Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab-PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab-C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control. PATIENTS AND METHODS: Eligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0-4N2b-2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0-3 or HPV-negative and T0-2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3-4. Patient reported outcomes were carried out. RESULTS: A total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups. CONCLUSION: The observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.

Improving team information sharing with a structured call-out in anaesthetic emergencies: a randomized controlled trial.

BACKGROUND: Sharing information with the team is critical in developing a shared mental model in an emergency, and fundamental to effective teamwork. We developed a structured call-out tool, encapsulated in the acronym 'SNAPPI': Stop; Notify; Assessment; Plan; Priorities; Invite ideas. We explored whether a video-based intervention could improve structured call-outs during simulated crises and if this would improve information sharing and medical management. METHODS: In a simulation-based randomized, blinded study, we evaluated the effect of the video-intervention teaching SNAPPI on scores for SNAPPI, information sharing, and medical management using baseline and follow-up crisis simulations. We assessed information sharing using a probe technique where nurses and technicians received unique, clinically relevant information probes before the simulation. Shared knowledge of probes was measured in a written, post-simulation test. We also scored sharing of diagnostic options with the team and medical management. RESULTS: Anaesthetists' scores for SNAPPI were significantly improved, as was the number of diagnostic options they shared. We found a non-significant trend to improve information-probe sharing and medical management in the intervention group, and across all simulations, a significant correlation between SNAPPI and information-probe sharing. Of note, only 27% of the clinically relevant information about the patient provided to the nurse and technician in the pre-simulation information probes was subsequently learnt by the anaesthetist. CONCLUSIONS: We developed a structured communication tool, SNAPPI, to improve information sharing between anaesthetists and their team, taught it using a video-based intervention, and provide initial evidence to support its value for improving communication in a crisis.

Influence of multi-lumen extensions on fluid flow through intravenous cannulae.

Multi-lumen extensions used to infuse multiple fluids via a single intravenous cannula might increase resistance and so limit the flow that can be achieved. We constructed low-pressure and high-pressure models and compared the effect of two different multi-lumen extensions on flow rate. Both multi-lumen extensions reduced flows by up to 76% (p < 0.001). The effect was greatest with large cannulae and in the high-pressure model, with the longer and narrower extension most impeding flow. Multi-lumen extensions can therefore significantly impede fluid flow, and should be avoided or removed when rapid infusion is required. These effects are less important in paediatric anaesthesia where smaller cannulae are used. Manufacturers should include internal diameter or flow effects on the packaging of these extensions to assist clinicians in making such decisions.

Studies on the effect of temperature and pH on the inactivation of fish viral and bacterial pathogens.

Disposal of fish by-products in the European Community must comply with Regulation (EC) No 1069/2009 which categorizes animal by-products according to risk, and specifies methods of disposal of by-products according to that risk. There is provision under the regulation for composting or ensiling to be used for by-products from aquatic animals. Biosecurity considerations require knowledge of the parameters of time and temperature, or time and pH, required to inactivate any fish pathogens that may be present. To provide those data, we undertook laboratory studies on the inactivation of a number of fish pathogenic viruses and bacteria at 60 °C, pH 4.0 and pH 12.0 as a preliminary to conducting subsequent trials with the most resistant viruses and bacteria in fish tissues. The most resistant bacterium to 60 °C, pH 4.0 as well as pH 12.0 was Lactococcus garvieae. Its concentration was reduced to the level of sensitivity of the test after 24-48 h exposure to 60 °C, but it survived for at least 7 days at pH 4.0 and 14 days at pH 12.0. The most resistant virus to 60 °C was infectious pancreatic necrosis virus, and to pH 12.0 was infectious salmon anaemia virus. The majority of the viruses tested survived exposure to pH 4.0 for up to 28 days. The results suggest that the process of acid ensiling alone is not an effective method for the inactivation of many viral and bacterial pathogens, and fish by-products would need further treatment by a method approved under the regulation following ensiling, whereas alkaline or heat treatment are likely to provide an increased degree of biosecurity for on-farm processing of mortalities.

Test-retest reliability of the oxygen uptake efficiency slope in surgical patients.

The oxygen uptake efficiency slope is a measure of cardiopulmonary fitness, that can be obtained from a sub-maximal cardiopulmonary exercise test. It has been evaluated in medical patients but its reliability in surgical populations remains uncertain. We conducted a test-retest study with the aim of establishing the reliability of the oxygen uptake efficiency slope in relation to that of the anaerobic threshold and peak oxygen uptake, in general surgical patients. Twenty-six patients over 60 years old completed two symptom-limited, incremental cycle ergometry tests within 7 days. The mean (SD) anaerobic threshold was 13.0 (3.0) mlO(2) .kg(-1) .min(-1) . There were no significant differences between mean test and retest values of anaerobic threshold (p = 0.50), peak oxygen uptake (p = 0.76) or oxygen uptake efficiency slope (p = 0.42). Reliability coefficients (95% CI) for the anaerobic threshold, oxygen uptake efficiency slope and peak oxygen uptake were 66.7% (45.3-87.9%), 89.0% (81.0-96.9%) and 91.7% (85.7-97.8%), respectively. The oxygen uptake efficiency slope was determined easily in all patients and found to have excellent reliability. Its clinical utility in determining pre-operative fitness warrants further evaluation.

The histology and management of ovarian cysts found in children and adolescents presenting to a children's hospital from 1991 to 2007: a call for more paediatric gynaecologists.

OBJECTIVE: To determine the nature and surgical management of ovarian cysts. DESIGN: Retrospective case-note study. SETTING: Large Childrens' Hospital: Alder Hey NHS Foundation Trust. SAMPLE: Children undergoing surgery for ovarian cysts between 1991 and 2007. METHODS: Cases identified using coding and the pathology database, and analysed using snap 9. MAIN OUTCOME MEASURES: Extent of surgery performed. Size and histological features of cysts removed. RESULTS: A total of 155 cases were identified. There were 62 ovarian cysts in children under nine who were prepubertal. There were 58 neoplastic cysts in total. Most were benign teratomas (36). Ten cysts were malignant, including five granulosa cell tumours, one yolk sac tumour, one endodermal sinus tumour and one dysgerminoma. Tumour markers were performed in only 16 cases (10%). Sixty-one (39%) had an ultrasound scan and 16 (10%) had a computed tomography (CT) or magnetic resonance imaging (MRI) scan. Ninety girls (58%) had an oophorectomy and 40 (25%) had an ovarian cystectomy. Oophorectomies were performed for all cases of malignancy, but 75 were also performed for benign or normal pathology. Only 16% of cases were referred to the paediatric gynaecologist and all were for post-operative management. CONCLUSIONS: We recommend the greater use of imaging of the pelvis and tumour markers preoperatively. There should be greater use of conservative expectant management or ovarian-sparing surgery in view of the low risk of malignancy in this age group. The practice of removing ovaries for benign cysts may be overcome by appointing more gynaecologists with advanced training skills training in paediatric and adolescent gynaecology.

Interactive website for head and neck cancer patients: Adherence and coping program to prevent dysphagia after radiation.

INTRODUCTION: Pharyngeal and laryngeal cancers are highly curable; however survivors are at high risk for long-term dysphagia after radiation. To address lack of access to preventive care in community settings, we developed a responsive web-based application to help patients adhere to preventive swallowing exercises and cope with radiation side effects. We conducted an interim study analysis to determine website usage characteristics and to examine the effect size for future trials. METHODS: Pharyngeal and laryngeal cancer patients were recruited for enrollment by speech language pathologists before primary radiation and introduced to the interactive website. The program (English and Spanish) features tracking logs for preventive exercises, instructional videos, patient stories and search features. Patients' self-reported swallowing function was assessed with the MD Anderson Dysphagia Inventory (MDADI) at baseline and at 6 months. Adherence to preventive exercises was assessed during the 10 week intervention. Number of unique website visits, total duration of website exposure, and rankings of the most popular webpages were calculated. Preliminary regression models were run using adherence and MDADI as outcomes. RESULTS: Of the 160 enrolled, 96 had 10-week adherence data and 61 had 6-month MDADI data. The average age was 63 (SD = 12.26), 49.4% were from rural counties, 44% had a high school education or lower, and 42% reported annual income of $30,000 or less. The average number of visits was 5.49 (SD = 9.96) and the average total time spent with the website was 41.09 min (SD =88.48). Preliminary analyses indicated that number of unique visits to the website was independently associated with increased adherence to preventive exercises (p = .001-.008). CONCLUSION: Our website showed significant effects in promoting adherence to swallowing exercises. However, our return visit rate showed that the platform needs improvement in navigability and usability for this older population undergoing challenging treatment in community settings with low resources.

Towards a safer culture: implementing multidisciplinary simulation-based team training in New Zealand operating theatres - a framework analysis.

AIM: NetworkZ is a simulation-based multidisciplinary team-training programme designed to enhance patient safety by improving communication and teamwork in operating theatres (OTs). In partnership with the Accident Compensation Corporation, its implementation across New Zealand (NZ) began in 2017. Our aim was to explore the experiences of staff - including the challenges they faced - in implementing NetworkZ in NZ hospitals, so that we could improve the processes necessary for subsequent implementation. METHOD: We interviewed staff from five hospitals involved in the initial implementation of NetworkZ, using the Organising for Quality model as the framework for analysis. This model describes embedding successful quality improvement as a process of overcoming six universal challenges: structure, infrastructure, politics, culture, motivation and learning. RESULTS: Thirty-one people participated. Structural support within the hospital was considered essential to maintain staff enthusiasm, momentum and to embed the programme. The multidisciplinary, simulation-based approach to team training was deemed a fundamental infrastructure for learning, with participants especially valuing the realistic in situ simulations and educational support. Participants reported positive changes to the OT culture as a result of NetworkZ and this realisation motivated its implementation. In sites with good structural support, NetworkZ implementation proceeded quickly and participants reported rapid cultural change towards improved teamwork and communication in their OTs. CONCLUSION: Implementation challenges exist and strategies to overcome these are informing future implementation of NetworkZ. Embedding the programme as business as usual across a nation requires significant and sustained support at all levels. However, the potential gains in patient safety and workplace culture from widespread multidisciplinary team training are substantial. Trial registration number ACTRN12617000017325.

Expectations and experience of labial reduction: a qualitative study.

OBJECTIVE: To understand women's reasons for undergoing labial reduction surgery, their expectations and experiences. DESIGN: A retrospective qualitative study. SETTING: British National Health Service Hospital. SAMPLE: Six women who had experienced surgery for labial reduction. Method Qualitative study using semi-structured interviews. RESULTS: Results relating to 'Normality and defect', 'Sex lives' and 'The process of accessing surgery' are presented in this study. The women had seen their presurgery genital appearance as 'defective' and sought a 'normal' genital appearance. They thought that their presurgery genital appearance impacted on their sex lives, but their expectations of the effects of surgery on their sex lives were not all fulfilled. Information about labial surgery came from both the popular media and the health services. An emphasis on, for example, physical discomfort rather than appearance may have been used to legitimise a request for surgery. The process of accessing surgery had exposed them to potentially conflicting messages about their genital appearance. CONCLUSIONS: Women presenting for labial reduction may have unrealistic expectations of surgery, but their perceptions and expectations are long-standing and seem to be based on strong cultural norms. The gynaecologist is also meeting those women who have already negotiated the referral process. As demand for this surgery appears to be increasing, further research is needed. These findings may add to the case for the potential value of specialist staff to provide psychosocial interventions within gynaecology services.

Radiotherapy for head and neck cancer.

The length and quality of head and neck cancer survivorship continues to improve. Radiotherapy has been central to this process through advances in treatment technology, fractionation schemas, radiosensitizing chemotherapy, and surgical technique. The future of head and neck radiotherapy looks brighter still with progress in radiosensitizing biologic therapy, molecular characterization, functional imaging, and rehabilitative strategies fast approaching. Head and neck cancer, a disease once fraught with nihilism and failure, is evolving into a major success story of multidisciplinary solid tumor management. Continued dedication and work on the part of provider and patient alike will be required to make this promise a reality.

Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck.

PURPOSE: To define further the role of concurrent chemoradiotherapy for patients with advanced squamous carcinoma of the head and neck. PATIENTS AND METHODS: The Radiation Therapy Oncology Group developed this three-arm randomized phase II trial. Patients with stage III or IV squamous carcinoma of the oral cavity, oropharynx, or hypopharynx were eligible. Each of three arms proposed a radiation schedule of 70 Gy in 35 fractions. Patients on arm 1 were to receive cisplatin 10 mg/m(2) daily and fluorouracil (FU) 400 mg/m(2) continuous infusion (CI) daily for the final 10 days of treatment. Treatment on arm 2 consisted of hydroxyurea 1 g every 12 hours and FU 800 mg/m(2)/d CI delivered with each fraction of radiation. Arm 3 patients were to receive weekly paclitaxel 30 mg/m(2) and cisplatin 20 mg/m(2). Patients randomly assigned to arms 1 and 3 were to receive their treatments every week; patients on arm 2 were to receive their therapy every other week. RESULTS: Between 1997 and 1999, 241 patients were entered onto study; 231 were analyzable. Ninety-two percent, 79%, and 83% of patients on arms 1, 2, and 3, respectively, were able to complete their radiation as planned or with an acceptable variation. Fewer than 10% of patients had unacceptable deviations or incomplete chemotherapy in the three arms. Estimated 2-year disease-free and overall survival rates were 38.2% and 57.4% for arm 1, 48.6% and 69.4% for arm 2, and 51.3% and 66.6% for arm 3. CONCLUSION: We have demonstrated that three different approaches of concurrent multiagent chemotherapy and radiation were feasible and could be delivered to patients in a multi-institutional setting with high compliance rates.

Phase I/II trial of radiation with chemotherapy "boost" for advanced squamous cell carcinomas of the head and neck: toxicities and responses.

PURPOSE: Extrapolating from our experience delivering a "boost" field of radiation concurrently with fields treating both gross and subclinical disease at the end of a course of radiation therapy, we developed a regimen to deliver concurrent chemotherapy during the last 2 weeks of a conventionally fractionated course of radiation. PATIENTS AND METHODS: Patients had stage III or IV biopsy-proven squamous cell carcinoma originating from a head and neck mucosal site. The regimen was 70 Gy delivered over 7 weeks with concurrent fluorouracil (5-FU) and cisplatin given daily with each radiation dose during the last 2 weeks. A phase I study was performed to determine the maximum-tolerated dose (MTD) before a phase II study was conducted. RESULTS: The MTD was 400 mg/m(2) per day for 5-FU and 10 mg/m(2) per day for cisplatin. Mucositis persisting more than 6 weeks after therapy was the dose-limiting toxicity. A total of 60 patients were treated on the two phases of the study. Eighteen patients (35%) treated at the MTD developed prolonged mucositis. There were two cases of neutropenic sepsis, including one fatality. The actuarial 2-year rates for overall survival, freedom from relapse, and local control were 62%, 59%, and 80%, respectively. CONCLUSION: Preliminary locoregional control rates seem to be higher than those reported for treatment with radiation alone. Toxicity was also greater than that seen with radiation alone, but the regimen was designed to deliver an intense treatment schedule, which could be completed without significant interruptions, and to obtain high control rates above the clavicles. These end points were achieved.

Combined interferon-alfa, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: novel bioadjuvant phase II trial.

PURPOSE: Retinoids and interferons (IFNs) have single-agent and synergistic combined effects in modulating cell proliferation, differentiation, and apoptosis in vitro and clinical activity in vivo in the head and neck and other sites. Alpha-tocopherol has chemopreventive activity in the head and neck and may decrease 13-cis-retinoic acid (13-cRA) toxicity. We designed the present phase II adjuvant trial to prevent recurrence or second primary tumors (SPTs) using 13-cRA, IFN-alpha, and alpha-tocopherol in locally advanced-stage head and neck cancer. PATIENTS AND METHODS: After definitive local treatment with surgery, radiotherapy, or both, patients with locally advanced SCCHN were treated with 13-cRA (50 mg/m(2)/d, orally, daily), IFN-alpha (3 x 10(6) IU/m(2), subcutaneous injection, three times a week), and alpha-tocopherol (1,200 IU/d, orally, daily) for 12 months, with a dose modification. Screening for recurrence or SPTs was performed every 3 months. RESULTS: Tumors of 11 (24%) of the 45 treated patients were stage III, and 34 (76%) were stage IV. Thirty-eight (86%) of 44 patients completed the full 12-month treatment (doses modified as needed). Toxicity generally was consistent with previous IFN and 13-cRA reports and included mild to moderate mucocutaneous and flu-like symptoms; occasional significant fatigue (grade 3 in 7% of patients), mild to moderate hypertriglyceridemia in 30% of patients who continued treatment along with antilipid therapy, and mild hematologic side effects. Six patients did not complete the planned treatment because of intolerable toxicity or social problems. At a median 24-months of follow-up, our clinical end point rates were 9% for local/regional recurrence (four patients), 5% for local/regional recurrence and distant metastases (two patients), and 2% for SPT (one patient), which was acute promyelocytic leukemia (ie, not of the upper aerodigestive tract). Median 1- and 2-year rates of overall survival were 98% and 91%, respectively, and of disease-free survival were 91% and 84%, respectively. CONCLUSION: The novel biologic agent combination of IFN-alpha, 13-cRA, and alpha-tocopherol was generally well tolerated and promising as adjuvant therapy for locally advanced squamous cell carcinoma of the head and neck. We are currently conducting a phase III randomized study of this combination (v no treatment) to confirm these phase II study results.

Comparative susceptibility of turbot Scophthalmus maximus to different genotypes of viral haemorrhagic septicaemia virus.

Viral haemorrhagic septicaemia (VHS) disease has exerted a significant impact on the development of turbot aquaculture in the British Isles. The source of such outbreaks is believed to be naturally occurring marine isolates of viral haemorrhagic septicaemia virus (VHSV), which are endemic in the marine environment of Northern Europe. Genetic studies have classified these marine VHSV isolates into genotypes based on their geographic rather than host-species origin. This study set out to explore the hypothesis that susceptibility of turbot to VHSV might be genotype specific. Immersion infection of turbot with a range of isolates, selected according to genotype, identified significant differences between susceptibility and genotype. Viruses belonging to Genotypes Ib (Baltic marine isolates) and III (North Sea/E. Atlantic marine isolates) caused significantly higher mortality than isolates from Genotypes Ia (isolates associated with rainbow trout aquaculture) and II (Baltic marine isolates). This study serves to highlight the importance of thoroughly investigating the susceptibility of any given species to the range of pathogens to which they might be exposed prior to considering them resistant to any disease. Furthermore, it highlights different risk factors that might be associated with turbot aquaculture undertaken in different environments. Finally, an increased knowledge of the relative virulence of different isolates in turbot will assist in understanding virulence determinants, which could lead to advances in disease control.

Debriefing after simulation-based non-technical skill training in healthcare: a systematic review of effective practice.

Non-technical skills training in healthcare frequently uses high-fidelity simulation followed by a facilitated discussion known as debriefing. This type of training is mandatory for anaesthesia training in Australia and New Zealand. Debriefing by a skilled facilitator is thought to be essential for new learning through feedback and reflective processes. Key elements of effective debriefing need to be clearly identified to ensure that the training is evidence-based. We undertook a systematic review of empirical studies where elements of debriefing have been systematically manipulated during non-technical skills training. Eight publications met the inclusion criteria, but seven of these were of limited generalisability. The only study that was generalisable found that debriefing by novice instructors using a script improved team leader performance in paediatric resuscitation. The remaining seven publications were limited by the small number of debriefers included in each study and these reports were thus analogous to case reports. Generally, performance improved after debriefing by a skilled facilitator. However, the debriefer provided no specific advantage over other post-experience educational interventions. Acknowledging their limitations, these studies found that performance improved after self-led debrief, no debrief (with experienced practitioners), standardised multimedia debrief or after reviewing a DVD of the participants' own eye-tracking. There was no added performance improvement when review of a video recording was added to facilitator-led debriefing. One study reported no performance improvement after debriefing. Without empirical evidence that is specific to the healthcare domain, theories of learning from education and psychology should continue to inform practices and teaching for effective debriefing.

Hyperfractionated radiation in the treatment of squamous cell carcinomas of the head and neck: a comparison of two fractionation schedules.

PURPOSE: In 1984 we began treating patients with squamous cell carcinomas of the larynx and hypopharynx with hyperfractionated radiotherapy. Patients received 76.8 Gy in 1.2 Gy fractions twice daily, with a 4 h interfraction interval. In 1988, this schedule was modified in patients treated with shrinking field techniques. The dose per fraction was slightly reduced (while not changing the total dose), and the interfraction interval was increased to 6 h. The goal was to decrease toxicity while maintaining satisfactory local-regional control. This retrospective study analyzes the results of this schedule modification. METHODS AND MATERIALS: Two hundred thirty-six patients were included in the analysis. Distribution of patients by primary site and T stage was as follows: supraglottic larynx, 120 patients; hypopharynx, 70; true vocal cord, 24; and oropharynx, 22; T1, 5 patients; T2, 118; T3, 93; T4, 19; and Tx, 1. Ninety-nine patients presented with cervical nodal disease. Seventy-eight patients (group A), including 16 treated with induction chemotherapy, were treated throughout with 1.2 Gy fractions twice daily and a 4-h interfraction interval. Subsequently, 158 patients (group B), 57 of whom received chemotherapy, received 1.1 Gy fractions to 55 Gy, and then 1.2 Gy fractions to their boost volumes to 76.6 Gy. The interfraction interval was 6 h. Median follow-up was 91 and 35 months for group A and B, respectively. RESULTS: Two-year actuarial survival, local control, and ultimate local rates were 70%, 75%, and 85%, respectively. Differences between survival rates for group A and group B were not statistically significant, with 2-year rates of 66% and 72%, respectively. Overall local control rates at 2 years were 77% and 74%, respectively, for groups A and B (p = 0.22). However, there was a trend toward inferior results in group B patients with T3 disease (67% at 2 years compared to 76% in group A, p = 0.13). Confluent mucositis and persistent mucositis developed in 52% and 14% of group A patients, but only 37% and 4% of group B patients (p = 0.02 and p < 0.01, respectively). There was a near significant trend toward fewer late complications in group B who developed an 8% complication rate at 3 years compared to 15% of group A patients (p = 0.07). CONCLUSIONS: The net effect of reducing the dose per fraction to 1.1 Gy twice daily for fields covering gross disease and subclinical sites, and increasing the interfraction interval to 6 h was to reduce the incidence of both acute and late complications. Excellent overall local control rates (85%) for T2 lesions were achieved with both hyperfractionation regimens and we, therefore, continue to treat patients with T2 tumors with the modified schedule. The overall results in selected patients with T3 lesions was also satisfactory (69%), but as there was a trend towards poorer local control in patients treated with 1.1 Gy fractions, we recommend using 1.2 Gy for the entire treatment of these patients, while maintaining the 6 h interfraction interval to reduce the risk of late complications.

The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.

PURPOSE: Surgery is the primary treatment for adenoid cystic carcinomas arising from major and minor salivary glands of the head and neck. However, local recurrence is frequent because of the infiltrative growth pattern and perineural spread associated with these tumors. At UTMDACC, we have had a longstanding policy of using postoperative radiotherapy to reduce the risk of local recurrence and to avoid the need for radical surgery; this 30-year retrospective study analyzes the results of this combined modality approach. METHODS AND MATERIALS: Between 1962 and 1991, 198 patients ages 13-82 years, with adenoid cystic carcinomas of the head and neck, received postoperative radiotherapy for known or suspected microscopic residual disease following surgery. Distribution of primary sites was: parotid: 30 patients; submandibular/sublingual: 41 patients; lacrimal: 5 patients; and minor salivary glands: 122 patients. Eighty-three patients (42%) had microscopic positive margins and an additional 55 (28%) had close (< or = 5 mm) or uncertain margins. One hundred thirty-six patients (69%) had perineural spread with invasion of a major (named) nerve in 55 patients (28%). Using radiation techniques appropriate to the primary site, a median dose of 60 Gy (range 50-69 Gy) was delivered to the tumor bed. Follow-up ranged from 5-341 months (median, 93 months). All surviving patients had a minimum of 2 years follow-up. RESULTS: Twenty-three patients (12%) had local recurrences with 5-, 10-, and 15-year actuarial local control rates of 95%, 86%, and 79%, respectively. Fifteen of the 83 patients (18%) with positive margins developed local recurrences, compared to 5 of 55 patients (9%) with close or uncertain margins, and 3 of 60 patients (5%) with negative margins (p = 0.02). Patients with and without a major (named) nerve involved had crude failure rates of 18% (10 out of 55) and 9% (13 out of 143), respectively (p = 0.02). There was a trend toward better local control with increasing dose. This was significant in patients with positive margins, in whom crude control rates were 40 and 88% for doses of < 56 Gy and > or = 56 Gy, respectively (p = 0.006). Actuarial 5-, 10-, and 15-year freedom from relapse rates were 68%, 52%, and 45%, respectively. Base of skull and neck failures were uncommon with or without elective treatment, developing in 2 and 3% of patients, respectively. Distant metastases were the most common type of disease recurrence, developing in 74 patients (37%) of whom 62 (31%) were disease-free at the primary site. CONCLUSIONS: Excellent local control rates were obtained in this population using surgery and postoperative radiotherapy and we recommend this combined approach for most patients with adenoid cystic carcinomas of the head and neck. Perineural invasion was an adverse prognostic factor only when a major (named) nerve was involved. Microscopic positive margins was also an adverse prognostic factor, but even when present, local control was achieved in over 80% of our patients. We recommend a dose of 60 Gy to the tumor bed, supplemented to 66 Gy for patients with positive margins. Despite effective local therapy, one-third of patients fail systemically, and good treatment to address this problem is lacking.

Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation.

PURPOSE: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. METHODS AND MATERIALS: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. RESULTS: An unexpected 97% (29 out 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. CONCLUSIONS: A high proportion of neurologically normal patients was limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration.