Search

This study examines psychosocial difficulties faced by Chinese patients with colorectal cancer, and attempts to identify factors that contribute to the meaning searching process that in turn brings about growth and transformation. Twenty-six patients with colorectal cancer were interviewed. Data were analyzed using the constant comparative method. Two domains of psychosocial disorientation states were identified, namely, cognitive disorientation and emotional disorientation. Factors that facilitate meaning searching were identified and categorized into personal factors and external factors. The areas of growth and transformation through meaning searching were presented with narratives. Findings from the present study not only shed light on psychosocial hindrances among colorectal cancer patients but also have the potential to inform the design of intervention strategies to bring about meaning-orientated transformation through cancer experiences. [ABSTRACT FROM AUTHOR]

NK cells and αβ- and γδ-CTL play important roles in cellular immunity against tumors. We previously demonstrated that NPC patients have a quantitative and qualitative deficit in γδ-CTL and EBV-specific αβ-CTL when compared to normal subjects and NPC long-term survivors. In this study we report further observations of a complementary activation of peripheral NK cells in NPC patients. The NK cells in these patients, compared to those of healthy subjects and NPC survivors, were preferentially activated in response to the stimulation of myeloma cell line XG-7 and expanded in the presence of exogenous IL-2. The production of IFN-γ was lowest in the patient group, whereas IL-12, IL-15 and TNF-α were produced in higher levels in patients than in the donors and survivors. The cytolytic effect of the NK cells against NPC cells in the patient group was also higher than that of the donors and survivors. Furthermore, the patients at later stages of NPC had lower γδ-CTL activity but higher NK cytotoxicity towards NPC targets, with higher production of IL-12, IL-15 and TNF-α but lower production of IFN-γ than in patients at earlier stages. This might be part of a triggered compensatory re-activation of the innate immunity, believed to be mediated through various cytokines and chemokines when adaptive T cell immunity is breached. Together, these data suggest complementary roles of innate and adaptive immune response in tumor immunity where NK cells, γδ- and αβ-CTL compensate for the deficits of one another at different stages of tumor invasion. ( Cancer Sci 2006; 97: 912–919) [ABSTRACT FROM AUTHOR]

Summary Incidence of nasopharyngeal carcinoma has remained high in endemic regions. Diagnosing the disease in the early stages requires a high index of clinical acumen and, although most cross-sectional imaging investigations show the tumor with precision, confirmation is dependent on histology. Epstein-Barr virus (EBV)-encoded RNA signal is present in all nasopharyngeal carcinoma cells, and early diagnosis of the disease is possible through the detection of raised antibodies against EBV. The quantity of EBV DNA detected in blood indicates the stage and prognosis of the disease. Radiotherapy with concomitant chemotherapy has increased survival, and improved techniques (such as intensity-modulated radiotherapy), early detection of recurrence, and application of appropriate surgical salvage procedures have contributed to improved therapeutic results. Screening of high-risk individuals in endemic regions together with developments in gene therapy and immunotherapy might further improve outcome. [ABSTRACT FROM AUTHOR]

: PurposeTo determine whether the tumor volume can predict the treatment outcome in early-stage nasopharyngeal carcinoma (NPC) treated by radiotherapy alone.: Methods and materialsThe pretreatment CT scans of 116 patients with American Joint Committee on Cancer Stage I-II NPC treated by radiotherapy alone were retrospectively reviewed. The clinician outlined the tumor extent. The primary tumor volume (PTV) and nodal volume (NV) were then calculated by a summation-of-areas technique. The PTV and NV were correlated with locoregional control, distant failure, and survival. The median follow-up time was 105 months.: ResultsPatients with Stage I disease had a 5-year locoregional control rate of 95% and a disease-specific survival (DSS) rate of 97%; for Stage II disease, the corresponding rates were 81% and 79%. The PTV ranged from 1.3 to 75.5 cm3 (median, 12.6 cm3), with substantial overlap between T1 and T2 disease. The NV ranged from 0 to 35.4 cm3. Patients with a PTV >15 cm3 had significantly worse local control (5-year control rate, 82% vs. 93%; p = 0.033), but no statistically significant difference was noted in survival (5-year DSS rate, 83% vs. 89%; p = 0.30). The difference in local control was mainly seen in those with T2 disease. Patients with NV >4 cm3 had a greater distant failure rate (5-year distant metastasis-free rate, 72% vs. 90%; p = 0.011) and worse survival (5-year DSS rate, 76% vs. 94%; p = 0.0038). Nodal control was excellent with no difference between a NV of ≤4 cm3 and a NV of >4 cm3 (5-year control rate, 97% vs. 100%). The survival rate was worst in patients with a PTV >15 cm3 and a NV >4 cm3 (5-year DSS rate, 68%) and best in those with a PTV of ≤15 cm3 and a NV of ≤4 cm3 (5-year DSS rate, 92%). Multivariate analysis, however, showed that only parapharyngeal extension (T2b) and N1 stage were independent factors that predicted locoregional control and survival, and N1 stage was the only factor that predicted distant failure.: ConclusionThe pretreatment tumor volume has a limited prognostic value in early-stage NPC compared with the usual T and N classification, with Stage T2b and N1 as independent factors that predicted treatment outcome. Within T2 disease, the estimation of tumor volume may identify a subgroup of patients with a greater risk of local failure that warrants more aggressive treatment. [Copyright &y& Elsevier]

The poor prognosis of hepatocellular carcinoma (HCC) has been associated with recurrence and metastasis. Recently, we established a pair of HCC cell lines from a primary (H2-P) and its matched metastatic (H2-M) HCC tumors. A high density of cDNA microarray with 9184 human cDNA was used to identify the differentially expressed genes between H2-P and H2-M. Comparing with H2-P, eight upregulated and six downregulated genes were detected in H2-M. One interesting finding is the overexpression of Vimentin (VIM), a well-defined intermediate filament, which has been linked to a more aggressive status in various tumors. The correlation of overexpression of VIM and HCC metastasis was studied by immunohistochemistry using a tissue microarray with 200 primary HCCs and 60 pairs of primary and matched metastatic HCC samples. Tissue microarray demonstrated that the overexpression of VIM was significantly associated with HCC metastasis (P<0.01). This finding strongly suggests that the overexpression of VIM may play an important role in the metastasis of HCC.Oncogene (2004) 23, 298-302. doi:10.1038/sj.onc.1206483 [ABSTRACT FROM AUTHOR]

Objective: Complications after ventilation tube insertion for middle ear effusion in patients with nasopharyngeal carcinoma are frequent. This may compromise the overall benefit obtained from the procedure. This study evaluates the hearing improvement after tube insertion compared with observation alone to see if the benefits of the procedure outweigh its potential complications. Design: Prospective randomized controlled trial. Setting: Full clinical and emergency otolaryngologic services hospital in an academic institution. Methods: Patients with nasopharyngeal carcinoma and middle ear effusion were randomized for preradiotherapy ventilation tube insertion or observation. Audiologic assessment with a pure-tone audiogram was performed before the procedure, after ventilation tube insertion, and at fixed intervals after irradiation. Audiologic outcome was compared between the two groups. Main Outcome Measure: Air-conduction threshold and air-bone gap on a pure-tone audiogram at different intervals after radiotherapy. Results: There was no significant difference in hearing threshold changes between the two groups for up to 4 years. Both groups had air-bone gap improvement following radiotherapy and the improvement was not significantly different between the two groups. The proportion of patients with closure of the air-bone gap on follow-up was not different between the two groups. Conclusions: Ventilation tube insertion before radiotherapy did not offer additional hearing benefit when compared with observation alone. The procedure had no deleterious effect on hearing for up to 4 years. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the changes in salivary function and oral health-related quality of life for patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy (IMRT)., Methods and Materials: A total of 57 patients with early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva flow was measured, and the Medical Outcomes Study 36-item short form, European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire 35-item head-and-neck module, and Oral Health Impact Profile questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months after IMRT., Results: Parotid saliva flow recovered fully after 1 year and maintained. Whole saliva flow recovered partially to 40% of baseline. A general trend of deterioration in most quality of life scales was observed after IMRT, followed by gradual recovery. Persistent oral-related symptoms were found 2 years after treatment., Conclusion: IMRT for early-stage nasopharyngeal carcinoma could only partially preserve the whole salivary function and oral health-related quality of life., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Adjuvant chemotherapy alongside radiotherapy is one of the effective therapies in nasopharyngeal carcinoma (NPC) treatment. However, the appearance of drug resistance is a major obstacle for anti-cancer chemotherapy and often causes failure of the chemotherapy. In this study, a drug-resistant gene annexin I (ANX-I) was identified by comparing differentially expressed proteins between a cisplatin (CDDP)-resistant NPC cell line CNE2-CDDP and parental CNE2 cells using 2-DE. When ANX-I was transfected into CNE2 cells, the CDDP resistance of CNE2 cells was dramatically increased. The drug-resistant ability of ANX-I was demonstrated by both in vitro and in vivo assays. The association of ANX-I expression with clinical features was also investigated. Increased expression of ANX-I was significantly associated with disease relapse in NPC (p<0.05). In breast and gastric cancer, increased expression of ANX-I was significantly associated with drug resistance (p<0.001) and poor prognosis (p<0.001), respectively. Taken together, our findings suggest that ANX-I plays an important role in drug resistance., (Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Capecitabine monotherapy had activity in recurrent/metastatic nasopharyngeal carcinoma (NPC) as demonstrated previously in a small pilot study. We conducted a retrospective review of patients who received capecitabine for recurrent and metastatic NPC to further evaluate its clinical benefits., Methods: Forty-nine patients with recurrent and metastatic NPC received capecitabine at a dose of 1-1.25 G/m(2) twice daily for 14 days in 3-week cycles. Disease sites were locoregional in 29%, distant in 45% and locoregional plus distant in 26%. All except one had prior platinum-based chemotherapy for relapse or as adjunctive treatment. Median follow-up was 10 months (range: 3-41)., Results: Treatment was generally well tolerated. Hand-foot syndrome was common and occurred in 86% (25% Grade 3). Grade 3 hematological toxicity occurred in 6%. Partial response rate was 31% (95% CI: 18%, 44%) and complete response rate was 6% (95% CI: 0%, 13%), for an overall response rate of 37% (95% CI: 23%, 50%). Median time-to-progression was 5 months and median survival was 14 months. One- and two-year survival rates were 54 and 26%, respectively. Significantly better survival was observed in patients treated for locoregional recurrence and those with severe hand-foot syndrome., Conclusions: Capecitabine has single agent activity in NPC and severe hand-foot syndrome predicts favorable outcome. Based on our experience, capecitabine monotherapy should be considered in patients with recurrent/metastatic NPC.

Purpose: Local recurrence remains one of the major causes of failure in nasopharyngeal carcinoma (NPC). Stereotactic radiosurgery and fractionated stereotactic radiation therapy (FSRT) have recently evolved as a salvage option of NPC. This study was conducted to review the treatment outcome after FSRT for NPC., Methods and Materials: Between September 1999 and December 2005, 90 patients with persistent (Group 1: n = 34, relapse within 6 months of RT) or recurrent (Group 2: n = 56, relapse beyond 6 months) NPC received FSRT using multiple noncoplanar arcs of 8-MV photon to the target. Median FSRT dose was 18 Gy in three fractions (Group 1) or 48 Gy in six fractions (Group 2). Median follow-up was 20.3 months., Results: Complete response rate after FSRT was 66% for Group 1 and 63% for Group 2. One-, 2-, and 3-year disease-specific survival (DSS) and progression-free survival (PFS) rates for all patients were 82.6%, 74.8%, 57.5%, and 72.9%, 60.4%, 54.5%, respectively. Three-year local failure-free survival, DSS, and PFS rates were 89.4%, 80.7%, and 72.3% for Group 1, and 75.1%, 45.9%, and 42.9% for Group 2, respectively. Multivariate analysis showed that recurrent disease and large tumor volume were independent factors that predicted poorer DSS and PFS. Seventeen patients developed late complications, including 2 with fatal hemorrhage., Conclusions: Our results indicate that FSRT is effective for patients with persistent and recurrent NPC. Compared with reported results of radiosurgery, FSRT provides satisfactory tumor control and survival with a lower risk of complications and it may be a better treatment for local failures of NPC.

Background: Limited local failure of nasopharyngeal carcinoma (NPC) can often be salvaged by reirradiation using different techniques. Both gold grain implantation (GGI) and stereotactic radiosurgery (SRS) have been used as salvage treatment of NPC but the relative efficacy of these two treatments is not known., Methods and Materials: A total of 74 patients with local NPC failure were included in this retrospective analysis. Of these patients, 37 underwent SRS (median dose, 12.5 Gy) and 37 split-palatal GGI at a dose of 60 Gy. The two groups were individually matched for prognostic factors, except for tumor volume. The median follow-up was 42 months., Results: Local control was better in the GGI group. The 3-year local failure-free rate was 77.9% for the GGI group compared with 68.3% for the SRS group. However, the difference was not statistically significant (p = 0.098). In the subgroup with a tumor volume of

Recently, we established a hepatocellular carcinoma (HCC) cell line (named H4-M) from a metastatic HCC tumor. In H4-M, a marker chromosome containing a homogeneously staining region (hsr) was identified by cytogenetic analysis. The hsr was characterized by chromosome microdissection and the result showed that the hsr was composed of DNA sequence from 11q13. Oncogenes CCND1 and FGF3 were localized within the complicon and overexpressions of CCND1 and FGF3 were confirmed by Northern blot analysis. Clinical significance of FGF3 overexpression was studied by immunohistochemistry (IHC) using an HCC tissue microarray (TMA) containing 60 pairs of primary/metastatic HCCs and 30 pairs of primary/recurrent HCCs. TMA study showed that overexpression of FGF3 was significantly associated with HCC metastasis and recurrence (p<0.01), suggesting that up-regulation of FGF3 may play an important role in HCC metastasis and recurrence.

This study examines psychosocial difficulties faced by Chinese patients with colorectal cancer, and attempts to identify factors that contribute to the meaning searching process that in turn brings about growth and transformation. Twenty-six patients with colorectal cancer were interviewed. Data were analyzed using the constant comparative method. Two domains of psychosocial disorientation states were identified, namely, cognitive disorientation and emotional disorientation. Factors that facilitate meaning searching were identified and categorized into personal factors and external factors. The areas of growth and transformation through meaning searching were presented with narratives. Findings from the present study not only shed light on psychosocial hindrances among colorectal cancer patients but also have the potential to inform the design of intervention strategies to bring about meaning-orientated transformation through cancer experiences.

Background: Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome., Patients and Methods: A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months., Results: Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%., Conclusion: Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.

Purpose: To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC)., Methods and Materials: Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H&N35) were completed at baseline and 2, 6, and 12 months after radiotherapy., Results: Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy., Conclusions: IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.

Purpose: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC)., Methods and Materials: All patients were irradiated with the same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil)., Results: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p > or = 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05)., Conclusions: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.

NK cells and alphabeta- and gammadelta-CTL play important roles in cellular immunity against tumors. We previously demonstrated that NPC patients have a quantitative and qualitative deficit in gammadelta-CTL and EBV-specific alphabeta-CTL when compared to normal subjects and NPC long-term survivors. In this study we report further observations of a complementary activation of peripheral NK cells in NPC patients. The NK cells in these patients, compared to those of healthy subjects and NPC survivors, were preferentially activated in response to the stimulation of myeloma cell line XG-7 and expanded in the presence of exogenous IL-2. The production of IFN-gamma was lowest in the patient group, whereas IL-12, IL-15 and TNF-alpha were produced in higher levels in patients than in the donors and survivors. The cytolytic effect of the NK cells against NPC cells in the patient group was also higher than that of the donors and survivors. Furthermore, the patients at later stages of NPC had lower gammadelta-CTL activity but higher NK cytotoxicity towards NPC targets, with higher production of IL-12, IL-15 and TNF-alpha but lower production of IFN-gamma than in patients at earlier stages. This might be part of a triggered compensatory re-activation of the innate immunity, believed to be mediated through various cytokines and chemokines when adaptive T cell immunity is breached. Together, these data suggest complementary roles of innate and adaptive immune response in tumor immunity where NK cells, gammadelta- and alphabeta-CTL compensate for the deficits of one another at different stages of tumor invasion.

Purpose: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage., Methods and Materials: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months., Results: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053)., Conclusions: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.

Background and Purpose: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique., Patients and Methods: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n = 2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (< or =40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed., Results: On multivariate analysis, T-stage (P < 0.01; hazard ratio [HR], 1.58) and optimal boost (P = 0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P = 0.01; HR, 0.33); use of a boost (P < 0.01; HR, 0.60) and age (P = 0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications., Conclusions: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity.

Purpose: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC)., Methods and Materials: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil)., Results: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%., Conclusions: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

Background: Lung cancer is a prevalent cancer with a poor prognosis. To develop a useful in vitro cell model, a cell line of lung squamous cell carcinoma (SCC-35) was established., Methods: The SCC-35 cell was characterized by comparative genomic hybridization (CGH) and spectral karyotyping (SKY). Chromosome microdissection, fluorescence in situ hybridization (FISH), and Southern and Northern blots analyses were used to study target genes., Results: Two amplicons were found at chromosomes 7p12 and 11q13. Amplification and overexpression of epidermal growth factor receptor (EGFR) at 7p12 and fibroblast growth factor 3 (FGF3) at 11q13 were found. To understand the correlation between these two genes in nonsmall cell lung carcinoma (NSCLC) more comprehensively, overexpression of FGF3 and EGFR was investigated by immunohistochemistry with a tissue microarray containing 406 NSCLC samples. Cytoplasmic overexpression of FGF3 and EGFR was detected in 61% and 69% NSCLC cases, respectively. More interestingly, a significant correlation between overexpression of FGF3 and EGFR was found in NSCLC., Conclusion: These results suggest that co-overexpression of FGF3 and EGFR may play an important role in the pathogenesis of lung carcinoma., (Copyright 2005 American Cancer Society.)

Background and Purpose: To evaluate the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT)., Materials and Methods: Between October 2001 and May 2004, 31 patients with locally recurrent NPC received re-irradiation using IMRT. The rT classification distribution was 3 for rT1, 5 for rT2, 9 for rT3, and 14 for r T4. Median time from first course of radiotherapy to re-irradiation was 51 months. IMRT was performed using step-and-shoot method with nine 4-6 MV photon fields and median prescribed dose was 54 Gy (range: 50-60 Gy). Additional treatments included cisplatin-based induction chemotherapy in 68% and radiosurgery boost with a single dose which ranged from 8.5 to 12.5 Gy in 32%. Median follow-up time was 11 months., Results: After re irradiation, 58% of patients had complete regression of primary tumor. One-year loco-regional progression-free, distant metastasis-free and overall survival rates were 56, 90, and 63%, respectively. Significantly better 1-year local progression-free rate was observed in rT1-3 than r T4 tumor (100 vs. 35%). Grade 3 late toxicities, mostly ototoxicity/cranial neuropathy, occurred in six patients (19%). One-year actuarial rates of late toxicities were 70% for all grades and 25% for Grade 3., Conclusion: Our preliminary results showed that good control of rT1-3 NPC can be achieved using IMRT with a dose between 50 and 60 Gy, whereas the outcome for r T4 tumor remained poor. Late toxicities were common but incidence of severe toxicities was relatively low.

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.

Amplification of SEI-1, a cell cycle regulatory gene at 19q13.1, is commonly detected in ovarian cancer, suggesting a role in the pathogenesis of ovarian cancer. In the present study, the oncogenic potential of SEI-1 was shown by anchorage-independent growth and tumor formation in nude mice with SEI-1-transfected NIH 3T3 mouse fibroblast cells. Silencing of SEI-1 gene expression by small interfering RNAs in ovarian cancer cell line SKOV3 could inhibit cell growth as well as colony formation on soft agar. Chromosomal alterations including the formation of double minutes were observed in tumor cells derived from SEI-1-transformed NIH 3T3 cells. Micronulei formation, which is an indicator of nuclear abnormality and genomic instability, was markedly increased in SEI-1-transfected cells. These data suggest that the oncogenic role of SEI-1 might be mediated at least in part via an effect on genomic instability. Furthermore, overexpression of SEI-1 was associated with higher tumor grades and late Fesddration Internationale des Gynaecologistes et Obstetristes (FIGO) stages in ovarian carcinomas. These data strongly suggest that SEI-1 plays an important role in the development and progression of ovarian cancer.

AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on 20q12 and is a candidate oncogene in human breast cancer. It is commonly amplified and overexpressed in several types of human cancers. In this study, we examined the expression of AIB1, as related to clinicopathologic features, in 85 human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53 expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In addition, the overexpression of AIB1 was observed more frequently in CRCs in later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage (P < .05). These results suggest that overexpression of AIB1 might provide a selective advantage for the developmental growth and/or progression of subsets of CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1 with p53 overexpression as well as with aneuploid DNA content was observed in these CRCs. The overexpression of p53 was also correlated significantly with CRC DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA content; most of these were in the later clinical stage. These findings suggest a possible convergence of AIB1 with a pathway involving p53, which might induce chromosomal instability and affect the clinical phenotype of a subset of CRCs.