Siew Wan Hee

Treatment of Nasopharyngeal Carcinoma using Intensity Modulated Radiotherapy - The National Cancer Centre, Singapore Experience

PURPOSE The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating nasopharyngeal carcinoma (NPC) patients with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS A review was conducted on case records of 195 patients with histologically proven, nonmetastatic NPC treated with IMRT between 2002 and 2005. MRI of the head and neck was fused with CT simulation images. All plans had target volumes at three dose levels, with a prescribed dose of 70 Gy to the gross disease, in 2.0-2.12 Gy/fraction over 33-35 fractions. Cisplatin-based chemotherapy was offered to Stage III/IV patients. RESULTS Median patient age was 52 years, and 69% were male. Median follow-up was 36.5 months. One hundred and twenty-three patients had Stage III/IV disease (63%); 50 (26%) had T4 disease. One hundred and eighty-eight (96%) had complete response; 7 (4%) had partial response. Of the complete responders, 10 (5.3%) had local recurrence, giving a 3-year local recurrence-free survival estimate of 93.1% and a 3-year disease-free survival of 82.1%. Fifty-one patients (26%) had at least one Grade 3 toxicity. CONCLUSIONS Results from our series are comparable to those reported by other centers. Acute toxicity is common. Local failure or persistent disease, especially in patients with bulky T4 disease, are issues that must be addressed in future trials.

Prognostic factors in patients with diffuse large B cell lymphoma: Before and after the introduction of rituximab

This study attempted to evaluate the usefulness of the International Prognostic Index (IPI) as a prognostic model in patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone) chemotherapy. We compared 279 patients with DLBCL. Among them, 183 received CHOP while 96 received R-CHOP. Results showed that there were no statistically significant differences between the two groups of patients in terms of both the patient and the lymphoma characteristics. The estimated 2-year survival was significantly higher among patients treated with R-CHOP compared to CHOP alone (85.6% vs. 64.7%, P = 0.004). Both the IPI and age-adjusted IPI were less useful as prognostic models in patients receiving R-CHOP compared to CHOP. In the multivariate analysis, age ≥ 60, elevated serum LDH, low serum albumin and advanced stages of disease were each independently associated with decreased survival in patients treated with CHOP. In contrast, among those treated with R-CHOP, only male sex and advanced stage of disease were each independently associated with decreased survival. Using these two factors, patients treated with R-CHOP could be separated into three prognostic groups with 5-year estimated survival ranging from 47% to 100% (P < 0.0001). In summary, we can conclude that with the significant improvement in survival following the use of rituximab, the relevance of previously recognized prognostic factors has to be reassessed and re-evaluated.

Comparative analysis of extra-nodal NK/T-cell lymphoma and peripheral T-cell lymphoma: significant differences in clinical characteristics and prognosis

Aim: We aimed to compare the frequencies, clinical characteristics, and prognostic factors of peripheral T‐cell lymphoma (PTCL) vs. extra‐nodal natural killer (NK)/T‐cell lymphoma and to characterize the subtypes of extra‐nodal NK/T‐cell lymphoma. Methods: We reviewed 97 consecutive patients with PTCL and extra‐nodal NKT lymphoma from 2000 to 2006. During this period, a total of 780 patients with malignant lymphomas were treated in our center. The diagnostic criteria used were based on the WHO classification system of malignant lymphomas. Results: Extra‐nodal‐NK/T‐cell lymphoma and PTCL comprised 5.0% (39/780) and 7.4% (58/780) of all cases. Of the PTCL cases, histology was PTCL‐NOS in 25, anaplastic large cell in 11, angioimmunoblastic T cell in 18 and other subtypes in four patients. Compared with PTCL, extra‐nodal NK/T‐cell lymphoma was associated with a significantly inferior rates of complete remission (33% vs. 53%, P = 0.05) and 3 yr overall survival (29.5% vs. 47.5%, P = 0.003). On multivariate analysis, extra‐nodal NK/T‐cell histology was independently associated with decreased survival. Further analysis into this subtype showed the nasal variant (n = 25) differed significantly from extra‐nasal variant (n = 14) in terms of stage at presentation (stages III/IV, 36% vs. 79%), international prognostic index scores (high intermediate or high IPI scores, 24% vs. 64%), complete remission rates (48% vs. 7%), and median survival (10 months vs. 1 month, P < 0.0001). Conclusions: Extra‐nodal NK/T‐cell lymphoma was associated with a poorer prognosis compared with PTCL and is likely to comprise two distinct variants with different clinical behavior and prognosis.

Triplet combination of gemcitabine, paclitaxel, and carboplatin followed by maintenance 5‐fluorouracil and folinic acid in patients with metastatic nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a disease that is highly responsive to various chemotherapeutic agents. In the metastatic setting, 2‐drug combination chemotherapy generally provides a response rate of 55% to 75%, and median survival of 10 to 12 months. The objective of the current study was to assess the efficacy of a 3‐drug combination followed by maintenance treatment in patients with metastatic NPC.

Clinical Benefit of Allogeneic Melanoma Cell Lysate–Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

Purpose: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)–pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. Experimental Design: DCs were cultured from peripheral blood mononuclear cells (PBMC), pulsed with the allogeneic MCL, and matured using cytokines that achieved high CD83- and CCR7-expressing DCs. Each patient received up to 10 intradermal vaccinations (3-5 × 106 cells per dose) at biweekly intervals. Results: Twenty patients received a total of 161 vaccinations. Treatment was well tolerated and quality of life measurements did not vary much across time. One patient experienced partial response [5%; 95% confidence interval (CI), 1-24%] and seven achieved stable disease (35%; 95% CI, 18-57%), one of whom also achieved late tumor regression, yielding a clinical benefit response rate of 40% (95% CI, 22-61%). Although overall median progression-free survival was 2.4 months (95% CI, 1.9-4.1 months), five patients (25%) experienced prolonged progression-free survival (>6 months), two of whom (10%) remain progression-free for >27 and >37 months, respectively. This result is particularly meaningful as all patients had progressive disease before treatment. Overall, DC vaccination was associated with a serial decline in regulatory T cells. Using an antibody array, we characterized plasma protein profiles in responding patients that may correlate with vaccine activity and report a prevaccination protein signature distinguishing responders from nonresponders. Conclusion: This phase II vaccine study using mature, MCL-pulsed DCs has shown promising results and warrants further evaluation in a prospective randomized setting. (Clin Cancer Res 2009;15(24):7726–36)

Retropharyngeal nodal metastasis related to higher rate of distant metastasis in patients with N0 and N1 nasopharyngeal cancer

Retropharyngeal lymph node (RLN) staging in nasopharyngeal carcinoma (NPC) can be controversial.

HPV-associated lung cancers : an international pooled analysis

Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship.

Underestimation of malignancy of atypical ductal hyperplasia diagnosed on 11-gauge stereotactically guided Mammotome breast biopsy: An Asian breast screen experience

The incidence of malignancy in excision biopsies performed for atypical ductal hyperplasia (ADH) diagnosed on needle biopsies has decreased since the advent of larger tissue sampling and improved accuracy using vacuum-assisted Mammotome biopsy. We undertook a retrospective study to identify predictive factors for understaging of ADH diagnosed on 11-gauge Mammotome biopsy, to determine whether it was possible to avoid surgical excision in women where mammographically visible calcifications had been completely removed. Sixty-one biopsy diagnosed ADH lesions were correlated with surgical excision findings that revealed DCIS in 14 (23%). The mammographic and biopsy features were statistically analyzed using Fishers exact test. There was no association between morphology, extent of calcifications, number of cores sampled with underestimation of malignancy (P=0.503, 0.709, 0.551 respectively). In the absence of residual calcifications, the frequency of underestimation of carcinoma still occurred in 17%.

Correlation between epidermal growth factor receptor mutations and expression of female hormone receptors in East-Asian lung adenocarcinomas.

Introduction: Epidermal growth factor receptor (EGFR) mutations are more common in lung adenocarcinoma and in female patients of East-Asian origin. We aimed to assess the expression of female hormone receptors in East-Asian lung adenocarcinomas, their correlation with EGFR mutations, and prognostic significance. Methods: Estrogen receptor (ER)&agr;, ER&bgr;, progesterone receptor (PR), and Her-2 expression were examined using immunohistochemical methods on 109 lung adenocarcinoma cases. EGFR mutations were analyzed by partially denaturing high performance liquid chromatography. Association of hormone receptor with clinical factors was assessed using the Fishers exact test. Associations with survival were assessed using the Cox proportional hazard model. Results: Using scoring criteria routinely used for breast cancer, there were four (4%) ER&agr;, one (1%) ER&bgr;, six (6%) PR, and one (1%) Her-2 positive cases. Considering any staining as positive, 14 (14%) ER&agr;, 10 (9%) ER&bgr;, 12 (12%) PR, and 26 (24%) Her-2 cases were positive. Thirty-nine patients (39%) had EGFR mutations. ER&agr; positivity was significantly associated with ER&bgr; and PR positivity. There were more EGFR mutations seen in tumors with ERß positivity (60%) compared with those with negative expression (37.9%), and there was a trend toward a poorer outcome for patients with tumor that were positive for ERß and Her-2. Conclusions: We found that ER&agr;, ER&bgr;, PR, and Her-2 expression in lung adenocarcinoma are present but limited. This suggests that hormonal influence may not be an important factor to account for the high prevalence of lung cancer among the East-Asian women.

A Standardized Transcutaneous Electric Acupoint Stimulation for Relieving Tobacco Urges in Dependent Smokers

The efficacy of acupuncture in smoking cessation, and its effect on the urge to smoke are unclear. We evaluated the effect of a standardized protocol of transcutaneous electric acupoint stimulations (TEAS) on alleviating the urge to smoke. Ninety-eight smokers were recruited in two double-blind studies. Participants abstained from smoking for 26 h, and were randomized to receive TEAS alternating between 2 and 100 Hz at four acupoints (LI4 and PC8, PC6 and TE5) at four different intensities (10, 5, Intermittent 5 or 0 mA). The urge to smoke was assessed by the Questionnaire of Smoking Urges (QSU-Brief). In Experiment 1, the 10 mA group (n = 20) was compared with the 5 mA group (n = 20); the increase in smoking urges did not differ significantly. Considering the possibility that 5 mA may be an active intervention, in Experiment 2, a true placebo (0 mA), and a proxy of placebo [Intermittent 5 mA (i5 mA)] were compared with 10 mA TEAS. In this experiment, 10 mA (n = 20) TEAS showed a tendency to alleviate smoking urges compared with 0 mA (n = 16), and i5 mA (n = 19) TEAS. Only when the data of smokers with Fagerstöm Test for Nicotine Dependence score ≥5 were analyzed that the difference between the 10 mA group and the control group (0 and i5 mA) became significant. Based on these preliminary findings, we conclude that TEAS applied on the skin may antagonize the increase in urge to smoke in abstinent-dependent smokers. It seems warranted to assess the efficacy of TEAS in smoking cessation clinical trials involving a larger population of dependent smokers.