Intensity modulated radiotherapy in locally advanced thyroid cancer: Outcomes of a sequential phase I dose-escalation study.

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.

A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.

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.

Direct skin involvement of cervical lymph node metastasis from mucosal squamous cell carcinoma of the head and neck.

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.

Target volume definition for head and neck intensity modulated radiotherapy: pre-clinical evaluation of PARSPORT trial guidelines.

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.

Clinical use of intensity-modulated radiotherapy: part II.

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.

Clinical use of intensity-modulated radiotherapy: part I.

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.