Case report: The lesson from opioid withdrawal symptoms mimicking paraganglioma recurrence during opioid deprescribing in cancer pain

Pain is one of the predominant and troublesome symptoms that burden cancer patients during their whole disease trajectory: adequate pain management is a fundamental component of cancer care. Opioid are the cornerstone of cancer pain relief therapy and their skillful management must be owned by physicians approaching cancer pain patients. In light of the increased survival of cancer patients due to advances in therapy, deprescription should be considered as a part of the opioid prescribing regime, from therapy initiation, dose titration, and changing or adding drugs, to switching or ceasing. In clinical practice, opioid tapering after pain remission could be challenging due to withdrawal symptoms’ onset. Animal models and observations in patients with opioid addiction suggested that somatic and motivational symptoms accompanying opioid withdrawal are secondary to the activation of stress-related process (mainly cortisol and catecholamines mediated). In this narrative review, we highlight how the lack of validated guidelines and tools for cancer patients can lead to a lower diagnostic awareness of opioid-related disorders, increasing the risk of developing withdrawal symptoms. We also described an experience-based approach to opioid withdrawal, starting from a case-report of a symptomatic patient with a history of metastatic pheochromocytoma-paraganglioma

An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas

Temozolomide cytoreductive treatment in a giant cabergoline-resistant prolactin-secreting pituitary neuroendocrine tumor

Dopamine agonists (DAs, especially cabergoline) are recommended as first-line treatment in patients with prolactin-secreting pituitary adenomas, to reduce hormone secretion and tumor size. Pituitary surgery, suggested in nonresponsive patients, cannot achieve a gross total resection or is not feasible in some cases. Temozolomide (TMZ) has been proposed in patients with aggressive pituitary neuroendocrine tumors (PitNETs) who do not respond to conventional treatments. We present a 47-year-old man with a giant (70 751 764\u2009mm) prolactin-secreting PitNET. Cabergoline treatment (at first 1.5\u2009mg/week, and then increased to 3.5\u2009mg/week after 3 months) achieved prolactin suppression; however, magnetic resonance revealed a stable mass. After explanation of surgical complications, the patient rejected the procedure. Therefore, a primary neoadjuvant cytoreductive TMZ treatment was discussed during a meeting of the Pituitary Multidisciplinary Team, and added to cabergoline. After 13 cycles of TMZ (1 year of treatment), we observed dramatic reduction of the PitNET (from 18\u2009cm of adenoma to 6\u2009cm of necrotic tissue). MRI performed 4, 12, and 18 months after TMZ discontinuation revealed a stable residual PitNET, and 1.5\u2009mg/week of cabergoline has been continued until today. Recently, the criteria for developing Pituitary Tumors Centers of Excellence have been proposed, indicating that a multidisciplinary team is the best care for patients. Surgery, rejected by the patient, could only achieve a partial resection; therefore, we decided to combine TMZ and cabergoline. An early initiation of TMZ could be considered in selected cases, especially when surgery could be only partially effective

The Combination of Carmustine Wafers and Fotemustine in Recurrent Glioblastoma Patients: A Monoinstitutional Experience

Background. To date, there is no standard treatment for recurrent glioblastoma. We analyzed the feasibility of second surgery plus carmustine wafers followed by intravenous fotemustine. Methods. Retrospectively, we analyzed patients with recurrent glioblastoma treated with this multimodal strategy. Results. Twenty-four patients were analyzed. The median age was 53.6; all patients had KPS between 90 and 100; 19 patients (79%) performed a gross total resection > 98% and 5 (21%) a gross total resection > 90%. The median progression-free survival from second surgery was 6 months (95% CI 3.9–8.05) and the median OS was 14 months (95% CI 11.1–16.8 months). Toxicity was predominantly haematological: 5 patients (21%) experienced grade 3-4 thrombocytopenia and 3 patients (12%) grade 3-4 leukopenia. Conclusion. This multimodal strategy may be feasible in patients with recurrent glioblastoma, in particular, for patients in good clinical conditions

Advanced Adrenocortical Carcinoma: From Symptoms Control to Palliative Care

The prognosis of patients with advanced adrenocortical carcinoma (ACC) is often poor: in the case of metastatic disease, five-year survival is reduced. Advanced disease is not a non-curable disease and, in referral centers, the multidisciplinary approach is the standard of care: if a shared decision regarding several treatments is available, including the correct timing for the performance of each one, overall survival is increased. However, many patients with advanced ACC experience severe psychological and physical symptoms secondary to the disease and the cancer treatments. These symptoms, combined with existential issues, debase the quality of the remaining life. Recent strong evidence from cancer research supports the early integration of palliative care principles and skills into the advanced cancer patient's trajectory, even when asymptomatic. A patient with ACC risks quickly suffering from symptoms/effects alongside the disease; therefore, early palliative care, in some cases concurrent with oncological treatment (simultaneous care), is suggested. The aims of this paper are to review current, advanced ACC approaches, highlight appropriate forms of ACC symptom management and suggest when and how palliative care can be incorporated into the ACC standard of care

Hepatocellular carcinoma in elderly patients: a concise review on systemic therapy with sorafenib

The treatment of hepatocellular carcinoma (HCC) in elderly patients is unclear. In particular, the efficacy and safety of sorafenib as a systemic treatment in these patients is still under debate. We performed a concise review of sorafenib therapy in this population. However, it is important to make any decisions on treatment for elderly patients with HCC through a multidisciplinary team that includes experts in the liver disease. Patients with good clinical conditions should be treated with sorafenib

Diagnostic Value of Plasma and Urinary 2-Hydroxyglutarate to Identify Patients With Isocitrate Dehydrogenase-Mutated Glioma

BACKGROUND. Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma. MATERIALS AND METHODS. All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry. RESULTS. A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment. CONCLUSION. Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients