ABSTRACT
Purpose: Insomnia in cancer patients is a common symptom contributing to poor quality of life and poor functioning. Sleep disturbances have been associated with inflammatory activity, and systemic cancer therapies chemotherapy, hormonal therapy, and immunotherapy may cause insomnia. We have carried out a meta-analysis to estimate the occurrence of insomnia in patients with solid cancer treated with immunotherapy using checkpoint inhibitors (CPI). Methods: PubMed and ClinicalTrials.gov were searched for phase 3 studies in solid tumours where treatment included a checkpoint inhibitor in the experimental arm. Data on the incidence of insomnia were acquired from the adverse events tables available from clinicaltrials.gov and/or from the full texts. Random effect logistic model was used to compare pooled data. Heterogeneity between studies was assessed using Cochrane Q statistics and I2 statistics. Results: A total of 54 studies (including six three-arm studies) involving 37,352 patients were included in the analysis. Insomnia was reported in 8.3% of subjects (95% confidence interval [CI] 8.0%-8.7%) treated with immunotherapy. Insomnia was significantly more common in patients receiving immunotherapy compared to those enrolled in study arms with inactive treatment (odds ratio [OR] 1.49, 95% CI 1.13-1.96). The odds for insomnia were similar between the arms for studies comparing CPI versus chemotherapy and CPI versus non-immunologic targeted therapies (OR 1.07, 95% CI 0.94-1.22 and OR 1.40, 95% CI 0.90-2.18, respectively). The OR for insomnia was higher for cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor inhibitors compared to the inhibitors of programmed death-1 (PD-1) receptor (OR 1.36, 95% CI 1.06 - 1.74). Conclusion: Cancer immunotherapy using CPI is associated with insomnia but the odds of developing the symptom are not greater with immunotherapy than with other systemic modalities including chemotherapy and non-immunologic targeted therapies.
ABSTRACT
The treatment of patients with cervical lymph node metastases without detectable primary tumor remains an important challenge, until today, no standard therapy is available. The present study investigated the multimodal treatment of patients with head and neck CUP syndrome (HNCUP) and their follow-up retrospectively. 81 patients with cervical lymph node metastases without a primary tumor were treated at the Departments of Otorhinolaryngology as well as Radiotherapy and Radiation Oncology at the University of Saarland in Homburg, Germany in the period between 1991 and 2013. All patients received routine work-up consisting of CUP panendoscopy and imaging. Neck dissection was then performed in 77% of the patients. The most common histology was squamous cell carcinoma (80%). Ten percent of the patients had distant metastases. All patients underwent primary or adjuvant radiation therapy, or simultaneous radiochemotherapy. After a median follow-up of 3.5 years, the 5-year survival rate was 30%. There was a local recurrence that was known in 20/63 patients (31%) and distant metastases were documented in 19/61 M0 patients (31%). Higher grade late toxicity (grade 3-4) was observed in 12% of patients. Neck dissection and radiation therapy remains an integral part of HNCUP therapy, while the use of chemotherapy could be considered in selected cases. Prospective multicenter randomized trials would be necessary to identify the best target volume and to clarify the role of chemotherapy.
