Biomedical subjects

Nancy Lee

Publications and source records attributed to Nancy Lee.

At least 37 records · Page 2Linked to original sources

PubMed2004

A study of planning dose constraints for treatment of nasopharyngeal carcinoma using a commercial inverse treatment planning system.

PURPOSE: The purpose of this study was to develop and test planning dose constraint templates for tumor and normal structures in the treatment of nasopharyngeal carcinoma (NPC) using a specific commercial inverse treatment planning system. METHODS AND MATERIALS: Planning dose constraint templates were developed based on the analyses of dose-volume histograms (DVHs) of tumor targets and adjacent sensitive structures by clinically approved treatment plans of 9 T1-2 and 16 T3-4 NPC patients treated with inverse planned intensity-modulated radiation therapy (IP-IMRT). DVHs of sensitive structures were analyzed by examining multiple defined endpoints, based on the characteristics of each sensitive structure. For each subgroup of patients with T1-2 and T3-4 NPC, the resulting mean values of these defined endpoint doses were considered as templates for planning dose constraints and subsequently applied to a second group of patients, 5 with T1-2 NPC and 5 with T3-4 NPC. The 10 regenerated plans (called new plans) were compared to the original clinical plans that were used to treat the second group of patients, based on plan conformity index and DVHs. RESULTS: The conformity indices of the new plans were comparable to the original plans with no statistical difference (p = 0.85). Among the serial sensitive structures evaluated, there was a significant decrease with the new plans in the dose to the spinal cord when analyzed by the maximum dose (p = 0.001), doses encompassing 1 cc of the spinal cord volume (p = 0.001) and 3 cc of the spinal cord volume (p = 0.001). There was no significant difference in the mean maximum dose to the brainstem between the new plans and the original plans (p = 0.36). However, a significant difference in the mean maximum dose to the brainstem was seen among the different T-stages (p = 0.04). A decrease with the new plan to the brainstem in the doses encompassing 5% and 10% of the volume was of borderline statistical significance (p = 0.08 and p = 0.06, respectively). There were no statistical differences between the new plans and the original plans in the mean doses to the chiasm, optic nerve, or eye for each of the endpoints considered. For parallel sensitive structures in the new plans, there was a significant increase in the average mean dose to the parotid glands (p = 0.01), a decrease that was of borderline significance in the average mean dose to the temporomandibular joint (p = 0.07), but no difference in the average mean dose to the ear. CONCLUSIONS: The statistical analysis showed that new plans are comparable to the original plans for most of the sensitive structures except for a trade-off between a dose reduction to the spinal cord in the new plans and an increase in the mean dose to the parotid glands. These tested planning dose constraint templates can serve as good "starting points" for an inverse plan of NPC using a specific commercial inverse treatment planning system.

Brain Stem↗

PubMed2004

A forward-planned treatment technique using multisegments in the treatment of head-and-neck cancer.

PURPOSE: To describe in detail a forward-planned multisegment technique (FPMS) as an alternative treatment method for patients who are not suitable for inverse-planned intensity-modulated radiation therapy (IP-IMRT), or for situations where IP-IMRT is not available in a medical clinic. METHODS AND MATERIALS: Between April 1995 and February 2002, 38 primary head-and-neck patients were treated using the FPMS technique, which has evolved over the past 7 years at our medical center. In the most recent version of the FPMS technique, which includes 5 patients examined in this analysis, the primary tumor and the upper neck nodes were treated with 7 gantry angles, including an anterior, 2 lateral, 2 anterior oblique, and 2 posterior oblique beams with a total of 13 beam shapes formed by multileaf collimators (MLC), called MLC segments. The shape of each MLC segment was carefully designed, and the associated weights were optimized through manual iterations. The lower neck nodes and the supraclavicular nodes were treated with a split-beam anterior field, matched to the inferior border of the FPMS plan at the isocenter. With an autosequencing delivery system, all fields, including dynamic wedges, can be automatically treated. The dosimetric accuracy of this technique was verified with a phantom plan and measured with an ionization chamber, as well as film dosimetry. A sample FPMS plan is described in detail, and the average results for the 5 patients treated with FPMS are retrospectively compared to results for similar patients treated with IP-IMRT. RESULTS: The gross tumor volume was prescribed to 70 Gy (2.12 Gy/fraction) at the 88% isodose line, whereas the clinical target volume received a dose of 59.4 Gy (1.8 Gy/fraction) at the 75% isodose line. The maximum dose to the brainstem and spinal cord was below 54 and 45 Gy, respectively, comparable to IP-IMRT. The mean dose to the parotid glands was 32 Gy with FPMS vs. 26 Gy with IP-IMRT. Average delivery time was shorter for FPMS (15 min) than IP-IMRT (30 min), whereas the planning time depended on the expertise of the planner. Dosimetric accuracy for FPMS and IP-IMRT plans using phantom measurements was similar, within 1% of the phantom plan. With a median follow-up of 31 months, there was no local-regional recurrence, and the incidence of xerostomia is reduced compared to conventional techniques. CONCLUSION: FPMS achieved plans comparable to those for IP-IMRT and is an ideal alternative treatment technique for a center without the capabilities of IP-IMRT or for a patient who is not a suitable candidate, because of prolonged treatment time. The treatment outcomes from our clinical experience indicate that FPMS can achieve excellent local freedom from progression rates without causing excessive toxicity. Lastly, IP-IMRT plans should be comparable to, if not better than, FPMS plans in the treatment of head-and-neck cancer.

Brain Stem↗

PubMed2004

Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.

BACKGROUND: Despite the use of resection and postoperative radiotherapy, high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed. We tested the hypothesis that concurrent postoperative administration of cisplatin and radiotherapy would improve the rate of local and regional control. METHODS: Between September 9, 1995, and April 28, 2000, 459 patients were enrolled. After undergoing total resection of all visible and palpable disease, 231 patients were randomly assigned to receive radiotherapy alone (60 to 66 Gy in 30 to 33 fractions over a period of 6 to 6.6 weeks) and 228 patients to receive the identical treatment plus concurrent cisplatin (100 mg per square meter of body-surface area intravenously on days 1, 22, and 43). RESULTS: After a median follow-up of 45.9 months, the rate of local and regional control was significantly higher in the combined-therapy group than in the group given radiotherapy alone (hazard ratio for local or regional recurrence, 0.61; 95 percent confidence interval, 0.41 to 0.91; P=0.01). The estimated two-year rate of local and regional control was 82 percent in the combined-therapy group, as compared with 72 percent in the radiotherapy group. Disease-free survival was significantly longer in the combined-therapy group than in the radiotherapy group (hazard ratio for disease or death, 0.78; 95 percent confidence interval, 0.61 to 0.99; P=0.04), but overall survival was not (hazard ratio for death, 0.84; 95 percent confidence interval, 0.65 to 1.09; P=0.19). The incidence of acute adverse effects of grade 3 or greater was 34 percent in the radiotherapy group and 77 percent in the combined-therapy group (P<0.001). Four patients who received combined therapy died as a direct result of the treatment. CONCLUSIONS: Among high-risk patients with resected head and neck cancer, concurrent postoperative chemotherapy and radiotherapy significantly improve the rates of local and regional control and disease-free survival. However, the combined treatment is associated with a substantial increase in adverse effects.

Adolescent↗

PubMed2004

Temporal gene expression patterns in G93A/SOD1 mouse.

Amyotrophic lateral sclerosis (ALS) is a generally fatal degenerative disorder of motor neurons that has no known cure. Many pathological processes have been implicated. However, the early, initiating events in the disease are poorly understood. We performed multivariate analyses of gene expression of 21 selected genes from categories including glutamate neurotoxicity, oxidative stress, neuroinflammation, aberrant metal ion regulation, apoptosis, and abnormal microglial function on G93A SOD1 mice. These animals develop symptoms of motor neuron dysfunction at about 12 weeks of age, and die at age 18 to 20 weeks. We analyzed animals at both presymptomatic and symptomatic stages. Differential regulation of several genes involved in neuroinflammation, including TNF-alpha, IL- RA, CD86, CD200R and Groalpha, was observed in presymptomatic mice, aged 6-9 weeks, while expression of genes representative of other processes was not altered until the animals reached symptomatic stages. Analysis of expression of inflammatory genes and microglia related genes together also revealed a highly significant change in mutant mice relative to wildtype at 6-9 weeks. These changes were due to the presence of the mutant gene, and not simply to overexpression of a SOD1 gene. These findings are discussed in relation to possible roles of microglia function in the development of ALS.

Age Factors↗

PubMed2003

Intensity-modulated radiation therapy for head-and-neck cancer: the UCSF experience focusing on target volume delineation.

PURPOSE: To review the University of California-San Francisco (UCSF) experience of using intensity-modulated radiation therapy (IMRT) to treat head-and-neck cancer focusing on the importance of target volume delineation and adequate target volume coverage. METHODS AND MATERIALS: Between April 1995 and January 2002, 150 histologically confirmed patients underwent IMRT for their head-and-neck cancer at our institution. Sites included were nasopharynx 86, oropharynx 22, paranasal sinus 22, thyroid 6, oral tongue 3, nasal cavity 2, salivary 2, larynx 2, hypopharynx 1, lacrimal gland 1, skin 1, temporal bone 1, and trachea 1. One hundred seven patients were treated definitively with IMRT +/- concurrent platinum chemotherapy (92/107), whereas 43 patients underwent gross surgical resection followed by postoperative IMRT +/- concurrent platinum chemotherapy (15/43). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator, and 3) sequential tomotherapy using dynamic multivane intensity-modulating collimator. Forty-two patients were treated with a forward plan, 102 patients with an inverse plan, and 6 patients with both forward and inverse plans. The gross target volume (GTV) was defined as tumor detected on physical examination or imaging studies. In postoperative cases, the GTV was defined as the preoperative gross tumor volume. The clinical target volume (CTV) included all potential areas at risk for microscopic tumor involvement by either direct extension or nodal spread including a margin for patient motion and setup errors. The average prescription doses to the GTV were 70 Gy and 66 Gy for the primary and the postoperative cases, respectively. The site of recurrence was determined by the diagnostic neuroradiologist to be either within the GTV or the CTV volume by comparison of the treatment planning computed tomography with posttreatment imaging studies. RESULTS: For the primary definitive cases with a median follow-up of 25 months (range 6 to 78 months), 4 patients failed in the GTV. The 2- and 3-year local freedom from progression (LFFP) rates were 97% and 95%. With a median follow-up of 17 months (range 8 to 56 months), 7 patients failed in the postoperative setting. The 2-year LFFP rate was 83%. For the primary group, the average maximum, mean, and minimum doses delivered were 80 Gy, 74 Gy, 56 Gy to the GTV, and 80 Gy, 69 Gy, 33 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose. For the postoperative group, the average maximum, mean, and minimum doses delivered were 79 Gy, 71 Gy, 37 Gy to the GTV and 79 Gy, 66 Gy, 21 Gy to the CTV. An average of only 6% of the GTV and 6% of the CTV received less than 95% of the prescribed dose. CONCLUSION: Accurate target volume delineation in IMRT treatment for head-and-neck cancer is essential. Our multidisciplinary approach in target volume definition resulted in few recurrences with excellent LFFP rates and no marginal failures. Higher treatment failure rates were noted in the postoperative setting in which lower doses were prescribed. Potential dose escalation studies may further improve the local control rates in the postoperative setting.

Academic Medical Centers↗

PubMed2003

Phase III quality-of-life study results: impact on patients' quality of life to reducing xerostomia after radiotherapy for head-and-neck cancer--RTOG 97-09.

PURPOSE: To determine whether prevention of hyposalivation after curative radiotherapy (RT) to the head and neck improves patients' quality of life (QOL). METHODS AND MATERIALS: Patients were to receive at least 50 Gy to 50% of the volume of the major salivary glands, provide unstimulated and stimulated saliva samples, and complete the University of Washington head-and-neck QOL tool before RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5 mg or placebo q.i.d. RESULTS: A total of 249 patients was randomized between March 1998 and January 2000. Of these, 214 were eligible for QOL analysis. Patients were evenly distributed between arms by race, gender, tobacco use, tumor site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status of 90% was more common in the pilocarpine arm. Twenty percent of the patients on the pilocarpine arm and 29% of the patients on the placebo arm were taking nutritional supplements. The placebo arm patients had greater mouth pain and chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and 50%, respectively. Despite statistically significant (p = 0.047 and p = 0.049, respectively) preservation of salivary function in the pilocarpine arm, patients on the pilocarpine arm reported difficulties with swallowing (75%), activity (80%), hyposalivation (64%), and taste (81%). No difference was noted between arms at 3 months in mucositis scores, with both arms demonstrating increased requirement for oral nutrients. CONCLUSION: Objective prevention of hyposalivation did not affect patients' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT.

Female↗

PubMed2003

Comparison of treatment plans using intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for paranasal sinus carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conformal radiotherapy (3D-CRT) planning for paranasal sinus carcinoma. MATERIALS AND METHODS: Treatment plans using traditional 3-field technique, 3D-CRT planning, and inverse planning IMRT were developed for a case of paranasal sinus cancer requiring adjuvant radiotherapy. Plans were compared with respect to dose conformality, dose-volume histograms, doses to critical normal tissues, and ease of treatment delivery. RESULTS: The inverse-planned IMRT technique was more conformal around the tumor target volume than conventional techniques. The dose-volume histograms demonstrated significantly better critical normal-tissue sparing with the IMRT plans, while able to deliver a minimum dose of 60 Gy to the clinical tumor volume and 70 Gy to the gross tumor volume. Acute toxicities in our analysis were minimal. CONCLUSIONS: IMRT planning provided improved tumor target coverage when compared to 3D-CRT treatment planning. There was significant sparing of optic structures and other normal tissues, including the brainstem. Inverse planning IMRT provided the best treatment for all paranasal sinus carcinomas, but required stringent immobilization criteria. Further studies are needed to establish the true clinical advantage of this modality.

Aged↗

PubMed2003

Of smuts, blasts, mildews, and blights: cAMP signaling in phytopathogenic fungi.

cAMP regulates morphogenesis and virulence in a wide variety of fungi including the plant pathogens. In saprophytic yeasts such as Saccharomyces cerevisiae, cAMP signaling plays an important role in nutrient sensing. In filamentous saprophytes, the cAMP pathway appears to play an integral role in vegetative growth and sporulation, with possible connections to mating. Infection-related morphogenesis includes sporulation (conidia and teliospores), formation of appressoria, infection hyphae, and sclerotia. Here, we review studies of cAMP signaling in a variety of plant fungal pathogens. The primary fungi to be considered include Ustilago maydis, Magnaporthe grisea, Cryphonectria parasitica, Colletotrichum and Fusarium species, and Erisyphe graminis. We also include related information on Trichoderma species that act as mycoparasites and biocontrol agents of phytopathogenic fungi. We point out similarities in infection mechanisms, conservation of signaling components, as well as instances of cross-talk with other signaling pathways.

Cyclic AMP↗

PubMed2003

Management of cervical metastases in advanced squamous cell carcinoma of the base of tongue.

OBJECTIVE: To clarify the role of neck dissection following primary radiotherapy for treatment of squamous cell carcinoma of the base of tongue. DESIGN: Case series. SETTING: Academic, tertiary care medical center. PATIENTS OR OTHER PARTICIPANTS: A consecutive series of 45 patients with biopsy-proven squamous cell carcinoma of the base of tongue and cervical metastases treated with primary radiotherapy at The University of California, San Francisco, was examined. Patients with a prior history of neck irradiation, neck dissection, or head and neck cancer within 5 years were excluded. MAIN OUTCOME MEASURES: Overall survival and regional control. RESULTS: Of the 45 patients treated with definitive radiotherapy, 25 (56%) achieved a complete response, 13 (29%) achieved a partial response, 4 (9%) were nonresponders, and 3 (7%) did not complete radiotherapy. Two thirds of the complete responders had N2 or N3 disease; 3 had recurrences in the neck, 1 of which was an isolated neck recurrence. Of the 13 partial responders, 5 had isolated persistence of disease, with 4 undergoing neck dissections. The only long-term survivors among the partial responders were those 4 who underwent a neck dissection. Overall survival was 50% at 3 years and 32% at 5 years. Regional control for complete responders was 84% at 5 years. CONCLUSIONS: The low rate of isolated regional recurrence in patients with a complete response to radiotherapy supports the practice of surveillance alone in such patients. Patients with less than a complete response appear to benefit from prompt surgical salvage.

Adult↗

PubMed2003

Gamma knife radiosurgery for recurrent salivary gland malignancies involving the base of skull.

BACKGROUND: The management of skull base recurrence of salivary gland tumors is challenging, because complete surgical resection and fractionated reirradiation are seldom possible. Experience is being gained with radiosurgery for this indication. METHODS: From 1994-2000, eight patients with 16 skull base recurrences of salivary gland tumors underwent Gamma Knife radiosurgery at the University of California San Francisco. Local freedom from progression (FFP), regional FFP, locoregional FFP, and survival times were measured from the date of radiosurgery and estimated using the Kaplan-Meier method. RESULTS: All patients experienced symptomatic response, usually pain resolution. The median local FFP, regional FFP, locoregional FFP, and survival times were 15.4, 12.0, 10.0, and 21.2 months, respectively. The 1-year local FFP probabilities are 93% and 59%, respectively. Local FFP, allowing for salvage radiosurgery, was 100% at 1 year and 75% at 2 years. Five of seven patients with locoregional failure underwent repeat radiosurgery, successfully achieving control for an additional 4.4 to 13.4 months in four patients. One patient had radiation necrosis develop. CONCLUSION: Radiosurgery provided good local control and symptomatic relief in patients with recurrent salivary gland malignancies involving the base of skull. In patients with good performance status, radiosurgery should be considered as salvage treatment.

Aged↗

PubMed2003

CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines.

BACKGROUND AND PURPOSE: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals--the so-called Brussels guidelines from Grégoire et al., and the so-called Rotterdam guidelines from Nowak et al.--emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies. MATERIALS AND METHODS: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck. RESULTS AND CONCLUSIONS: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described.

Head and Neck Neoplasms↗

PubMed2003

Programmed cell death in trypanosomatids and other unicellular organisms.

In multicellular organisms, cellular growth and development can be controlled by programmed cell death (PCD), which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms, features of PCD similar to those in multicellular organisms have been reported, suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However, more extensive studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms could delineate the evolutionary origin of this pathway. Further characterisation of the PCD pathway in the unicellular parasites could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause.

Amphotericin B↗

PubMed2003

RNA-mediated inhibition of HIV in a gene therapy setting.

At present, treatment for HIV-1 infection employs highly active anti-retroviral therapy (HAART), which utilizes a combination of RT and protease inhibitors. Unfortunately, HIV can escape many therapies because of its high mutation rate and the complexity of its pathogenesis. HIV-1 integrates into the cellular genome, which facilitates persistence and acts as a reservoir for reactivation and replication. As an alternative or adjuvant to chemotherapy we have been developing an RNA-based gene therapy approach for the treatment of HIV-1 infection. This article summarizes the various RNA based technologies that we have developed for potential application in a gene therapy setting.

Anti-HIV Agents↗

PubMed2002

An atypical protein disulfide isomerase from the protozoan parasite Leishmania containing a single thioredoxin-like domain.

In higher eukaryotes, secretory proteins are under the quality control of the endoplasmic reticulum for their proper folding and release into the secretory pathway. One of the proteins involved in the quality control is protein disulfide isomerase, which catalyzes the formation of protein disulfide bonds. As a first step toward understanding the endoplasmic reticulum quality control of secretory proteins in lower eukaryotes, we have isolated a protein disulfide isomerase gene from the protozoan parasite Leishmania donovani. The parasite enzyme shows high sequence homology with homologs from other organisms. However, unlike the four thioredoxin-like domains found in most protein disulfide isomerases, of which two contain an active site, the leishmanial enzyme possesses only one active site present in a single thioredoxin-like domain. When expressed in Escherichia coli, the recombinant parasite enzyme shows both oxidase and isomerase activities. Replacement of the two cysteins with alanines in its active site results in loss of both enzymatic activities. Further, overexpression of the mutated/inactive form of the parasite enzyme in L. donovani significantly reduced their release of secretory acid phosphatases, suggesting that this single thioredoxin-like domain protein disulfide isomerase could play a critical role in the Leishmania secretory pathway.

Amino Acid Sequence↗

PubMed2002

Racial/ethnic differences in CD4 T cell count and viral load at presentation for medical care and in follow-up after HIV-1 infection.

The baseline characteristics of antiretroviral-naive patients were compared by ethnic/racial groups. First CD4 T cell counts were lower for Latino (P = 0.0004) and black patients (P = 0.10) when compared with white patients. First HIV-1-RNA levels were higher in Latino patients (P = 0.08), who were also more likely to present with major opportunistic infections (P < 0.004). Once in care, changes in CD4 T cell counts and viral loads over time did not differ significantly between groups.

Academic Medical Centers↗

PubMed2002

Skin toxicity due to intensity-modulated radiotherapy for head-and-neck carcinoma.

PURPOSE: To investigate the cause of acute skin toxicity observed in the treatment of head-and-neck cancer with extended-field intensity-modulated radiotherapy (EF-IMRT). METHODS AND MATERIALS: EF-IMRT was used to treat head-and-neck cancer, with the gross target volume receiving 70 Gy and the clinical target volume 60 Gy. A thermoplastic mask covering the head, neck, and shoulder was used for immobilization. Dosimetric studies were conducted to investigate the possible causes of the skin reactions, such as the bolus effect of the mask, the use of multiple tangential beams with IMRT plans, and the way in which the physicians contoured the lymph nodes. The dose-volume histograms of conventional opposed-lateral fields were compared with that of the multiple tangential EF-IMRT fields. IMRT plans with neck nodes contoured up to and including the skin surface were compared with plans that contoured the neck nodes 5 mm away from the skin surface. In addition, IMRT plans defining the skin as a sensitive structure were compared with plans that did not define the skin as a sensitive structure. All plans were created using an anthropomorphic Rando phantom, and the skin doses were measured with and without the mask. In each measurement, 6 thermoluminescent dosimeters (TLDs) were placed at the lateral and medial surfaces of the neck. RESULTS: For all four plans, the measured skin doses with the mask were consistently higher than those without the mask. The average dose increase was about 18% owing to the bolus effect of the mask. Multiple tangential fields used in IMRT plans contributed to an increase in skin dose by about 19% and 27%, with and without the mask, respectively. If the skin of the neck was contoured as a sensitive structure for dose optimization, the volume of skin that received >45 Gy was further reduced by about 20%. Five patients immobilized with head and shoulder masks were treated with EF-IMRT plans with the neck nodes carefully delineated away from the skin surface. The neck skin was identified as a sensitive structure for dose optimization. Grade 1 toxicity was observed in 3 patients, Grade 2 in 1 patient, and Grade 3 in 1 patient toward the end of treatment. CONCLUSION: Multiple factors contributed to the observed acute skin reaction for head-and-neck cancer patients treated with EF-IMRT. By taking into consideration the skin as a sensitive structure during inverse planning, it was possible to reduce the skin dose to a tolerable level without compromising tumor target coverage.

Female↗

PubMed2002

Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience.

PURPOSE: To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17-82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50-60 Gy to the clinically negative neck, and 5-7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose. CONCLUSION: Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.

Adolescent↗

PubMed2002

Expression of calreticulin P-domain results in impairment of secretory pathway in Leishmania donovani and reduced parasite survival in macrophages.

The secretory proteins of Leishmania are thought to be involved in the parasite survival inside the insect vector or mammalian host. It is clear from studies in higher eukaryotes that proper folding in the endoplasmic reticulum and targeting out of the endoplasmic reticulum is critical for the function of secretory proteins. The endoplasmic reticulum chaperones such as calreticulin play an important role in the quality control of secretory proteins. However, very little is known about the secretory pathway of trypanosomatid parasites such as Leishmania. In the present study, we show that overexpression of the P-domain of Leishmania donovani calreticulin in transfected L. donovani resulted in a significant reduction in the secretion of the parasite secretory acid phosphatases. This effect is associated with an intracellular accumulation of active enzyme in these transfected parasites. In addition, parasites expressing the P-domain calreticulin showed a significant decrease in survival inside human macrophages. This study suggests that altering the function of an endoplasmic reticulum chaperone such as calreticulin in Leishmania may affect the targeting of proteins that are associated with the virulence of the parasite during their trafficking through the parasite secretory pathway.

Acid Phosphatase↗