Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease.

Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing.

Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large interpatient variability, partly due to genetic variations in the gene encoding cytochrome P450 (CYP)2C9 (CYP2C9). Furthermore, the variant allele HLA-B*15:02, encoding human leukocyte antigen, is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this guideline is to provide information for the interpretation of HLA-B and/or CYP2C9 genotype tests so that the results can guide dosing and/or use of phenytoin. Detailed guidelines for the use of phenytoin as well as analyses of cost-effectiveness are out of scope. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are periodically updated at http://www.pharmgkb.org.

Performance of pattern recognition myoelectric control using a generic electrode grid with targeted muscle reinnervation patients.

Targeted muscle reinnervation (TMR) is a surgical technique that creates myoelectric prosthesis control sites for high-level amputees. The electromyographic signal patterns provided by the reinnervated muscles are well-suited for pattern recognition (PR) control. PR control uses more electrodes compared to conventional amplitude control techniques but their placement on the residual limb is less critical than for conventional amplitude control. In this contribution, we demonstrate that classification error and real-time control performances using a generically placed electrode grid were equivalent or superior to the performance when using targeted electrode placements on two transhumeral amputee subjects with TMR. When using a grid electrode layout, subjects were able to complete actions 0.290 sec to 1 sec faster and with greater accuracy as compared to clinically localized electrode placement (mean classification error of 1.35% and 3.2%, respectively, for a 5 movement-class classifier).These findings indicate that a grid electrode arrangement has the potential to improve control of a myoelectric prosthesis while reducing the time and effort associated with fitting the prosthesis due to clinical localization of control sites on amputee patients.

UK surveillance: provision of quality assured information from combined datasets.

Surveillance information is most useful when provided within a risk framework, which is achieved by presenting results against an appropriate denominator. Often the datasets are captured separately and for different purposes, and will have inherent errors and biases that can be further confounded by the act of merging. The United Kingdom Rapid Analysis and Detection of Animal-related Risks (RADAR) system contains data from several sources and provides both data extracts for research purposes and reports for wider stakeholders. Considerable efforts are made to optimise the data in RADAR during the Extraction, Transformation and Loading (ETL) process. Despite efforts to ensure data quality, the final dataset inevitably contains some data errors and biases, most of which cannot be rectified during subsequent analysis. So, in order for users to establish the 'fitness for purpose' of data merged from more than one data source, Quality Statements are produced as defined within the overarching surveillance Quality Framework. These documents detail identified data errors and biases following ETL and report construction as well as relevant aspects of the datasets from which the data originated. This paper illustrates these issues using RADAR datasets, and describes how they can be minimised.

Progress with enhancing veterinary surveillance in the United Kingdom.

The UK has experienced various animal health events that have had national impact in recent years. In response, a ;Veterinary Surveillance Strategy' (VSS) was published in 2003, with the objective of enhancing and coordinating national veterinary surveillance practice in a way that would enable important animal health events to be detected and assessed more rapidly and reliably. The VSS adopts an integrated UK-wide approach, which includes widespread engagement with interested parties both within government and beyond. It proposes enhancing surveillance through improved collaboration; transparent and defensible prioritisation of government resources to surveillance; deriving better value from existing resources, and assuring quality of the surveillance reports and source data. This article describes progress with implementing the VSS, in particular the methodology for developing a functional network and creating an effective, quality-assured, information management system, RADAR.

Thyroid cancer in pregnancy.

OBJECTIVE: To compare stage at diagnosis, treatment and survival among pregnant women with thyroid cancer to non-pregnant women with thyroid cancer, and to assess the impact of treatment on maternal and perinatal outcomes. METHODS: A database containing maternal and newborn discharge records linked to the California Cancer Registry was queried to obtain information on all thyroid cancers from 1991-1999. Women with thyroid cancer occurring during pregnancy were compared to age-matched non-pregnant women with thyroid cancer. RESULTS: 595 cases of thyroid cancers were identified (129 antepartum and 466 postpartum). About 64% of thyroid cancers were diagnosed at stage 2 among pregnant women versus 58% among non-pregnant controls. The odds of thyroid cancer were 1.5 times higher among Asian/Pacific Islanders than among Non-Hispanic White women. Pregnancy had no significant effect on mortality after diagnosis of thyroid cancer. Thyroidectomy during pregnancy was not associated with adverse maternal or neonatal outcomes. CONCLUSIONS: Thyroid cancer discovered during or after pregnancy does not appear to have a significant impact on the prognosis of the disease.

Chemoradiation for primary invasive squamous carcinoma of the vagina.

OBJECTIVE: To report outcomes for patients with primary, invasive, squamous carcinoma of the vagina treated with chemoradiation. METHODS: Between 1986 and 1996, 14 patients were treated with primary therapy consisting of synchronous radiation and chemotherapy. Patients were judged not to be surgical candidates based on tumor size, location, and concerns related to urinary, bowel, or sexual function. Three patients were FIGO stage I, ten patients stage II, and one patient stage III. Radiation consisted of teletherapy alone (six patients) or in combination with intravaginal brachytherapy (eight patients). Total radiation dose ranged from 5700 to 7080 cGy (median 6300 cGy). Chemotherapy consisted of 5-fluorouracil alone (seven patients), or with cisplatin (six patients) or mitomycin-C (one patient). RESULTS: One patient failed locally at 7 months and died of disease at 11 months. Four patients died of intercurrent illness (46, 92, 104, 109 months) and nine are alive and cancer-free 74-168 months after treatment (median 100 months). There were no vesicovaginal or enterovaginal fistulae. CONCLUSIONS: Radiation with synchronous chemotherapy is an effective treatment for squamous carcinoma of the vagina. Cancer control outcomes compare favorably with previously published results employing higher dose radiation as monotherapy.

Endometriosis-related malignancies.

The purpose of this study is to describe the clinical findings, treatment, and outcome of patients with endometriosis-related cancers. Patients meeting Sampson and Scott's criteria for cancer associated with endometriosis in the Sacramento region were identified by chart review and pathology reports. Twenty-seven patients were identified with endometriosis-related malignancies (mean age 51.4 years). The site of origin was ovary in 17 (63.0%) and extra-ovarian in 10 (37%) including vagina, fallopian tube or mesosalpinx, pelvic sidewall, colon, and parametrium. The pattern of spread was local in five (18.5%), regional in 20 (74.1%) and distant in two (7.4%). Six patients had taken unopposed estrogen replacement (mean duration 23.4 years) and all six had extragonadal disease. Surgical procedures included hysterectomy, salpingo-oophorectomy, radical local excision, partial colectomy, and surgical staging. Eighteen patients received postoperative chemotherapy since the majority of patients had ovarian involvement. Fifteen patients received regional radiation therapy. Nineteen patients are without evidence of recurrence (70.4%, mean follow-up of 31 months). Endometriosis-related malignancies have a favorable prognosis. Extragonadal disease was commonly associated with unopposed estrogen replacement therapy. The predominance of local and regional disease strongly influence the application of treatment modalities.

Altered morphology in cultured rat intestinal epithelial IEC-6 cells is associated with alkaline phosphatase expression.

Non-transformed, rat intestinal epithelial cells (IEC-6), and human intestinal colonic carcinoma cells (CACO-2) have both been used to study processes of epithelial cell differentiation. However, only CACO-2 cells have been described as spontaneously expressing phenotypic changes of differentiation in culture. We report here that when IEC-6 cells are grown in post-confluent culture, they develop structural changes similar to those seen in cells induced to differentiate by culture on Englebreth-Holm-Swarm (EHS) extracellular matrix proteins. Correlated with this morphological change is loss of nuclear localization of c-myc protein and development of cell surface alkaline phosphatase (ALP) enzymatic activity. Messenger RNAs for liver and intestinal isoforms of ALP were expressed in both pre- and post-confluent cells. Inhibition of ALP activity in post-confluent cells by levamisole indicated the expressed ALP activity to be of the liver isoform. We suggest the expression of ALP activity, which occurs concomitantly with morphological alterations in post-confluent IEC-6 cells, represents increased expression and localization to the cell surface of the liver isoform of ALP. Cultured IEC-6 cells may provide a non-transformed, in vitro alternative to CACO-2 cells for study of epithelial cell differentiation.

Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997.

OBJECTIVE: This study aims to characterize the rate of occurrence and nature of outcomes associated with obstetrical deliveries in women with malignant neoplasms among 3,168,911 women who delivered in California in 1992 through 1997. DESIGN: The study is a population-based retrospective review of infant birth and death certificates and maternal and neonatal discharge records. Cases of malignant neoplasms associated with obstetrical delivery were attributed to 1 of 3 categories, depending on the earliest documented hospital discharge diagnosis, as follows: "prenatal" if the diagnosis was first documented by hospitalization within 9 months preceding delivery, "at delivery" if the diagnosis was established from the delivery hospitalization, or "postpartum" if the diagnosis was first documented by hospitalization within 12 months after delivery. METHODS: Computer-linked infant birth and death certificates and maternal and neonatal discharge records were used to identify cases and outcomes. Cases of malignant neoplasms were identified by using International Classification of Diseases, Ninth Revision codes (140-208). Noninvasive neoplasms and carcinoma in situ neoplasms were excluded. In analysis of outcomes, the Mantel-Haenszel estimate for adjusted odds ratios was used. RESULTS: Among 3,168,911 obstetrical deliveries over the 6-year span, a total of 2247 cases of primary malignancy were identified. The observed rate of occurrence for primary malignant neoplasms was 0.71 per 1000 live singleton births. Most cases (53.3%) were first documented in the postpartum period as follows: prenatal, 587 cases (0.18 per 1000); at delivery, 462 cases (0.15 per 1000); and postpartum, 1198 cases (0.38 per 1000). The most frequently documented primary malignant neoplasms associated with obstetrical delivery were breast cancer (423 cases, 0.13 per 1000), thyroid cancer (389 cases, 0.12 per 1000), cervical cancer (266 cases, 0.08 per 1000), Hodgkin's disease (172 cases, 0.05 per 1000), and ovarian cancer (123 cases, 0.04 per 1000). Odds ratios for a variety of demographic factors identified maternal age as the most significant risk factor for development of malignant neoplasms (age greater than 40 vs 20-25, odds ratio 5.7, CI 4.6-6.9). Age-adjusted odds ratios for maternal cancer of any type suggested significantly elevated risks for cesarean delivery (odds ratio 1.4, CI 1.3-1.6), blood transfusion (odds ratio 6.2, CI 4.5-8.5), hysterectomy (odds ratio 27.4, CI 20.8-36.1), and maternal postpartum hospital stay greater than 5 days (odds ratio 30.6, CI 27.9-33.6), but not for postpartum maternal death (odds ratio 0.8, CI 0.6-1.0). Odds ratios also suggested significantly elevated risks for premature newborn (odds ratio 2.0, CI 1.8-2.2), very low birth weight (odds ratio 2.9, CI 2.2-3.8), and newborn hospital stay longer than 5 days (odds ratio 2.6, CI 2.4-3.0), but not for neonatal death (odds ratio 1.6, CI 0.8-3.1) or infant death (odds ratio 1.2, CI 0.5-3.3). However, several types of malignant neoplasms did confer significant elevations in risk for neonatal death. Hospital charges for both maternal and neonatal care were significantly elevated in the maternal malignant neoplasm group. CONCLUSION: A lower than expected occurrence rate of obstetrical delivery associated with maternal malignancy was seen when compared with previously published hospital-based reports. Malignant neoplasms associated with obstetrical delivery were most frequently first documented in the postpartum period. Maternal and neonatal morbidity were significantly increased, yet the risk of in-hospital maternal death was not significantly elevated. A significant increase in risk of neonatal death for infants of mothers with cervical cancer was found.

Cyclic AMP- and IL6-signaling cross talk: comodulation of proliferation and apoptosis in the 7TD1 B cell hybridoma.

Proliferation of the 7TD1 B cell hybridoma is dependent on the survival factor interleukin-6 (IL6). IL6 inhibits physiological cell death and allows expansion of populations of serum-stimulated cells. In this report, we demonstrate that cyclic AMP (cAMP)- and IL6-dependent signaling pathways can interact, controlling proliferation of 7TD1 cells through modulation of apoptosis. Cyclic AMP analogues inhibited proliferation, as well as other treatments that increased intracellular cAMP. The cAMP-induced inhibition could be reversed after 24 h by the removal of dibutyryl-cAMP from the culture medium and readdition of IL6. In the absence of IL6, cAMP induced a slow loss of viable cells. This decrease in viable cells in the presence of cAMP was accompanied by a marked increase in apoptosis. The increase in apoptotic cells after 48 h was preceded at 24 h by a parallel increase in DEVD-caspase activity after treatment with cell-permeable cAMP analogues. Increased DEVD-caspase activity and subsequent apoptosis could both be blocked by the addition of IL6. These coregulating actions may represent a cross-talk signaling mechanism modulating cytokine activation of cellular proliferation and survival.

Phenotypic expression of primary hyperoxaluria: comparative features of types I and II.

BACKGROUND: The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available. METHODS: Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation. RESULTS: PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03). CONCLUSION: The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.

Genetic diversity and transcriptional analysis of the bys1 gene from Blastomyces dermatitidis.

Blastomyces dermatitidis, a pathogenic fungal organism, is able to exist in two different morphologies, a multicellular mycelium or a unicellular yeast, according to temperature, 25 degrees C and 37 degrees C respectively. The switching between morphologies must be accompanied by a cascade of signaling events in which expression of genes responsible for the change of morphology is increased or decreased. bys1, a gene from B. dermatitidis isolate #58, is expressed at high levels in the unicellular yeast, but gradually diminishes as the temperature is lowered and the organism converts to the mycelial phase where there is no transcription of bys1. We explored if bys1 homologs are found in other B. dermatitidis isolates and if the transcription of the homologs were regulated by temperature. bys1 was identified in all B. dermatitidis isolates tested and could be grouped into two classes by Southern blot, PCR, and DNA sequence. Although the bys1 transcripts of both classes were regulated by temperature, transcription rates varied between the three isolates tested.

Dietary restrictions for patients with neutropenia: a survey of institutional practices.

PURPOSE/OBJECTIVES: To describe institutional practices related to dietary restrictions for patients with neutropenia to determine whether restrictions are used and when they are implemented and discontinued. DESIGN: Descriptive survey. SAMPLE: 156 institutions belonging to the Association of Community Cancer Centers. METHODS: Mailed survey. FINDINGS: Of the institutions surveyed, 78% (n = 120) placed patients with neutropenia on restricted diets. Participating institutions responded that patients were placed on restricted diets at a variety of different white blood cell and neutrophil counts, including neutrophils < 1,000 (43%) and < 500 (46%). The majority of institutions (92%) placed patients on restricted diets once neutropenia was documented, while only 9% of institutions restricted diets when cancer treatment was initiated. Of the participating institutions, 83% (n = 96) restricted diets only when patients were neutropenic rather than throughout the duration of the chemotherapy regimen. The most commonly restricted foods were fresh fruits and juices (92%), fresh vegetables (95%), and raw eggs (74%). Few institutions restricted tap water (12%). Wine was restricted at 39% of institutions, and beer was restricted at 40% of institutions. CONCLUSIONS: The role of diet in the development of infection in patients with neutropenia is unclear. This unclear role contributes to the variation in dietary restrictions among institutions. IMPLICATIONS FOR NURSING PRACTICE: Additional research should focus on dietary factors contributing to neutropenic infections and establishing criteria for implementation of specific dietary modifications. Nursing assessment should include nutritional status and risk factors for neutropenia and bacterial translocation. Nursing protocols for neutropenic dietary restrictions should be based on research findings.

A gene expression database for the molecular pharmacology of cancer.

We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology.

MedMiner: an Internet text-mining tool for biomedical information, with application to gene expression profiling.

The trend toward high-throughput techniques in molecular biology and the explosion of online scientific data threaten to overwhelm the ability of researchers to take full advantage of available information. This problem is particularly severe in the rapidly expanding area of gene expression experiments, for example, those carried out with cDNA microarrays or oligonucleotide chips. We present an Internet-based hypertext program, MedMiner, which filters and organizes large amounts of textual and structured information returned from public search engines like GeneCards and PubMed. We demonstrate the value of the approach for the analysis of gene expression data, but MedMiner can also be extended to other areas involving molecular genetic or pharmacological information. More generally still, MedMiner can be used to organize the information returned from any arbitrary PubMed search.

Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging.

BACKGROUND: Current imaging modalities, such as contrast angiography, accurately determine the degree of luminal narrowing but provide no direct information on plaque size. Magnetic resonance imaging (MRI), however, has potential for noninvasively determining arterial wall area (WA). This study was conducted to determine the accuracy of in vivo MRI for measuring the cross-sectional maximum wall area (MaxWA) of atherosclerotic carotid arteries in a group of patients undergoing carotid endarterectomy. METHODS AND RESULTS: Fourteen patients scheduled for carotid endarterectomy underwent preoperative carotid MRI using a custom-made phased-array coil. The plaques were excised en bloc and scanned using similar imaging parameters. MaxWA measurements from the ex vivo MRI were used as the reference standard and compared with MaxWA measurements from the corresponding in vivo MR study. Agreement between the in vivo and ex vivo measurement was analyzed using the Bland-Altman method. The paired in vivo and ex vivo MaxWA measurements strongly agreed: the mean difference (in vivo minus ex vivo) in MaxWA was 13.1+/-6.5 mm2 for T1-weighted (T1W) imaging (mean MaxWA in vivo=94.7 mm2, ex vivo=81.6 mm2) and 14.1+/-11.7 mm2 for proton density-weighted (PDW) imaging (mean MaxWA in vivo=93.4 mm2, ex vivo=79.3 mm2). Intraobserver and interobserver variability was small, with intraclass correlation coefficients ranging from 0.90 to 0.98. CONCLUSIONS: MRI is highly accurate for in vivo measurement of artery WA in atherosclerotic carotid lesions. This imaging technique has potential application monitoring lesion size in studies examining plaque progression and/or regression.

Clinical expression and long-term outcomes of primary hyperoxaluria types 1 and 2.

Primary hyperoxaluria, types 1 and 2, are rare disorders. Much of the information in the literature has been derived from case reports and data registries limited to patients requiring dialysis and/or transplantation. We present a single-center experience of 42 patients and 437 patient years of clinical experience with primary hyperoxaluria. Median age at onset of symptoms for patients with type 1 PH was 9 years, type 2 15.7 years. Sixty-four percent of the patients were less than 15 years of age at onset of symptoms. There was no correlation between urine oxalate excretion rates and age at onset of symptoms. Stone forming activity was greater in patients with type 1 PH than type 2. Ten patients presented initially with ESRD, and an additional seven developed ESRD during the course of follow-up. ESRD occurred in 54 percent of the patients with type 1 and 12 percent of patients with type 2 PH. Eight patients received nine renal allografts, five patients received combined kidney/liver transplants, and one patient received a hepatic allograft only. Ten of the transplanted patients were surviving at the time of the most recent follow up. Eight of them have functioning renal grafts and four have functioning hepatic grafts. There have been no deaths since 1988 among the 32 patients followed since that time. These data may suggest a broad range of clinical expression of primary hyperoxaluria. With current management strategies, outcomes are more favorable than has been reflected in previous literature.

Prophylactic chemoradiation of inguinofemoral lymph nodes in patients with locally extensive vulvar cancer.

OBJECTIVE: Primary surgical resection of locally advanced squamous cancer of the vulva may compromise the integrity of important midline structures such as the anus, clitoris, urethra, and vagina. Chemoradiation (synchronous radiation and cytotoxic chemotherapy) has been used as alternative initial treatment which may serve as definitive management for some patients, or may reduce the scope and functional sequelae of subsequent surgery in others. Inguinofemoral node dissection is associated with substantial risk of both acute and late morbidity, prompting consideration of elective inclusion of groin nodes within the irradiated volume and deletion of subsequent groin surgery. Concern that disease relapse in the groins is potentially fatal suggested the prudence of formal outcome assessment of our recent experience with prophylactic treatment of clinically uninvolved groin nodes in the context of concurrent chemoradiation for locally advanced primary vulvar cancer. METHODS: A review was conducted of 23 previously untreated patients with locally advanced squamous cancer of the vulva (2 T2, 20 T3, 1 T4) and clinically uninvolved groin nodes (1969 FIGO stages 14 N0, 4 N1, and 5 N2 with negative node biopsies) who were treated since 1987 with chemoradiation administered to a volume electively including bilateral inguinofemoral nodes. These patients did not undergo subsequent groin surgery. RESULTS: With follow-up from 6 to 98 months (mean, 45.3 months; median, 42 months), no patient has failed in the prophylactically irradiated inguinofemoral nodes. No patient has developed lymphedema, vascular insufficiency, or neurological injury in a lower extremity, and no patient has experienced aseptic necrosis of a femur. CONCLUSIONS: Elective irradiation of the groin nodes in the context of initial chemoradiation for locally advanced vulvar cancer is an effective therapy associated with acceptable acute toxicity and minimal late sequelae. It constitutes a sensible alternative to groin dissection in this patient population.