Severe complications leading to an emergency unit visit and hospitalisation are common among HNC patients in their relatively short palliative period reflecting the need for early-integrated palliative care. Collaboration with a specialised palliative home-care team seems to increase end-of-life care at home.
Management of head and neck cancer influences both physical and mental wellbeing. Measuring the health-related quality of life (HRQoL) is important, as various treatment modalities are associated with significant morbidity and mortality. In this prospective cohort study, we tested the feasibility of the generic 15D HRQoL instrument in 214 head and neck cancer patients managed with surgery, definitive (chemo)radiotherapy, or with combined modality treatment. HRQoL was assessed at baseline and three times after treatment onset during 1 year, and compared with that of general population standardized for age and sex. At baseline, the patients' mean 15D score was significantly worse compared with general population. Overall HRQoL was at lowest at 3 months after treatment onset, it gradually improved towards 12 months but never reached baseline levels. The dimensions "vitality", "distress", "depression" and "sexual activity" showed marked deterioration at 3 months after the treatment onset, but improved gradually during 12 months. The 15D instrument seems useful for evaluation of HRQoL of head and neck cancer patients. Dimensions reflecting mental wellbeing improved gradually after 3 months, but they seldom reached baseline levels. The support for patients at the time of diagnosis, during treatment, and recovery is emphasized.
Oncological treatment of head and neck carcinoma is associated with high morbidity. Measuring of health-related quality of life (HRQoL) is crucial in this patient group but there is no consensus on which measure would be preferable to be used. In this study, HRQoL was measured with the generic 15D, which has not been used before for assessing this patient population. It is a prospective cohort study among 64 patients with laryngeal, pharyngeal or nasal cavity carcinoma treated with definitive (chemo) radiotherapy between November 2007-July 2012. HRQoL was assessed with the 15D before and at 3, 6 and 12 months after the treatment onset. HRQoL results of the patients were compared with those of the age-standardized general population. Overall HRQoL declined significantly during the first 3 months after the treatment onset but then gradually improved towards the end of the follow-up. At baseline or at 12 months, no significant differences were detected in overall HRQoL between the patients and the general population. Dimensions reflecting mental well-being showed gradual improvement, exceeding the baseline scores at the end of the follow-up. Nevertheless, on these dimensions, the patient group presented with consistently lower scores compared with the general population. The mean HRQoL was lower among patients with pharyngeal carcinoma compared with the laryngeal carcinoma patients. The 15D instrument is feasible for evaluation of HRQoL in oncologically treated head and neck cancer patients. It seems to detect differences among different patient subgroups. Multidisciplinary supportive management of this patient population is recommended to ensure improved mental well-being.
Renal cell carcinomas (RCCs) have a tendency to metastasize at an early stage, therefore, the patients frequently exhibit metastatic disease at the time of diagnosis. Common locations for the metastases are adjacent organs and abdominal lymph nodes; however, occasionally metastasis to the peripheral organs may be the initial clinical symptom. The 71-year-old male patient in the current case suffered from radioresistant and aggressively behaving RCC metastasis in the mandible and lower lip, which was successfully managed by surgical resection. RCC metastasis to the facial area is considered to be uncommon based on a review of the existing literature. RCC are somewhat radioresistant and therefore, palliative surgery must be considered when treating patients with this metastatic disease.
Immune checkpoint inhibitors (ICI) have provided significant improvement in clinical outcomes for some patients with solid tumors. However, for patients with head and neck cancer, the response rate to ICI monotherapy remains low, leading to the exploration of combinatorial treatment strategies. In this preclinical study, we use an oncolytic adenovirus (Ad5/3) encoding hTNFα and hIL-2 and non-replicate adenoviruses (Ad5) encoding mTNFα and mIL-2 with ICI to achieve superior tumor growth control and improved survival outcomes. The in vitro effect of Ad5/3-E2F-D24-hTNFa-IRES-hIL-2 was characterized through analyses of virus replication, transgene expression and lytic activity using head and neck cancer patient derived cell lines. Mouse models of ICI naïve and refractory oral cavity squamous cell carcinoma were established to evaluate the local and systemic anti-tumor immune response upon ICI treatment with or without the non-replicative adenovirus encoding mTNFα and mIL-2. We delineated the mechanism of action by measuring the metabolic activity and effector function of CD3+ tumor infiltrating lymphocytes (TIL) and transcriptomic profile of the CD45+ tumor immune compartment. Ad5/3-E2F-D24-hTNFa-IRES-hIL-2 demonstrated robust replicative capability in vitro across all head and neck cell lines screened through potent lytic activity, E1a and transgene expression. In vivo, in both ICI naïve and refractory models, we observed improvement to tumor growth control and long-term survival when combining anti-PD-1 or anti-PD-L1 with the non-replicative adenovirus encoding mTNFα and mIL-2 compared to monotherapies. This observation was verified by striking CD3+ TIL derived mGranzyme b and interferon gamma production complemented by increased T cell bioenergetics. Notably, interrogation of the tumor immune transcriptome revealed the upregulation of a gene signature distinctive of tertiary lymphoid structure formation upon treatment of murine anti-PD-L1 refractory tumors with non-replicative adenovirus encoding mTNFα and mIL-2. In addition, we detected an increase in anti-tumor antibody production and expansion of the memory T cell compartment in the secondary lymphoid organs. In summary, a non-replicative adenovirus encoding mTNFα and mIL-2 potentiates ICI therapy, demonstrated by improved tumor growth control and survival in head and neck tumor-bearing mice. Moreover, the data reveals a potential approach for inducing tertiary lymphoid structure formation. Altogether our results support the clinical potential of combining this adenovirotherapy with anti-PD-1 or anti-PD-L1.
Background. Reduction of saliva secretion is a common side effect following radiotherapy (RT) for cancer of the head and neck region. The aim of this study is to predict the post-RT salivary function for individual patients prior to treatment and to recognise possible differences in individual radiosensitivity. Conclusions. The salivary fl ow model was validated for 64 patients. The results imply, that one explanation for the discrepancies between the predicted and the measured salivary fl ow rate values and the common variations found in Δ rEF for the parotid glands may be differences in patients ' individual response to radiation. However, quantitative extraction of individual radiosensitivity would require further studies in order to take it into account in predictive models.
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