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The purpose of this study was to evaluate the degree of radiation-induced trismus after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). From 2003 to 2004, 17 non-metastatic NPC patients treated with parotid-sparing IMRT were enrolled. The maximal interincisal distance (MID) was measured to represent the maximum mouth opening. All 17 patients had both pre- and post-IMRT measurements taken, and the normalized MID (post-IMRT MID/pre-IMRT MID) was analysed to evaluate the percentage decrease in MID after IMRT. The median follow-up time was 20.5 months. One patient had nodal failure and was successfully salvaged with radiotherapy. All 17 patients were alive without cancer at the last follow-up. The average MID before IMRT was 46.2 mm (standard deviation (SD), 8.6 mm). The average MID at 12 months post-IMRT was 45.4 mm (SD, 8.9 mm). The averages of normalized MID were 94% (SD, 3.9%) at 5 months post-IMRT and 98.1% (SD, 4.2%) at 12 months post-IMRT. Based on the satisfactory preservation of normalized MID (average of 98.1% at 12 months post-IMRT), we demonstrate that IMRT reduces radiation-induced trismus in NPC patients. The recovery of normalized MID exists in the period from 5-12 months post-IMRT.

BACKGROUND. It was reported previously that the dosimetric superiority of conformal radiotherapy (RT), either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT), over conventional 2D-RT translated into clinical benefits for patients with nasopharyngeal carcinoma (NPC). In this study, the authors compared quality-of-life (QOL) outcomes of NPC survivors who received treatment with 1 of 4 different RT techniques at a single institute during different periods. METHODS. The authors analyzed QOL data of from 237 patients with NPC who were cancer free for 2 or 3 years when their QOL was assessed. The study population included 152 patients who received conventional RT (2D-RT, 61 patients; 2D-RT plus 3D-CRT boost, 91 patients) and 85 patients who received conformal RT (3D-CRT, 33 patients; IMRT, 52 patients). The European Organization for the Research and Treatment of Cancer (EORTC) Core QOL questionnaire and the EORTC Head and Neck QOL questionnaire were completed. RESULTS. Compared with patients who received with conventional RT, patients who received conformal RT had both statistically (P < .05) and clinically (a difference in mean scores ≥10 points) significant improvements in the scales of global QOL, pain, appetite loss, senses, speech, social eating, teeth, opening mouth, xerostomia, sticky saliva, and feeling ill. No significant difference was observed in any of the scales that compared 2D-RT with 2D-RT plus 3D-CRT boost or that compared 3D-CRT with IMRT. Survivors who received conformal RT had a 2.01-fold higher probability (odds ratio [OR], 2.01; 95% confidence interval [95% CI], 1.19–3.68) of reporting good global QOL and a 2.70-fold lower probability (OR, 0.37; 95% CI, 0.20–0.66) of reporting a high level of xerostomia than survivors who received conventional RT. CONCLUSIONS. Conformal RT substantially improved head and neck-related symptoms and broad aspects of QOL for survivors of NPC. Cancer 2007. © 2006 American Cancer Society.

Inactivation of p16(INK4A) promotes G1/S progression of cell cycle. Minichromosome maintenance protein-2 (Mcm2), a novel cell proliferation marker, is known to better correlate with clinical outcomes than Ki-67 in many carcinomas. Since gastrointestinal stromal tumors (GISTs) sometimes remains challenging in prognostication, we analyzed the utility of these three markers in GISTs.Immunohistochemistry was performed in tissue microarrays of 277 primary GISTs and correlated with NIH consensus criteria and clinical outcomes.The increment of NIH risk levels significantly correlated with increasing labeling indices (LI) of both Ki-67 (P.001) and Mcm2 (P.001) and loss of p16(INK4A) expression (P.035). However, the latter aberration did occur in 23% of very low/low-risk GISTs. The relationship between Mcm2 and Ki-67 LIs could be modeled as linear (P.001, r = 0.697), while Mcm2 LI was considerably higher (P.001) with a stepwise escalation related to risk levels. Ki-67 LI5% (P.0001) and Mcm2 LI10% (P.0001) were strongly predictive of inferior disease-specific survival (DSS), while aberrant loss of p16(INK4A) only reached a trend (P = .0954). In multivariate analyses, independent adverse factors of DSS were high-risk category (RR = 16.93, P.0001), metastatic disease (RR = 4.12, P = .0015), Ki-67 LI5% (RR = 3.55, P = .001), and presence of epithelioid histology (RR = 2.17, P = .0308).Prognostic efficacy of NIH consensus criteria is substantiated. P16(INK4A) deregulation can occur early in GIST tumorigenesis and marginally correlates with patient survival. Despite Ki-67 LI being an independent prognosticator, simultaneous detection of Mcm2 is recommended as a prognostic adjunct of GISTs, given its better sensitivity and stepwise escalation with increasing risk levels.

Purpose: We retrospectively analyzed factors of locoregional (LR) recurrence and skin complications in patients after postmastectomy radiotherapy (PMRT). Methods and Materials: From January 1988 to December 1999, a total of 246 women with Stage II and III breast cancer received PMRT. Doses of 46 to 52.2 Gy/23 to 29 fractions were delivered to the chest wall (CW) and peripheral lymphatic drainage with 12 to 15 MeV single-portal electrons or 6MV photons. Of the patients, 84 patients received an additional 6 to 20 Gy boost to the surgical scar using 9 MeV electrons. We used the Cox regression model for multivariate analyses of CW, supraclavicular nodes (SCN), and LR recurrence. Results: N3 stage (positive nodes >9) ( p = 0.003) and diabetes ( p = 0.004) were independent factors of CW recurrence. Analysis of ipsilateral SCN recurrence showed that N3 stage ( p p = 0.006) were independent factors. For LR recurrence, N3 ( p p = 0.033) and electrons ( p = 0.003) were significant factors. Analysis of skin telangiectasia revealed that electrons ( p p = 0.003) were independent factors. Conclusions: Photons are superior to single-portal electrons in patients receiving postmastectomy radiotherapy because of better locoregional control and less skin telangiectasia. In patients in whom the number of positive axillary nodes is >9, more aggressive treatment may be considered for better locoregional control.

Purpose: Two SCFSkp2 ubiquitin ligase–related proteins, Skp2 and cyclin-dependent kinase subunit 1 (Cks1), are involved in posttranscriptional degradation of p27Kip1 tumor suppressor. We analyzed the prognostic utility of p27Kip1 and its interacting cell cycle regulators in myxofibrosarcomas. Experimental Design: Clinicopathologic features and tissue microarray–based immunohistochemical expression of p27Kip1, Skp2, Cks1, cyclin E, cyclin A, Ki-67, and minichromosome maintenance protein 2 (Mcm2) were assessed in 70 primary myxofibrosarcomas and correlated with clinical outcomes. Skp2 mRNA expression and the relationship between Skp2 and p27Kip1 proteins were examined in six cases by semiquantitative reverse transcription-PCR and Western blotting, respectively. Results: High indices of Skp2 (≥10%), cyclin A (≥10%), and Mcm2 (≥50%) were adverse prognosticators at the univariate level. Furthermore, co-overexpression of Skp2 and cyclin A identified highly lethal cases in the entire cohort [P < 0.0001 for disease-specific survival (DSS), P = 0.0004 for overall survival (OS)] and the lower-grade subset (Fédération Nationale des Centres de Lutte Contre le Cancer grade 1 and 2; P = 0.0006 for DSS, P = 0.0093 for OS). In multivariate analyses, Skp2 overexpression overshadowed most intrinsic clinicopathologic factors and independently correlated with worse metastasis-free survival (P = 0.0012), DSS (P = 0.0234), and OS (P = 0.0056). Notably, positive margins independently predicted inferior local recurrence-free survival (P = 0.0012) and also negatively affected metastasis-free survival (P = 0.0471), DSS (P = 0.0152), and OS (P = 0.0173). Reverse transcription-PCR showed up-regulation of Skp2 mRNA in four cases and Western blotting displayed a matched expression pattern of Skp2. Conclusions: Margin status and intrinsic property of myxofibrosarcomas both affect patient survival. Skp2 overexpression is highly representative of the biological aggressiveness of myxofibrosarcomas and plays an important prognostic role.

The purpose of this study was to evaluate the treatment results and failure patterns of lymphoepithelioma-like carcinoma (LELC) of salivary glands. From June 1987 to May 2001, nine patients with LELC of salivary glands were treated at our hospital. One patient was excluded due to the loss of clinical follow-up after surgery. For the remaining eight patients, the primary tumour sites were parotid glands (4 patients), submandibular glands (3), and the minor salivary glands in right cheek (1), respectively. Seven patients underwent surgical treatment and post-operative radiotherapy, while the other one patient was treated with surgery only. The total radiation dose to the salivary tumour bed ranged from 39.6 Gy to 67.6 Gy (mean dose: 58.3 Gy and median dose: 59 Gy). The treatment results and failure patterns were analysed. The survival time ranged from 21.4 months to 145.2 months (mean: 69.1 months, median: 54.5 months). At the end of follow-up, six patients were still alive and two died. One patient died of distant metastases 21.5 months after the surgical treatment of LELC. The other case died of intercurrent disease (pontine haemorrhage) 53 months after surgery. No patient had local or regional failure after the treatments. Distant failure was noted in two patients. The patients with LELC of salivary glands were shown to have favourable prognoses. No local or regional failure was noted. However, distant failure developed in two patients. The risk of distant metastasis should be carefully monitored, especially for those patients with more advanced neck node involvement.

Purpose: Accumulating reports suggest that quality of life (QOL) may predict survival in cancer patients. In this study, we longitudinally investigated whether the QOL data assessed before, during, and after treatment are prognostic for the survival of patients with esophageal squamous cell carcinoma treated with primary radiotherapy (RT). Methods and Materials: A total of 110 consecutive new esophageal squamous cell carcinoma patients treated with primary RT were studied. The European Organization for the Research and Treatment of Cancer questionnaire QLQ-C30 (in the Taiwan Chinese version) plus the scales concerning dysphagia and odynophagia were completed before, during, and 2 months after RT. Cox proportional hazards models were used to analyze the impact of clinical and QOL variables on survival. Results: A clinical model that included clinical and sociodemographic variables to predict survival using multivariate analysis revealed weight loss, American Joint Committee on Cancer stage, and radiation dose to be statistically significant survival predictors. For QOL scores before RT, physical functioning was the most significant survival predictor. The 2-year survival rate was 30% for patients with a physical functioning score of >80.0 compared with a survival rate of 20% for those with a score of

Purpose : To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures. Methods and Materials : Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5–13 mm from the target. Targets with radii of curvature from 1 to 2.75 cm were paired with normal tissues with radii between 0.5 and 2.25 cm. The target was constrained to a prescription dose of 100% and minimum and maximum doses of 95% and 105% with relative penalties of 25. Maximum dose constraint parameters for the NT varied from 10% to 70% with penalties from 10 to 1000. Plans were evaluated using the PTV uniformity index (PTV Dmax/PTV D95) and maximum normal tissue doses (NT Dmax/PTV D95). Results : In nearly all situations, the achievable PTV uniformity index and the maximum NT dose exceeded the corresponding constraints. This was particularly true for small PTV-NT separations (5–8 mm) or strict NT dose constraints (10%–30%), where the achievable doses differed from the requested by 30% or more. The same constraint parameters applied to different PTV-NT separations yielded different dose distributions. For most geometries, a range of constraints could be identified that would lead to acceptable plans. The optimization results were fairly independent of beam energy and radius of curvature, but improved as the number of beams increased, particularly for small PTV-NT separations or strict dose constraints. Conclusion : Optimized dose distributions are strongly affected by both the constraint parameters and target-normal tissue geometry. Standard site-specific constraint templates can serve as a starting point for optimization, but the final constraints must be determined iteratively for individual patients. A strategy whereby NT constraints and penalties are modified until the highest acceptable PTV uniformity index is achieved is discussed. This strategy can be used, in simple patient geometries, to ensure the lowest possible normal tissue dose. Strategies for setting the optimum dose constraints and penalties may vary for different optimization algorithms and objective functions. Increasing the number of beams can significantly improve normal tissue dose and target uniformity in situations where the PTV-NT separation is small or the normal tissue dose limits are severe. Setting unrealistically severe constraints in such situations often results in dose distributions that are inferior to plans achieved with more lenient constraints.

Purpose: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC. Methods and Materials: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5–7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied. Results: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D 05 , the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively ( p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were ( 1 ) vertical length of target >7 cm, ( 2 ) minimal distance between target and brainstem 3 ) maximal AP overlap of target and brainstem >0.6 cm, ( 4 ) maximal AP overlap of target and spinal cord >1 cm, and ( 5 ) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients ( p = 0.005, Fisher's exact test). Conclusion: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.

To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer.From July 1987 through July 1994, 109 women with stage II and III breast cancer receiving modified radical mastectomies were managed by postoperative electron beam irradiation. Doses of 46 to 50.4 Gy were delivered to the chest wall covered with bolus, internal mammary nodes, supraclavicular nodes and axillary lymph nodes via 12 or 15 MeV single portal electron beam. Seventeen patients received additional 10-16 Gy surgical scar boost via 9 MeV electron beam. Comparison of pre-treatment and post-treatment chest X-ray films were used to monitor the development of pulmonary fibrosis.Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis.In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis.

PURPOSE To discuss the technical aspect, dose prescription, clinical results, and biological responsiveness of linear accelerator-based stereotactic radiosurgery for choroidal melanoma. METHODS From March 1995 to December 1995, three choroidal melanoma patients were treated with Linac-based radiosurgery in our department. Two patients underwent one dose of radiosurgery with 18 and 20 Gy in single fraction, respectively. The third patient received two doses of radiosurgery with a total dose of 35 Gy. RESULTS Follow-up time ranged from 19 to 25 months (median: 24 months). One patient had near-total regression, while the other two patients had partial response on the last MR images. Visual acuity was deteriorated in all patients. One patient developed a radiation-induced cataract in the treated eye. CONCLUSION Linac-based radiosurgery is technically feasible for management of choroidal melanoma. Although visual acuity was not improved in these patients, they appreciated the preserving of the eyeball without affecting their general appearance.

Objectives/Hypothesis: The objectives were to measure the degree of trismus induced after radiation therapy for nasopharyngeal cancer and assess its progress over time. Study Design: A prospective, single-armed measurement study with long-term follow-up. Methods: Seventeen patients with nasopharyngeal cancer treated between 1997 and 1999 were studied. Patients were given radiation therapy with bilateral parallel-opposing ports of 45 Gy, 25 fractions, then with a reduced volume to 68.4 to 70.2 Gy. The end point was the degree of trismus, which was measured by serial changes of the maximal interincisal distance (MID) at various specified time points before, during, and after radiation therapy. Results: During the 9 weeks of radiation therapy there was no significant change of MID (normalized MID ranged from 99.8% to 97%). The rate of decrease during this period was 1.3% per month. After radiation therapy there was a rapid decrease of MID between 1 and 9 months (normalized MID values at 1 and 9 mo were 95.5% ± 3.1% and 74.2% ± 5.7%, respectively). The rate of decrease during this period was dramatic (2.4%/mo). One year after radiation therapy, the rate of decrease became slower but was still measurable (0.2%/mo for the period from 12 to 24 mo). For the period from 24 to 48 months. the rate dropped to 0.1% per month. By the end of 48 months, normalized MID was 67.8% ± 7.6%. Conclusion: By means of measurement over a period of time, it was found that patients with nasopharyngeal cancer had a mean decrease in initial interincisal distance of 32% at 4 years after radiotherapy. The trismus process evolved at different rates. It was rapid at 1 to 9 months after radiation therapy, then became slower and protracted over later years.

Despite improvement in surgical techniques, prognosis of gallbladder carcinoma remains poor. It is desirable to identify prognostic biomarkers to aid in the development of targeted therapeutic strategies. Two SCF(Skp2) ubiquitin ligase-related proteins, Skp2 and cyclin-dependent kinase subunit 1 (Cks1), are involved in post-transcriptional degradation of p27(Kip1) tumor suppressor, which inhibits both cdk2/cyclin E and cdk2/cyclin A complexes and thus prevents transition to the S phase. However, the prognostic utility of p27(Kip1)-interacting cell cycle regulators has not been systematically assessed in gallbladder carcinoma. Immunohistochemistry was performed for p27(Kip1), Skp2, Cks1, cyclin E, cyclin A, and Ki-67 in tissue microarrays of 62 gallbladder carcinomas with follow-up. The data were correlated with clinicopathological features and overall survival (OS). The cumulative OS rate for all 62 cases was 42.9% at 3 years. Aberrant labeling indices (LIs) of p27(Kip1) (20%), cyclin E (or=5%), cyclin A (or=5%), Cks1 (or=40%), and Skp2 (or=10%) were identified in 29, 58, 66, 21, and 57% of gallbladder carcinomas, respectively. By log-rank tests, downregulation of p27(Kip1) (P=0.0319) and high LIs of Skp2 (P=0.0006), Cks1 (P=0.0460), cyclin E (P=0.0070), and Ki-67 (P=0.0037) were predictive of inferior OS. Furthermore, the combined expression status of Skp2 and Ki-67 robustly defined three prognostically different groups (P=0.0001). In multivariate comparison, Skp2 overexpression represented the strongest independent adverse prognosticator (P=0.004, risk ratio (RR): 5.538), followed by Ki-67 LIor=50% (P=0.016, RR: 3.254) and American Joint Committee on Cancer stages II-IV (P=0.013, RR: 3.163). In conclusion, aberrations of p27(Kip1)-interacting cell cycle regulators are common in gallbladder carcinomas. Skp2 overexpression is highly representative of biological aggressiveness and independently associated with poor OS, suggesting that it is a promising novel target for therapeutic intervention in aggressive cases. The combined assessment of Skp2 and Ki-67 LIs effectively risk-stratifies gallbladder carcinomas with different prognosis, which is worth being prospectively validated in future study.

By reappraising the National Institutes of Health (NIH) consensus criteria, we worked on establishing a modified scheme to identify highly lethal gastrointestinal stromal tumors (GISTs), which have an imperative demand for sequencing analysis to assess the suitability of an adjuvant imatinib trial.Clinicopathologic features, including NIH and modified schemes, were retrospectively analyzed for 289 patients with localized GISTs. We combined the very low/low-risk GISTs into a single "risk level I" group (or=5 cm,5/50 high power fields [HPFs]) and redesignated the intermediate-risk GISTs as "risk level II" (either5 cm, 6 to 10/50 HPFs or 5 to 10 cm,5/50 HPFs). The GISTs of "risk level IV" group were5 cm and10/50 HPF, with the rest of high-risk GISTs defined as "risk level III."The cumulative 5-year rate of disease-specific survival (DSS) for all 289 patients was 82%, and the DSS rates for patients with GISTs classified as risk levels I to IV were 100%, 96%, 67%, and 25% at 5 years, respectively. The prognostic differences were striking between the risk level II and III groups (P.0001) and between the risk level III and IV groups (P = .0002). The higher risk level of our scheme represented the strongest independent adverse factor (risk ratio [RR] = 11.299 for risk level III; RR = 33.815 for risk level IV; P.0001), followed by mixed/epithelioid histology (RR = 2.837, P = .003) and older age (or=70 years, RR = 1.955, P = .044).Remarkable prognostic heterogeneity exists in the high-risk category of the NIH scheme, which is not as effective as the modified criteria in identifying highly lethal GISTs that we classified as risk level IV.

To evaluate the parotid function after parotid-sparing intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC).From March 2003 to May 2004, 16 patients with nonmetastatic NPC underwent parotid-sparing IMRT. Eight of these patients had Stage III or IV NPC based on the 1997 American Joint Committee on Cancer staging system. The post-IMRT parotid function was evaluated by quantitative salivary scintigraphy and represented by the maximal excretion ratio (MER) of the parotid gland after sialogogue stimulation. The parotid function of 16 NPC patients who were previously treated with conventional radiotherapy was reviewed as the historical control.In the parotid-sparing IMRT group, all 16 patients were alive and without cancer at the end of follow-up period (median, 24.2 months). The mean parotid MER was 53.5% before radiotherapy, 10.7% at 1 month post-IMRT, and 23.3% at 9 months post-IMRT. In the conventional radiotherapy group, the mean parotid MER was 0.6% at 6 to 12 months postradiotherapy. The difference was statistically significant (23.3% vs. 0.6%, p0.001, Mann-Whitney test). In the IMRT group, the mean parotid doses ranged from 33.2 Gy to 58.8 Gy (average, 43.9 Gy). The correlation between the mean parotid dose and the percentage decrease of parotid MER at 9 months post-IMRT (dMER) was statically significant (p=0.008, Pearson correlation).Although the mean parotid doses are relatively high, the significant preservation of parotid function is achieved with IMRT for NPC patients. The significant correlation between mean parotid dose and parotid dMER demonstrates the dose-function relationship of the parotid gland.

Background Myxofibrosarcomas (MFS) are characterized by tumor progression with increased metastases after local recurrences (LR). Few series had appropriately addressed what parameters independently affect prognosis. Methods Seventy primary localized MFS were analyzed for local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS). Follow-up was obtained in 61 cases. Results Thirty-eight males and 32 females had primary tumors ranging from 1.5 to 24 cm. Thirty and 40 tumors were superficial and deep, respectively, with 26 cases (38%) having positive margins. The 5-year LRFS-, MeFS-, and DSS-rates were 30%, 60%, and 73%. Positive margins (P = 0.0003) were the only inferior LRFS predictor. High grade (FNCLCC 2 and 3) was a negative factor of both MeFS (P = 0.0078) and DSS (P = 0.0174), and high stage (AJCC stage 3) was predictive of MeFS (P = 0.0470). However, both grading and staging were not prognostically independent. In multivariate analyses, mitoses ≥20/10 HPF (P = 0.0009, RR = 9.71) and positive margins (P = 0.0203, RR = 4.27) were independent adverse DSS predictor. However, tumor necrosis ≥10% (P = 0.0092, RR = 3.91) independently correlated with worse MeFS, together with mitoses ≥20/10 HPF (P = 0.0176, RR = 3.80) and positive margins (P = 0.0121, RR = 3.41). Conclusions Margin status and histologic property both affect the prognosis of MFS. The former correlates with improved LRFS and translates into final survival benefits. J. Surg. Oncol. 2006;93:294–303. © 2006 Wiley-Liss, Inc.

Background. Lymphoepithelioma-like carcinomas (LEC) of salivary glands represent rare epithelial malignancies, with most cases affecting the parotid gland. To our knowledge, there was only one LEC arising from the minor salivary gland described in the English-language literature. Methods. We report the second LEC of the minor salivary gland in the buccal area of a 50-year-old Taiwanese woman, who underwent surgical resection and adjuvant radiotherapy and remained alive and well after 120 months of follow-up. Histologically, irregular tumor nests of undifferentiated epithelial cells with syncytial cell boundaries were found embedded within rich lymphoplasmacytic stroma. The tumor cells also showed strong c-KIT expression and evidence of Epstein-Barr virus (EBV) infection. Conclusions. Our case suggests potential pathogenic implications of both c-KIT and EBV in LEC of the minor salivary gland that can be cured by the combination of surgery and radiotherapy and has a very favorable long-term prognosis. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005

Low-grade gliomas account for 10-15% of all adult primary intracranial tumours. Currently, there is no consensus on the treatment strategy for low-grade gliomas. This study was designed to evaluate the treatment outcomes, prognostic factors and radiation-related late complications, as well as to assess whether or not post-operative radiotherapy has benefit on local control and overall survival in this population. We retrospectively reviewed 93 consecutive adult patients with supratentorial low-grade gliomas diagnosed at our institution from July 1985 to December 1997. All patients underwent surgical intervention and 60 of them received post-operative radiotherapy. With a median follow-up of 110 months for surviving patients, the 5-year overall and progression-free survival rates were 57% and 47%, respectively. 46 patients experienced local progression of disease during the follow-up period. In multivariate analysis, age at diagnosis, extent of surgery and post-operative Karnofsky performance status showed independent prognostic significance for progression-free and overall survival rates. Post-operative radiotherapy had independent prognostic value for progression-free survival. This analysis has changed our practice and we suggest that aggressive surgical resection and post-operative radiotherapy might be considered for patients with low-grade gliomas. Further efforts should be made to optimize radiotherapy techniques and to integrate new therapeutic modalities.

The current study demonstrates that the large increase in normal tissue penalty often degrades target dose uniformity without a concomitant large improvement in normal tissue dose, especially in anatomically unfavorable patients. The excessively large normal tissue penalties do not improve treatment plans for patients having unfavorable geometry.

Objective: The purpose of this study was to investigate the longitudinal changes in quality of life (QoL) for patients with advanced stage (stage III or IV) head and neck squamous cell carcinoma (HNSCC) following primary radiotherapy (RT) or concomitant chemoradiotherapy. Methods: From January 2001 to January 2003, 149 patients with advanced HNSCC were enrolled. The data pertaining to their QoL were collected using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the EORTC Head and Neck Module (QLQ-H&N35) before and 1 year after RT. Results: Sixty-eight (46%) patients dropped out during the study period. Thirty-nine (57%) of them died of cancer. Those who were older, stage IV, treated by RT alone, or had worse pretreatment EORTC QoL scales were significantly more likely to drop out. For those completing the study, only the problems of swallowing, dry mouth, and sticky saliva were found to become more serious with both statistical (p < 0.05) and clinical (difference >10 points) significance 1 year after RT. Those subjects with cancer at the hypopharynx/larynx had a 3.3-fold higher probability to report an improvement in global QoL (95% confidence interval, CI: 1.11–6.82) than those with cancer at the oral cavity/oropharynx. Those alive without cancer 1 year after RT had a 3.6-fold higher probability to report an improvement in global QoL (95% CI: 1.32–7.13) than those alive with cancer. Conclusion: The study showed a high dropout rate in this longitudinal QoL study for patients with advanced HNSCC. Pretreatment cancer sites and living with cancer or not after treatment significantly affected the change in global QoL 1 year after RT.

To measure the degree of attenuation of radiation dose by the skull base bone in patients with nasopharyngeal carcinoma (NPC) and to study its clinical importance.Isodose distribution in 11 patients with NPC who received bilaterally opposed large-field irradiation (1.8 Gy per fraction) was studied with a three-dimensional treatment planning system with tissue inhomogeneity correction. Also studied were the sites of local tumor recurrence in 37 patients with NPC and skull base destruction (/=0.5 cm) or intracranial invasion treated with radiation therapy from January 1989 to December 1992. Regression analyses were performed.In the dosimetric study, the low-dose areas (1.65 Gy) were located at the level of the skull base in all 11 patients. A significantly positive correlation between the maximum width of the skull base bone and the low-dose volume (1.65 Gy) was demonstrated (P =.003, linear regression). In the clinical study, local tumor recurrence was noted in 18 patients (49%). The sites of local recurrence included skull base in 16 patients (43%) and nasopharynx in six patients (16%). Wider skull base bone was a significant predictor of skull base recurrence after radiation therapy (P =.03, logistic regression).Herein demonstrated is the inadequacy of the radiation dose over the skull base due to attenuation by the skull base bone. The relationship between width of skull base bone and skull base tumor recurrence also is established.

The aim of this study was to evaluate the relationship between external parametrial dose and radiation proctitis after external irradiation and high-dose-rate intracavitary (HDR-IC) brachytherapy among patients with cervical cancer.From May 1993 through December 1996, 191 patients with stage IB-IVA cervical cancer were managed by curative-intent radiotherapy. External irradiation to the whole pelvis (44-45 Gy/ 22-25 fractions) was delivered to all patients initially. One hundred twenty-seven patients received additional bilateral parametrial and sidewall boost (5.4-14.4 Gy/ 3-8 fractions) with 4-cm midline shielding. HDR-IC brachytherapy, 19.2-24 Gy/ 5 fractions to Point A, was given after external irradiation. Patients receiving an external dose of 44-45, 50-54, and54 Gy were categorized as no parametrial boost (NPMB), low parametrial boost (LPMB), and high parametrial boost (HPMB) group, respectively. The actuarial proctitis rate was compared among the three groups.Three-year overall and Grade 2-4 proctitis rates were 30 and 15%, respectively. Overall proctitis rates were 12, 34, and 51% in the NPMB, LPMB, and HPMB groups (P0.0001), respectively. Grade 2-4 proctitis rates were 5, 17, and 27% in the NPMB, LPMB, and HPMB groups (P = 0.0022), respectively. In multivariate analysis of overall and Grade 2-4 radiation proctitis, external parametrial dose was the only independent prognostic factor (P = 0.0002 and 0.0030, respectively).Regardless of central shielding after 44-45 Gy whole pelvis irradiation, more patients with high external parametrial dose developed radiation proctitis. Incomplete midline shielding of the upper rectum may be the cause. Diminishing the external beam doses further may decrease rectal complications.

Purpose: The radiation therapy results for patients with inoperable non–small-cell lung cancer (NSCLC) have been disappointing. Tumor dose escalation using concomitant boost technique (CBT) has been shown to improve local control in a few prospective studies. This trial was carried out to prospectively assess the radiation response and acute toxicity of CBT in comparison to the conventional treatment technique (CTT). Methods and Materials: Ninety-seven consecutive eligible patients were entered in this prospective clinical trial between November 1994 and February 1998. Patients were randomized to receive either CBT (43 patients) or CTT (54 patients) radiation therapy. These patients either refused chemotherapy or were judged as unsuitable for chemotherapy. Patients in the CBT group received 46.8 Gy in 26 fractions using large fields that encompassed the gross and occult disease. A concomitant boost of 18.2 Gy (0.7 Gy per fraction) was delivered to the gross disease using small fields with 1.5-cm margins. The small fields were treated concurrently with the large fields and the total dose to the tumor area was 65 Gy in 26 fractions. Patients in the CTT group received 70.8 Gy in 38 fractions. The acute toxicity between each group was compared. The response rate was analyzed and compared by treatment group, gender, age, stage, histology, initial Karnofsky performance score (KPS), severity of acute toxicity, and maximum body weight loss (MBWL) during treatment course. Results: The demographic parameters such as sex, age, and stage were evenly distributed in each treatment group. The majority of these patients had Stage IIIA and IIIB disease. Overall median treatment times were 39 days for the CBT group of patients and 62 days for the CTT group. No treatment-related mortality was found. There were 2 patients in the CTT group with acute RTOG Grade 3 lung toxicity, and no Grade 3 lung or esophageal toxicity was observed in CBT group. The response rates, assessed by radiographic images, were 69.8% and 48.1% for the CBT and CTT patients, respectively. Univariate and multivariate analysis revealed that patients in the CBT group, patients with better KPS, and patients with more severe acute toxicity had a higher response rate. Conclusion: This study demonstrates that concomitant boost radiation therapy is tolerable, and produces a superior response rate than conventional radiation therapy for patients with inoperable NSCLC. The length of treatment was reduced from 38 to 26 treatment days, almost a 30% reduction.

Purpose: To evaluate the influence of oral glutamine on radiation-induced oral mucositis in the radiotherapy of head and neck cancer. Methods and Materials: From July 1997 through June 1998, 17 patients with head and neck cancer receiving primary or adjuvant irradiation were randomized to either glutamine suspension (16 g in 240 ml normal saline) ( n = 8) or placebo (normal saline) ( n = 9) arm. Patients were instructed to swish the test solutions (30 ml) four times per day. All patients received half-mouth irradiation at least. Patients were treated 1.8 Gy per fraction daily, 5 days a week. We evaluated the grading of oral mucositis daily fraction at each day of treatment until 45 Gy/25 fractions. World Health Organization (WHO) step analgesic medication and body weight change were compared between the two arms. Results: The duration of objective oral mucositis ≥ Grade 1 ( p = 0.0097), Grade 2 ( p = 0.0232), and Grade 3 ( p = 0.0168) was shorter in the glutamine arm. Mean maximum grade of objective oral mucositis was less severe in the glutamine arm (1.6 vs. 2.6) ( p = 0.0058). Glutamine did not reduce the duration and severity of subjective oral mucositis except for duration ≥ Grade 3 ( p = 0.0386). In the analysis of mean maximum WHO step of analgesic medication, there was no statistical difference ( p = 0.5374) between the two arms. Mean body weight change was also not significantly different ( p = 0.8070). Conclusions: Oral glutamine may significantly reduce the duration and severity of objective oral mucositis during radiotherapy. It may shorten the duration of ≥ Grade 3 subjective mucositis.