Psychometric evaluation of Oral Mucositis Daily Questionnaire: A cross-cultural adaptation of the Malay version in multiethnic adult autologous stem cell transplant.

Objective: Mucositis is one of the most feared side effects of cancer treatment. Psychometric analysis of a patient self-assessment score, the oral mucositis daily questionnaire in Malay (OMDQ-Mal) and its construct validity by means of confirmatory factor analysis (CFA) is lacking. This research aimed to test the validity and reliability of OMDQ-Mal. Methods: A total of 114 autologous stem-cell transplantation patients aged ≥ 18 years old at a national hematology center in Malaysia from April 2019 to December 2020 completed OMDQ-Mal concurrently with physician scores. Internal consistency and reproducibility were determined by Cronbach alpha and intraclass correlation coefficient, respectively. Correlations with physician scores were determined by Spearman correlation. Discriminative validity and construct validity were determined by Mann-Whitney U and CFA, respectively. Results: OMDQ-Mal demonstrated high internal consistency (α â€‹= â€‹0.874). Test-retest reliability between paired days were moderate to excellent (95% CI â€‹= â€‹0.676-0.953). Items in OMDQ-Mal had moderate to strong correlations with physician scores (ρ â€‹= â€‹0.503-0.721). Discriminative validity indicated that the scores of scales were significantly different between participants with severe and mild conditions. Construct validity results of loading factors 0.708-0.952; composite reliability 0.879-0.974; average variant extracted 0.710-0.841; and heterotrait-monotrait ratio 0.528 established the convergent and divergent validity. Conclusions: In conclusion, the OMDQ-Mal, which captured important quality of life responses, demonstrated adequate validity and reliability. This was supported by a two-component model CFA. The strong correlation of OMDQ-Mal with both physician scores indicated its potential as a comprehensive patient-reported outcome measure of mucositis of the entire alimentary tract.

Improvement in Dysphagia Outcomes Following Clinical Target Volume Reduction in the De-ESCALaTE Study.

AIMS: The De-ESCALaTE study showed an overall survival advantage for the administration of synchronous cisplatin chemotherapy with radiotherapy in low-risk oropharyngeal cancer when compared with synchronous cetuximab. During the trial, a radiotherapy quality assurance protocol amendment permitted centres to swap from the original radiotherapy contouring protocol (incorporating the whole oropharynx into the high-dose clinical target volume (CTV); anatomical protocol) to a protocol that incorporated the gross tumour volume with a 10 mm margin into the CTV (volumetric protocol). The purpose of this study was to examine both toxicity and tumour control related to this protocol amendment. MATERIALS AND METHODS: Overall survival and recurrence at 2 years were used to compare tumour control in the two contouring cohorts. For toxicity, the cohorts were compared by both the number of severe (grades 3-5) and all grades acute and late toxicities. In addition, quality of life and swallowing were compared using EORTC-C30 and MD Anderson Dysphagia Inventory, respectively. RESULTS: Of 327 patients included in this study, 185 were contoured according to the anatomical protocol and 142 by the volumetric protocol. The two cohorts were well balanced, with the exception of significantly more patients in the anatomical cohort undergoing prophylactic feeding tube insertion (P < 0.001). With a minimum of 2 years of follow-up there was no significant difference in overall survival or recurrence between the two contouring protocols. Similarly, there was no significant difference in the rate of reported severe or all grades acute or late toxicity and no sustained significant difference in quality of life. However, there was a significant difference in favour of volumetric contouring in several domains of the MD Anderson Dysphagia Inventory questionnaire at 1 year, which persisted to 2 years in the dysphagia functional (P = 0.002), dysphagia physical (P = 0.009) and dysphagia overall function (P = 0.008) domains. CONCLUSION: In the context of the unplanned post-hoc analysis of a randomised trial, measurable improvement in long-term dysphagia has been shown following a reduction in the CTV. Further reductions in the CTV should be subject to similar scrutiny within the confines of a prospective study.

Radiotherapy for Oropharyngeal Carcinoma With an Uninvolved Contralateral Neck: The Safety of Omission of Contralateral High Level II and Retropharyngeal Lymph Nodes From Elective Target Volumes.

AIMS: To analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of contralateral high level II lymph nodes (HLII) and retropharyngeal lymph nodes (RPLN) in the contralateral uninvolved neck. MATERIALS AND METHODS: Patients with OPC treated between January 2016 and July 2019 were retrospectively identified. In the absence of contralateral neck disease, institutional protocols allowed omission of contralateral HLII and contralateral RPLN in the additional absence of ipsilateral RPLN, soft palate/posterior pharyngeal wall primary. RESULTS: In total, 238 patients with OPC and an uninvolved contralateral neck received definitive (chemo)radiotherapy with bilateral neck treatment. The median follow-up was 30.6 months. Two-year local control, regional control and overall survival were 91.0, 91.6 and 86.5%, respectively. Contralateral HLII were omitted in 159/238 (66.8%) patients; this included 106 patients in whom the primary tumour was at/crossed the midline. The contralateral RPLN region was omitted from elective target volumes for 175/238 (73.5%); this included 114 patients with a primary tumour at/crossed the midline. The mean contralateral parotid dose when contralateral HLII and RPLN were both omitted was 24.4 Gy, compared with 28.3 Gy without HLII/RPLN omission (P < 0.001). Regional progression occurred in 18/238 (7.6%) patients, all involving the ipsilateral neck with one bilateral. There were no recurrences in the contralateral HLII or RPLN regions. CONCLUSION: In patients with OPC and an uninvolved contralateral neck receiving bilateral (chemo)radiotherapy, the omission of contralateral RPLN and HLII from elective target volumes was safe and could lead to reduced contralateral parotid doses.

A Multicentre UK Study of Outcomes of Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy ± Chemotherapy.

AIMS: To report the outcomes of nasopharyngeal carcinoma in adults across three large centres in a non-endemic region in the era of intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Adult patients with nasopharyngeal carcinoma treated in three large cancer centres with IMRT ± chemotherapy with curative intent between 2009 and 2016 were identified from institutional databases. Radiotherapy was delivered with 70 Gy in 33-35 daily fractions. A univariable analysis was carried out to evaluate the relationship of patient, tumour and treatment factors with progression-free survival (PFS) and overall survival. RESULTS: In total, 151 patients were identified with a median follow-up of 5.2 years. The median age was 52 years (range 18-85). Seventy-five per cent were of Caucasian origin; 75% had non-keratinising tumours; Epstein Barr virus status was only available in 23% of patients; 74% of patients had stage III or IV disease; 54% of patients received induction chemotherapy; 86% of patients received concurrent chemotherapy. Five-year overall survival, PFS, local disease-free survival, regional disease-free survival and distant disease-free survival were 70%, 65%, 91%, 94% and 82%, respectively. Keratinising squamous cell carcinoma, older age, worse performance status, smoking and alcohol intake were associated with inferior overall survival and PFS. CONCLUSIONS: Local, regional and distant disease control are relatively high following IMRT ± chemotherapy in a non-endemic population. There was considerable heterogeneity in terms of radiotherapy treatment and the use of chemotherapy, encouraging the development of treatment protocols and expert peer review in non-endemic regions.

Evaluation of Locoregional Recurrence Patterns Following Adjuvant (Chemo)Radiotherapy for Oral Cavity Carcinoma.

AIMS: To evaluate patterns of locoregional recurrence following adjuvant (chemo)radiotherapy for oral cavity squamous cell carcinomas. MATERIALS AND METHODS: One hundred and one patients who received adjuvant radiotherapy ± chemotherapy for oral cavity squamous cell carcinoma between 2013 and 2016 were analysed. For documented locoregional recurrence, recurrence imaging was deformably co-registered to the planning computed tomography scan. The volume of recurrence was delineated (Vrec). Vrec coverage by 95% of the corresponding planning target volume prescription dose was determined and the location compared with planning target volumes. Sites of recurrence were classified using a combined volume and centroid-based method: (A) central high dose, (B) peripheral high dose, (C) central low dose, (D) central peripheral dose, (E) extraneous. RESULTS: The median follow-up was 36 months. Forty-three per cent and 53% of patients received radiotherapy to the ipsilateral neck only and bilateral neck, respectively. Three-year overall survival, disease-free survival, local control, regional control and distant metastases-free survival were 63.0, 65.6, 88.0, 85.1 and 85.3%, respectively. Of 10 episodes of primary site recurrences, five were type A, four type B and one was type E. Of 14 episodes of regional recurrence, five were type A, two type C, two type D and five type E. Five of 21 (24%) patients with oral tongue carcinoma with an undissected/unirradiated contralateral neck had a type E contralateral neck recurrence, including 2/11 with pN0, 1/4 with pN1 and 2/6 with pN2 disease. CONCLUSIONS: Marginal and out-of-field recurrences remain a significant pattern of failure. We advocate generous target delineation postoperatively and, for oral tongue carcinomas, a comprehensive approach with bilateral neck irradiation.

An unusual case of idiopathic inflammatory myopathy presenting with organizing pneumonia as cavitary lesions.

A young woman presented with gradually progressive breathlessness, cough and muscle weakness for one and a half year. Her chest radiograph showed multiple, bilateral thin-walled cavitary lesions. Her serum was found to be positive for anti-Jo1 antibodies on serology. Histopathology of lung lesions was suggestive of organizing pneumonia. The muscle biopsy demonstrated a myopathic pattern. On the basis of these findings she was diagnosed to be the case of idiopathic inflammatory myopathy. Her condition improved significantly after treatment with steroids.

Quality Assurance Peer Review of Head and Neck Contours in a Large Cancer Centre via a Weekly Meeting Approach.

AIMS: To assess the impact of weekly scheduled peer review of head and neck contours for definitive and adjuvant radiotherapy cases based on rates of recommended changes. MATERIALS AND METHODS: Retrospective analysis of a prospective database. Recommended changes were prospectively classified as 'major' (change in gross tumour volume and/or high-dose clinical target volume, dose/fractionation) or 'minor' (change in intermediate or elective dose clinical target volumes or organs at risk). Univariate analysis to explore associations between recommended changes and tumour site/stage and radical/adjuvant indication. RESULTS: In total, 307/375 (82%) head and neck cases treated with volumetric-modulated arc therapy were prospectively peer reviewed over a 12-month period; 195 (64%) cases received definitive and 112 (36%) received adjuvant radiotherapy. Overall, 43/307 (14.0%) changes were recommended within the peer review meetings. This comprised 27/307 (8.8%) major changes and 16/307 (5.2%) minor changes; 33/43 (77%) changes were in the clinical target volume. Rates of recommended changes were significantly higher for adjuvant versus definitive radiotherapy (odds ratio 2.26, P = 0.014) and for larynx compared with oropharynx (odds ratio 3.02, P = 0.02). There was no overall correlation between clinician experience and rates of change (P = 0.62). CONCLUSION: Routine weekly meeting contour-based peer review resulted in a number of major and minor changes to treatment. Compliance was high. Peer review was potentially beneficial for all tumour sites/stages/indications and any degree of clinician experience.

Accuracy of Response Assessment Positron Emission Tomography-Computed Tomography Following Definitive Radiotherapy Without Chemotherapy for Head and Neck Squamous Cell Carcinoma.

AIM: There are few data to inform on the use of response assessment 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following radical radiotherapy without chemotherapy for head and neck squamous cell carcinoma (HNSCC). This retrospective study evaluated the accuracy of PET-CT in HNSCC following radical radiotherapy. MATERIALS AND METHODS: In total, 138 patients with HNSCC treated with radical radiotherapy without chemotherapy who underwent a baseline and response assessment FDG PET-CT were identified. FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes. RESULTS: The median follow-up was 26 months. FDG-avid disease at baseline was present for the primary site and lymph nodes in 118 and 86 patients, respectively. With regard to the primary tumour, the negative predictive value (NPV) of a complete metabolic response (CMR) was 95%; the positive predictive value (PPV) of equivocal uptake and a positive scan were 6% and 82%, respectively. The likelihood ratios for a CMR, equivocal and positive scans of the primary site were 0.19, 0.22, 14.8, respectively. With regard to lymph node disease, the NPV of a CMR was 91%, the PPV of equivocal uptake and a positive scan were 33% and 88%, respectively. Likelihood ratios for lymph node disease for CMR, equivocal and positive scans were 0.19, 0.97 and 15.1, respectively. CONCLUSION: Compared with the accuracy reported in the literature following chemoradiotherapy, response assessment FDG PET-CT following radical radiotherapy without chemotherapy had a similarly high NPV, whereas the PPV following a positive scan was higher.

Changes in Patient-reported Swallow Function in the Long Term After Chemoradiotherapy for Oropharyngeal Carcinoma.

AIMS: To assess long-term patient-reported swallow function after chemoradiotherapy for oropharyngeal carcinoma and to evaluate the frequency of deterioration/improvement over years. MATERIALS AND METHODS: Fifty-nine patients with oropharyngeal carcinoma treated with parotid-sparing intensity-modulated radiotherapy and concurrent chemotherapy between 2010 and 2012 had previously completed the MD Anderson Dysphagia Inventory (MDADI) at a median of 34 months (range 24-59) after treatment. An MDADI was posted to 55 alive and disease-free patients after a 30 month interval; 52/55 replies were received, a median of 64 months (range 52-88) after treatment; 27/52 (52%) had been managed with a prophylactic gastrostomy. A 10 point or greater change in the MDADI scores was defined as clinically significant. RESULTS: Overall, in the whole cohort, patient-reported swallow function showed a small absolute improvement in MDADI composite score on the second MDADI questionnaire (>5 years after treatment) compared with the first MDADI (>2 years after treatment); mean 68.0 (standard deviation 19.3) versus 64.0 (standard deviation 16.3), P = 0.021. Using the composite score, swallow function was stable over time in 29/52 (56%) patients; a clinically significant improvement in swallow function over time was noted in 17/52 (33%) patients; conversely 6/52 (12%) patients experienced a clinically significant deterioration with time. Abnormality of pre-treatment diet and a prophylactic gastrostomy correlated with an inferior MDADI composite score on the later questionnaire (P = 0.029 and P = 0.044, respectively). CONCLUSIONS: Long-term dysphagia is prevalent >5 years after treatment. Although long-term swallow function is stable in most patients, it is not static in a minority. On MDADI composite summary scores, 33% of patients experienced an improvement, whereas 12% deteriorated with time. Further investigation is needed to determine underlying mechanisms behind these divergent outcomes.

Transoral laser resection or radiotherapy? Patient choice in the treatment of early laryngeal cancer: a prospective observational cohort study.

OBJECTIVES: The choices made by patients offered treatment for early laryngeal cancer with radiotherapy or transoral laser resection were reviewed. METHODS: A prospective review was conducted of all patients diagnosed and treated for early laryngeal carcinoma from December 2002 to September 2009 at the Leeds Teaching Hospitals NHS Trust. A total of 209 patients with tumour stage T1 or T2 laryngeal cancer were treated; each new patient suitable for radiotherapy or transoral laser resection was seen jointly by the clinical (radiation) oncologist and head and neck surgeon, and offered the choice of treatment. RESULTS: Of the patients, 47.4 per cent were given a choice between radiotherapy and transoral laser resection; 51.2 per cent were advised to have radiotherapy, and there were no records for the remaining 1.4 per cent. From those given the choice, 59.6 per cent chose transoral laser resection (p < 0.02 (t-test)) and 35.4 per cent chose radiotherapy. CONCLUSION: When given the choice, a statistically significant majority of patients choose transoral laser resection rather than radiotherapy.

p16 controls epithelial cell growth and suppresses carcinogenesis through mechanisms that do not require RB1 function.

The p16/RB1 tumor suppressor pathway is inactivated in the vast majority, if not all, human cancers. The current paradigm is that p16 and RB1 function in a linear pathway to suppress tumorigenesis; however p16 is preferentially lost in human cancers suggesting that p16 has critical tumor suppressive functions not mediated through RB1. Carcinomas arise from transformed epithelial cells and account for 80% of adult malignancies highlighting the need to understand p16/RB1 pathway function in organ epithelia. Lung cancer is the leading cause of cancer deaths and is associated with p16/RB1 pathway deregulation. We demonstrate that p16 is upregulated in the lung epithelium after Rb1 ablation in genetically engineered mouse models. In contrast to fibroblasts, loss of RB1 family proteins, p107 or p130, did not result in p16 induction, demonstrating that p16 suppression is a unique RB1 pocket protein function in the lung epithelium in vivo. p16 upregulation did not induce cellular senescence but rather promoted survival of RB1-deficient lung epithelial progenitor cells. Mechanistic studies show that p16 protects RB1-deficient cells from DNA damage. Consequently, additional loss of p16 led to genetic instability and increased susceptibility to cellular immortalization and transformation. Mice with combined RB1/p16-deficient lungs developed lung tumors including aggressive metastatic lung cancers. These studies identify p16 loss as a molecular event that causes genetic instability and directly demonstrate that p16 protects against DNA damage in the absence of RB1 function providing an explanation for why p16 is preferentially targeted in human cancers.

Postoperative (Chemo)Radiotherapy for Oral Cavity Squamous Cell Carcinomas: Outcomes and Patterns of Failure.

AIMS: To determine outcomes after adjuvant radiotherapy for squamous cell carcinoma of the oral cavity and to correlate locoregional recurrence patterns with radiotherapy target volumes. MATERIALS AND METHODS: All patients receiving adjuvant radiotherapy±chemotherapy after surgery with curative intent for oral cavity squamous cell carcinoma between 2007 and 2012 were retrospectively analysed. Locoregional recurrences were reconstructed on the planning computed tomography scan by both deformable image co-registration and by visual assessment. Recurrences were categorised as in-field, marginal or out-of-field if >95%, 20-95%, and <20% of the recurrence volume was encompassed by 95% of the prescription isodose, respectively. RESULTS: In total, 106 patients with a median follow-up of 42 months were included. Oral cavity subsites included oral tongue (54%) and floor of mouth (32%). Thirty (28%) patients received concurrent chemotherapy. Fifty-five (52%) patients received bilateral neck radiotherapy. Two year overall, disease-free, local disease-free, regional disease-free and distant metastases-free survival were 72, 83, 92, 89, 94%, respectively. On multivariate analysis, extracapsular nodal spread was the only factor significantly associated with inferior overall survival. Fourteen (13%) patients have experienced locoregional failure. Of the eight local recurrences at the primary tumour site, four, three and one were classified as in-field, marginal and out-of-field, respectively. Of 10 regional recurrences, one, one and eight were in-field, marginal and out-of-field. There were 7/21 (33%) contralateral regional recurrences in patients with pN2a/b disease who did not receive contralateral neck irradiation; there were 0/21 (0%) and 0/9 (0%) contralateral regional recurrences in patients with pN0 or pN1 disease, respectively, who did not receive contralateral neck irradiation. CONCLUSION: Marginal recurrences highlight the need for generous target volume delineation. Based upon rates of contralateral regional recurrences, a comprehensive approach to target volume selection should be advised for tumour subsites with bilateral lymphatic drainage in the presence of pN2a/b disease.

Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. A rational plan to manage the neck is necessary for all head and neck primaries. With the emergence of new level 1 evidence across several domains of neck metastases, this guideline will identify the evidence-based recommendations for management. Recommendations • Computed tomographic or magnetic resonance imaging is mandatory for staging neck disease, with choice of modality dependant on imaging modality used for the primary site, local availability and expertise. (R) • Patients with a clinically N0 neck, with more than 15-20 per cent risk of occult nodal metastases, should be offered prophylactic treatment of the neck. (R) • The treatment choice of for the N0 and N+ neck should be guided by the treatment to the primary site. (G) • If observation is planned for the N0 neck, this should be supplemented by regular ultrasonograms to ensure early detection. (R) • All patients with T1 and T2 oral cavity cancer and N0 neck should receive prophylactic neck treatment. (R) • Selective neck dissection (SND) is as effective as modified radical neck dissection for controlling regional disease in N0 necks for all primary sites. (R) • SND alone is adequate treatment for pN1 neck disease without adverse histological features. (R) • Post-operative radiation for adverse histologic features following SND confers control rates comparable with more extensive procedures. (R) • Adjuvant radiation following surgery for patients with adverse histological features improves regional control rates. (R) • Post-operative chemoradiation improves regional control in patients with extracapsular spread and/or microscopically involved surgical margins. (R) • Following chemoradiation therapy, complete responders who do not show evidence of active disease on co-registered positron emission tomography-computed tomography (PET-CT) scans performed at 10-12 weeks, do not need salvage neck dissection. (R) • Salvage surgery should be considered for those with incomplete or equivocal response of nodal disease on PET-CT. (R).

Impact of a dedicated emergency surgical unit on early laparoscopic cholecystectomy for acute cholecystitis.

INTRODUCTION: Emergency general surgery (EGS) accounts for 50% of the surgical workload, and yet outcomes are variable and poorly recorded. The management of acute cholecystitis (AC) at a dedicated emergency surgical unit (ESU) was assessed as a performance target for EGS. METHODS: The outcomes for AC admissions were compared one year before and after inception of the ESU. The impact on cost and compliance with national guidance recommending early laparoscopic cholecystectomy (ELC) within seven days of diagnosis was assessed. RESULTS: The overall ELC rate increased from 26% for the 126 patients admitted in the pre-ESU period to 45% for the 152 patients admitted in the post-ESU period (p=0.001). With those unsuitable for ELC excluded, the ELC rate increased from 34% to 82% (p<0.001). The proportion of patients precluded from ELC for avoidable reasons, particularly owing to 'surgeon preference/skill', was reduced from 69% to 18% (p<0.001). The mean total length of stay (LOS) and postoperative LOS fell by 1.7 days (from 8.3 to 6.6 days, p=0.040) and 2 days (from 5.6 to 3.6 days, p=0.020) respectively. The higher ELC rate and the reduction in LOS produced additional tariff income (£111,930) and estimated savings in bed day (£90,440) and readmission (£27,252) costs. CONCLUSIONS: A dedicated ESU incorporating national recommendations for EGS improves alignment of best practice with best evidence and can also result in financial rewards for a busy district general hospital.

Implementation of a novel emergency surgical unit significantly improves the management of gallstone pancreatitis.

INTRODUCTION: Emergency surgery is changing rapidly with a greater workload, early subspecialisation and centralisation of emergency care. We describe the impact of a novel emergency surgical unit (ESU) on the definitive management of patients with gallstone pancreatitis (GSP). METHODS: A comparative audit was undertaken for all admissions with GSP before and after the introduction of the ESU over a six-month period. The impact on compliance with British Society of Gastroenterology (BSG) guidelines was assessed. RESULTS: Thirty-five patients were treated for GSP between December 2013 and May 2014, after the introduction of the ESU. This was twice the nationally reported average for a UK trust over a six-month period. All patients received definitive management for their GSP and 100% of all suitable patients received treatment during the index admission or within two weeks of discharge. This was a significantly greater proportion than that prior to the introduction of the ESU (57%, p=0.0001) as well as the recently reported national average (34%). The mean length of total inpatient stay was reduced significantly after the ESU was introduced from 13.7 ± 4.7 days to 7.8 ± 2.1 days (p=0.03). The mean length of postoperative stay also fell significantly from 6.7 ± 2.6 days to 1.8 ± 0.8 days (p=0.001). CONCLUSIONS: A dedicated ESU following national recommendations for emergency surgery care by way of using dedicated emergency surgeons and a streamlined protocol for common presentations has been shown by audit of current practice to significantly improve the management of patients presenting to a busy district general hospital with GSP.

Assessment of outcomes with delayed (18)F-FDG PET-CT response assessment in head and neck squamous cell carcinoma.

OBJECTIVE: To assess the accuracy of a 4-month post-(chemo)radiotherapy 18-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-CT for head and neck squamous cell carcinoma (HNSCC). METHODS: 105 patients who underwent a baseline and response assessment (18)F-FDG PET-CT scan between 2008 and April 2013 were identified. (18)F-FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes. RESULTS: 79 of 105 (75%) (18)F-FDG PET-CT scans demonstrated a complete metabolic response; 19 of 101 (19%) for assessable primary tumours were positive; and 19 of 93 (20%) for patients with nodal disease were equivocal (n = 10) or positive (n = 9). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for primary and nodal disease were 90%, 89%, 47%, 99% and 91%, 89%, 53% and 99%, respectively. Eight of nine patients with a positive nodal response scan had clinicopathological evidence of residual nodal disease (PPV, 89%). 2 of 10 patients with equivocal nodal responses had clinicopathological evidence of residual nodal disease (PPV, 20%). CONCLUSION: (18)F-FDG PET-CT 4 months post treatment has a very high NPV. A positive (18)F-FDG PET-CT has a high PPV for residual nodal disease. By contrast, patients who have an equivocal nodal response have a low PPV. ADVANCES IN KNOWLEDGE: Response assessment (18)F-FDG PET-CT is a valuable tool in guiding the selective use of neck dissection following (chemo)radiotherapy for HNSCC. An equivocal lymph node response has a limited predictive value for persistent disease, and optimal management remains a clinical challenge.

Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

AIM: To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: This was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was permitted after progression. RESULTS: Objective response rate in both arms was 5.7% (95% CI 1.2-15.7%) by independent assessment. Disease control was 37.7% for patients on combination (24.8-52.1%) and 43.4% on control (29.8-57.7%). Neither independent nor investigator assessments showed significant differences between study arms. Median progression-free survival was 1.5 months (1.3-2.6) for patients on combination, and 1.9 months (1.5-2.9) on control. The most frequent adverse events in the combination arm were rash (29.6%), acneiform dermatitis (22.2%), and injection site reactions (20.4%). Grade 3/4 dyspnea and hypokalemia were more frequent with cetuximab monotherapy (7.5% and 5.7% vs 1.9% each, respectively), and grade 3/4 respiratory failure and disease progression were more frequent with combination (5.6% each vs 1.9% each). CONCLUSION: EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy.

Patterns of failure after intensity-modulated radiotherapy in head and neck squamous cell carcinoma using compartmental clinical target volume delineation.

AIMS: To determine the pattern of disease recurrence in non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) patients treated with radical intensity-modulated radiotherapy (IMRT) with or without chemotherapy, and to correlate the sites of locoregional recurrence with radiotherapy target volumes. MATERIALS AND METHODS: In total, 136 patients treated with radical IMRT with or without chemotherapy between 2008 and 2011 for non-nasopharyngeal HNSCC were retrospectively identified. A compartmental approach to clinical target volume (CTV) delineation was routinely utilised during this period and IMRT was delivered using a 5-7 angle step and shoot technique. Locoregional recurrences were reconstructed on the planning computed tomography scan by both deformable image coregistration and by visual assessment, and were analysed in relation to target volumes and dosimetry. RESULTS: The median follow-up was 31 (range 3-53) months. Two year local control, regional control, disease-free survival, distant metastasis-free survival and overall survival were 86, 93, 78, 89 and 79%, respectively. One hundred and twenty of 136 (88%) patients achieved a complete response to treatment and 7/120 (6%) have subsequently had a locoregional recurrence. Analysis of these recurrences revealed five to be infield; one to be marginal to the high-dose CTV; one to be out-of-field. Overall the marginal/out-of-field recurrence rate was 2/136 (1.5%). CONCLUSIONS: IMRT utilising a compartmental approach to CTV delineation was associated with a low rate of marginal/out-of-field recurrence.

Effects of the Pringle manoeuvre on the healing of left colonic anastomoses in rats.

BACKGROUND: Whether to perform colorectal cancer and liver metastasis resections simultaneously or in separate procedures is controversial. The aim of the present study was to investigate the effect of the Pringle manoeuvre on the healing of left-sided colonic anastomoses in rats. METHODS: Sixteen rats were randomly separated into two groups. In Groups 1 and 2, 1 cm of descending colon was resected and a primary anastomosis was performed. In Group 2, an intermittent pedicle clamp (the Pringle manoeuvre) was performed. On postoperative day 5, laparotomy was performed and the bursting pressures of all colon anastomoses were determined. Tissues were sampled for assay of hydroxyproline levels. Cultures of intraperitoneal swabs were also performed. RESULTS: Clostridium was twice as abundant in the Pringle manoeuvre group as in the control group (p < 0.05). Anastomosis-bursting pressures and tissue hydroxyproline levels were significantly lower in the Pringle manoeuvre group than in the control group (p < 0.05). CONCLUSIONS: The Pringle manoeuvre may compromise the viability of colonic anastomoses.