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Nancy Lee

Publications and source records attributed to Nancy Lee.

At least 19 recordsLinked to original sources
PubMed2007

Intensity-modulated radiation therapy in head and neck cancers: an update.

Intensity-modulated radiation therapy (IMRT), an advent of three-dimensional conformal radiotherapy (3D CRT), has excited the profession of radiation oncology more than any other new invention since the introduction of the linear accelerator. Approximately 1000 articles have been published on this topic to date, more than 200 of which focus on head and neck cancer. IMRT is based on computer-optimized treatment planning and a computer-controlled treatment delivery system. The computer-driven technology generates dose distributions that sharply conform to the tumor target while minimizing the dose delivered to the surrounding normal tissues. The high dose volume that tailors to the 3D configuration of the tumor along with the ability to spare the nearby normal tissues allows the option of tumor dose escalation. The head and neck region is an ideal target for this new technology for several reasons. First, IMRT offers the potential for improved tumor control through delivery of high doses to the target volume. Second, because of sharp dose gradients, IMRT results in the relative sparing of normal structures, such as the parotid glands, in the head and neck region. Third, organ motion is virtually absent in the head and neck region so, with proper immobilization, treatment can be accurately delivered. Although this is a relatively new technology, single-institution retrospective studies show better dosimetric profiles compared with conventional radiation techniques, as well as excellent clinical results. Salivary gland sparing using IMRT has also resulted in reduced incidence and severity of xerostomia, and this has been tested in a randomized trial against conventional radiotherapy for early-stage nasopharyngeal cancer. The results do confirm that IMRT does decrease xerostomia compared with conventional radiotherapy.

Head and Neck Neoplasms↗
PubMed2007

Oral cavity and oropharynx tumors.

Cancers of the oral cavity and pharynx are the most common head and neck cancers in the United States, and squamous cell carcinoma is the most frequent histologic type. The clinical behavior and outcome of tumors in the oral cavity is distinct from those of the oropharynx. As a general rule, surgical resection is the primary treatment for oral cavity squamous cell carcinoma, whereas oropharyngeal squamous cell carcinomas are treated with radiation with or without chemotherapy. A clear understanding of the anatomy and knowledge of clinical behavior and spread patterns of oral cavity and oropharyngeal squamous cell carcinoma are essential for radiologists to make a meaningful contribution to the treatment of these patients.

Carcinoma, Squamous Cell↗
PubMed2006

Geometric factors influencing dosimetric sparing of the parotid glands using IMRT.

PURPOSE/OBJECTIVE: To determine the relationship between the parotid volume, parotid-planning target volume (PTV) overlap, and dosimetric sparing of the parotid with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Parotid data were collected retrospectively for 51 patients treated with simultaneous boost IMRT. Unresectable patients received 54 or 59.4 Gy to subclinical disease, 70 Gy to gross disease. Patients treated postoperatively received 54, 60, and 66 Gy to low-risk, high-risk, and tumor bed regions. Volume and mean dose of each gland and gland segments outside of and overlapping the PTV were collected. Proximity of each gland to each PTV was recorded. RESULTS: Dosimetric sparing (mean dose 21% overlap (p = <0.0001). Among spared glands, the median mean dose in the overlap region was 55.0 Gy in glands with < or =21% overlap, but only 45.4 Gy when overlap >21%. Median mean dose was 25.9 Gy to glands overlapping PTV(54) or PTV(59) alone and 30.0 Gy to those abutting PTV(70) (p < 0.001). Although proximity to PTV(70) was associated with higher parotid dose, satisfactory sparing was achieved in 24 of 43 ipsilateral glands. CONCLUSIONS: Dosimetric sparing of the parotid is feasible when the parotid-PTV overlap is less than approximately 20%. With more overlap, sparing may result in low doses within the overlap region, possibly leading to inadequate PTV coverage. Gland proximity to the high-dose PTV is associated with higher mean dose but does not always preclude dosimetric sparing.

Algorithms↗
PubMed2006

The S1P2 sphingosine 1-phosphate receptor is essential for auditory and vestibular function.

Sphingosine 1-phosphate (S1P) is an endogenous growth factor with potent effects on many different cell types. Most of these effects are produced by activation of one or more of a family of G-protein coupled receptors. The S1P2 receptor can mediate S1P-induced proliferation, differentiation and survival in a wide variety of cells in culture. However, identifying essential in vivo functions for S1P2 has been hampered by its ubiquitous expression and the failure to detect any anatomical abnormalities in initial analyses of S1P2 knockout mice. We report here that all S1P2 knockout mice are profoundly deaf from postnatal day 22 and approximately half display a progressive loss of vestibular function with aging. Anatomically, both the auditory and vestibular systems appear to develop normally but then degrade. Morphological defects associated with hearing are first detected at 3 weeks postnatal as deformations of the organ of Corti/Nuel's space. By one year of age structures within the scala media are dramatically altered. The S1P2 knockout mice also display a loss of otoconia consistent with the vestibular impairment. The present data are the first to indicate that S1P signaling plays critical roles, in vivo, in auditory and vestibular functions. The data further establish that the S1P signaling occurs through the S1P2 receptor and makes an essential contribution to the structural maintenance of these systems, raising the possibility that properly targeted enhancement of this signaling may prove to be clinically beneficial.

Animals↗
PubMed2006

Mating factor linkage and genome evolution in basidiomycetous pathogens of cereals.

Sex in basidiomycete fungi is controlled by tetrapolar mating systems in which two unlinked gene complexes determine up to thousands of mating specificities, or by bipolar systems in which a single locus (MAT) specifies different sexes. The genus Ustilago contains bipolar (Ustilago hordei) and tetrapolar (Ustilago maydis) species and sexual development is associated with infection of cereal hosts. The U. hordei MAT-1 locus is unusually large (approximately 500 kb) and recombination is suppressed in this region. We mapped the genome of U. hordei and sequenced the MAT-1 region to allow a comparison with mating-type regions in U. maydis. Additionally the rDNA cluster in the U. hordei genome was identified and characterized. At MAT-1, we found 47 genes along with a striking accumulation of retrotransposons and repetitive DNA; the latter features were notably absent from the corresponding U. maydis regions. The tetrapolar mating system may be ancestral and differences in pathogenic life style and potential for inbreeding may have contributed to genome evolution.

Edible Grain↗
PubMed2006

Results of surgical salvage after failure of definitive radiation therapy for early-stage squamous cell carcinoma of the glottic larynx.

OBJECTIVE: To report the outcome of surgical salvage performed for early-stage squamous cell carcinoma of the glottic larynx that recurred or progressed after definitive radiotherapy. DESIGN: Retrospective outcome analysis. SETTING: Tertiary referral center specializing in head and neck cancer. PATIENTS: Forty-three patients who underwent salvage surgery after definitive radiation therapy for early-stage (T1-T2) glottic cancer were identified from a preexisting database of 662 patients with squamous cell carcinoma of the larynx treated at Memorial Sloan-Kettering Cancer Center between the years 1984 and 1998. The T stage at initial presentation was T1 in 20 (18%) and T2 in 23 (32%). Twenty-one patients (49%) were amenable to salvage partial laryngectomy (SPL), but 22 (51%) required salvage total laryngectomy (STL). Details on patient characteristics, tumor characteristics, postoperative complications, and survival outcome were extracted from the database. MAIN OUTCOME MEASURES: Overall survival, disease-specific survival, neck recurrence-free survival, and distant recurrence-free survival. RESULTS: No postoperative death occurred following salvage surgery. The overall incidence of complications was 21%, with no difference between the SPL and STL groups. Patients who required STL had poorer overall survival and disease-specific survival compared with patients who required SPL (overall survival, 50% vs 89%; P = .003; disease-specific survival, 51% vs 93%; P = .002). This difference in survival was associated with a poorer neck recurrence-free survival and distant recurrence-free survival in the STL group compared with the SPL group (neck recurrence-free survival, 80% vs 100%; P = .04; distant recurrence-free survival, 71% vs 93%; P = .06). Univariate analysis showed that age and clinical T stage at recurrence were predictors of overall survival, disease-specific survival, and distant recurrence-free survival. CONCLUSIONS: Careful selection of patients with early-stage glottic tumors that recur or progress after radiation allows patients to be successfully treated by partial laryngectomy with excellent survival outcome. However, despite an aggressive policy of performing partial laryngectomy when feasible, up to 50% of patients will require a total laryngectomy owing to progression of disease. These patients have poorer survival outcomes manifested by local, regional, and distant disease progression.

Adult↗
PubMed2006

The role of external beam radiotherapy in the treatment of papillary thyroid cancer.

The role of external beam radiotherapy (EBRT) in treating thyroid cancer has brought forth controversy. Due to various histologic presentations and different natural histories, there is no uniform approach/recommendation among centers and/or authorities regarding the role of EBRT for thyroid cancer. This is particularly true for papillary thyroid carcinoma (PTC) where the clinical course can range from a disease that is cured with simple surgery to an aggressive form of poorly differentiated thyroid cancer with high rates of recurrence/death from disease. In addition, because the majority of the patients with PTC undergo postoperative radioactive iodine (RAI) treatment, the question remains as to what is the exact role of EBRT for PTC in the setting of RAI treatment? In this issue of Endocrine-Related Cancer, Chow and colleagues identified indications for EBRT and RAI therapy for PTC based on a retrospective review of 1300 patients. The authors concluded that postoperative RAI treatment is indicated in patients with pT2-pT4, pN0-pN1b while postoperative EBRT is recommended for patients with gross residual, positive margin, pT4, pN1b, and lymph nodes>2 cm disease. Other centers have also published their experience on the value of EBRT for PTC but with different indications. The reasons for the variations from different centers are complex. However, when all published results are taken together, the findings confirm the added value of EBRT to the present management of PTC in a select group of patients, particularly those with high risk features. In this commentary, these issues will be discussed and recommendations regarding the role of EBRT will be given.

Carcinoma, Papillary↗
PubMed2006

Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients.

Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer. However, radiation-induced changes in the oral cavity, such as xerostomia and mucositis, are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy, and attempts at ameliorating these side effects have been poor at best. Pilocarpine has been approved for post-radiation xerostomia, and the effect of its use during radiation therapy on salivary flow, xerostomia, mucositis, and quality of life (QOL) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group (RTOG 97-09). In total, 245 evaluable patients were randomized to pilocarpine or placebo. Selected patients were required to have > or = 50% of the volume of the major salivary glands receive > or = 50Gy; to agree to provide stimulated and unstimulated samples of saliva (measured in g) before treatment, at the end of treatment, and 3 and 6 months after completion of radiation therapy; and to complete the University of Washington Head and Neck Symptom Scale. Following the completion of radiation therapy, the average unstimulated salivary flow was statistically greater in the pilocarpine group, whereas no difference was noted following parotid stimulation. There was no effect on the amelioration of mucositis. The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis. The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia. However, the absent correlation between improved salivary flow and QOL scores is of some concern (though not a new finding) and may be related to the existence of comorbidities and the lack of effect on mucositis.

Female↗
PubMed2006

Genetically modified live attenuated parasites as vaccines for leishmaniasis.

Leishmaniasis causes significant morbidity and mortality worldwide and is an important public health problem. Even though it is endemic in developing countries in tropical regions of the world,in recent years economic globalization and increased travel has extended its reach to people in developed countries. Leishmania is usually spread by the bite of the female sandfly. In addition, naïve populations can be exposed to Leishmania infection through transfusion of blood and blood products from infected asymptomatic individuals. There are several clinical forms of leishmaniasis caused by different species of the parasite. In some cases, the only possible cure for this disease is drug treatment. However, prolonged use of such drugs has led to parasite drug resistance. At present there are no effective vaccines against Leishmania. Many vaccine strategies have been pursued, including the use of whole cell lysate, killed, avirulent or irradiated parasites. Additionally, DNA vaccines and purified or recombinant parasite antigens have also been tested. Most of these strategies have shown some degree of effectiveness in animal models but little or no protection in humans. There is now a general consensus among Leishmania vaccine researchers that parasite persistence may be important for effective protective response and could be achieved by live attenuated parasite immunization. In this article we reviewed the efforts in developing genetically defined live attenuated Leishmania parasites as vaccine candidates with the goal of achieving a low level of parasite persistence without being virulent in the host and inducing protective immunity.

Animals↗
PubMed2005

Method to account for dose fractionation in analysis of IMRT plans: modified equivalent uniform dose.

PURPOSE: To propose a modified equivalent uniform dose (mEUD) to account for dose fractionation using the biologically effective dose without losing the advantages of the generalized equivalent uniform dose (gEUD) and to report the calculated mEUD and gEUD in clinically used intensity-modulated radiotherapy (IMRT) plans. METHODS AND MATERIALS: The proposed mEUD replaces the dose to each voxel in the gEUD formulation by a biologically effective dose with a normalization factor. We propose to use the term mEUD(D(o))(/n(o)) that includes the total dose (D(o)) and number of fractions (n(o)) and to use the term mEUD(o) that includes the same total dose but a standard fraction size of 2 Gy. A total of 41 IMRT plans for patients with nasopharyngeal cancer treated at our institution between October 1997 and March 2002 were selected for the study. The gEUD and mEUD were calculated for the planning gross tumor volume (pGTV), planning clinical tumor volume (pCTV), parotid glands, and spinal cord. The prescription dose for these patients was 70 Gy to >95% of the pGTV and 59.4 Gy to >95% of the pCTV in 33 fractions. RESULTS: The calculated average gEUD was 72.2 +/- 2.4 Gy for the pGTV, 54.2 +/- 7.1 Gy for the pCTV, 26.7 +/- 4.2 Gy for the parotid glands, and 34.1 +/- 6.8 Gy for the spinal cord. The calculated average mEUD(D(o))(/n(o)) using 33 fractions was 71.7 +/- 3.5 Gy for mEUD(70/33) of the pGTV, 49.9 +/- 7.9 Gy for mEUD(59.5/33) of the pCTV, 27.6 +/- 4.8 Gy for mEUD(26/33) of the parotid glands, and 32.7 +/- 7.8 Gy for mEUD(45/33) of the spinal cord. CONCLUSION: The proposed mEUD, combining the gEUD with the biologically effective dose, preserves all advantages of the gEUD while reflecting the fractionation effects and linear and quadratic survival characteristics.

Algorithms↗
PubMed2005

Postoperative complications of salvage total laryngectomy.

BACKGROUND: The objectives of the current study were to report the incidence of postoperative complications for salvage total laryngectomy (STL) compared with primary total laryngectomy (PTL) and to identify patient and tumor-related factors predictive of postoperative complications. METHODS: A sample of 183 patients who had received a total laryngectomy were identified from an existing database of 662 patients treated for squamous cell carcinoma of the larynx. PTL and STL were performed in 113 and 70 patients, respectively. Initial therapy in the patients who required salvage surgery included radiotherapy (RT) in 32 (46%) and chemoradiotherapy (CTRT) in 38 (54%). Postoperative complications were recorded for each group and categorized into local, swallowing, airway, and systemic complications. Postoperative complication rates for STL after RT and CTRT were compared with those after PTL by univariate analysis. Patient and tumor-related predictors of complications were identified by univariate and multivariate analyses. RESULTS: The overall mortality rate was 0.5%. Forty percent of all patients developed a postoperative complication after total laryngectomy. Local complications, which were the most frequent, occurred in 52 (28%) patients. Pharyngocutaneous fistula occurred in 31 (17%) patients. Statistical analysis showed that there was a greater number of patients with local wound (45% vs. 25%, P = 0.02) and fistula complications (32% vs. 12%, P = 0.012) in the STL-CTRT group compared with the primary laryngectomy group. Multivariate analysis showed that primary CTRT was an independent predictor of local complications and pharyngocutaneous fistula. CONCLUSIONS: Salvage laryngectomy was more frequently associated with postoperative complications after CTRT compared with PTL. Problems related to local wound healing, especially the development of pharyngocutaneous fistula, constituted the most common postoperative complication in these patients. Multivariate analysis showed that primary CTRT was an independent predictor of local wound complications and pharyngocutaneous fistula.

Adult↗
PubMed2005

Advances in nasopharyngeal carcinoma.

PURPOSE OF REVIEW: Intergroup 0099 established the role of concurrent chemotherapy with radiation therapy in the treatment of locally advanced nasopharyngeal carcinoma, but its reproducibility was unclear and chemotherapy compliance was poor. Multiple concurrent chemoradiation phase III trials were initiated in response to the Intergroup trial, and technologic advances in radiotherapy were explored to improve the therapeutic ratio. This review highlights recent advances in the management of nasopharyngeal carcinoma as a result of these endeavors. RECENT FINDINGS: Five randomized phase III trials confirmed the benefit of concurrent chemoradiation over radiation therapy alone, firmly establishing concurrent chemoradiation as the standard of care in locally advanced nasopharyngeal carcinoma. Each of these studies used conventional radiation therapy and noted an increase in toxicity over radiation therapy alone. Intensity-modulated radiation therapy is an advanced form of three-dimensional conformal radiotherapy which allows delivery of high doses of radiation to the tumor while sparing adjacent normal tissues, leading to improved local control and decreased radiation therapy-induced toxicities. Distant metastasis remains a significant problem despite intensity-modulated radiation therapy. Taxane-based induction chemotherapy seems promising in phase II studies. Targeted therapies remain a major area of interest and require further investigation. SUMMARY: Cisplatin-based concurrent chemoradiation followed by adjuvant chemotherapy is the standard of care for locally advanced nasopharyngeal carcinoma. Intensity-modulated radiation therapy has undergone a rapid evolution and is replacing conventional radiation therapy in many institutions. A multidisciplinary effort is under way to explore more effective systemic therapy to improve the distant metastasis free rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Intensity-modulated radiation therapy in head and neck cancers: dosimetric advantages and update of clinical results.

Intensity-modulated radiation therapy (IMRT) is an exciting new modality in radiation therapy. The head and neck region is an ideal target for this new technology for several reasons. First, IMRT offers the potential for improved tumor control through delivery of high doses to the target volume. Second, because of sharp dose gradients, IMRT results in the relative sparing of normal structures in the head and neck region. Third, organ motion is virtually absent in the head and neck region, so, with proper immobilization, treatment can be delivered accurately. Although this is a relatively new technology, preliminary studies show excellent dosimetric profiles and clinical results. Salivary gland sparing has also resulted in reduced incidence and severity of xerostomia. Early reports of improvement in tumor control with better side effect profiles versus conventional techniques are promising, but will need to be confirmed with longer follow-up.

Adult↗
PubMed2005

Adenoid cystic carcinoma of the major salivary glands treated with surgery and radiation.

OBJECTIVE: To examine patient characteristics, pathologic features, and treatment outcomes of adenoid cystic carcinoma of the major salivary glands. STUDY DESIGN: Retrospective review of patients in an academic medical center. METHOD: Review of medical records regarding demographics, extent of tumor, stage, histologic characteristics, and treatment outcomes of patients treated with surgery and postoperative radiation. RESULTS: Of the 33 patients, 19 (58%) were male, and 14 (42%) were female. The average age of presentation was 49 (range 22-81) years. Of the 29 patients fully staged at the time of diagnosis, 7 (24%) presented at American Joint Committee on Cancer stage I, 9 (31%) at stage II, 4 (14%) at stage III, and 9 (31%) at stage IV. The cribriform histologic subtype was predominant (64%). The majority originated in the parotid gland (21, 64%), with the remaining originating in either the submandibular gland (10, 30%) or the sublingual gland (2, 6%). Local control was 94% at 5 years and 73% at 10 years. Metastatic control was 82% at 5 years and 63% at 10 years. Four patients failed locally and nine failed distally. Overall survival was 85% at 5 years and 69% at 10 years, with a median of 12.9 years. CONCLUSION: Surgical excision with postoperative radiation provides a long period of disease-free survival. Patients were more likely to fail with metastases than with local recurrence.

Adult↗
PubMed2004

Penetrating brain injury leads to activation of ciliary neurotrophic factor receptors.

Endogenous injury response mechanisms likely reduce secondary neuronal loss following CNS trauma by activating growth factor receptors. Therefore, it is important to determine which growth factor receptors are activated in vivo by CNS trauma and which signal transduction pathways are affected in which cell types. We present a model of penetrating brain injury utilizing stereotaxic insertion of a fine needle. This procedure can be used to anatomically characterize injury response mechanisms through immediate, local application of pharmacological agents. We find, through immunohistochemistry, that injury of the rat facial motor nucleus leads to activation of STAT3, a neuronal survival factor, in the dendrites, nuclei and cytoplasm of the motor neurons. A similar response was observed with the trigeminal motor nucleus. Use of the ciliary neurotrophic factor (CNTF) receptor antagonist, AADH-CNTF, indicated that the STAT3 activation resulted largely, and perhaps entirely, from injury-induced activation of CNTF receptors.

Animals↗
PubMed2004

A population-based atlas and clinical target volume for the head-and-neck lymph nodes.

PURPOSE: To develop a population-based three-dimensional lymph node target volume of the head and neck. METHODS AND MATERIALS: The T2 weighted axial magnetic resonance imaging (MRI) images of 35 patients with known head and neck cancer were reviewed. An experienced head and neck radiologist marked each lymph node (LN) electronically. The images were distributed to one of 12 axial levels of the head and neck with each level representing a distinct portion of the neck based on external contours and the presence of anatomic structures. The LNs were marked with five different symbols to distinguish the superior/inferior extent of each LN within each level. With the categorization of each image into a different superior/inferior level of the neck, the registration of the images was limited to two dimensions. Nonlinear transformation accounted for inter-patient differences although no local warping was used. The co-registration used recognizable anatomic landmarks (vertebral body, mandible, maxilla, clivus as well as the sternocleidomastoid muscle, external skin contour, spinal cord) to match the patient anatomy. RESULTS: In total, 503 images were co-registered with the baseline images. The majority of the co-registrations were of good quality; 361, 122, and 20 image co-registrations scored as global, limited, and poor co-registrations respectively. One thousand and fifty seven LNs were marked, with 122 LNs marked as submandibular and submental LN. Among the levels A, B, C, D, E, F, G, H, 22, 44, 206, 199, 196, 175, 63, 35 LN were marked respectively. Noteworthy anatomic variation was observed among the different nodal groups that are summarized in the representative baseline images. CONCLUSIONS: Image registration of a series of head and neck images generates a valuable population-based lymph node map that can be used to guide the three-dimensional delineation of the elective lymph node target volume. Significant variation in the lymph node location was seen in all LN groups. The medial border of the internal jugular vein can be used as an important landmark structure in delineating the jugular LN clinical target volume and, for that reason, intravenous contrast is recommended to improve visualization. The location of the submandibular LN appear to be limited to the space anterior and lateral to the submandibular gland and are found mostly along the inferior edge of the mandible. The location of the retropharyngeal LN does vary but their location does not appear to vary with any other recognizable axial structure. The lymph node map provides another collaborating piece of evidence in defining the head and neck LN clinical target volume.

Adolescent↗
PubMed2004

STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: potential role for STAT3 as a retrograde signaling transcription factor.

STAT3 is a latent transcription factor that is activated by plasma membrane growth factor receptor complexes. Conditional gene disruption data indicate that it contributes to the survival of cranial motor neurons after peripheral nerve lesion. In agreement, levels of activated STAT3 (Tyr705-phosphorylated STAT3) have been shown to increase in the nuclei of adult cranial motor neurons during their regeneration after the same injury. The data presented here demonstrate that STAT3 is similarly but not identically affected in sciatic motor neurons after sciatic nerve injury. In addition, we find that sensory neuron nuclei also display an analogous increase in activated STAT3, thereby supporting a role for STAT3 in the survival and regeneration of these cells. Most interesting, the present data indicate that peripheral nerve lesion leads to a very rapid activation of STAT3 in axons at the lesion site. This response increases during the first 24 hours after injury and extends back to the motor and sensory neurons such that phospho-STAT3-immunoreactive axons are first detected in the dorsal root ganglia and ventral spinal cord at the same postlesion time intervals at which the activated STAT3 is first detected in the neuronal nuclei. Together these data raise the possibility that axonal STAT3, activated at the injury site, acts as a retrograde signaling transcription factor, which promotes the survival and regeneration of both sensory and motor neurons.

Animals↗