A comprehensive assessment protocol including patient reported outcomes,physical tests,and biological sampling in newly diagnosed patients with head and neck cancer: is it feasible?

Purpose

Large cohort studies are needed taking into account cancer-related, personal, biological, psychobehavioral, and lifestyle-related factors, to guide future research to improve treatment and supportive care. We aimed to evaluate the feasibility of a comprehensive baseline assessment of a cohort study evaluating the course of quality of life (QoL).

Methods

Newly diagnosed head and neck cancer (HNC) patients were asked to participate. Assessments consisted of questionnaires (635 items), a home visit (including a psychiatric interview, physical tests, and blood and saliva collection), and tissue collection. Representativeness of the study sample was evaluated by comparing demographics, clinical factors, depression, anxiety, and QoL between responders and non-responders. Feasibility was evaluated covering the number of questions, time investment, intimacy, and physical burden.

Results

During the inclusion period (4 months), 15 out of 26 (60 %) patients agreed to participate. Less women participated, 13 % in responders group versus 63 % in non-responders group (p?=?0.008). No other differences were found between responders and non-responders. Responders completed more than 95 % of the questionnaires’ items and rated the number of questions, time investment and intimacy as feasible, and the physical and psychological burden as low. It took on average 3 h to complete the questionnaires and 1.5 h for the home visit.

Conclusions

This study reveals that a comprehensive assessment including various questionnaires, physical measurements, and biological assessments is feasible according to patients with newly diagnosed HNC. A large prospective cohort study has started aiming to include 739 HNC patients and their informal caregivers in the Netherlands.     

Quantification of striatal dopamine transporters with 123I-FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo-controlled, crossover study in healthy control subjects.

Dopamine transporter (DAT) imaging with (123)I-FP-CIT ((123)I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) SPECT is frequently used to detect loss of nigrostriatal cells in parkinsonism. Recent (123)I-beta-CIT ((123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) studies have shown a significant increase in striatal-to-nonspecific beta-CIT binding ratios after treatment with selective serotonin reuptake inhibitors (SSRIs). Due to similarities between (123)I-beta-CIT and (123)I-FP-CIT (both are derived from cocaine and show relatively high affinity for the DAT and the serotonin transporter [SERT]), we hypothesized that quantification of striatal (123)I-FP-CIT binding may be influenced by SSRIs. Moreover, we hypothesized that (123)I-FP-CIT in humans binds not only to DATs but also to central and peripheral SERTs. METHODS: To study the influence of the SSRI paroxetine on (123)I-FP-CIT binding to DATs in the striatum, we conducted a double-blind, placebo-controlled, crossover study with paroxetine in 8 healthy young male control subjects. In addition, we studied whether paroxetine was able to block (123)I-FP-CIT binding in SERT-rich brain areas and in lung tissue, as lung tissue contains a considerable amount of SERTs. Participants were pretreated for 2 d with paroxetine (20 mg/d) or placebo at 2 sessions (crossover design), and brain SPECT was performed 1 and 3 h after (123)I-FP-CIT injection, whereas lung uptake was measured 2 h after injection. RESULTS: Compared with placebo pretreatment, we found after paroxetine pretreatment a statistically significant increase (approximately 10%) in specific striatal-to-nonspecific (123)I-FP-CIT binding ratios at 3 h after injection, a time point at which striatal (123)I-FP-CIT binding ratios are stable. In addition, after paroxetine treatment, statistically significantly lower binding ratios were found in SERT-rich brain areas (e.g., at 1 h after injection, midbrain-to-cerebellar ratios were approximately 90% lower) as well as significantly lower uptake in lung tissue was found (approximately 40% lower after paroxetine). CONCLUSION: In this study we show that the quantification of striatal (123)I-FP-CIT binding to DAT is significantly increased by the SSRI paroxetine in humans. To our knowledge, this is the first study which shows that (123)I-FP-CIT binds in vivo in humans not only to DATs but also to central SERTs and SERTs in lung tissue.     

Strict peptide length is not required for the induction of cytotoxic T lymphocyte-mediated antiviral protection by peptide vaccination

Sendai virus nuclear protein peptides of different lengths were titrated in peptide vaccination experiments. We observed that peptide length was not important in inducing cytotoxic T lymphocyte-mediated protective immunity in vivo against a challenge with a lethal dose of virus. These results suggest that long peptides are trimmed in vivo to peptides that fit into the groove of major histocompatibility complex class I molecules. In addition several adjuvants were screened for their effectiveness in peptide vaccination protocols. Incomplete Freund's adjuvant and Titermax? turned out to be useful, whereas alum was much less effective.     

Incidence,risk factors,and outcome of antithymocyte globulin treatment of steroid-resistant rejection after liver transplantation

We retrospectively analyzed the incidence and outcome of steroid-resistant rejection (SRR) during the first 6 months after OLT in 126 patients receiving triple immunosuppression. A total of 95 patients either did not experience acute rejection at all or had acute rejection that subsided without additional treatment. A total of 31 patients had biopsy-proven acute rejection that required therapy: 18 patients had acute rejection that responded to steroid therapy (steroidsensitive rejection, SSR); the remaining 13 patients had SRR and received ATG. At the onset of acute rejection, no differences in clinical, biochemical, or immunological parameters were present between patients with SSR and SRR. However, the histological grade of acute rejection in the initial biopsy was higher in patients with SRR (P=0.05). ATG treatment was effective in 10 of the 13 patients and was not associated with an increased incidence of opportunistic infections. Patient and graft survival rates at 2 years were comparable in the three groups. These data show that the incidence of SRR during the first 6 months after OLT is low, and that its treatment with ATG is both effective and well tolerated.     

Iodine-123 labelled nor-β-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats

Iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)nortropane (nor-β-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [¹²³I]nor-β-CIT resulted in high accumulation of radioactivity in brain areas with high densities of serotonin (hypothalamus) and dopamine transporters (striatum), although the binding was less pronounced in the hypothalamus. While binding of [¹²³I]nor-β-CIT in the hypothalamus was blocked significantly by fluvoxamine (a selective serotonin transporter blocker) but not by GBR12,909 (a selective dopamine transporter blocker), the opposite was observed in the striatum. The results of this study indicate that [¹²³I]nor-β-CIT, although not being a selective radioligand, binds specifically to serotonin transporters in the hypothalamus in vivo and thus suggest that [¹²³I]nor-β-CIT promises to be a suitable radioligand for single-photon emission tomography imaging of serotonin transporters in humans. Received 21 May and in revised form 7 August 1998     

The significance of anemia in squamous cell head and neck cancer treated with surgery and postoperative radiotherapy

The objective of this study was to investigate the prognostic significance of the hemoglobin (Hb) levels at different timepoints in locally advanced squamous cell carcinoma of the head and neck (SCCHN). Included were 111 patients. The hemoglobin levels were assessed before surgery (PreS-Hb), between surgery and radiotherapy (HbAAC), before postoperative radiotherapy (PreRT-Hb) and at the end of radiotherapy (EndRT-Hb). HbAAC takes into account the duration of anemia during the interval between surgery and radiotherapy. Higher HbAAC corresponds with lower Hb levels. Five year locoregional control (LRC) among patients with HbAAC > or = median was 72% and significantly worse as compared to the 88% in case of HbAAC < median (p = 0.0097). Multivariate analysis for LRC showed that the HbAAC was a prognostic factor. Overall survival (OS) after 3 years was 77% in case of HbAAC < median and 34% in case of HbAAC > or = median (p < 0.0002). Multivariate analysis for OS showed that the PreS-Hb and HbAAC were prognostic factors. Hb level between surgery and radiotherapy is an important prognostic factor for both LRC and OS among patients with SCCHN treated with surgery and postoperative radiotherapy.     

Intratumoural expression of TNF-R1 and EMAP-II in relation to response of patients treated with TNF-based isolated limb perfusion

Tumour necrosis factor-alpha (TNF) has been used in the clinic for more than 10 years in an isolated limb perfusion (ILP). However, intra-tumoural expression of TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We determined the expression of TNF-R1, proEMAP and endothelial monocyte-activating polypeptide-II (EMAP-II) before and after ILP and evaluated this against clinical response. Tumour biopsies were taken before and after ILP of patients (n = 27) with advanced sarcoma or metastatic melanoma. Biopsies were randomly analysed by western blotting for proEMAP/EMAP-II and TNF-R1 expression. Appropriate melanoma biopsies were stained for EMAP-II, TNF-R1, CD31 and CD68. For melanomas we found that an up-regulation of EMAP-II, in contrast to proEMAP or TNF-R1, directly after ILP significantly correlated with a complete tumour response. No correlation was found for sarcoma patients. In a comparative analysis we found that the overall proEMAP and EMAP-II expression was higher in melanoma as compared to sarcoma cases and measurements in cell lines revealed high proEMAP expression by melanoma cells. We report high EMAP-II expression by endothelial cells and association with macrophages. In addition, macrophages are recruited to vessel-remnants after ILP. An upregulation of EMAP-II directly after ILP of melanoma patients correlates with and might predict a complete response to TNF-based ILP. The association of macrophages with EMAP-II expression and vascular damage suggests a role for EMAP-II in regulating the TNF-based anti-tumour effects observed with an ILP. Analysis of EMAP-II expression in melanoma biopsies should be implemented in the ILP procedure.     

Results of postoperative reirradiation for recurrent or second primary head and neck carcinoma

BACKGROUND: In this prospective study, the effects of a second course of postoperative radiation therapy on locoregional control, survival, toxicity, and quality of life were investigated in patients who underwent resection of a second primary or locoregional recurrent head and neck tumor in a previously irradiated area. METHODS: In total, 39 patients who underwent surgery for second primary tumors (n = 19 patients) or for recurrent locoregional tumors (n = 20 patients) were retreated with postoperative radiotherapy (RE-PORT). Indications for RE-PORT were extranodal spread (49%), positive surgical margins (44%), and/or other risk factors (8%). The target volume for RE-PORT was confined to the high-risk area. No elective radiotherapy was applied in regions that were situated in the formerly high-dose area. A total dose of 46 grays (Gy) was given to elective areas with boosts from 60 Gy to 66 Gy to the high-risk region with conventional fractionation. The results of RE-PORT were compared with the results from patients who were treated in the same period with primary adjuvant radiotherapy (PRI-PORT) at the authors' institution. RESULTS: The mean follow-up was 32 months (range, 3-84 mos). The locoregional control rate after 3 years in the RE-PORT group was 74%, and the 3-year overall survival rate was 44%. This did not differ significantly compared with survival rates in the PRI-PORT group. Although a higher rate of late radiation-induced morbidity and more head and neck symptoms were observed in the RE-PORT group compared with the PRI-PORT group, no differences were observed with regard to the more general dimensions of quality of life. CONCLUSIONS: RE-PORT after surgery for recurrent locoregional tumors and/or second primary tumors should be considered in patients who have high-risk histopathologic features.     

Impulsivity in obese women

In our obesogenic environment, self-control might be necessary in order to prevent overeating. Impulsivity is supposed to make it more difficult to resist the temptation to eat too much and can thereby contribute to overweight. In the present study, the hypotheses is tested that obese individuals are more impulsive. Thirty-one obese and 28 lean women, sampled from the normal population, are tested on a behavioural measure and three self-report measures of impulsivity. The obese women appeared more impulsive on the last part of the behavioural task, but not on the self-report measures. Implications of the results are discussed.