Reporting the whole story: Analysis of the 'out-of-scope' questions from the James Lind Alliance Teenage and Young Adult Cancer Priority Setting Partnership Survey.

OBJECTIVE: We conducted a UK-wide survey to identify the top 10 research questions for young people's cancer. We conducted secondary analysis of questions submitted, which were 'out-of-scope' of the original survey aim. We sought to disseminate these questions, to inform practice, policy and the development of potential interventions to support young people with cancer. DESIGN: James Lind Alliance Priority Setting Partnership. PARTICIPANTS: Young people aged 13-24 with a current/previous cancer diagnosis, their families/friends/partners and professionals who work with this population. METHODS: Eight hundred and fifty-five potential research questions were submitted, and 326 were classified as 'out-of-scope'. These questions, along with 49 'free-text' comments, were analysed using thematic analysis. RESULTS: The 375 out-of-scope questions and comments were submitted by: 68 young people, 81 family members/partners/friends and 42 professionals. Ten overarching themes were identified: diagnostic experience; communication; coordination of care; information needs and lack of information; service provision; long-term effects and aftercare support; family support; financial impact; end-of life care; and research methods and current research. CONCLUSIONS: The need to tailor services, information and communication is a striking thread evidenced across the 'out-of-scope' questions. Gaps in information highlight implications for practice in revisiting information needs throughout the cancer trajectory. We must advocate for specialist care for young people and promote the research priorities and these findings to funding bodies, charities, young people and health and social care policymakers, in order to generate an evidence base to inform effective interventions across the cancer trajectory and improve outcomes. PATIENT/PUBLIC CONTRIBUTIONS: Patients and carers were equal stakeholders throughout.

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.

Post-treatment FDG PET-CT in head and neck carcinoma: comparative analysis of 4 qualitative interpretative criteria in a large patient cohort.

There is no consensus regarding optimal interpretative criteria (IC) for Fluorine-18 fluorodeoxyglucose (FDG) Positron Emission Tomography - Computed Tomography (PET-CT) response assessment following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). The aim was to compare accuracy of IC (NI-RADS, Porceddu, Hopkins, Deauville) for predicting loco-regional control and progression free survival (PFS). All patients with histologically confirmed HNSCC treated at a specialist cancer centre with curative-intent non-surgical treatment who underwent baseline and response assessment FDG PET-CT between August 2008 and May 2017 were included. Metabolic response was assessed using 4 different IC harmonised into 4-point scales (complete response, indeterminate, partial response, progressive disease). IC performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy) were compared. Kaplan-Meier and Cox proportional hazards regression analyses were performed for survival analysis. 562 patients were included (397 oropharynx, 53 hypopharynx, 48 larynx, 64 other/unknown primary). 420 patients (75%) received CRT and 142 (25%) had radiotherapy alone. Median follow-up was 26 months (range 3-148). 156 patients (28%) progressed during follow-up. All IC were accurate for prediction of primary tumour (mean NPV 85.0% (84.6-85.3), PPV 85.0% (82.5-92.3), accuracy 84.9% (84.2-86.0)) and nodal outcome (mean NPV 85.6% (84.1-86.6), PPV 94.7% (93.8-95.1), accuracy 86.8% (85.6-88.0)). Number of indeterminate scores for NI-RADS, Porceddu, Deauville and Hopkins were 91, 25, 20, 13 and 55, 70, 18 and 3 for primary tumour and nodes respectively. PPV was significantly reduced for indeterminate uptake across all IC (mean PPV primary tumour 36%, nodes 48%). Survival analyses showed significant differences in PFS between response categories classified by each of the four IC (p <0.001). All four IC have similar diagnostic performance characteristics although Porceddu and Deauville scores offered the best trade off of minimising indeterminate outcomes whilst maintaining a high NPV.

Second-look PET-CT following an initial incomplete PET-CT response to (chemo)radiotherapy for head and neck squamous cell carcinoma.

OBJECTIVES: The limited positive predictive value of an incomplete response on PET-CT following (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) means that the optimal management strategy remains uncertain. The aim of the study is to assess the utility of a 'second-look' interval PET-CT. METHODS: Patients with HNSCC who were treated with (chemo)radiotherapy between 2008 and 2017 and underwent (i) baseline and (ii) response assessment PET-CT and (iii) second-look PET-CT following incomplete (positive or equivocal scan) response were included. Endpoints were conversion rate to complete response (CR) and test characteristics of the second-look PET-CT. RESULTS: Five hundred sixty-two patients with HNSCC underwent response assessment PET-CT at a median of 17 weeks post-radiotherapy. Following an incomplete response on PET-CT, 40 patients underwent a second-look PET-CT at a median of 13 weeks (range 6-25) from the first response PET-CT. Thirty-four out of 40 (85%) patients had oropharyngeal carcinoma. Twenty-four out of 40 (60%) second-look PET-CT scans converted to a complete locoregional response. The primary tumour conversion rate was 15/27 (56%) and the lymph node conversion rate was 14/19 (74%). The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the second-look PET-CT were 75%, 75%, 25% and 96% for the primary tumour and 100%, 92%, 40% and 100% for lymph nodes. There were no cases of progression following conversion to CR in the primary site or lymph nodes. CONCLUSIONS: The majority of patients who undergo a second-look PET-CT convert to a CR. The NPV of a second-look PET-CT is high, suggesting the potential to avoid surgical intervention. KEY POINTS: • PET-CT is a useful tool for response assessment following (chemo)radiotherapy for head and neck squamous cell carcinoma. • An incomplete response on PET-CT has a limited positive predictive value and optimal management is uncertain. • These data show that with a 'second-look' interval PET-CT, the majority of patients convert to a complete metabolic response. When there is doubt about clinical and radiological response, a 'second-look' PET-CT can be used to spare patients unnecessary surgical intervention.

Research priorities for young people with cancer: a UK priority setting partnership with the James Lind Alliance.

OBJECTIVES: To conduct a UK-wide survey of young people who have experienced cancer, carers and professionals, to identify and prioritise research questions to inform decisions of research funders and support the case for research with this unique cancer population. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative and partner organisations were recruited. Unanswered questions were collected in an online survey. Evidence searching verified uncertainties. An interim survey was used to rank questions prior to a final prioritisation workshop. PARTICIPANTS: Young people aged 13-24 years with a current or previous cancer diagnosis, their families, friends, partners and professionals who work with this population. RESULTS: Two hundred and ninety-two respondents submitted 855 potential questions. Following a refining process and removal of 'out of scope' questions, 208 unique questions remained. Systematic evidence checking identified seven answered questions and 16 were the subject of ongoing studies. The interim survey was completed by 174 participants. The top 30 questions were prioritised at a workshop attended by 25 young people, parents and multidisciplinary professionals. The top three priorities are: (1) What psychological support package improves psychological well-being, social functioning and mental health during and after treatment? (2) What interventions, including self-care, can reduce or reverse adverse short-term and long-term effects of cancer treatment? (3) What are the best strategies to improve access to clinical trials? The remaining questions reflect the complete cancer pathway: new therapies, life after cancer, support, education/employment, relapse and end-of-life care. CONCLUSIONS: We have identified shared research priorities for young people with cancer using a rigorous, person-centred approach involving stakeholders typically not involved in setting the research agenda. The breadth of priorities suggest future research should focus on holistic and psychosocial care delivery as well as traditional drug/biology research.

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.

Retropharyngeal Lymph Node Involvement in Oropharyngeal Carcinoma: Impact upon Risk of Distant Metastases and Survival Outcomes.

The influence of retropharyngeal lymph node (RPLN) involvement on prognosis in oropharyngeal carcinoma remains poorly defined. The aim of this study was to assess the impact of RPLN involvement upon outcomes. A single-centre retrospective analysis of 402 patients with oropharyngeal carcinoma treated nonsurgically between 2010 and 2017 was performed. All had a baseline 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) PET-CT and contrast-enhanced MRI and/or CT. RPLN status was determined by radiology review of cases with reported abnormal RPLN. Multivariate backwards logistic regression was used to examine impact on outcomes of factors. Abnormal RPLNs were identified in 40/402 (10%) of patients. Median follow up was 42.9 months. RPLN involvement was associated with inferior 3 year outcomes for overall survival (OS) (67.1% vs. 79.1%, p = 0.006) and distant metastases-free survival (DMFS) (73.9% versus 88.0%, p = 0.011), with no significant difference in local control (81.6% vs. 87.7%, p = 0.154) or regional control (80.7% vs. 85.4%, p = 0.252). On multivariate analysis abnormal RPLN, no concurrent chemotherapy and ongoing smoking were associated with inferior DMFS and OS, while advanced T stage was also associated with inferior OS. In summary, RPLN involvement, present in 10% of patients, was an independent prognostic factor for the development of distant disease failure translating into inferior OS. These findings need confirmation in future studies.

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.

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.

Definitive hypofractionated radiotherapy for early glottic carcinoma: experience of 55Gy in 20 fractions.

INTRODUCTION: A wide variety of fractionation schedules have been employed for the treatment of early glottic cancer. The aim is to report our 10-year experience of using hypofractionated radiotherapy with 55Gy in 20 fractions at 2.75Gy per fraction. METHODS: Patients treated between 2004 and 2013 with definitive radiotherapy to a dose of 55Gy in 20 fractions over 4 weeks for T1/2 N0 squamous cell carcinoma of the glottis were retrospectively identified. Patients with prior therapeutic minor surgery (eg. laser stripping, cordotomy) were included. The probabilities of local control, ultimate local control (including salvage surgery), regional control, cause specific survival (CSS) and overall survival (OS) were calculated. RESULTS: One hundred thirty-two patients were identified. Median age was 65 years (range 33-89). Median follow up was 72 months (range 7-124). 50 (38 %), 18 (14 %) and 64 (48 %) of patients had T1a, T1b and T2 disease respectively. Five year local control and ultimate local control rates were: overall - 85.6 % and 97.3 % respectively, T1a - 91.8 % and 100 %, T1b - 81.6 and 93.8 %, and T2 - 80.9 % and 95.8 %. Five year regional control, CSS and OS rates were 95.4 %, 95.7 % and 78.8 % respectively. There were no significant associations of covariates (e.g. T-stage, extent of laryngeal extension, histological grade) with local control on univariate analysis. Only increasing age and transglottic extension in T2 disease were significantly associated with overall survival (both p <0.01). Second primary cancers developed in 17 % of patients. 13 (9.8 %) of patients required enteral tube feeding support during radiotherapy; no patients required long term enteral nutrition. One patient required a tracheostomy due to a non-functioning larynx on long term follow up. CONCLUSIONS: Hypofractionated radiation therapy with a dose of 55Gy in 20 fractions for early stage glottic cancer provides high rates of local control with acceptable toxicity.

Definitive and adjuvant radiotherapy for sinonasal squamous cell carcinomas: a single institutional experience.

BACKGROUND: The aim of this study was to evaluate the disease outcomes of patients treated with definitive and adjuvant radiotherapy for squamous cell carcinomas of the nasal cavity and paranasal sinuses in a single institution. METHODS: Between 2007-2012 patients were retrospectively identified from electronic databases who had undergone surgery and adjuvant radiotherapy or definitive radiotherapy for sinonasal squamous cell carcinomas with curative intent. RESULTS: Fourty three patients with sinonasal squamous cell carcinoma were identified (22 nasal cavity, 21 paranasal sinuses). 31/43 (72%) had T3 or T4 disease; nodal stage was N0 in 38, N1 in 4, Na/b in 0 and N2c in 1 patient. Median age was 67 years (range 41-86). 18 (42%) received definitive and 25 (58%) adjuvant radiotherapy. Radiotherapy was delivered using either conventional radiotherapy (n = 39) or intensity modulated radiotherapy (n = 4). Elective neck radiotherapy was delivered to two patients. Chemotherapy was delivered to 6/43 (14%) of patients. Two-year local control, regional control, distant metastases free survival, progression free survival, cause specific survival and overall survival were 81%, 90%, 95%, 71%, 84% and 80% respectively. There was no significant difference in outcome comparing patients who underwent surgery and adjuvant radiotherapy with patients receiving definitive radiotherapy (2 year locoregional disease free survival 75% and 70% respectively, p = 0.98). Pooly differentiated tumours were significantly associated with inferior disease outcomes. Local, regional, combined local and regional, and distant failure occurred in 7 (16%), 3 (7%), 1 (2%) and 2 (5%) of patients; all 3 regional recurrences were in patients with nasal cavity squamous cell carcinomas who had not undergone elective neck treatment. CONCLUSIONS: Definitive or adjuvant radiotherapy provides an effective treatment for sinonasal malignancies. The main pattern of failure remains local, suggesting the need for investigation of intensified local therapy. Whilst remaining uncommon, the cases of regional failure mean that the merits of elective lymph node treatment should be considered on an individual basis.

Outcomes following chemoradiotherapy for N3 head and neck squamous cell carcinoma without a planned neck dissection.

OBJECTIVES: The optimal management of the N3 neck in head and neck squamous cell carcinoma (HNSCC) remains controversial. We report the outcomes of patients with N3 disease treated with a strategy of concurrent chemo-radiotherapy (CRT)±induction chemotherapy (ICT) without a planned neck dissection. MATERIALS AND METHODS: Forty patients with HNSCC N3 disease treated between January 2004 and December 2010 were retrospectively identified. Inclusion criteria for the study were: non-nasopharyngeal HNSCC, N3 nodal disease, intention to treat with CRT±ICT. RESULTS: Median age was 60 (range 39-74). Median follow up was 32 months (range 8-88). 34 (85%) of patients received ICT. 35 patients received cisplatin-CRT, 4 carboplatin-CRT and 1 patient was treated with radiotherapy alone due to ICT toxicity. 27 (67.5%) patients had a complete response (CR) to CRT. 5 (12.5%) patients had an incomplete response in both the primary and nodal sites. 8 (20%) patients had a CR in the primary site but incomplete in the nodal regions. The crude rate of regional failure following a CR was 3/27 (11.2%). Isolated regional failure occurred in 1/27 (3.7%) patients who had achieved a CR post-CRT. 3 year overall survival, disease free survival, locoregional control, local control and regional control in the whole cohort were 51.4%, 49.6%, 65.7%, 77.3%, 69.3%, and in patients with a CR were 73.3%, 70.0%, 86.6%, 90.5% and 91.7% respectively. CONCLUSION: Isolated regional nodal failure is rare following a complete response to CRT for N3 HNSCC managed without a planned neck dissection.

The Impact of (18)F-FDG PET CT Prior to Chemoradiotherapy for Stage III/IV Head and Neck Squamous Cell Carcinoma.

Introduction. To determine the value of a FDG-PET-CT scan in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) prior to chemoradiotherapy. Materials and Methods. Consecutive patients with stage III or IV HNSCC who had undergone a staging FDG-PET-CT scan prior to chemoradiotherapy between August 2008 and April 2011 were included. Clinical details and conventional imaging (CT and/or MRI) were, retrospectively, reviewed, a TNM stage was assigned, and levels of cervical lymph node involvement were documented. This process was repeated with the addition of FDG-PET-CT. Radiotherapy plans were reviewed for patients with an alteration identified on TNM staging and/or nodal level identification with FDG-PET-CT and potential alterations in radiotherapy planning were documented. Results. 55 patients were included in the analysis. FDG-PET-CT altered the TNM stage in 17/55 (31%) of patients, upstaging disease in 11 (20%) and downstaging in 6 (11%); distant metastases were identified by FDG-PET-CT in 1 (2%) patient. FDG-PET-CT altered the lymph node levels identified in 22 patients (40%), upclassifying disease in 16 (29%) and downclassifying in 6 (11%). Radiotherapy plans were judged retrospectively to have been altered by FDG-PET-CT in 10 patients (18%). Conclusions. The use of FDG-PET-CT potentially impacts upon both treatment decisions and radiotherapy planning.

Enteral feeding outcomes after chemoradiotherapy for oropharynx cancer: a role for a prophylactic gastrostomy?

To determine the outcomes of patients managed with different routes of enteral feeding during chemoradiotherapy for oropharynx cancer. The hospital and dietetic records of consecutive patients with oropharynx squamous cell carcinoma treated between January 2007 and June 2009 with concurrent chemoradiotherapy were reviewed retrospectively. One hundred and four patients were analysed. Seventy-one received a prophylactic gastrostomy, 21 were managed with a strategy of NG tube as required and 12 received a therapeutic gastrostomy. Patients with a prophylactic gastrostomy commenced enteral feeding a median of 24 days after commencing radiotherapy, compared with a median of 41 days (p<0.001) for the NG as required group. Comparing prophylactic gastrostomy, NG as required and therapeutic gastrostomy, median number of unplanned inpatient days were 6, 14 and 7, respectively (p<0.01 for prophylactic gastrostomy vs. NG as required). Mean percentage weight loss at the end of treatment (6.1% vs. 7.1% vs. 5.2%, respectively) and at 6 months post-radiotherapy (11.7%, 14.3% and 8.9%) were similar in all groups (p=0.23). There was no significant difference in type of diet post-radiotherapy between prophylactic gastrostomy and NG as required groups (p=0.22). Median duration of enteral feeding was 181, 64 and 644 days, respectively (p<0.01 for prophylactic gastrostomy vs. NG as required). Use of a prophylactic gastrostomy (p<0.01) and higher T stage (p<0.01) were associated with increased duration of enteral feeding on a multivariate analysis. These data reinforce concerns regarding the detrimental impact of prophylactic gastrostomy placement upon long-term enteral feed dependence.

Feasibility and efficacy of induction docetaxel, cisplatin, and 5-fluorouracil chemotherapy combined with cisplatin concurrent chemoradiotherapy for nonmetastatic Stage IV head-and-neck squamous cell carcinomas.

PURPOSE: To report the experience of treating selected fit patients with locally advanced head-and-neck squamous cell carcinoma with three cycles of induction TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), 5-fluorouracil 750 mg/m(2), Days 2-5) followed by concurrent three-weekly bolus cisplatin 100 mg/m(2) chemoradiotherapy. METHODS AND MATERIALS: Between March 2006 and February 2010, 66 patients with nonmetastatic Stage IV head-and-neck squamous cell carcinoma were treated in a single institution with three cycles of induction TPF, followed by radical radiotherapy with concurrent cisplatin 100 mg/m(2). RESULTS: Median age was 54 years (range, 33-69 years). Median follow-up was 21 months (range, 4-55 months). During TPF, Grade 3 toxicity occurred in 18 patients (27%), dose modifications in 10 (15%), delays in 3 (5%), and unplanned admissions in 6 (9%); a clinical tumor response was documented in 60 patients (91%). Median time from the final cycle of TPF to commencing radiotherapy was 22 days. Sixty-two patients (94%) received radical radiotherapy, and all completed treatment with no delays ≥3 days. One, two, and three cycles of concurrent cisplatin were delivered to 18 patients (29%), 38 patients (61%), and 3 patients (5%), respectively. Ninety-two percent of patients received enteral feeding; median weight loss during treatment was 7%. Forty-two patients (68%) had unplanned admissions with no on-treatment deaths. Three unrelated deaths occurred after treatment. At 1 year after treatment, 21% of patients without disease progression remained gastrostomy dependent. Of 58 assessable patients, 50 (86%) achieved a complete response after treatment. One- and 2-year progression-free survival, cause-specific survival, and overall survival were 88%, 92%, and 86% and 80%, 85%, and 80%, respectively. CONCLUSION: The combination of induction TPF with concurrent cisplatin chemoradiotherapy in patients with locally advanced head and neck squamous cell carcinoma is tolerable, with encouraging efficacy.

Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy.

BACKGROUND: To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes METHOD: 151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist. RESULTS: Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences. CONCLUSION: The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority.

A single centre experience with sequential and concomitant chemoradiotherapy in locally advanced stage IV tonsillar cancer.

BACKGROUND: Chemo-radiotherapy offers an alternative to primary surgery and adjuvant therapy for the management of locally advanced stage IV squamous cell carcinomas of the tonsil. METHODS: A retrospective analysis was performed of the outcomes of 41 patients with locoregionally advanced squamous cell carcinoma of the tonsil treated non-surgically at the Yorkshire Cancer Centre between January 2004 and December 2005. Due to long radiotherapy waiting times, patients received induction chemotherapy with cisplatin and 5-fluorouracil followed by either cisplatin concurrent chemoradiotherapy or radiotherapy alone. RESULTS: Median age was 55 years (range 34-76 years) and 28 (68%) patients were male. 35/41 patients (85%) received 2 or more cycles of induction chemotherapy. Following induction chemotherapy, 32/41 patients (78%) had a clinical response. Concomitant chemotherapy was given to 30/41 (73%). All patients received the planned radiotherapy dose with no delays. There were no treatment related deaths. Six (15%) patients had gastrostomy tubes placed before treatment, and 22 (54%) required nasogastric tube placement during or after treatment for nutritional support. 17 patients required unplanned admissions during treatment for supportive care. At 4 months post treatment assessment 35 out of 41 (85%) patients achieved complete clinical and radiographic response. Median follow-up is 38 months (8-61 months). Local and regional control rate in complete responders at 3 years was 91%. Distant metastases have been found in 4 (9.8%) patients. Three year progression-free survival rate in all patients is 75%. The 3-year cause specific survival and overall survival are 75% and 66% respectively. CONCLUSION: Cisplatin-based induction and concurrent chemoradiotherapy provides excellent tumour control with acceptable toxicity for patients with locally advanced tonsillar cancer.

Nonrigid image registration for head and neck cancer radiotherapy treatment planning with PET/CT.

PURPOSE: Head and neck radiotherapy planning with positron emission tomography/computed tomography (PET/CT) requires the images to be reliably registered with treatment planning CT. Acquiring PET/CT in treatment position is problematic, and in practice for some patients it may be beneficial to use diagnostic PET/CT for radiotherapy planning. Therefore, the aim of this study was first to quantify the image registration accuracy of PET/CT to radiotherapy CT and, second, to assess whether PET/CT acquired in diagnostic position can be registered to planning CT. METHODS AND MATERIALS: Positron emission tomography/CT acquired in diagnostic and treatment position for five patients with head and neck cancer was registered to radiotherapy planning CT using both rigid and nonrigid image registration. The root mean squared error for each method was calculated from a set of anatomic landmarks marked by four independent observers. RESULTS: Nonrigid and rigid registration errors for treatment position PET/CT to planning CT were 2.77 +/- 0.80 mm and 4.96 +/- 2.38 mm, respectively, p = 0.001. Applying the nonrigid registration to diagnostic position PET/CT produced a more accurate match to the planning CT than rigid registration of treatment position PET/CT (3.20 +/- 1.22 mm and 4.96 +/- 2.38 mm, respectively, p = 0.012). CONCLUSIONS: Nonrigid registration provides a more accurate registration of head and neck PET/CT to treatment planning CT than rigid registration. In addition, nonrigid registration of PET/CT acquired with patients in a standardized, diagnostic position can provide images registered to planning CT with greater accuracy than a rigid registration of PET/CT images acquired in treatment position. This may allow greater flexibility in the timing of PET/CT for head and neck cancer patients due to undergo radiotherapy.