized head and neck squamous cell carcinoma (HNSCC) treatment, but <20% of patients achieve durable responses. Persistent activation of the PI3K/AKT/mTOR signaling circuitry represents a key oncogenic driver in HNSCC; however, the potential immunosuppressive effects of PI3K/AKT/mTOR inhibitors may limit the benefit of their combination with ICB. Here we employ an unbiased kinome-wide siRNA screen to reveal that HER3, is essential for the proliferation of most HNSCC cells that do not harbor PIK3CA mutations. Indeed, we find that persistent tyrosine phosphorylation of HER3 and PI3K recruitment underlies aberrant PI3K/AKT/mTOR signaling in PIK3CA wild type HNSCCs. Remarkably, antibody-mediated HER3 blockade exerts a potent anti-tumor effect by suppressing HER3-PI3K-AKT-mTOR oncogenic signaling and concomitantly reversing the immune suppressive tumor microenvironment. Ultimately, we show that HER3 inhibition and PD-1 blockade may provide a multimodal precision immunotherapeutic approach for PIK3CA wild type HNSCC, aimed at achieving durable cancer remission.

Rare Features of Dermatomyositis in a Patient with Ovarian Cancer

Despite a classical presentation of dermatomyositis, a patient with ovarian cancer had several uncommon features: (i) unexpected onset of dermatomyositis in spite of cancer remission, (ii) development of Evans’ syndrome and subcutaneous edema, and (iii) dysphagia. We discuss the occurrence of these clinical situations as well as the treatments.

Extended Gumbel Type-2 Distribution: Properties and Applications

In this paper, we proposed a new four-parameter Extended Gumbel type-2 distribution which can further be split into the Lehman type I and type II Gumbel type-2 distribution by using a generalized exponentiated G distribution. The distributional properties of the proposed distribution have been studied. We derive the p th moment; thus, we generalize some results in the literature. Expressions for the density, moment-generating function, and r th moment of the order statistics are also obtained. We discuss estimation of the parameters by maximum likelihood and provide the information matrix of the developed distribution. Two life data, which consist of data on cancer remission times and survival times of pigs, were used to show the applicability of the Extended Gumbel type-2 distribution in modelling real life data, and we found out that the new model is more flexible than its submodels.