Can elective nodal irradiation be omitted in stage III non-small-cell lung cancer? Analysis of recurrences in a phase II study of induction chemotherapy and involved-field radiotherapy

PURPOSE: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS: Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.     

Gene expression profiling of non-small cell lung cancer

Functional genomics has emerged over the past 10 years as a novel technology to study genetic alterations. Gene expression arrays are one genomic technique employed to discover changes in the DNA expression that occur in neoplastic transformation. Microarrays have been applied to investigating lung cancer. Specific applications include discovering novel genetic changes that occur in lung tumors. Microarrays can also be applied to improve diagnosis, staging and discover prognostic markers. The eventual goal of this technology is to discover new markers for therapy and to customize therapy based on an individual tumor genetic composition. In this review, we present the current state of gene expression array technology in its application to lung cancer.     

Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2

Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E(2)17betaG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic.     

A New Technique for CT/MR Fusion For Skull Base Imaging

This paper presents our initial experience utilizing a new technique which allows CT and MR image fusion in patients with skull base lesions. Eleven patients with a variety of skull base lesions underwent CT and MR imaging prior to surgery. Both sets of images were coregistered using customized software. The CT and MR data sets were then combined and viewed in a single interactive image formar using a high-speed graphic computing system. Image fusion allowed simultaneous visualization of the bony skull base anatomy (CT) and detailed soft tissue anatomy (MR) using a single image format. Combining both modalities was felt to provide a better assessment of the extent of lesions and improve understanding of their relationship to adjacent bony and neurovascular anatomy. Specifically, image fusion enhanced awareness of location of skill base lesions with respect to the cavernous sinuses. Gasserian ganglia, carotid arteries, and jugular foramina. For tumors arising within the internal auditory canal (IAC), fused images allowed better delineation of the lateral aspect of the lesion with respect to the fundus of the IAC. Thus, fusion of CT and MR studies provides a unique image format which has advantages over single modality display. We believe image fusion is beneficial for surgical planning and for treatment planning of complex skull base malignancies treated with radiotherapy.     

AcrySof acrylic intraocular lens implantation in children: Clinical indications of biocompatibility

PURPOSE: To assess the clinical biocompatibility of AcrySof (Alcon, Ft Worth, Tex) acrylic intraocular lenses (IOLs) in the highly reactive eyes of infants and children. METHODS: A database of 230 pediatric IOL implantations was queried to allow retrospective review of all eyes implanted with an AcrySof IOL. Eyes implanted with polymethyl methacrylate (PMMA) IOLs were also reviewed and were used as a historical comparison group. Follow-up examinations were conducted by the surgeon on postoperative day 1, day 7, week 4, and week 8 and every 3 months during the first year and every 6 months thereafter. The presence of synechiae, lens deposits, and posterior capsule opacification were noted in the record at each visit. Examination notes were photocopied, and data were extracted from each visit note and entered into a computerized database. RESULTS: One hundred and ten eyes had an AcrySof IOL at an average age of 60.4 months and had an average postoperative follow-up of 64.6 weeks. In comparison, 120 eyes had PMMA IOLs inserted at an average age of 71.9 months with an average postoperative follow-up of 136.9 weeks. IOL cell deposits were seen at the slit lamp in 7 of 110 (6.4%) AcrySof lenses as compared with 26 of 120 (21.75%) PMMA lenses (P =.002). Posterior synechiae were seen in 5 of 110 (4.5%) AcrySof lenses as compared with 23 of 120 (19.2%) PMMA lenses (P =.001). Twenty-two AcrySof-implanted eyes had an intact posterior capsule. Twenty-eight PMMA-implanted eyes had an intact posterior capsule. The YAG laser capsulotomy rate was similar in the 2 groups at 45.4% for AcrySof and 50% for PMMA (P =.973). The average time from surgery to YAG posterior capsulotomy was 18.6 months with an AcrySof lens and 18.3 months with a PMMA lens (P =.951; t test). A total of 60 patients (68%) implanted with AcrySof IOLs were able to cooperate for Snellen visual acuities. Of their 67 eyes, 48 (72%) had a 20/40 or better visual acuity at the last follow-up examination, and 63 eyes (94%) had a 20/100 or better visual acuity. Thirty-five eyes (52%) required amblyopia therapy, and patching continues as needed. CONCLUSIONS: The AcrySof IOL is representative of a new group of foldable IOLs made from flexible hydrophobic acrylic material. The AcrySof IOL appears clinically to be biocompatible when placed in the eyes of children despite the increased tissue reactivity known to occur in young patients.     

Anaesthetic management of a child with Bartter’s syndrome

We report the anaesthetic management of an eight-year-old asthmatic boy with Bartter’s syndrome who had bilateral orchidopexy with caudal epidural analgesia. Bartter’s syndrome is a rare congenital disorder characterized by hypokalaemic hypochloraemic metabolic alkalosis, hyperaldosteronism, hyperreninaemia and hyperplasia of the juxtaglomerular apparatus of the kidneys. Characteristically, although these patients are normotensive they may be hypovolaemic. They may have unstable baroreceptor responses and show marked resistance to vasopressors. Hence, fluid, acid-base and electrolyte imbalances along with haemodynamic instability pose particular problems in their anaesthetic management. Previous case reports have described the management of these patients with general anaesthesia, our patient had his orchidopexy with caudal epidural analgesia using plain bupivacaine 0.5%. The patient was haemodynamically stable throughout surgery and was comfortable with caudal analgesia as the sole anaesthetic. Hypovalaemia, acid-base status and electrolyte imbalance were treated before instituting caudal epidural analgesia. We present this case report which describes the anaesthetic considerations in the light of the pathophysiology of Bartter’s syndrome.     

Decision and forecast horizons in a stochastic environment: A survey

This paper constructs a unified framework to survey most of the work done to date on decision

1 decision horizon replaces the term planning horizon used in the literature in the context of this paper. This is done because of an alternate and more popular use of the term planning horizon as simply the given length of the horizon in a finite horizon problem.

and forecast horizons in a stochastic environment. The paper is divided into sections by type of model. For each model type, the issues of existence of these horizons and of derivation of sufficient conditions for their determination are studied. Appropriate examples are presented.