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.

Management of chronic constipation in general practice.

BACKGROUND: Chronic constipation is often diagnosed and treated by general practitioners (GPs). The aim of the study was to evaluate the management of constipation by a cohort of Italian GPs. METHODS: Over the course of 1 month, 41 GPs recorded tests and therapies suggested to patients complaining of chronic constipation. They were classified according to the Rome III criteria as constipated irritable bowel syndrome (C-IBS), functional constipation (FC), or "self-perceived constipation" (SPC) (not consistent with the Rome criteria). RESULTS: The most frequently prescribed tests for the 229 patients (147 FC, 50 C-IBS, 32 SPC) were routine blood tests (59.3 %), abdominal ultrasounds (37.2 %), thyroid function (36.7 %), fecal occult blood tests (36.7 %), and tumor markers (35 %). Patient sex and age, GP age, and whether the diagnosis was new influenced the GP's request, but FC, C-IBS, or SPC status did not. Dietary suggestions (81.9 %), fiber supplements (59.7 %), reassurance (50.9 %), and laxatives (30.5 %) were the most frequently prescribed treatments. Antispasmodics were more frequently suggested for C-IBS patients; dietary suggestions, fiber, and enemas were more frequently prescribed in SPC patients. Patient and GP age and whether the diagnosis was new influenced the GP's choice of treatment. CONCLUSIONS: The Rome III criteria do not influence diagnostic strategies and only slightly influence therapeutic strategies of GPs. Other factors (age, gender, new or old diagnosis) have more influence on GPs choice of investigations and treatment.

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.

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.

Can the irradiated uterus sustain a pregnancy? A literature review.

A significant number of adult pre- menopausal women are offered pelvic radical radiotherapy as part of the management of their malignancy. Advances in human reproductive research are making pregnancy a possibility for these women, but ovarian function, however, is not the only requirement for establishing and maintaining a pregnancy that will result in the delivery of a normal infant. The processes of implantation, fetal and placental development and labour require normal cervical structure and function. Radiation induces acute and late changes in the uterus that have a permanent impact. This article aims to summarise the published data on this complex subject. To date, the majority of reports of successful pregnancies refer to women who had hemi-pelvis or abdominal irradiation suggesting that partial volume irradiation of the uterus may not preclude pregnancy. However, with the current available information, women receiving a radical dose of radiotherapy to the whole uterus are very unlikely to have a successful pregnancy even if ovarian function is maintained. Systematic studies and, in particular, studies looking at modern radiotherapy techniques are required, as well as a register of pregnancies and outcomes to be able to provide answers for this group of patients.

Preparing preschool programs to care for children with HIV infection.

As a consequence of the increasing incidence and prevalence of HIV infection, preschools are seeking help in developing and implementing nondiscriminatory policies. Pediatric nurse practitioners are in an ideal position to provide leadership in adapting preschool programs to meet the special health care needs of these children.

Developing case managers for chronically ill children: Florida's registered nurse specialist program.

This article describes the Florida Health and Rehabilitative Services/Children's Medical Services Nurse Specialist Program. This program is a statewide training and service delivery system designed to prepare selected nurses to provide comprehensive, family-centered case management services to children with special health care needs, within the home and community settings.

Comparison of axillary, rectal and skin-based temperature assessment in preschoolers.

This study describes a clinical comparison of temperatures taken by rectal and axillary routes and by the Clinitemp II fever detector, which is a forehead-adhering strip that measures body temperature. Simultaneous temperatures were taken on a convenience sample of 70 ambulatory preschool children. Readings obtained by the Clinitemp II were found to be similar to those obtained using a rectal thermometer. Recommendations are made for the use of the Clinitemp II fever-detector strip as an acceptable screening alternative for determining body temperature trends in ambulatory children from 1 to 5 years of age.

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.

Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.

The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.