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The incidence of metastases following neck dissection in the apparent lymph node negative neck in oral cancer is between 7% and 33%; early resection of cervical metastases may well increase survival. Modern imaging techniques can reduce the yield of previously undiagnosed metastatic nodes in elective neck dissection (END). An audit of 112 consecutive cases was conducted to determine the proportion of undiagnosed nodal metastases, after END. There were neck metastases in 10 cases (9%), which were mainly (but not all) micrometastic. The 20% likelihood of nodal metastases was only apparent in primary tumours greater than 6 mm thick. The length of inpatient stay was increased from 3.7 to 16.5 days with free vascularised transfer. There were complications including cranial nerve damage. There were two peri-operative deaths. No ipsilateral neck failures occurred, median follow up was 937 days. To reduce unnecessary END, resection can be undertaken as a prior procedure, subsequently only carrying out END on tumours greater than 6 mm, or with unfavourable tumour characteristics., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. All rights reserved.)

Background and Purpose: To determine the safety and tolerability of dose-escalation using modestly accelerated IMRT in high-risk locally advanced thyroid cancer requiring post-operative radiotherapy, and to report preliminary data on efficacy., Materials and Methods: A sequential Phase I dose-escalation design was used. Dose level one (DL1) received 58.8 Gy/28F to the post-operative bed and 50 Gy/28F to elective nodes. DL2 received 66.6 Gy/30F to the thyroid bed, 60 Gy/30F to post-operative nodal levels and 54 Gy/30F to elective nodal levels. Acute (NCICTCv.2.0) and late toxicities (RTOG and modified LENTSOM) were recorded. The primary endpoint was the number of patients with ≥Grade 3 (G3) toxicity at 12 months post-treatment., Results: Fifteen patients were recruited to DL1 and twenty-nine to DL2. At 12 months ≥G3 toxicities were 8.3% in both DL1 and DL2. At 60 months, ≥G3 toxicity was reported in 3 (33%) patients in DL1 and 1 (7%) in DL2. One patient in DL2 died at 24 months from radiation-induced toxicity. Time to relapse and overall survival rates were higher in DL2, but this was not statistically significant. Dose-escalation using this accelerated regimen can be safely performed with a toxicity profile similar to reported series using conventional doses., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Purpose: To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ⩾G2 subjective xerostomia., Methods: Patients with midline tumours were enrolled to a phase II trial to receive induction platinum/5-fluorouracil and concomitant platinum with combined superficial lobe parotid-sparing IMRT. The primary site and involved nodal levels received 65 Gy in 30 fractions (f) and at risk nodal levels, 54 Gy/30f. Incidence of ⩾G2 subjective xerostomia was defined as the primary endpoint. Secondary endpoints included incidences of acute and late toxicities and survival outcomes dependent on human papilloma virus (HPV) status., Results: One hundred and twenty patients with midline cancers completed treatment between December 2005 and May 2010 with median follow-up of 50 months. Incidences of ⩾G2 acute toxicities were: dysphagia 75%; xerostomia 65%; mucositis 86%; pain 83%; and fatigue 64%. At 12 months, ⩾G2 subjective xerostomia was observed in 21% (17% in HPV +ve). Two-year loco-regional progression-free survival (PFS) was 90.7% (95% CI: 85.2-96.2). According to HPV status, there was a significant difference for 2-year loco-regional PFS, 76.8% (HPV-negative) vs 98.6% (HPV-positive), P=0.001. 2-year overall survival was 93% for HPV-positive compared with 52% for HPV-negative cases, P<0.001., Conclusions: Sequential chemotherapy/chemo-IMRT for midline tumours is feasible, with excellent survival outcomes. At 1 year, 21% experience ⩾G2 subjective xerostomia. Two-year survival outcomes differ significantly between HPV-positive and HPV-negative disease, suggesting development of different treatment schedules for the different disease entities.

Carcinoma of unknown primary of the neck (CUP) is a metastasis presenting in one or more cervical lymph nodes, with no primary mucosal site identified. Retrospective case notes review of 25 consecutive patients (median age 55, 72% males) diagnosed as CUP who underwent neck dissection in a UK tertiary referral comprehensive cancer centre between 2000 and 2011. Median follow-up was 33 months. Nineteen patients underwent comprehensive neck dissections (six extended), six patients had selective neck dissection. Five year disease specific survival and regional recurrence free survival were 76 and 80% respectively. The overall rate of occult disease (disease not identified on preoperative evaluation, but found on histopathologic examination) was 8%, with rates of 0% in level I and 6% in level V. Our study suggests that in patients without preoperative evidence of disease in levels I or V selective neck dissection might be considered as an option, to facilitate preservation of the submandibular gland and accessory nerve without compromising oncological outcome. Larger studies should be performed before a change in practice can be advised.

Introduction: Direct skin involvement of nodal metastasis from mucosal head and neck squamous cell carcinoma has traditionally been considered a poor prognostic indicator., Methods: This retrospective review identified eight patients (five with mucosal upper aerodigestive and three with occult primary squamous cell carcinoma) who presented between 2000 and 2007 with direct skin involvement of nodal metastasis., Results: Five patients were treated with extended radical and three with extended modified radical neck dissection. Closure was achieved directly (four cases), with local (two) or pedicled (two) flaps. Surgery was always followed by radiotherapy (pan-mucosal or to the primary site). The five-year recurrence-free and disease-specific survival rates were 100 per cent., Conclusion: It is exceptionally rare to encounter direct skin involvement of metastatic lymph nodes from mucosal head and neck squamous cell carcinoma without evidence of involvement of other anatomical structures. Surgical intervention is possible and combined modality treatment with curative intent is essential, as most patients can have a favourable outcome.

Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H)., Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded., Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2., Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Purpose: PARSPORT was a multi-centre randomised trial in the UK which compared Intensity-Modulated Radiotherapy (IMRT) and conventional radiotherapy (CRT) for patients with head and neck cancer. The dosimetry audit goals were to verify the plan delivery in participating centres, ascertain what tolerances were suitable for head and neck IMRT trials and develop an IMRT credentialing program., Materials and Methods: Centres enrolling patients underwent rigorous quality assurance before joining the trial. Following this each centre was visited for a dosimetry audit, which consisted of treatment planning system tests, fluence verification films, combined field films and dose point measurements., Results: Mean dose point measurements were made at six centres. For the primary planning target volume (PTV) the differences with the planned values for the IMRT and CRT arms were -0.6% (1.8% to -2.4%) and 0.7% (2.0% to -0.9%), respectively. Ninety-four percent of the IMRT fluence films for individual fields passed gamma criterion of 3%/3mm and 75% of the films for combined fields passed gamma criterion 4%/3mm (no significant difference between dynamic delivery and step and shoot delivery)., Conclusions: This audit suggests that a 3% tolerance could be applied for PTV point doses. For dose distributions tolerances of 3%/3mm on individual fields and 4%/3mm for combined fields are proposed for multi-centre head and neck IMRT trials.

Aims: There is considerable controversy surrounding target volume definition for parotid-sparing intensity modulated radiotherapy (IMRT) for head and neck cancer. The aim of this study was to evaluate the dosimetric and radiobiological predictors of outcome anticipated by application of the detailed target volume definition guidelines agreed for the UK multicentre randomised controlled trial of parotid-sparing IMRT (PARSPORT)., Materials and Methods: Five patients eligible for the study were delineated using the trial guidelines. Following the protocol, plans were produced to treat these volumes with three-dimensional radiotherapy (control arm) and IMRT aimed to spare dose to the contralateral parotid gland (experimental arm). Dosimetric comparisons were made between plans, and normal tissue complication probability (NTCP) modelling for salivary glands was carried out., Results: Doses delivered to the planning target volumes (PTV) were similar with each technique, although IMRT produced more homogeneous irradiation of the PTV. Mean doses to the contralateral parotid gland were 22.4+/-1.7 Gy with the IMRT plans vs 60.0+/-7.2 Gy with three-dimensional radiotherapy, P=0.0003. Calculated contralateral parotid gland NTCP values for grade 2 xerostomia were 20-22% for IMRT and 98-100% for three-dimensional radiotherapy (P<0.0001)., Conclusion: Pre-clinical evaluation of the PARSPORT trial target volume definition guidelines provides theoretical support for a significant reduction in xerostomia rates. These data await confirmation from the clinical trial results.

Purpose: To investigate the potential for intensity-modulated radiotherapy (IMRT) to spare the bowel in rectal tumors., Methods and Materials: The targets (pelvic nodal and rectal volumes), bowel, and bladder were outlined in 5 patients. All had conventional, three-dimensional conformal RT and forward-planned multisegment three-field IMRT plans compared with inverse-planned simultaneous integrated boost nine-field equally spaced IMRT plans. Equally spaced seven-field and five-field and five-field, customized, segmented IMRT plans were also evaluated., Results: Ninety-five percent of the prescribed dose covered at least 95% of both planning target volumes using all but the conventional plan (mean primary and pelvic planning target volume receiving 95% of the prescribed dose was 32.8 +/- 13.7 Gy and 23.7 +/- 4.87 Gy, respectively), reflecting a significant lack of coverage. The three-field forward planned IMRT plans reduced the volume of bowel irradiated to 45 Gy and 50 Gy by 26% +/- 16% and 42% +/- 27% compared with three-dimensional conformal RT. Additional reductions to 69 +/- 51 cm(3) to 45 Gy and 20 +/- 21 cm(3) to 50 Gy were obtained with the nine-field equally spaced IMRT plans-64% +/- 11% and 64% +/- 20% reductions compared with three-dimensional conformal RT. Reducing the number of beams and customizing the angles for the five-field equally spaced IMRT plan did not significantly reduce bowel sparing., Conclusion: The bowel volume irradiated to 45 Gy and 50 Gy was significantly reduced with IMRT, which could potentially lead to less bowel toxicity. Reducing the number of beams did not reduce bowel sparing and the five-field customized segmented IMRT plan is a reasonable technique to be tested in clinical trials.

Purpose: To evaluate set-up reproducibility of a cabulite shell and determine CTV-PTV margins for head and neck intensity-modulated-radiotherapy., Materials and Methods: Twenty patients were entered into the study. A total of 354 anterior and lateral isocentric electronic portal images (EPIs) were compared to simulator reference images., Results: About 94% of all translational displacements were < or =3 mm, and 99% < or =5 mm. The overall systematic error was 0.9 mm (+/-1.0SD) in the Right-Left, 0.7 mm (+/-0.9SD) in the Superior-Inferior and -0.02 mm (+/-1.1SD) in the Anterior-Posterior directions. The corresponding SDs of the random errors were +/-0.4, +/-0.6 and +/-0.7 mm. The estimated margins required from CTV-PTV were calculated according to the Van Herk formula was 2.9, 2.6 and 3.3 mm, respectively., Conclusions: This head and neck immobilisation system is of sufficient accuracy for its use with IMRT treatments and a 3 mm CTV-PTV margin has been adopted.

Intensity-modulated radiotherapy (IMRT) is a novel conformal radiotherapy technique which is gaining increasingly widespread use. This second clinical article aims to summarize the published data pertaining to prostate cancer, pelvic irradiation, gynaecological and breast cancer. Prostate cancer patients represent the largest group treated to date. The main indication has been radiation dose escalation within acceptable normal tissue late toxicity. Phase II data are promising, but no randomized clinical trial data are available to support its use. Pelvic IMRT aims to deliver radical radiation doses to pelvic lymph nodes while sparing the bowel and bladder. Indications for breast IMRT data are reviewed, and current data presented. Further data from randomized trials are required to confirm the anticipated benefits of IMRT in patients.

Intensity-modulated radiotherapy (IMRT) is a novel conformal radiotherapy technique which is gaining increasing clinical use worldwide. This article aims to summarize the published data pertaining to clinical indications of this therapy for head and neck, central nervous system, and lung tumours. The main indications in head and neck cancer are parotid gland sparing and dose escalation to tumours close to organs at risk. For central nervous system tumours, IMRT has been used to reduce normal tissue radiation by more conformal dose distributions. To date, the majority of reports concern patients treated in the context of clinical trials, and for most tumour types longer term follow up of treated patients will be required to confirm the clinical benefits of IMRT.