To analyze the effect of adjuvant oral application of honey for treating postoperative pain after tonsillectomy.
Single centre prospective cohort study.
Two cohorts of patients after tonsillectomy.
...56 patients treated with honey 8 times per day (honey group), 18 patients treated without honey (control group); baseline analgesia were non-steroidal anti-inflammatory drugs (NSAID) or coxibs; opioids were used as pro re nata (PRN) medication; mean age 34.4 ± 13.4 years; 36% women.
On first to fifth postoperative day, patients rated their pain using the validated questionnaire of the German-wide project Quality Improvement in Postoperative Pain Treatment (QUIPS) including a numeric rating scale (NRS, 0-10) for determination of patient's pain. QUIPS allows standardized assessment of patients' characteristics andpain-associated patient-reported outcomes (PROs). The influence of preoperative and postoperative parameters on patients' postoperative pain were estimated by univariate and multivariate statistical analysis.
Average pain in activity in the control group was greater than 4 (NRS 4.4 ± 2.4) during the first five postoperative days, with a renewed increase in pain intensity on the fifth day (4.3 ± 2.5). In the honey group, the pain in activity decreased without any further pain increase and was only higher than 4 on the first three postoperative days (4.3 ± 2.1, all p>0.05). However; neither minimal nor maximal pain were significantly different between both groups on the first postoperative day (p = 0.217, p = 0.980). Over the five postoperative days, the minimal and maximal pain in the honey group decreased continuously and faster than in the control group. With regard to pain-related impairments on the first day, the honey group reported less pain-related sleep disturbance (p = 0.026), as well as significantly fewer episodes of postoperative oral bleeding (p = 0.028) than the control group. Patients without honey consumption had on the first and fifth postoperative day a higher risk of increased minimal pain (OR = -2.424, CI = -4.075 --0.385). Gender was an independent factor for compliance of honey consumption on the second postoperative day (p = 0.037). Men had a lower probability for compliance of honey consumption (OR = -0.288, CI = -2.863 --0.090).
There was a trend of reduced postoperative pain after oral honey application. Honey also seems to reduce pain-related impairments. The need for additional opioids on the first day could be reduced. A larger controlled trial is now needed to varify the effect of honey on pain after tonsillectomy.
German Clinical Trials Register DRKS00006153. The authors confirm that all ongoing and related trials for this drug/intervention are registered.
The prognostic role of circulating tumor cells (CTCs) after induction chemotherapy using docetaxel, cisplatin and fluorouracil (TPF) prior to surgery and adjuvant (chemo)radiation in locally advanced ...oral squamous cell cancer (OSCC) was evaluated.
In this prospective study, peripheral blood samples from 40 patients of the phase II study TISOC-1 (NCT01108042) with OSCC before, during, and after treatment were taken. CTCs were quantified using laser scanning cytometry of anti- epithelial cell adhesion molecule-stained epithelial cells. Their detection was correlated with clinical risk factors, recurrence-free (RFS) and overall survival (OS).
Before starting the treatment CTCs were detected in 32 of 40 patients (80%). The median number at baseline was 3295 CTCs/ml. The median maximal number of CTCs during treatment was 5005 CTCs/ml. There was a significant increase of CTCs before postoperative radiotherapy compared to baseline before 1st cycle of IC (p = 0.011), 2nd cycle of IC (p = 0.001), 3rd cycle of IC (p = 0.004), and before surgery (p = 0.002), but not compared to end of therapy (p = 0.118). CTCs at baseline >median was also associated to risk of recurrence (p = 0.014). Maximal CTCs during therapy >median was more frequently observed in tumors of the oral cavity (p=0.022) and related to higher risk of death during follow-up (p = 0.028). Patients with CTCs at baseline >median value had significant lower RFS than patients with CTCs at baseline <median value (p = 0.025). Patients with maximal CTCs values >median during the complete course of therapy had a significantly lower OS than patients with values <median (p = 0.049). Finally, the multivariate analysis revealed that OS was significantly lower in patients with maximal CTCs during treatment higher than the median value (HR=6.151; CI: 1.244-30.420).
Baseline CTCs and maximal CTCs during therapy both seem to be good prognostic markers for OSCC when treated by TPF induction chemotherapy, surgery, and postoperative (chemo)radiation.
Purpose
The purpose of this study was to investigate the impact of the type of data capture on the time and help needed for collecting patient-reported outcomes as well as on the proportion of ...missing scores.
Methods
In a multinational prospective study, thyroid cancer patients from 17 countries completed a validated questionnaire measuring quality of life. Electronic data capture was compared to the paper-based approach using multivariate logistic regression.
Results
A total of 437 patients were included, of whom 13% used electronic data capture. The relation between data capture and time needed was modified by the emotional functioning of the patients. Those with clinical impairments in that respect needed more time to complete the questionnaire when they used electronic data capture compared to paper and pencil (OR
adj
24.0;
p
= 0.006). This was not the case when patients had sub-threshold emotional problems (OR
adj
1.9;
p
= 0.48). The odds of having the researcher reading the questions out (instead of the patient doing this themselves) (OR
adj
0.1;
p
= 0.01) and of needing any help (OR
adj
0.1;
p
= 0.01) were lower when electronic data capture was used. The proportion of missing scores was equivalent in both groups (OR
adj
0.4,
p
= 0.42).
Conclusions
The advantages of electronic data capture, such as real-time assessment and fewer data entry errors, may come at the price of more time required for data collection when the patients have mental health problems. As this is not uncommon in thyroid cancer, researchers need to choose the type of data capture wisely for their particular research question.
Purpose
The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation ...for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43.
Methods
In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods.
Results
From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |
r
|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from − 3 to − 14.
Conclusions
For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.
Induction chemotherapy (IC) is likely to be effective for biologically distinct subgroups of oral cancer and biomarker development may lead to identification of those patients.
We evaluated immune ...cell infiltration, stroma formation and structure of the invasive front as well as the immunohistochemical expression of alpha smooth muscle actin (ASMA), CD163, E-cadherin, N-cadherin, and the laminin gamma 2 chain in pretreatment biopsy specimens and surgical resections after IC in 20 patients with locally advanced oral cancer who were treated in a prospective, ongoing, phase II trial on IC using docetaxel, cisplatin, and 5-fluorouracil (TPF).
Significant negative prognostic factors for incomplete pathological tumor response to IC were alcohol abuse (
=0.032), cN+ (
=0.042), and <30% tumor reduction after first cycle of IC (
=0.034). Of the investigated histological parameters and biomarkers only a low membrane-bound expression of E-cadherin showed a trend to be associated with incomplete response to IC (
=0.061). Low expression of ASMA in stromal vessels and a strong tumor invasion front were significantly associated to tumor recurrence (
=0.024 and
=0.004, respectively). The median follow-up of all patients was 35 months. Alcohol abuse (
<0.001), <30% tumor reduction after first cycle of IC (
=0.005), and a strong tumor invasion front (
=0.019) were negative prognostic factors for overall survival.
A strong predictive biomarker among the investigated parameters for benefitting from TPF IC could not be found. The extent of the tumor invasion front was a negative prognostic marker for recurrence and survival in oral cancer treated by TPF IC followed by surgery and postoperative radiochemotherapy.
The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 ...HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were 'dry mouth' (DM) (
= 476; 46%), 'difficulty swallowing/eating' (DSE) (
= 408; 40%), 'hoarseness/difficulty speaking' (HDS) (
= 169; 16%), and 'pain in the head and neck' (PHN) (
= 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5-9.0; OR: 2.1, CI: 1.1-3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1-0.6; OR: 0.2, CI: 0.1-0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2-3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3-0.6) but increased odds of HDS (OR: 7.2, CI: 4.3-12.3). This study provides evidence of the serious long-term problems among HNCS.
To examine the impact of comorbidity on overall survival (OS) in a population‐based study of patients with head and neck cancer who were treated between 2009 and 2011. Data of 1094 patients with ...primary head and neck carcinomas without distant metastasis from the Thuringian cancer registries were evaluated concerning the influence of patient's characteristics and comorbidity on OS. Data on comorbidity prior to head and neck cancer diagnosis was adapted to the Charlson Comorbidity (CCI), age‐adjusted CCI (ACCI), head and neck CCI (HNCCI), simplified comorbidity score (SCS), and to the Adult Comorbidity Evaluation–27 (ACE‐27). Most patients were male (80%; median age: 60 years; 50% stage IV tumors). Smoking, alcohol abuse, and anemia were registered for 38%, 33%, and 23% of the patients, respectively. Predominant therapy was surgery + radiochemotherapy (30%), surgery (29%), and surgery + radiotherapy (21%). Mean CCI, ACCI, HNCCI, SCS and ACE‐27 were 1.0 ± 1.5, 2.6 ± 2.1, 0.6 ± 0.8, 4.4 ± 4.2, and 0.9 ± 0.9, respectively. Median follow‐up was 25.7 months. Multivariable analyses showed that higher age, higher UICC stage, no therapy, including surgery or radiotherapy, alcohol abuse, and anemia, higher comorbidity were independent risk factors for worse OS (all P < 0.05). According to the discriminatory power analysis none of the five comorbidity scores was superior to the other scores to prognosticate OS. This population‐based study showed that comorbidity is frequent in German patients with head and neck cancer and is an important risk factor for poor OS. Comorbidity should be routinely assessed and taken into account in prospective clinical trials.
Comorbidity is frequent in German patients with head and neck cancer and is an important risk factor for poor overall survival. None of the five applied comorbidity scores was superior to the other scores to prognosticate overall survival. Comorbidity should be routinely assessed and taken into account in prospective clinical trials.
Results from a phase 2 trial of the TPEx chemotherapy regimen (docetaxel–platinum–cetuximab) showed promising results, with a median overall survival of 14·0 months in first-line recurrent or ...metastatic head and neck squamous-cell carcinoma (HNSCC). We therefore aimed to compare the efficacy and safety of the TPEx regimen with the standard of care EXTREME regimen (platinum–fluorouracil–cetuximab) in this setting.
This was a multicentre, open-label, randomised, phase 2 trial, done in 68 centres (cancer centres, university and general hospitals, and private clinics) in France, Spain, and Germany. Eligible patients were aged 18–70 years with histologically confirmed recurrent or metastatic HNSCC unsuitable for curative treatment; had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1; and had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less. Participants were randomly assigned (1:1) using the TenAlea website by investigators or delegated clinical research associates to the TPEx regimen or the EXTREME regimen, with minimisation by ECOG performance status, type of disease evolution, previous cetuximab treatment, and country. The TPEx regimen consisted of docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both intravenously on day 1, and cetuximab on days 1, 8, and 15 (intravenously 400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently). Four cycles were repeated every 21 days with systematic granulocyte colony-stimulating factor (G-CSF) support at each cycle. In case of disease control after four cycles, intravenous cetuximab 500 mg/m2 was continued every 2 weeks as maintenance therapy until progression or unacceptable toxicity. The EXTREME regimen consisted of fluorouracil 4000 mg/m2 on day 1–4, cisplatin 100 mg/m2 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently) all delivered intravenously. Six cycles were delivered every 21 days followed by weekly 250 mg/m2 cetuximab as maintenance therapy in case of disease control. G-CSF support was not mandatory per the protocol in the EXTREME regimen. The primary endpoint was overall survival in the intention-to-treat population; safety was analysed in all patients who received at least one dose of chemotherapy or cetuximab. Enrolment is closed and this is the final analysis. This study is registered at ClinicalTrials.gov, NCT02268695.
Between Oct 10, 2014, and Nov 29, 2017, 541 patients were enrolled and randomly assigned to the two treatment regimens (271 to TPEx, 270 to EXTREME). Two patients in the TPEx group had major deviations in consent forms and were not included in the final analysis. Median follow-up was 34·4 months (IQR 26·6–44·8) in the TPEx group and 30·2 months (25·5–45·3) in the EXTREME group. At data cutoff, 209 patients had died in the TPEx group and 218 had died in the EXTREME group. Overall survival did not differ significantly between the groups (median 14·5 months 95% CI 12·5–15·7 in the TPEx group and 13·4 months 12·2–15·4 in the EXTREME group; hazard ratio 0·89 95% CI 0·74–1·08; p=0·23). 214 (81%) of 263 patients in the TPEx group versus 246 (93%) of 265 patients in the EXTREME group had grade 3 or worse adverse events during chemotherapy (p<0·0001). In the TPEx group, 118 (45%) of 263 patients had at least one serious adverse event versus 143 (54%) of 265 patients in the EXTREME group. 16 patients in the TPEx group and 21 in the EXTREME group died in association with adverse events, including seven patients in each group who had fatal infections (including febrile neutropenia). Eight deaths in the TPEx group and 11 deaths in the EXTREME group were assessed as treatment related, most frequently sepsis or septic shock (four in each treatment group).
Although the trial did not meet its primary endpoint, with no significant improvement in overall survival with TPEx versus EXTREME, the TPEx regimen had a favourable safety profile. The TPEx regimen could provide an alternative to standard of care with the EXTREME regimen in the first-line treatment of patients with recurrent or metastatic HNSCC, especially for those who might not be good candidates for up-front pembrolizumab treatment.
Merck Santé and Chugai Pharma.
Abstract
Purpose
Surgical complications such as hypoparathyroidism (HPT) or vocal cord palsy are seldom assessed when the quality of life (QOL) in thyroid cancer patients is investigated. The aim of ...this study was to measure the QOL difference in thyroid cancer survivors with and without HPT.
Methods
Participants for this analysis were enrolled in 13 countries from a study that pilot-tested a thyroid cancer–specific QOL instrument. They were included if they had been diagnosed with thyroid cancer at least 9 months previously. QOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) and some items on HPT symptoms (eg, tingling in fingers or toes). HPT status and other clinical data were extracted from the patients’ medical charts. Comparisons of QOL domains between patients with and without HPT were performed using Mann-Whitney U test. The occurrence of HPT-related symptoms was compared using chi-square tests. Multiple ordinal regression analysis was performed to evaluate factors that might affect QOL.
Results
Eighty-nine patients participated in this study, 17 of whom were considered to have HPT. Patients in the HPT group reported significantly reduced QOL in 9 of the 15 scales of the EORTC QLQ-C30 compared to patients without HPT. Regression analysis showed that HPT was independently negatively associated with various scales of the QLQ-C30. Both groups showed a high prevalence of typical HPT symptoms.
Conclusion
Thyroid cancer patients with HPT report significantly impaired QOL compared to thyroid cancer survivors without HPT. The assessment of HPT should be considered when measuring QOL in thyroid cancer patients.
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