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.

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.

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.

Recruitment of patients into head and neck clinical trials: acceptability of studies to patients from perspective of the research team.

We reviewed longitudinal recruitment data to assess recruitment into head and neck cancer trials, and to identify factors that could influence this and affect their acceptability to patients. We retrieved data from the prospective computerised database (2009-2016) to measure acceptability to patients using the recruitment:screening ratio, and compared observational with interventional studies, single specialty (or site) with multispecialty (or site) studies, and "step-up" randomisation with "non-inferiority" randomisation designs. A total of 1283 patients were screened and 583 recruited. The recruitment:screening ratio for all National Institute for Health Research (NIHR) portfolio studies combined was 0.47 (486/1133). Studies that involved treatment by several specialties or at several sites had a significantly adverse impact on acceptability (p=0.01). Recruitment into non-inferiority randomised controlled studies was lower than that into step-up randomised studies (p=0.06). The complexity of a study's design did not compromise recruitment. Treatment across several specialties or several sites and perceived non-inferiority designs, reduced the acceptability of some trials.

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.

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.

Long-term swallow function after chemoradiotherapy for oropharyngeal cancer: the influence of a prophylactic gastrostomy or reactive nasogastric tube.

AIMS: Two contrasting approaches of a prophylactic gastrostomy or a nasogastric tube as needed are widely used to support patients receiving chemoradiotherapy for head and neck cancer. The influence of the type and timing of enteral feeding tube support upon long-term swallowing is uncertain. This study analysed the patients' perspective on long-term swallowing, comparing two groups of patients who received chemoradiotherapy for oropharyngeal cancer managed with the two approaches. MATERIALS AND METHODS: The MD Anderson Dysphagia Inventory (MDADI) was posted to 63 consecutive patients with oropharyngeal squamous cell cancer treated with concurrent chemoradiotherapy between January 2007 and June 2009, who had not required therapeutic enteral feeding before treatment and who were disease free on follow-up at least 2 years after treatment. RESULTS: In total, 56/63 patients completed questionnaires; 43 had been managed with a prophylactic gastrostomy and 13 with a policy of nasogastric tube as needed. There were no significant differences in all global, emotional, physical or functional domains of the MDADI according to enteral feeding strategy. Diet at 6 months after treatment was significantly correlated with better MDADI scores. CONCLUSIONS: In this study, the choice of a prophylactic gastrostomy or nasogastric tube as needed did not seem to influence long-term swallowing function.

The efficacy of induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil combined with cisplatin concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: a matched pair analysis.

AIMS: The role of induction chemotherapy (ICT) for head and neck squamous cell carcinoma (HNSCC) is controversial. The aim of the study was to assess the benefit of ICT with docetaxel, cisplatin and 5-fluorouracil (5-FU) (TPF) when combined with concurrent cisplatin chemoradiotherapy (CRT) for HNSCC. MATERIALS AND METHODS: Patients with HNSCC treated between January 2005 and December 2010 with radical intent with either TPF or cisplatin and 5-FU (PF) ICT and documented intention to proceed with concurrent cisplatin CRT were identified retrospectively. The use and choice of ICT regimen was at the clinician's discretion. In total, 68 patients treated with TPF were identified and were matched for T and N stage and tumour site to 68 patients treated with PF. A survival analysis was carried out using Kaplan-Meier and the Cox proportional hazards model. RESULTS: The median follow-up was 29.9 versus 36.3 months for the TPF and PF groups, respectively. Three year locoregional relapse-free survival (RFS), distant RFS, RFS, cancer-specific survival and overall survival rates for the TPF and PF groups were 84.2, 91.6, 82.6, 81.3 and 74.9% versus 73.7, 84.9, 71.9, 72.1 and 62.9%, respectively. On multivariate analysis, treatment with TPF predicted for improved locoregional RFS (P = 0.03) and overall survival (P = 0.05). CONCLUSION: The addition of docetaxel to a cisplatin doublet ICT regimen before concurrent CRT may improve disease control for locally advanced HNSCC.

Improving target definition for head and neck radiotherapy: a place for magnetic resonance imaging and 18-fluoride fluorodeoxyglucose positron emission tomography?

Defining the target for head and neck radiotherapy is a critical issue with the introduction of steep dose gradients associated with intensity-modulated radiotherapy. Tumour delineation inaccuracies are a major source of error in radiotherapy planning. The integration of 18-fluoride fluorodeoxyglucose positron emission tomography ((18)FDG-PET) and magnetic resonance imaging directly into the radiotherapy planning process has the potential to greatly improve target identification/selection and delineation. This raises a range of new issues surrounding image co-registration, delineation methodology and the use of functional data and treatment adaptation. This overview will discuss the practical aspects of integrating (18)FDG-PET and magnetic resonance imaging into head and neck radiotherapy planning.

The role of split-course hypofractionated palliative radiotherapy in head and neck cancer.

AIMS: A significant proportion of patients with head and neck squamous cell carcinoma are unsuitable for radical treatment due to factors including tumour stage, performance status and co-morbidity. Palliative radiotherapy has a useful role in the control of local symptoms. This study documented the outcome with split-course hypofractionated radiotherapy. MATERIALS AND METHODS: Thirty-three previously untreated patients with head and neck squamous cell carcinoma were treated with palliative intent with split-course radiotherapy, with an initial 20 Gy in five fractions over 1 week, a 2 week gap, and then a further 20 Gy in five fractions over 1 week at the Yorkshire Cancer Centre between January 2004 and December 2007. Data were collected retrospectively from case notes and radiotherapy records. RESULTS: Thirty (91%) patients had stage IV A-B disease. World Health Organization performance status was 2 or 3 in 19 (58%) patients. The median age was 76 years (range 48-91 years). Twenty-five (76%) patients were men. Symptomatic improvement was reported in 26 (79%) patients at 4-6 weeks of follow-up. Thirteen (39%) patients had a complete tumour response and 11 (33%) patients had a partial response as assessed clinically, and in some cases radiologically. The median overall survival was 9 months (range 3-43 months). Progression-free survival at 1 and 2 years was 35 and 25%, respectively. Overall survival at 1 and 2 years was 42 and 34%, respectively. Treatment was generally well tolerated; admission for nasogastric feeding and/or supportive care was required in only six patients. Radiation Therapy Oncology Group grade 3 toxicity was documented for skin in one patient, for mucosa in two patients and for oesophagitis in three patients. CONCLUSION: Split-course hypofractionated radiotherapy is an effective palliative regimen with acceptable toxicity.

Optimizing localization accuracy in head and neck, and brain radiotherapy.

The purpose of this study was to investigate the impact on localization of utilizing contrast-enhanced CT scans and the formal input of a radiologist in the planning process. 25 head and neck/brain patients had pre- and post-contrast CT scans in the treatment position. Radiotherapy treatment was planned on the unenhanced CT images as per standard practice. Retrospectively, their scans (unenhanced and enhanced) were re-contoured by two oncologists and a radiologist. These new contours were compared with the original unenhanced treatment contours and differences in contour volume, geographical isocentre position and tolerance coverage of the associated planning target volumes (PTVs) were evaluated using the original plans. The use of contrast enhanced CT data during localization by the oncologist shows little change in gross tumour volumes (GTVs) or PTVs, geographical position or tolerance coverage for the targets in the brain studied here. Larger changes in mean volume are seen for the head and neck cases alone. Changes are greater and statistically significant (p < 0.05, Wilcoxon signed rank test) for localization by the radiologist. Furthermore, when comparing the original PTV marked by the oncologist with a new PTV re-contoured by the oncologist, but based on a GTV marked-up by the radiologist, again statistically significant (p < 0.01) changes in percentage volume are noted. Intraoperator precision is good, percentage volume differences being of the order 3-6%. PTVs also show improved standard deviations compared with GTVs. Geographic shifts are generally within our departmental tolerance levels for daily patient setup. Comparing precision of unenhanced data with enhanced, mean percentage volume changes are smaller, but not statistically significant. The use of enhanced scan data for localization has little effect on size, geographical position or tolerance coverage of PTVs marked up by the oncologists in this study. However, more important is the input from a radiologist. Statistically significant differences due to mark-up on enhanced scans by the radiologist are shown. Furthermore, significant differences are also seen between PTVs based on oncologist-generated GTVs, and those based on radiologist-generated GTVs.

A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer.

AIMS: Whole-breast radiotherapy (WBRT) after conservative surgery for early breast cancer is a routine standard of care. Despite this, a number of uncertainties in management still exist. Over recent years, a number of new technologies have allowed the development of partial-breast irradiation, with the intention of improving the risk-benefit relationship of routine breast radiotherapy. We report the results of a trial comparing partial- with WBRT, with prolonged follow-up. MATERIALS AND METHODS: Between 1986 and 1990, 174 women were randomised to receive conventional whole-breast radiotherapy (WBRT) (40 Gy in 15 fractions), with a tumour-bed boost or partial-breast irradiation by a variety of techniques. Recruitment was problematic, and the trial closed prematurely well before meeting its recruitment target. RESULTS: A trend was observed towards higher local recurrence and a higher locoregional recurrence rate after irradiation of the tumour bed alone. Distant recurrence and survival were the same. CONCLUSIONS: Conclusions are limited in view of the failure to complete accrual of the target of 400 participants, and in the context of the techniques of partial-breast radiotherapy used during this study, which would not compare with those in current use. Tumour-bed irradiation alone cannot currently be recommended as routine treatment outside the context of clinical trial.

Posttransplant diffuse large B-cell lymphoma of "lymphomatoid granulomatosis" type.

The exact relationship between lymphomatoid granulomatosis (LyG) and posttransplant lymphoproliferative disorders (PTLDs) is not clear. Both are observed in immunodeficient patients and are Epstein-Barr virus driven. These disorders are, however, considered distinct based upon the immune response elicited; LyG is T-cell rich while PTLDs are T-cell poor. We describe a case of LyG-type diffuse large B-cell lymphoma (DLBCL) in a lung transplant recipient. The unusual features include rare occurrence of LyG in a posttransplant setting, systemic involvement by LyG variant of DLBCL in a solid organ transplant recipient, paucity of T-cells in this LyG type lymphoma, and subcutaneous panniculitic pattern in a B-cell lymphoproliferative disorder. This first report of systemic LyG variant of DLBCL in a posttransplant setting has features suggesting similarities and overlap between LyG and PTLD.