Determination of body image and self-efficacy levels in patients after cornea transplantation.

PURPOSE: The study aimed to determine body image and levels after surgery in cornea transplant patients. MATERIALS AND METHODS: The population of this cross-sectional study was composed of 383 patients presented to the Eye Bank unit of a University Hospital after corneal transplantation. Sample size of 193 patients was calculated with 0.5 power, a margin of error of 5%, representing 95% of the universe. The data were collected through face-to-face interviews with the patients by the researcher and the study was completed with 178 patients in September-November 2022. The data were collected using a Patient Information Form, the Body Image Scale, and the General Self-Efficacy Scale. Parametric tests, Pearson Correlation, Student's t-test, and One-Way Analysis of Variance tests were performed were used in the data analysis. RESULTS: It was determined that the mean Body Image Scale score of the transplant patients participating in the study was 159.41 ±â€¯36.99 and the mean Self-Efficacy Scale score was 30.37 ±â€¯8.31. When the comparison of the mean scores was examined, the difference between the mean scores of gender, marital status, occupation, and body image scale was statistically significant (p < .05), while the difference between the self-efficacy mean scores was not statistically significant (p > .05). There was a positive, moderately strong significant relationship between body image and the self-efficacy of the patients (p < .01) (r = .57). CONCLUSION: It was found that the patient's body image and self-efficacy levels were high, and self-efficacy increased as the body image increased.

CompARE: study protocol for a phase III randomised controlled platform trial comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer.

BACKGROUND: Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival. METHODS: CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1-T4, N1-N3 or T3-4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1-T4, N2b-N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2-induction chemotherapy followed by arm 1; arm 3-dose-escalated radiotherapy plus concomitant cisplatin; and arm 4-resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5-induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed. DISCUSSION: CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients. TRIAL REGISTRATION: ISRCTN ISRCTN41478539 . Registered on 29 April 2015.

Randomized Phase 3 Trial of the Hypoxia Modifier Nimorazole Added to Radiation Therapy With Benefit Assessed in Hypoxic Head and Neck Cancers Determined Using a Gene Signature (NIMRAD).

PURPOSE: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m2 daily, before IMRT) or placebo. The primary endpoint was freedom from locoregional progression (FFLRP) in patients with hypoxic tumors, defined as greater than or equal to the median tumor hypoxia score of the first 50 patients analyzed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients, allowing for signature generation in 85% and an assumed hazard ratio (HR) of 0.50 for nimorazole effectiveness in the hypoxic group and requiring 66 locoregional failures to have 80% power in a 2-tail log-rank test at the 5% significance level. RESULTS: Three hundred thirty-eight patients were randomized by 19 centers in the United Kingdom from May 2014 to May 2019, with a median follow-up of 3.1 years (95% CI, 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range, 44-88; IQR, 70-76). There were 36 (25.9%) locoregional failures in the hypoxic group, in which nimorazole + IMRT did not improve FFLRP (adjusted HR, 0.72; 95% CI, 0.36-1.44; P = .35) or overall survival (adjusted HR, 0.96; 95% CI, 0.53-1.72; P = .88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or overall survival in the whole population. In total (N = 338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (Common Terminology Criteria for Adverse Events version 4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; P < .05). CONCLUSIONS: Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve locoregional control or survival.

Rational design and synthesis of lumican stapled peptides for promoting corneal wound healing.

PURPOSE: Lumican is a major extracellular matrix (ECM) component in the cornea that is upregulated after injury and promotes corneal wound healing. We have recently shown that peptides designed based on the 13 C-terminal amino acids of lumican (LumC13 and LumC13C-A) are able to recapitulate the effects of lumican on promoting corneal wound healing. Herein we used computational chemistry to develop peptide mimetics derived from LumC13C-A with increased stability and half-life that are biologically active and non-toxic, thereby promoting corneal wound healing with increased pharmacological potential. METHODS: Different peptides staples were rationalized using LumC13C-A sequence by computational chemistry, docked to TGFßRI and the interface binding energies compared. Lowest scoring peptides were synthesized, and the toxicity of peptides tested using CCK8-based cell viability assay. The efficacy of the stapled peptides at promoting corneal wound healing was tested using a proliferation assay, an in vitro scratch assay using human corneal epithelial cells and an in vivo murine corneal debridement wound healing model. RESULTS: Binding free energies were calculated using MMGBSA algorithm, and peptides LumC13C and LumC13S5 displayed superior binding to ALK5 compared to the non-stapled peptide LumC13C-A. The presence of the hydrocarbon staple in LumC13C enhances the stability of the α-helical conformation, thereby facilitating more optimal interactions with the ALK5 receptor. The stapled peptides do not present cytotoxic effects on human corneal epithelial cells at a 300 nM concentration. Similar to lumican and LumC13C-A, both C13C and LumC13S5 significantly promote corneal wound healing both in vitro and in vivo. CONCLUSIONS: Highly stable and non-toxic stapled peptides designed based on LumC13, significantly promote corneal wound healing. As a proof of principle, our data shows that more stable and pharmacologically relevant peptides can be designed based on endogenous peptide sequences for treating various corneal pathologies.

Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial.

BACKGROUND: Radical (chemo)radiotherapy offers potentially curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated intensity-modulated radiotherapy (DE-IMRT) improved locoregional control. METHODS: We performed a phase III open-label randomised controlled trial in patients with laryngeal or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7). Patients were randomised (1:1) to DE-IMRT or standard dose IMRT (ST-IMRT) using a minimisation algorithm, balancing for centre, tumour site, nodal status and chemotherapy use. DE-IMRT was 67.2 gray (Gy) in 28 fractions (f) to the primary tumour and 56Gy/28f to at-risk nodes; ST-IMRT was 65Gy/30f to primary tumour and 54Gy/30f to at-risk nodes. Suitable patients received 2 cycles of concomitant cisplatin and up to 3 cycles of platinum-based induction chemotherapy. The primary end-point was time to locoregional failure analysed by intention-to-treat analysis using competing risk methodology. FINDINGS: Between February 2011 and October 2015, 276 patients (138 ST-IMRT; 138 DE-IMRT) were randomised. A preplanned interim futility analysis met the criterion for early closure. After a median follow-up of 47.9 months (interquartile range 37.5-60.5), there were locoregional failures in 38 of 138 (27.5%) ST-IMRT patients and 42 of 138 (30.4%) DE-IMRT patients; an adjusted subhazard ratio of 1.16 (95% confidence interval: 0.74-1.83, p = 0.519) indicated no evidence of benefit with DE-IMRT. Acute grade 2 pharyngeal mucositis was reported more frequently with DE-IMRT than with ST-IMRT (42% vs. 32%). No differences in grade ≥3 acute or late toxicity rates were seen. CONCLUSION: DE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer. The trial is registered: ISRCTN01483375.

A multi-centre survey reveals variations in the standard treatments and treatment modifications for head and neck cancer patients during Covid-19 pandemic.

BACKGROUND: The onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology in UK. There was a delay between the onset of the pandemic and the release of guidelines from cancer societies and networks, leading to a variable response of individual centres. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the first wave of the pandemic in UK. METHODOLOGY: The UK National Cancer Research Institute (NCRI) Head and Neck Clinical Studies Group initiated a multi-centre survey using questionnaire to investigate the effect on feeding tube practice, radiotherapy (RT) fractionation and volumes, use of chemotherapy in the neo-adjuvant, concurrent and palliative setting, the use of immunotherapy in the palliative setting, access to radiology and histopathology services, and availability of surgical procedures. RESULTS: 30 centres were approached across UK; 23 (76.7%) centres responded and were included in the survey. There were differences in the standard practices in feeding tube policy, RT dose and fractionation as well as concurrent chemotherapy use. 21 (91%) participating centres had at least one treatment modification. 15 (65%) centres initiated a change in radical RT; changing to either a hypofractionation or acceleration schedule. For post-operative RT 10 centres (43.5%) changed to a hypofractionation schedule. 12 (52.2%) centres stopped neo-adjuvant chemotherapy for all patients; 13 (56.5%) centres followed selective omission of chemotherapy in concurrent chemo-radiotherapy patients, 17 (73.9%) centres changed first-line chemotherapy treatment to pembrolizumab (following NHS England's interim guidance) and 8 (34.8%) centres stopped the treatment early or offered delays for patients that have been already on systemic treatment. The majority of centres did not have significant changes associated with surgery, radiology, histopathology and dental screening. CONCLUSION: There are variations in the standard of practice and treatment modifications for head and neck cancer patients during Covid-19 pandemic. A timely initiative is required to form a consensus on head and neck cancer management in the UK and other countries.

Radiotherapy for Head and Neck Cancer: Evaluation of Triggered Adaptive Replanning in Routine Practice.

PURPOSE AND OBJECTIVE: A proportion of patients receiving radiotherapy for head and neck squamous cell carcinoma (HNSCC) require ad hoc treatment re-planning. The aim of this retrospective study is to analyze the patients who required ad hoc re-planning and to identify factors, which may predict need for re-planning. MATERIALS AND METHODS: A single center evaluation of all patients receiving radical or adjuvant (chemo)radiotherapy (CRT) for HNSCC between January and December 2016 was undertaken. Patients who underwent ad hoc re-planning during the treatment were identified in electronic records. Reasons for re-planning were categorized as: weight loss, tumor shrinkage, changes in patient position and immobilization-related factors. Potential trigger factors for adaptive radiotherapy such as patient characteristics, primary tumor site, stage, concomitant chemotherapy, weight loss ratios, radical/adjuvant treatment, and nutritional interventions were investigated. RESULTS: 31/290 (10.6%) HNSCC patients who underwent radical/adjuvant radiotherapy required re-planning. The adaptive radiotherapy (ART) was performed at a mean fraction of 15. The most common documented reasons for re-planning were tumor shrinkage (35.5%) and weight loss (35.5%). Among the patient/tumor/treatment factors, nasopharyngeal primary site (p = 0.013) and use of concurrent chemotherapy with radiotherapy (p = 0.034) were found to be significantly correlated with the need for re-planning. CONCLUSION: Effective on-treatment verification schedules and close follow up of patients especially with NPC primary and/or treated with concurrent chemoradiotherapy are crucial to identify patients requiring ART. We suggest an individualized triggered approach to ART rather than scheduled strategies as it is likely to be more feasible in terms of utilization of workload and resources.

Influencing Factors on Radiotherapy Outcome in Stage I-II Glottic Larynx Cancer-A Multicenter Study.

Background and Purpose: Larynx cancer represents one of the most frequently diagnosed head and neck malignancies, which is most often confined to the glottic area. The aim of this study was to report the oncological outcome and identify prognostic factors in early-stage glottic squamous cell carcinoma treated with radiotherapy. Material and Methods: Patients (n = 761) diagnosed and treated in 10 centers between 1990 and 2015 were retrospectively analyzed. Probabilities of loco-regional control (LRC) and overall survival (OS) were calculated and possible prognostic factors were analyzed using Cox proportional hazards models. Results: The median follow-up was 63 months (range: 2-243). Three hundred and sixty-four, 148 and 249 patients had cT1a, cT1b, and cT2 stage I-II disease, respectively. Five and 10-years LRC/OS rates in the whole cohort were 83/82% and 80/68%, respectively. Three patients developed distant recurrences. In univariate analysis, male sex (HR: 3.49; 95% CI: 1.47-11.37; p < 0.01), T2 vs. T1a (HR: 1.62; 95% CI: 1.08-2.43; p = 0.02) and anterior commissure involvement (ACI) (HR: 1.66; 95% CI: 1.38-2.45; p < 0.01) were associated with impaired LRC. In multivariate analysis, male sex (HR: 3.42; 95% CI: 1.44-11.17; p < 0.01) and ACI (HR: 1.51; 95% CI: 1.01-2.28; p = 0.047) remained poor prognostic factors. No relation of treatment technique and biologically equivalent dose (BED) to oncological outcome was identified except for higher BED10(L = 25; T = 1) yielding better LRC in T1a tumors (p = 0.04) in univariate analyses. Conclusion: Our results highlight the negative impact of ACI on tumor control. A less-expected finding was the impact of sex on tumor control. Further research is needed to validate its prognostic value and investigate any related biologic or behavioral factors, which may be modified to improve oncologic outcome.

More than Ophelia syndrome: Multiple paraneoplastic syndromes in pediatric Hodgkin lymphoma.

Demirsoy U, Alparslan B, Sen MC, Anik Y, Akansel G, Görür G, Gürel B, Aksu G, Çorapçioglu F. More than Ophelia syndrome: Multiple paraneoplastic syndromes in pediatric Hodgkin lymphoma. Turk J Pediatr 2019; 61: 139-141. Paraneoplastic syndromes in Hodgkin lymphoma (HL) can be seen with different symptoms and organ findings within a significant time before definite diagnosis of the primary disease. Achalasia, Holmes-Adie pupil, and limbic encephalitis are rarely reported paraneoplastic components in pediatric HL. In this report, we present an 11-year-old girl who had all these three paraneoplastic components synchronously before HL was identified.

Ultrasound-guided dorsal penile nerve block vs neurostimulator-guided pudendal nerve block in children undergoing hypospadias surgery: A prospective, randomized, double-blinded trial.

BACKGROUND AND AIMS: Hypospadias is a common congenital malformation in pediatric patients. Surgical repair of this malformation is a painful procedure and has long-term effects. Pudendal and penile nerve blocks are commonly preferred techniques for maintaining postoperative analgesia. However, the conventional landmark-based penile block technique involves numerous potential complications and provides a shorter analgesic period compared to the pudendal block. A promising ultrasound-guided dorsal penile nerve block was recently described. We aimed to compare the analgesic effectiveness of ultrasound-guided penile nerve block with that of neurostimulator-guided pudendal nerve block. METHOD: Thirty-three patients aged 1-7 years were included in this prospective, double-blinded, randomized controlled trial. Patients were divided into two groups and received either ultrasound-guided dorsal penile nerve block or neurostimulator-guided pudendal nerve block. All blocks were performed by the same two anesthesiologists, and the same surgeons performed the surgical procedures. The Face, Legs, Activity, Cry, and Consolability (FLACC) scale was used for postoperative pain management. The primary outcome of the study was time to first analgesic requirement. Secondary outcomes were FLACC scores at different time points, and types and cumulative doses of analgesic drugs. RESULTS: Dorsal penile nerve block provided longer analgesia than pudendal nerve block (32.29 ± 5.47 hours and 21.13 ± 3.53 hours, respectively; differences in mean: 11.16, 95% CI: 7.873-14.465) (P < .001). FLACC scores at the time of first analgesic requirement were significantly lower in dorsal penile nerve block group than pudendal nerve block group (median [IQR]: 2 [2-2.5] and 3 [3-5], respectively; differences in median: -1, 95% CI: -1.851 to -0.149) (P < .001). CONCLUSION: Ultrasound-guided dorsal penile nerve block provided a longer analgesic period and reduced opioid consumption compared to neurostimulator-guided pudendal nerve block.

Impact of choice of feeding tubes on long-term swallow function following chemoradiotherapy for oropharyngeal carcinoma.

Background: Prior reports have raised concerns that a prophylactic gastrostomy may be detrimental to long-term swallow function. This study evaluates patient-reported swallow function following chemoradiotherapy for oropharyngeal carcinoma in relation to the use of a prophylactic gastrostomy or nasogastric (NG) tube as required. Material and methods: The MD Anderson Dysphagia Inventory (MDADI) was posted to 204 disease-free patients at least 2 years following chemoradiotherapy for oropharyngeal carcinoma between 2010 and 2014. Results: Overall, 181/204 (89%) patients returned questionnaire at a median of 34 months post-treatment. 97/181 (54%) and 84/181 (46%) were managed with an approach of a prophylactic gastrostomy or NG tube as required, respectively. A prophylactic gastrostomy was associated with higher rates of enteral feeding (92% vs. 58%, p < .001), lower median percentage weight loss (7.0% vs. 9.4%, p < .001), increased duration of enteral feed (median 3.3 vs. 1.1 months, p < .001). There was no significant difference in patient-reported swallow function measured by MDADI summary scores and subscales for patients managed with an approach of prophylactic gastrostomy or NG as required. Duration of enteral feed correlated negatively with composite MDADI scores. A subgroup of 116/181 (64%) patients were documented as having been offered a choice of enteral feeding approach and therefore can be considered to represent clinical equipoise; there were no significant differences in MDADI scores according to route. Conclusions: Despite concern regarding the use of a prophylactic gastrostomy in prior studies, the approaches of using a prophylactic gastrostomy or an NG tube as required to support patients during/after chemoradiotherapy for oropharyngeal carcinoma were associated with similar long-term swallow outcomes.

Erector Spinae Plane Block vs Quadratus Lumborum Block for pediatric lower abdominal surgery: A double blinded, prospective, and randomized trial.

STUDY OBJECTIVE: To evaluate and compare the analgesic effect of ultrasound-guided erector spinae plane (ESP) block with ultrasound-guided Quadratus Lumborum Block in pediatric lower abdominal surgeries. DESIGN: Randomized, prospective, double-blinded trial. SETTING: Operating room and surgical ward. PATIENTS: Sixty patients, aged 1 to 7 years with ASA scores of I-II scheduled for elective lower abdominal surgery were included in the study. INTERVENTIONS: Patients were randomized into two groups as ESPB group and QLB group. Ultrasound guided ESP block at L1 vertebral level was performed preoperatively using 0.5 ml/kg 0.25% bupivacaine (max 20 ml) to the patients in ESPB group. And ultrasound guided QLB block with transmuscular approach was performed preoperatively using 0.5 ml/kg 0.25% bupivacaine (max 20 ml) to the patients in QLB group. MEASUREMENTS: Face, Legs, Activity, Cry and Consolability (FLACC) scores for pain were recorded at 0, 1, 3 and 6 h postoperatively. Analgesic requirements and time to first analgesic requirement were also recorded. MAIN RESULTS: Fifty-seven patients were included in the final analyses. No significant difference was determined between the groups' FLACC scores at 0, 1, 3 or 6 h postoperatively (p > 0.05). No significant difference was also determined in times to first analgesia between the groups (p > 0.05). CONCLUSIONS: This study shows that the ESPB provides similar postoperative analgesia to the QLB in pediatric patients undergoing lower abdominal surgery. Clinicians could decide according to their clinical experiences. CLINICAL TRIALS: https://clinicaltrials.gov/ct2/show/NCT03463382.

Patients' experience of enteral feeding following (chemo) radiotherapy for head and neck cancer: A qualitative study.

BACKGROUND & AIMS: Enteral feeding is commonly required during radiotherapy treatment for head and neck cancer. Only limited qualitative research into head and neck cancer patients' experiences of enteral tube feeding has been undertaken. The aim of this qualitative study was to evaluate patients' experiences of EF and the surrounding decision making process. METHODS: Semi-structured, face-to face interviews were conducted with ten patients who had completed (chemo)radiotherapy/radiotherapy for head and neck cancer at a cancer centre in the North of England. Interviews were recorded, transcribed verbatim and analysed qualitatively using Thematic Analysis. RESULTS: Participants described the restrictions on daily living caused by enteral feeding tubes and enteral feeding. Despite these restrictions, participants recognised the value of the enteral feeding tube including its role in their survival and the importance of their involvement in decision making. Participants described coping mechanisms used to deal with the difficulties associated with enteral feeding. CONCLUSIONS: The results of this study provide a unique qualitative insight into the lived experiences of H&N cancer patients managed with enteral feeding and the impact of the decision making process. The results have relevance for professionals supporting this patient group with enteral feeding.

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.

BACKGROUND: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. METHODS: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. FINDINGS: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007). INTERPRETATION: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. FUNDING: Cancer Research UK.

Assessment of the Impact of Deformable Registration of Diagnostic MRI to Planning CT on GTV Delineation for Radiotherapy for Oropharyngeal Carcinoma in Routine Clinical Practice.

BACKGROUND: Aim of study was to assess impact of deformable registration of diagnostic MRI to planning CT upon gross tumour volume (GTV) delineation of oropharyngeal carcinoma in routine practice. METHODS: 22 consecutive patients with oropharyngeal squamous cell carcinoma treated with definitive (chemo)radiotherapy between 2015 and 2016, for whom primary GTV delineation had been performed by a single radiation oncologist using deformable registration of diagnostic MRI to planning CT, were identified. Separate GTVs were delineated as part of routine clinical practice (all diagnostic imaging available side-by-side for each delineation) using: CT (GTVCT), MRI (GTVMR), and CT and MRI (GTVCTMR). Volumetric and positional metric analyses were undertaken using contour comparison metrics (Dice conformity index, centre of gravity distance, mean distance to conformity). RESULTS: Median GTV volumes were 13.7 cm³ (range 3.5⁻41.7), 15.9 cm³ (range 1.6⁻38.3), 19.9 cm³ (range 5.5⁻44.5) for GTVCT, GTVMR and GTVCTMR respectively. There was no significant difference in GTVCT and GTVMR volumes; GTVCTMR was found to be significantly larger than both GTVMR and GTVCT. Based on positional metrics, GTVCT and GTVMR were the least similar (mean Dice similarity coefficient (DSC) 0.71, 0.84, 0.82 for GTVCT⁻GTVMR, GTVCTMR⁻GTVCT and GTVCTMR⁻GTVMR respectively). CONCLUSIONS: These data suggest a complementary role of MRI to CT to reduce the risk of geographical misses, although they highlight the potential for larger target volumes and hence toxicity.

Estrogen Receptor Beta-Mediated Modulation of Lung Cancer Cell Proliferation by 27-Hydroxycholesterol.

27-hydroxycholesterol (27HC) is an abundant cholesterol metabolite in human circulation and promotes breast cancer cell proliferation. Although lung is one of the organs that contain high levels of 27HC, the role of 27HC in lung is unknown. In this study, we found that 27HC promotes lung cancer cell proliferation in an estrogen receptor ß (ERß)-dependent manner. The expression of 27HC-generating enzyme CYP27A1 is higher in lung cancer cells than in normal lung cells. Treatment with 27HC increased cell proliferation in ERß-positive lung cancer cells, but not in ERα-positive or ER-negative cells. The effect on cell proliferation is specific to 27HC and another oxysterol, 25-hydroxycholesterol that has a similar oxysterol structure with 27HC. Moreover, among ligands for nuclear receptors tested, only estrogen had the proliferative effect, and the effect by 27HC and estrogen was inhibited by ERß-specific, but not ERα-specific, inhibitors. In addition, the effect by 27HC was not affected by membrane-bound estrogen receptor GPR30. Interestingly, despite the high expression of CYP27A1, endogenously produced 27HC was not the major contributor of the 27HC-induced cell proliferation. Using kinase inhibitors, we found that the effect by 27HC was mediated by the PI3K-Akt signaling pathway. These results suggest that 27HC promotes lung cancer cell proliferation via ERß and PI3K-Akt signaling. Thus, lowering 27HC levels may lead to a novel approach for the treatment of lung cancer.

Long term patient reported swallowing function following chemoradiotherapy for oropharyngeal carcinoma.

BACKGROUND AND PURPOSE: Limited data are available to inform on long term swallowing outcomes following concurrent chemoradiotherapy for oropharyngeal carcinoma. The aims of this study are to determine long term patient-reported swallowing outcomes across two large UK centres in routine clinical practice and identify associated factors. MATERIAL AND METHODS: All patients treated for oropharyngeal squamous cell carcinoma with concurrent chemoradiotherapy, and irradiation of the bilateral neck, between 2011 and 2013 were identified. Those requiring therapeutic enteral feeding prior to treatment, or having subsequent disease relapse, were excluded from the study. Patients were sent postal invitations to complete the MD Anderson Dysphagia Inventory (MDADI), at least two years following completion of treatment. RESULTS: Completed MDADI were received from 201/242 eligible patients (83%) at a median of 3.4 years (range 2-5) post treatment. Median composite MDADI score was 68.4. 64 (32%) had composite MDADI <60 classed as 'poor' function, 76 (38%) scores ≥60-<80 classed as adequate function, and 61 (31%) had scores ≥80 classed as optimal function. Patients with normal and abnormal pre-treatment diet had median composite MDADI scores of 70.5 versus 47.4 respectively. Patients who did not require enteral feeding during treatment and those who did had median composite MDADI scores of 76.3 versus 65.3 respectively. On multivariate analysis poorer performance status, abnormal pre-treatment diet, and use of enteral feeding during radiotherapy were all significantly associated with lower composite, global and subscale MDADI scores. CONCLUSIONS: Patient reported swallowing dysfunction remains common in the long term post-chemoradiotherapy. Impaired pre-treatment diet and use of enteral feeding during treatment are key factors associated with poorer swallowing outcomes.

Accuracy of [18Fluorine]-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography-Computed Tomography Response Assessment Following (Chemo)radiotherapy for Locally Advanced Laryngeal/Hypopharyngeal Carcinoma.

INTRODUCTION: The accuracy of response assessment positron emission tomography (PET)-computed tomography (CT) following radiotherapy with or without chemotherapy for laryngeal/hypopharyngeal squamous cell carcinoma is uncertain. METHODS: In all, 35 patients with laryngeal or hypopharyngeal squamous cell carcinoma who were treated between 2009 and 2014 with (chemo)radiotherapy were identified. The accuracy of response assessment PET-CT was made by correlation with clinical follow-up and pathological findings. RESULTS: Of the 35 patients, 20 (57%) had an overall complete metabolic response. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for response assessment [18Fluorine]-fluoro-2-deoxy-d-glucose (FDG) PET-CT for primary and nodal sites, respectively, were 100%, 73%, 46%, and 100% and 83%, 95%, 83%, and 95%. CONCLUSIONS: Response assessment FDG PET-CT following (chemo)radiotherapy for laryngeal and hypopharyngeal carcinomas has a high NPV for both primary site and lymph nodes and can be used to guide treatment decisions. The PPV of residual FDG uptake at the primary tumour site is limited and requires examination and biopsy confirmation.