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Brian O'Sullivan

Publications and source records attributed to Brian O'Sullivan.

At least 19 recordsLinked to original sources

Radiation planning comparison for superficial tissue avoidance in radiotherapy for soft tissue sarcoma of the lower extremity.

PURPOSE: Three types of preoperative radiotherapy (RT) plans for extremity soft tissue sarcoma were compared to determine the amount of dose reduction possible to the planned surgical skin flaps required for tumor resection and wound closure, without compromising target coverage. METHODS AND MATERIALS: Twenty-four untreated patients with large, deep, lower extremity STS treated with preoperative RT and limb salvage surgery had their original conventional treatment plans re-created. The same clinical target volume was used for all three plans. The future surgical skin flaps were created virtually through contouring by the treating surgeon and regarded as an organ at risk. The original, conformal, and intensity-modulated RT (IMRT) plans were created to deliver 50 Gy in 25 fractions to the clinical target volume. Clinical target volume and organ-at-risk dose-volume histograms were calculated and the plans compared for conformality, target coverage, and dose sparing. RESULTS: The mean dose to the planned skin flaps was 42.62 Gy (range, 30.24-48.65 Gy) for the original plans compared with 40.12 Gy (range, 24.24-47.26 Gy) for the conformal plans and 26.71 Gy (range, 22.31-31.91 Gy) for the IMRT plans (p = 0.0008). An average of 86.4% (range, 53.2-97.4%) of the planned skin flaps received >or=30 Gy in the original plans compared with 83.4% (range, 36.2-96.2%) in the conformal plans and only 34.0% (range, 22.5-53.3%) in the IMRT plans (p = 0.0001). IMRT improved target conformality compared with the original and conformal plans (1.27, 2.34, and 1.76, respectively, p = 0.0001). CONCLUSION: In a retrospective review, preoperative IMRT substantially lowered the dose to the future surgical skin flaps, sparing a greater percentage of this structure's volume without compromising target (tumor) coverage.

Adult↗

East-West Symposium on nasopharyngeal cancer.

BACKGROUND: To achieve greater understanding of the epidemiology, pathogenesis, molecular oncology, diagnostic, and therapeutic aspects of nasopharyngeal cancer (NPC), an international meeting was held in June 2005, Toronto, Canada. RESULTS: Further insights were obtained into the role of EBV in NPC development, with its diverse effects ranging from proliferative signals via NF-kB, to immunesuppression, to angiogenic gene regulation. Subsequently, multiple pathways are dysregulated in NPC as revealed by expression array analyses, including apoptosis, integrin, and B-catenin cascades. Advances have been made in the diagnosis and monitoring of NPC, using transoral brushings and plasma levels of EBV transcripts, which may not directly correlate with the number of circulating tumor cells, but is nevertheless informative in predicting and tracking disease response. Many novel therapies have promising results, particularly in the areas of immunotherapies, and the exploration of molecularly targeted approaches such as cetuximab or histone deacetylase inhibitors. CONCLUSIONS: The results from large randomized trials and meta-analyses have consistently demonstrated the benefit of concurrent chemotherapy with curative radiation therapy, but at a cost of greater acute and late-tissue toxicities. Further advances are required to achieve an improved understanding on the inter-relationship between environmental and genetic determinants in NPC development, to reduce the global burden of this disease. At the same time, novel therapeutic approaches are necessary to increase curability of NPC, but with reduced long-term toxicities.

Epstein-Barr Virus Infections↗

Multiple dysregulated pathways in nasopharyngeal carcinoma revealed by gene expression profiling.

Gene expression profiling was conducted using primary human nasopharyngeal carcinoma (NPC) biopsy samples to improve the understanding of the molecular pathways defining NPC and to identify novel potential therapeutic targets. RNA samples were extracted from 36 patients suspected to have NPC and hybridized onto the Affymetrix U133A chip. NPC was diagnosed in 19 patients, 11 had lymphoid hyperplasia (LH), and 6 were "normal" biopsies. Clinical stages for these NPC patients ranged from I-IV, including one M1. All NPC patients (except the M1) were treated with curative intent, which included radiotherapy alone (4 patients), or combined with chemotherapy (14 patients). Unsupervised clustering demonstrated a distinct NPC expression pattern, compared to normal biopsies. Subsequent Significance Analysis of Microarrays (SAM) derived from 14 NPC and 6 normal samples discovered 1,089 differentially regulated genes. Pathway analyses revealed novel insights into the mechanisms leading to NPC, whereby upregulation of NFkappaB2 and survivin play central roles in increasing resistance to apoptosis, and changes in integrin and WNT/beta-catenin signaling leading to uncontrolled proliferation. The role of survivin in resisting apoptosis in NPC was confirmed by RNA interference. Our data provide novel insights into the development and progression of NPC, and suggest survivin as a novel therapeutic target for NPC.

Apoptosis↗

Prognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in nasopharyngeal cancer.

PURPOSE: Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma which is intimately associated with EBV. The latent presence of EBV affects the function of p53, Bcl-2, and survivin. We thus investigated the relationship between EBV status, p53, Bcl-2, and survivin in biopsy specimens from patients with primary NPC. EXPERIMENTAL DESIGN: Archival formalin-fixed, paraffin-embedded NPC biopsies were evaluated in 80 patients treated with curative radiation from a single institution. The presence of EBV was determined using EBER in situ hybridization, whereas p53, Bcl-2, and survivin were assessed using immunohistochemistry. RESULTS: The majority of NPC specimens in this patient cohort were EBER-positive (64 of 78, or 82%), which in turn, was significantly associated with ethnicity (P = 0.0007), and WHO subtype 2A/2B (P = 0.04). EBER-positive tumors were also associated with p53 (P = 0.002), Bcl-2 (P = 0.04), and nuclear survivin (P = 0.03) expression. Patients with EBER-positive NPC fared better, with a 10-year overall survival of 68% versus 48% for EBER-negative patients (P = 0.03). For nuclear survivin, patients with either low or high nuclear survivin fared worse than patients with intermediate survivin expression (P = 0.05), suggesting that there is an optimal proportion of survivin-expressing cells for best function and clinical outcome. CONCLUSIONS: With an extended median follow-up time of 11.4 years, EBV status remains a strong predictor for overall survival in NPC. EBV-positive NPC has strong molecular associations with p53, Bcl-2, and survivin expression. Furthermore, we provide clinical data revealing the potentially dual nature of survivin in predicting clinical outcome.

Carcinoma, Squamous Cell↗

Characterization of fibrinogen adsorption onto glass microcapillary surfaces by ELISA.

Adsorption of biomolecules onto microchannel surfaces remains a critical issue in microfluidic devices. This paper investigates the adsorption of fibrinogen on glass microcapillaries using an immunoassay method (ELISA) and X-ray photoelectron spectroscopy (XPS). Various adsorption conditions such as protein concentrations and incubation times, buffer pH, buffer ionic strengths and effects of flow are presented. ELISA is successfully demonstrated as a facile and robust technique to examine these phenomena. The highest adsorption level occurs near the isoelectric point of fibrinogen (pH 5.0) and low buffer ionic strengths (0-8 mM). Microchannel surface saturation was achieved at a fibrinogen solution concentration of approximately 50 microg ml(-1). Fibrinogen adsorption under flow was always higher than that seen in static systems. The importance of diffusion phenomena in microchannels on protein adsorption was demonstrated. ELISA experiments using fused silica and PEEK have also confirmed significant adsorption on these mass spectrometer transfer line materials.

Adsorption↗

Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.

BACKGROUND: Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival. METHODS: Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction. FINDINGS: 15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years (hazard ratio 0.92, 95% CI 0.86-0.97; p=0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years, p=0.02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at 5 years; p<0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (hazard ratio 0.78 [0.65-0.94] for under 50 year olds, 0.95 [0.83-1.09] for 51-60 year olds, 0.92 [0.81-1.06] for 61-70 year olds, and 1.08 [0.89-1.30] for over 70 year olds; test for trends p=0.007). INTERPRETATION: Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.

Aged↗

Bone invasion in extremity soft-tissue sarcoma: impact on disease outcomes.

BACKGROUND: The purpose of the current study was to evaluate histologic bone invasion as a predictor of oncologic outcome in extremity soft-tissue sarcoma (STS) patients presenting to a specialty sarcoma center between 1986 and 2001. METHODS: All patients who underwent surgery for extremity STS were identified from the prospective database at the study institution. Patient demographic features were compared using chi-square analyses or independent-sample Student t-tests. The disease outcomes were compared for those with and without bone invasion using Kaplan-Meier survival analysis and Cox modeling. RESULTS: In a review of 874 patients with STS of the extremity, 48 patients (5.5%) had evidence of bone invasion. Patients with bone invasion presented with larger tumors that were more frequently deep in the extremity and more often had metastases at presentation. Patients with bone invasion had lower metastasis-free survival but bone invasion was not found to be an independent prognostic factor (P = .274) on Cox modeling. Bone invasion was found to be prognostic of overall survival on multivariate analysis (P < .0001). CONCLUSIONS: In a small percentage of patients with STS, bone resection may be required to obtain an adequate surgical margin, thereby limiting the risk of local tumor recurrence. Histologic bone invasion portends a poorer prognosis in terms of overall survival.

Adult↗

Evaluating function and health related quality of life in patients treated for extremity soft tissue sarcoma.

OBJECTIVE: To evaluate how functional disability impacts on health related quality of life (HRQOL) of patients with extremity soft tissue sarcoma (STS) at 1 year post-surgery. DESIGN AND SETTING: Survey of extremity STS patients pre-surgery and one-year post-treatment. PARTICIPANTS: 100 participants who were treated for extremity STS between 2001 and 2003 at four Canadian hospitals. Patients were over 16 years, non-metastatic at diagnosis, and had limb salvage surgery. OUTCOME MEASURES: Musculoskeletal Tumor Society Rating Scale (MSTS), a measure of impairment; Toronto Extremity Salvage Score (TESS), a measure of activity limitations; Reintegration to Normal Living Index (RNL), a measure of participation restrictions; and EQ-VAS, a measure of HRQOL. RESULTS: After adjusting for demographic and clinical variables, impairment explained 54%, activity limitations explained 48%, and participation restrictions explained 61% of the variation in HRQOL. After adjustment, when all three functional measures were included in the model, only participation restrictions had a significant impact on HRQOL explaining 63% of the variation. CONCLUSION: Impairment and activity limitations affect the daily activities a patient can perform, but it is the restriction in participation of life roles and situations that has the greatest effect on patient's HRQOL.

Activities of Daily Living↗

Long-term results of two prospective trials of preoperative external beam radiotherapy for localized intermediate- or high-grade retroperitoneal soft tissue sarcoma.

BACKGROUND: The reported data on surgery plus radiotherapy for retroperitoneal soft tissue sarcomas (RPS) have been mostly from retrospective studies. We evaluated the long-term outcome of patients with operable RPS who were treated with protocol-based preoperative radiotherapy followed by complete surgical resection. METHODS: Data from two prospective trials that included preoperative radiotherapy and surgery for patients with radiographically resectable RPS were combined to define long-term relapse rates and survival. RESULTS: Seventy-two patients with intermediate- or high-grade RPS were treated with preoperative radiotherapy (median dose, 45 Gy; range, 18.0-50.4 Gy). Fifty-four patients (75%) had primary RPS, whereas 18 (25%) had recurrent disease. The median tumor size was 15.5 cm. Sixty-four patients completed the planned preoperative radiotherapy; 57 (89%) underwent laparotomy with curative intent, and 54 (95%) had a macroscopically complete (R0 or R1) resection. With a median follow-up of 40.3 months, 28 patients (52%) who received preoperative radiotherapy and underwent a macroscopically complete resection had recurrences. For the 54 patients who underwent R0 or R1 resection after preoperative radiotherapy, the 5-year local recurrence-free, disease-free, and overall survival rates were 60%, 46%, and 61%, respectively. The median overall survival has not been reached (>60 months). CONCLUSIONS: Patients with intermediate- or high-grade RPS treated with preoperative radiotherapy plus complete resection had a median survival >60 months. This compares favorably to historical data for similar patients treated with surgery alone.

Adult↗

Compromised local control due to treatment interruptions and late treatment breaks in early glottic cancer: Population-based outcomes study supporting need for intensified treatment schedules.

PURPOSE: This population-based study describes the treatment of early glottic cancer in Ontario, Canada and assesses whether treatment variations were associated with treatment effectiveness. METHODS AND MATERIALS: We studied 491 T1N0 and 213 T2N0 patients. Data abstracted from charts included age, sex, stage, treatment details, disease control, and survival. RESULTS: The total dose ranged from 50 to 70 Gy, and the daily dose ranged from 1.9 to 2.8 Gy. In 90%, treatment duration was between 25 and 50 days. Field sizes, field reductions, beam arrangement, and beam energy varied. Late treatment breaks occurred in 13.6% of T1N0 and 27.1% of T2N0 cases. Local control was comparable to other reports for T1N0 (82% at 5 years), but was only 63.2% in T2N0. Variables associated with local failure in T1N0 were age less than 49 years (relative risk [RR], 3.21; 95% confidence interval [CI], 1.49-6.90) and >3 treatment interruption days (RR, 2.43; 95% CI, 1.00-5.91). In T2N0, these were field reduction (RR, 2.33; 95% CI, 1.23-4.42) and late treatment breaks (RR, 2.19; 95% CI, 1.09-4.41). CONCLUSION: Some aspects of treatment for early glottic cancer were associated with worse local control. Problems with protracted treatment are of particular concern, underscoring the need for randomized studies to intensify radiotherapy.

Age Factors↗

Spinal cord planning risk volumes for intensity-modulated radiation therapy of head-and-neck cancer.

PURPOSE: To assess planning organ at risk volume (PRV) margins of the spinal cord in intensity-modulated radiotherapy (IMRT) of oropharyngeal cancers, by modeling the effect of geometric uncertainties to estimate the probability of the spinal cord receiving a particular dose. METHODS AND MATERIALS: Five patients with oropharyngeal cancer were treated by IMRT with simultaneous doses of 66 Gy (gross disease) and 54 Gy (subclinical disease) in 30 fractions. Spinal cord doses were limited to 45 Gy. The probability, due to random and systematic patient positioning uncertainties (3-mm standard deviation), of the cord receiving a particular dose was determined. The effect of an on-line setup correction protocol was also modeled. RESULTS: The mean probability of a maximum spinal cord dose of 45 Gy was 1%, with a 6-mm PRV margin. The mean probability of a maximum dose exceeding 40 Gy was 37% (range, 13-77%); this probability is reduced with a setup correction protocol. CONCLUSION: A spinal cord PRV generated with a 6-mm margin leads to a 99% probability of maintaining the maximum spinal cord dose below 45 Gy. The application of an on-line setup correction protocol reduces the cord dose by approximately 5 Gy.

Dose Fractionation, Radiation↗

Wound healing morbidity in STS patients treated with preoperative radiotherapy in relation to in vitro skin fibroblast radiosensitivity, proliferative capacity and TGF-beta activity.

BACKGROUND AND PURPOSE: In a recent study, we demonstrated that the ability of dermal fibroblasts, obtained from soft tissue sarcoma (STS) patients, to undergo initial division in vitro following radiation exposure correlated with the development of wound healing morbidity in the patients following their treatment with preoperative radiotherapy. Transforming growth factor beta (TGF-beta) is thought to play an important role in fibroblast proliferation and radiosensitivity both of which may impact on wound healing. Thus, in this study we examined the interrelationship between TGF-beta activity, radiosensitivity and proliferation of cultured fibroblasts and the wound healing response of STS patients after preoperative radiotherapy to provide a validation cohort for our previous study and to investigate mechanisms. PATIENTS AND METHODS: Skin fibroblasts were established from skin biopsies of 46 STS patients. The treatment group consisted of 28 patients who received preoperative radiotherapy. Eighteen patients constituted a control group who were either irradiated postoperatively or did not receive radiation treatment. Fibroblast cultures were subjected to the colony forming and cytokinesis-blocked binucleation assays (low dose rate: approximately 0.02 Gy/min) and TGF-beta assays (high dose-rate: approximately 1.06 Gy/min) following gamma-irradiation. Fibroblast radiosensitivity and initial proliferative ability were represented by the surviving fraction at 2.4 Gy (SF(2.4)) and binucleation index (BNI), respectively. Active and total TGF-beta levels in fibroblast cultures were determined using a biological assay. Wound healing complication (WHC), defined as the requirement for further surgery or prolonged deep wound packing, was the clinical endpoint examined. RESULTS: Of the 28 patients treated with preoperative radiotherapy, 8 (29%) had wound healing difficulties. Fibroblasts from patients who developed WHC showed a trend to retain a significantly higher initial proliferative ability after irradiation compared with those from individuals in the treatment group with normal wound healing, consistent with the results of our previous study. No link was observed between fibroblast radiosensitivity and WHC. Neither active nor total TGF-beta levels in cultures were significantly affected by irradiation. Fibroblast proliferation in unirradiated and irradiated cultures, as well as radiosensitivity, was not influenced by TGF-beta content. TGF-beta expression in fibroblast cultures did not reflect wound healing morbidity. CONCLUSIONS: These data are consistent with our previous study and combined the results suggest that in vitro fibroblast proliferation after irradiation may be a useful predictor of wound healing morbidity in STS patients treated with preoperative radiotherapy. TGF-beta levels in culture do not predict WHC, suggesting that the role of TGF-beta in wound healing is likely controlled by other in vivo factors.

Adolescent↗

Combination bcl-2 antisense and radiation therapy for nasopharyngeal cancer.

PURPOSE: A wide variety of tumors depend on the dysregulation of Bcl-2 family proteins for survival. The resulting apoptotic block can often provide a mechanism for resistance to anticancer treatments, such as chemotherapy and radiation. This current study evaluates the efficacy of combining systemically delivered Bcl-2 phosphorothioate antisense (Bcl-2 ASO) and radiation for nasopharyngeal cancer therapy. RESULTS: Antisense uptake was unaffected by 0, 3, or 6 Gy radiation. Radiation decreased the fraction of viable C666-1 cells to 60%, with a further decrease to 40% in combination with Bcl-2 ASO. Despite a modest in vitro effect, Bcl-2 ASO alone caused the regression of established xenograft tumors in mice, extending survival by 15 days in a C666-1 and by 6 days in a C15 model. The survival times for mice treated with both Bcl-2 ASO and radiation increased by 52 days in C666-1 and by 20 days in C15 tumors. This combination resulted in a more-than-additive effect in C666-1 tumors. Less impressive gains observed in C15 tumors might be attributable to higher expression of antiapoptotic Bcl-2 family proteins and limited drug distribution in the tumor. Retreatment of C666-1 tumors with the Bcl-2 ASO-radiation combination, however, was effective, resulting in mice surviving for >80 days relative to untreated controls. CONCLUSIONS: Our results show that the Bcl-2 ASO and radiation combination is a highly potent therapy for nasopharyngeal cancer. Further examination of combination therapy with radiation and other Bcl-2 family-targeted anticancer agents in both preclinical and clinical settings is definitely warranted.

Animals↗

The surgical and functional outcome of limb-salvage surgery with vascular reconstruction for soft tissue sarcoma of the extremity.

BACKGROUND: This study compared the surgical, oncological, and functional outcomes of patients undergoing limb-salvage surgery for extremity soft tissue sarcoma with vascular resection and reconstruction with the outcomes of those undergoing limb-salvage without vascular reconstruction. METHODS: Nineteen patients were identified from a prospective soft-tissue sarcoma database who underwent vascular resection and reconstruction as part of their limb-salvage surgery and who were followed up for at least 1 year or until death. Each of these 19 patients was case-matched to 2 additional patients on the basis of tumor location, size, and depth; patient age; and timing of radiation. To compare functional outcome, a subset of patients was case-matched with additional criteria including wound-complication status, motor nerve sacrifice, similar preoperative function as determined by the Toronto Extremity Salvage Score, and no metastases at diagnosis or the 1-year follow-up. RESULTS: Patients in the vascular reconstruction group were more likely to require a muscle transfer (53% vs. 18%; P = .008), experience a wound complication (68% vs. 32%; P = .03), experience deep venous thrombosis (26% vs. 0; P = .003), experience significant limb edema (87% vs. 20%; P = .001), and ultimately require an amputation (16% vs. 3%; P = .07). Patients who underwent vascular reconstruction had only slightly lower Toronto Extremity Salvage Score scores 1 year after surgery (78.5 vs. 84.2; P = .35). There were no significant differences in local or systemic tumor relapse between the two groups. CONCLUSIONS: Vascular reconstruction is a feasible option in limb-salvage surgery for soft tissue sarcoma but is associated with an increased risk for postoperative complications, including amputation. Although function is not significantly worse after vascular reconstruction, the results are less predictable.

Adult↗

Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group.

PURPOSE: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease. PATIENTS AND METHODS: Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127. RESULTS: From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024). CONCLUSION: Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.

Adult↗

Postradiotherapy quality of life for head-and-neck cancer patients is independent of xerostomia.

PURPOSE: To determine the relationship between quality of life (QOL) and xerostomia over time for patients undergoing radiotherapy (RT) for head-and-neck cancer in a prospective clinical trial. METHODS AND MATERIALS: Patients with head-and-neck cancer were randomized to pilocarpine (n = 65) vs. placebo (n = 65) during RT. QOL was measured using the McMaster Head and Neck Radiotherapy Questionnaire (HNRQ). Xerostomia was measured on a linear analog scale. No statistically significant differences were observed between arms; all 130 patients were analyzed together. RESULTS: Baseline QOL data were obtained for 98.5% of participants. The baseline HNRQ score of 5.7 declined significantly to 4.0 (p <0.0001) by RT Week 6 and returned to baseline (5.8) by 6 months after treatment. This represents a large, clinically important change of 1.7 of 7 (24%; effect size 1.34). The decline in HNRQ score during RT paralleled the onset of xerostomia on the linear analog scale (r = 0.36 at 1 month). After treatment, the QOL scores recovered without improvement in xerostomia. The trajectory of the linear analog scale score resembled that of the HNRQ's single xerostomia question (r = 0.75 at 1 month). CONCLUSION: Quality of life recovers to baseline after RT, despite persistent xerostomia. Either a response shift occurs or xerostomia in the absence of acute mucositis has a relatively small influence on overall QOL.

Carcinoma, Squamous Cell↗

Histologic assessment of peritumoral edema in soft tissue sarcoma.

PURPOSE: To evaluate whether satellite tumor cells can be identified histologically in the tissues surrounding a soft tissue sarcoma and whether their presence correlates with increased T(2)-weighted signal intensity on MRI. METHODS AND MATERIALS: Fifteen patients with a high-grade extremity or truncal soft tissue sarcoma underwent preoperative MRI. The extent of high T(2)-weighted signal changes in the tissues surrounding tumor, thought to represent peritumoral edema/reactive changes, was determined. Twelve patients received i.v. gadolinium, and contrast enhancement was determined. All patients underwent surgical resection in the absence of preoperative chemotherapy or radiotherapy. The presence of tumor cells in the surrounding tissues was determined histologically in representative paraffin-embedded sections and correlated with the MRI findings. RESULTS: The extent of peritumoral T(2)-weighted MRI signal changes ranged from 0 to 7.1 cm (mean, 2.5 cm); contrast enhancement ranged from 0 to 5.3 cm (mean, 1.1 cm). Sarcoma cells were identified histologically in the tissues beyond the tumor in 10 of 15 cases. In 6 cases, tumor cells were located within 1 cm of the tumor margin, and in 4 cases, malignant cells were found at a distance >1 cm and up to a maximum of 4 cm. The location of tumor cells beyond the margin did not correlate with tumor size nor did it correlate with the location or extent of peritumoral changes. CONCLUSION: The ability to identify tumor cells beyond the margin of a soft tissue sarcoma has important implications in planning appropriate targets for treatment. This could influence the use of new radiotherapy technologies such as intensity-modulated radiotherapy that aim to minimize treatment volumes through conformal planning.

Adult↗