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Angiosarcoma (AS) is a rare disease with a dismal prognosis. The treatment landscape and prognostic factors for advanced AS, including locally advanced, unresectable, and metastatic disease remain elusive. The Asian Sarcoma Consortium is an international collaborative effort to understand the sarcoma treatment landscape in Asia. We undertook a retrospective chart review of AS patients seen in 8 sarcoma academic centers across Asia. Patients with complete clinical, treatment, and follow‐up data were enrolled. Overall, 276 advanced AS patients were included into this study; 84 (30%) of the patients had metachronous metastatic AS. The median age was 67 y; primary sites of AS was cutaneous in 55% and visceral in 45% of patients. In total, 143 (52%) patients received at least 1 line of systemic chemotherapy. The most common first‐line chemotherapy regimen used was paclitaxel (47.6%) followed by liposomal doxorubicin (19.6%). The median overall survival (OS) was 7.8 mo. Significant prognostic factors for OS included age > 65 (hazard ratio (HR) 1.54, P = .006), male gender (HR 1.39, P = .02), and a cutaneous primary AS site (HR 0.63, P = .004). The median progression‐free survival (PFS) for first‐line chemotherapy was 3.4 mo. PFS for single vs combination or paclitaxel vs liposomal doxorubicin chemotherapy regimens were comparable. This study provides an insight into the treatment patterns and prognostic factors of advanced AS patients in Asia. Prognosis of advanced AS remains poor. Data from this study serve as a benchmark for future clinical study design., With a total of 276 advanced angiosarcoma patients, we provided the complete clinicopathological demographics, treatment patterns, and prognostic outcomes of advanced angiosarcoma in Asia.

Introduction: Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Epstein-Barr virus (EBV) represents a unique etiological culprit in the poorly differentiated nonkeratinizing and undifferentiated subtypes. EBV antigens are expressed on tumor cells albeit in a restricted manner. Treatment options for recurrent or metastatic disease are limited. Nevertheless, emerging data from immunotherapy studies in NPC have shed light into their potential antitumor efficacy. Areas covered: This article reviews existing clinical evidence for different immunotherapeutic approaches for NPC, including adoptive cellular therapy, therapeutic cancer vaccines, and immune checkpoint inhibitors. Expert opinion: There is a growing understanding on EBV virology and the immune evasion mechanisms in NPC. Immunotherapeutic strategies leveraging these properties have shown encouraging efficacy and safety results in early-phase clinical studies. Moving forward, areas to be addressed include appropriate patient selection, optimal incorporation into standard treatment paradigms, biomarker identification, as well as the development of scalable and reproducible immune product generation processes.

Purpose This is an updated combined analysis of 2 randomized studies (NPC-9901 and NPC-9902 trials) to evaluate the 10-year outcome attributed to the addition of concurrent-adjuvant chemotherapy for advanced locoregional nasopharyngeal carcinoma (NPC). Patients and Methods Eligible patients with stage III-IVB nonkeratinizing NPC were randomly assigned to radiation therapy alone (RT: 218 patients) or chemoradiation therapy (CRT: 223 patients) using 3 cycles of cisplatin (100 mg/m2) concurrent with RT, followed by 3 cycles of cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/day for 4 days). All of the patients were irradiated with conventional fractionation to ≥66 Gy. The median follow-up was 13.9 years. Results Intention-to-treat analysis confirmed that the CRT group achieved significant improvement in 10-year failure-free rate (FFR: 62% vs 52%, P = .016), progression-free survival rate (PFS: 56% vs 44%, P = .008), and overall survival rate (OS: 60% vs 50%, P = .044). There was no significant increase in overall late toxicity rate (51% vs 48%, P = .34) or noncancer deaths (19% vs 16%, P = .52). Exploratory studies showed no difference in disease control between 2 or 3 cycles of concurrent cisplatin; however, patients given 3 concurrent cycles had a significant increase in hearing impairment (40% vs 24%, P = .017). Only those who continued to receive 2 or more cycles of adjuvant cisplatin-fluorouracil achieved significant improvement in distant control (73% vs 65%, P = .037) and maximal survival gain. Conclusion The addition of concurrent cisplatin plus adjuvant cisplatin-fluorouracil could significantly improve overall survival and disease control without incurring a significant increase in late toxicity or noncancer deaths. Exploratory analyses suggested that both the concurrent and the adjuvant phases contributed to tumor control. Furthermore, the number of concurrent cycles could be reduced from 3 to 2 cycles in order to achieve a similar survival benefit without incurring an excessive increase in hearing impairment. This is a useful hypothesis that warrants further validation.

Aim Second primary tumor (SPT) is a serious late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). We evaluated the incidence, pattern, risk factors and survival impact of SPT in NPC patients following definitive intensity-modulated radiotherapy (IMRT). Methods A retrospective review of 780 consecutive IMRT-treated NPC patients between February 2003 and September 2011 was conducted. Cumulative SPT incidence and overall survival after SPT diagnosis were estimated. Associations between clinical characteristics and SPT risk were analyzed. Standardized incidence ratios (SIR) were calculated using age, gender and calendar-year-specific cancer incidences from the Hong Kong Cancer Registry. Results At a median follow-up of 7.5 years, 51 SPTs (6.7%) were identified, 22 (43.1%) of which occurred within previous radiotherapy fields. Tongue cancers (31.8%) and sarcomas of the head and neck (31.8%) were the most common in-field SPTs. Age [hazard ratio (HR), 1.051; 95% confidence interval (CI), 1.025-1.078] and smoking status (HR, 1.755; 95% CI, 1.002-3.075) were independent risk factors associated with SPT development. Median overall survival after SPT diagnosis was 2.9 years. There was an 84% increase in cancer risk (SIR, 1.84; 95% CI, 1.37-2.42) compared with the general population. Significant excess risks were observed for sarcoma, tongue, oropharyngeal, prostate and liver cancer. Excess risks were higher beyond 5 years of follow-up. Conclusion Substantial risk of SPT, especially for in-field sarcoma and tongue cancers, exists after definitive IMRT for NPC. SPT severely negates longevity of NPC survivors. High awareness and careful surveillance is warranted for this late lethal complication.

Purpose To evaluate treatment outcomes, failure patterns and late toxicities in patients with nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) in 6 public hospitals in Hong Kong over a 10-year period from 2001 to 2010. Material and methods Eligible patients were identified through the Hong Kong Cancer Registry data base. Clinical information was retrieved and verified by oncologists working in the individual centers. Treatment details, survival outcomes and late toxicities were analyzed. Results A total of 3328 patients were recruited. The median follow-up time was 80.2 months. The 8-year actuarial overall survival (OS), local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure free survival (DFFS), progression-free survival (PFS) for the whole group was 68.5%, 85.8%, 91.5%, 81.5% and 62.6% respectively. Male gender, older age, advanced T and N stage were adverse prognostic factors for OS, DFFS and PFS, whereas use of chemotherapy in form of concurrent chemo-irradiation (CRT), neoadjuvant + CRT, or CRT + adjuvant chemotherapy were favorable prognostic factors for OS and PFS. The local control was adversely affected by advanced T stage. N stage remained as the single adverse prognostic factor for regional control. Distant metastasis was the commonest site of failure. Conclusion IMRT is an effective treatment for NPC with excellent overall loco-regional control. Distant metastasis is the major site of failure. Concurrent chemotherapy with cisplatin has an established role in NPC patients treated by IMRT.

BACKGROUND Concurrent-adjuvant chemoradiotherapy (CRT) became a recommended treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) with the first report of a significant survival benefit from the Intergroup 0099 study. However, data on late toxicities are lacking. Previous reports from the current NPC-9901 trial have raised concerns about a failure to improve overall survival (OS) because of an inadequate impact on distant control and increases in toxicities/noncancer deaths. Validation of the long-term therapeutic ratio is needed. METHODS In this phase 3, randomized trial, patients with nonkeratinizing NPC (stage T1-4/N2-3/M0) were randomly assigned to radiotherapy alone (176 patients) or to CRT (172 patients) with concurrent cisplatin followed by adjuvant cisplatin plus fluorouracil. RESULTS The early findings of significant improvements in tumor control were maintained: the CRT group achieved significantly higher 10-year overall failure-free (62% vs 50%; P = .01) and progression-free survival rates (56% vs 42%; P = .006) because of superior locoregional control (87% vs 74%; P = .003), whereas the impact on distant control remained insignificant (68% vs 65%; P = .24). The initial differences in toxicities diminished with longer follow-up: 52% versus 47% at 10 years for late toxicities (P = .20), 4.1% versus 2.8% for deaths due to treatment toxicity, and 15.1% versus 13.1% for deaths due to incidental/unknown causes. The OS rate for the CRT group reached statistical superiority at 10 years (62% vs 49%; P = .047). CONCLUSIONS Long-term results have confirmed that CRT can significantly improve OS without excessive late toxicities for patients with regionally advanced NPC. However, more potent therapy is needed for improving distant control, especially for patients with stage IVA/B disease. Cancer 2017;123:4147–4157. © 2017 American Cancer Society.

6523 Background: Based on an individual patient data (IPD) network meta-analysis (NMA) of 20 randomized trials and 5,144 patients (pts), the MAC-NPC collaborative group has shown that the addition of adjuvant chemotherapy (AC) to chemo-radiotherapy (CRT) achieved the highest survival benefit in nasopharyngeal carcinoma (NPC; Ribassin-Majed JCO 2017). Here, we updated the meta-analysis with the addition of 8 trials. Methods: Trials of Radiotherapy (RT) with or without chemotherapy (CT) in patients with non-metastatic NPC were identified and updated IPD obtained. Both Western and Chinese medical literatures were searched. Overall Survival (OS) was the main endpoint. Fixed and random-effects frequentist NMA models were applied, network heterogeneity and consistency were evaluated. P-score was used to rank the treatments. R software - netmeta package was used to perform the analyses. Treatments were grouped in the following categories: RT alone (RT), induction chemotherapy followed by RT (IC-RT), induction chemotherapy without taxanes followed by concomitant chemoradiotherapy (ICtax(-)-CRT), induction chemotherapy with taxanes followed by concomitant chemoradiotherapy (ICtax(+)-CRT), concomitant chemoradiotherapy (CRT), concomitant chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and RT followed by adjuvant chemotherapy (RT-AC). Results: Overall 28 trials and 8,214 pts were included. Median follow-up was 7.2 years. There was no heterogeneity in the NMA. There was inconsistency in the main analysis, which disappeared after the exclusion of 2 outlier trials. ICtax(+)-CRT ranked the best treatment for OS with a P-Score of 91%. Hazard ratio [HR, 95% Confidence Interval] for ICtax(+)-CRT was 0.75 [0.59-0.96] compared to CRT and 0.92 [0.69-1.24] compared to CRT-AC (second best treatment in raking with a P-Score of 85%; see league table below). When the 2 types of IC were merged, CRT-AC ranked the first followed by IC-CRT with P-Scores of 93% and 86% respectively, with a HR of 0.97 [0.84-1.14] for CRT-AC vs. IC-CRT. Conclusions: This IPD NMA of the treatment of locally advanced NPC demonstrates that the addition of IC or AC to CRT improves disease control probability and survival over CRT alone. Data on progression-free survival, locoregional and distant control will be presented at the meeting. [Table: see text]

Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.

Elevated levels of circulating cell-free Epstein-Barr virus (EBV) DNA have been detected in plasma and serum samples from nasopharyngeal cancer (NPC) patients by quantitative real time PCR (qPCR) test. This qPCR test for circulating EBV DNA was found to be useful in the clinical management of NPC patients. For instance, EBV DNA qPCR test has good sensitivity and specificity in the detection of NPC at disease onset. Increase of the viral DNA load was found in NPC patients at late stages of disease. High EBV DNA load at disease onset or detectable viral load post-treatment was associated with poor survival or frequent relapse in NPC patients. Residual EBV DNA load after primary treatment could be a useful indicator to justify adjuvant chemotherapy. The qPCR test might also be applied to define a poor prognostic group in patients at early stage (I/II) for implementing concurrent chemo-radiotherapy (chemo-RT) to improve patients' outcome. The test is also useful to monitor distant metastases or response to radiotherapy, chemo-RT or surgery. Supplementary tests, however, are needed to pick up EBV negative WHO type I NPC and test improvement is needed to increase sensitivity in detecting stage I disease and local recurrence.

Radiation-induced hypoglossal nerve palsy is a debilitating and irreversible late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC) and other skull base tumors. This study sets to evaluate its incidence and clinical predictive factors, and to propose relevant dosimetric constraints for this structure to guide radiotherapy planning.We undertook a retrospective review of 797 NPC patients who underwent definitive intensity-modulated radiotherapy (IMRT) between 2003 and 2011. Cumulative incidence and clinical predictors for radiation-induced hypoglossal nerve palsy were evaluated. Archived radiotherapy plans were retrieved and 330 independent hypoglossal nerves were retrospectively contoured following standardized atlas. Optimal threshold analyses of dosimetric parameters (Dmax, D0.5cc, D1cc, D2cc, Dmean) were conducted using receiver operating characteristic curves. Normal tissue complication probability was generated with logistic regression modeling.With a median follow-up of 8.1 years, sixty-nine (8.7%) patients developed radiation-induced hypoglossal nerve palsy. High radiotherapy dose, premorbid diabetes, advanced T-stage and radiological hypoglossal canal involvement were independent clinical risk factors. Maximum dose received by 1 cc volume (D1cc) was the best predictor for the development of radiation-induced nerve palsy (AUC = 0.826) at 8 years after IMRT. Hypoglossal nerves with D1cc of 74 Gy EQD2 had an estimated palsy risk of 4.7%. Nerves with D1cc74 Gy EQD2 had significantly lower risk of palsy than those ≥74 Gy EQD2 (2.4% vs 20.8%, p0.001).Incidence of radiation-induced hypoglossal nerve palsy was high after definitive IMRT for NPC. D1cc74 Gy EQD2 can serve as a useful dose constraint to adopt during radiotherapy planning to limit palsy risk to5% at 8 years after IMRT.

Background: There is currently no standard treatment for patients (pts) with platinum refractory, recurrent metastatic (R/M) NPC. Spartalizumab, a humanized anti-PD-1 IgG4 mAb, blocks interaction with PD-L1 and PD-L2. This is the first randomized phase II study to evaluate efficacy and safety of spartalizumab vs CT in NPC. Methods: This phase II open-label study recruited pts with non-keratinizing locally advanced R/M NPC who progressed on/after platinum-based CT and received up to 2 systemic therapies. Pts were randomized (2:1) to receive spartalizumab or CT, per investigator’s choice. Spartalizumab was dosed 400 mg every 4 weeks intravenously. Pts in CT arm could cross over to receive spartalizumab if progression confirmed by RECIST v1.1, based on independent central review. Primary endpoint was progression free survival (PFS); secondary endpoints were overall response rate (ORR), based on central review by RECIST v1.1, duration of response (DOR), overall survival, safety and pharmacokinetics. Correlation between efficacy and expression of immunologic biomarkers and immune-related genes was also studied. Results: In total, 76 pts in spartalizumab arm and 37 pts in CT arm were randomized (median age 51 years, ECOG performance status 0-2). As of Jan 31, 2018, 18/76 (23.7%) spartalizumab-treated pts, 8/37 (21.6%) CT-treated pts and 4/20 (20.0%) pts in crossover group were ongoing. Discontinuation rates were similar between arms, mainly due to progressive disease in spartalizumab arm (67.0%) and CT arm (68.0%). Median PFS (95% CI) was 1.9 mo (1.8;3.5) in spartalizumab arm vs 6.6 mo (3.7;9.2) in CT arm; primary endpoint was not met, with hazard ratio of 1.53 (95% CI 1.02;2.27). ORR (95% CI) was 18.4% (10.5;29.0) vs 32.4% (18.0;49.8) in spartalizumab vs CT arm, respectively, and 5.0% (0.1;24.9) in crossover group. ORR for pts treated with monotherapy CT was 19.2% (5/26) and for pts treated with CT doublet/triplet was 63.3% (7/11). The Kaplan-Meier estimate of DOR rate at 12 mo in responding spartalizumab-treated pts was 61.0% (95% CI 20.2;85.8). In CT arm, 11/12 pts either progressed or discontinued at 12 mo; at data cut-off, 1 pt remained responding for 3.61 mo. Safety profile of spartalizumab was largely consistent with results obtained from other spartalizumab single-agent studies. Overall, treatment-related grade 3/4 adverse events were reported in 18.4% of spartalizumab-treated pts and 40.5% of CT-treated pts. No treatment-related deaths occurred. RNA sequencing analyses of tumors revealed a correlation between response to spartalizumab and IFN-γ signature, TIM3 and LAG3 gene expression; this correlation was not observed in pts treated with CT. Conclusions: Spartalizumab was well tolerated and despite the study not reaching its primary endpoint, long-lasting tumor responses were observed in a subset of spartalizumab-treated pts with NPC. Biomarker analysis is ongoing. Citation Format: Darren Wan-Teck Lim, Hung-Ming Wang, Shau-Hsuan Li, Roger Ngan, Arunee Dechaphunkul, Li Zhang, Chia Jui Yen, Po Chung Chan, Somvilai Chakrabandhu, Brigette Ma, Suebpong Tanasanvimon, Victor Lee, Pei-Jen Lou, Zujun Li, Alexander Spira, Ammar Sukari, Joël Guigay, Steven McCune, Yongjian Sun, Sebastian Szpakowski, Yao Yao, Xueqiang Fan, Luigi Manenti, Caroline Even. Phase II study of spartalizumab (PDR001) vs chemotherapy (CT) in patients with recurrent/metastatic nasopharyngeal cancer (NPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT150.

Soft-tissue sarcomas require tailored and multidisciplinary treatment and management. However, little is known about how sarcomas are treated and managed throughout the Asia-Pacific region.MEDLINE was systematically searched using prespecified criteria. Publications (previous 10 years) that reported tumour characteristics, treatment patterns, survival outcomes, and/or safety outcomes of patients with soft-tissue sarcoma were selected. Exclusion criteria were studies of patients18 years of age; ≤ 10 patients; countries other than Australia, Hong Kong, Indonesia, Korea, Malaysia, New Zealand, Philippines, Singapore, Taiwan, or Thailand;20% benign tumours; sarcomas located in bones or joints; gastrointestinal stromal tumour; Kaposi's sarcoma; or not reporting relevant outcomes.Of the 1,822 publications retrieved, 35 (32 studies) were included. Nearly all patients (98%, 1,992/2,024; 31 studies) were treated with surgery, and more studies used adjuvant radiotherapy than chemotherapy (24 vs 17 studies). Survival outcomes and recurrence rates varied among the studies because of the different histotypes, sites, and disease stages assessed. Only 5 studies reported safety findings.These findings highlight the lack of specific data available about soft-tissue sarcomas in the Asia-Pacific region. Better efforts to understand how the sarcoma is managed and treated will help improve patient outcomes in the region.

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Background The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional–fractionation radiotherapy plus concurrent–adjuvant chemotherapy as recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RTi group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg/m2/day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival (p ⩽ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant (p ⩾ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0–1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively. Interpretation Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.

Hormone therapy, rather than chemotherapy, is recommended for hormone-receptor positive (HR+), human epidermal receptor 2 negative (HER2-) advanced or metastatic breast cancer (A/MBC) according to the European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines, unless in visceral crisis in which chemotherapy is indicated. Hormonal monotherapy of selective estrogen receptor modulator (SERM) or selective estrogen receptor down-regulator (SERD), aromatase inhibitor (AI), or their combination as doublets, used to be the mainstay options as first-line (1L) therapy for most patients. More recently, combination targeted drugs plus AI or SERD (such as fulvestrant) has been extensively investigated in both 1L and second-line (2L) treatments of HR+ HER2- patients. Cyclin-D kinase 4/6 inhibitors (CDK4/6i) can halt tumor proliferation by blocking the ER related transcription signaling that drives the CDK4/6-dependent cell cycle in HR+ tumors, and they work best together with AI or SERD. On the other hand, favorable results were reported from inhibition of m-TOR pathway, both in 2L setting when PI3K-AKT-mTOR pathway is frequently overexpressed, as well as in 1L setting. Currently, the major guidelines have all included CDK4/6i plus AI as a standard 1L therapy, while Everolimus plus AI, and CDK4/6i plus fulvestrant, are recommended 2L options. Selecting appropriate patients for such therapeutic options and harnessing the sequence of these new therapies in the new paradigm of managing HR+ HER2- A/MBC are the key priorities for future clinical research.

Background: We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients. Methods: We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters. Results: We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interα-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4. Conclusions: Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.

Nineteen consecutive patients with metastatic or recurrent nasopharyngeal cancer (NPC) receiving combination chemotherapy were monitored for EBV DNA in their serum. EBV DNA (EBER-1) concentration in serum was measured before, during, and after chemotherapy. Thirteen patients had additional multiple prechemotherapy readings. There was a significant lead time from first detection of serum EBER-1 to clinical recurrence in 62% of patients by a mean of 17.4 weeks (range: 8-74.5 weeks; mean = 28.2 weeks if confined to the 8 patients with significant lead time). The median EBER-1 concentration was significantly higher in those with distant metastasis as compared to those with loco-regional recurrence only (17,468 vs. 684 pg/mL serum; p = 0.046, Mann-Whitney U test). Among the 13 patients who responded to chemotherapy, 4 exhibited clinical complete remission (CR) who were only found in the group with EBER-1 DNA drop to background level, while the magnitude of EBER-1 drop did not discriminate partial remission (PR) and stable disease (SD) patients clearly. Subsequent profile of EBER-1 DNA showed concordance with clinical course of either continuous remission or later progression. EBER-1 DNA in serum can become a useful adjunctive surrogate marker to monitor chemotherapeutic response in NPC patients with distant metastasis or advanced local recurrence.

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.

Nineteen Chinese patients with lymphoepithelioma-like carcinoma (LELC) of the lung were tested for Epstein-Barr virus (EBV) DNA in their serum samples by a quantitative polymerase chain reaction (PCR) technique. There was prospective serial monitoring of the serum in seven patients with advanced inoperable or relapsing disease. Five other patients at first diagnosis and two patients at relapse had only a single serum sample available. Serum samples were also taken from three other patients who had prior curative surgery and two patients with prolonged disease remission. Measurable levels of EBV DNA were detected in 11 of 12 patients with a pre-therapy serum sample and a clinically evident tumor. A low level of EBV DNA was also detectable in one of the two other patients whose first serum samples were obtained after some chemotherapy. There was no detectable EBV DNA in the five patients without evidence of tumor. The longitudinal serum EBV DNA profile of seven patients showed consistent correlation with response to therapy and clinical outcome. Patients with a pre-therapy serum EBV DNA >10,000 copies/mL had significantly inferior overall survival. This study suggests that circulating serum EBV DNA can be used as a tumor marker in the clinical management of patients with LELC of the lung.

Background & Aims: Hepatitis B virus reactivation is a serious cause of morbidity and mortality in hepatitis B surface antigen-positive patients treated with chemotherapy. We compared the efficacy of early and deferred preemptive lamivudine therapy in reducing the incidence of hepatitis due to hepatitis B virus reactivation in hepatitis B surface antigen-positive lymphoma patients treated with chemotherapy.Methods: Thirty consecutive hepatitis B surface antigen-positive lymphoma patients undergoing intensive chemotherapy were randomized (1:1) to receive lamivudine 100 mg daily 1 week before chemotherapy (group 1) or to have this treatment deferred until there was serological evidence of hepatitis B virus reactivation on the basis of serial 2-week-interval serum hepatitis B virus DNA monitoring by a Digene Hybrid Capture II assay (group 2).Results: Eight (53%) patients in group 2 and none in group 1 had hepatitis B virus virological reactivation after chemotherapy ( P = 0.002). Seven patients in group 2 still had hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1 hepatic failure). Survival free from hepatitis due to hepatitis B virus reactivation in group 1 patients was significantly longer than that in group 2 ( P = 0.002 on the log-rank test). The median onset of hepatitis B virus reactivation in these patients was 16 weeks (range, 4–36 weeks) after the initiation of chemotherapy. Three (13%) of the 23 patients treated with lamivudine had hepatitis B virus-related hepatitis after lamivudine withdrawal.Conclusions: Lamivudine should be considered preemptively before or at the initiation of chemotherapy for all hepatitis B surface antigen-positive lymphoma patients undergoing intense chemotherapy.

To determine the clinical outcome, prognostic factors, and effect of adding combination chemotherapy to radiation therapy on disease control and survival in early stage nasal natural killer (NK)/T-cell lymphoma.A retrospective "intent to treat" analysis was carried out on 79 patients treated consecutively with curative intent between 1977 and June 2001. They all had early stage (Ann Arbor Stage I(E): 63, II(E):16) nasal NK/T-cell lymphoma. Sixty-one were planned for combined modality treatment (CMT); radiotherapy alone (RT) was intended for 18. Three to 6 cycles of anthracycline-containing regimens were aimed at for patients intended for CMT. Patients selected for RT were generally older or treated during the earlier part of the study period.The overall complete response (CR) rate was 68.4% (54/79), of whom 44.4% (24/54) relapsed after 54.9 months median follow-up of the survivors. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 35.5% and 37.9%, respectively. On multivariate analysis, good performance status (Eastern Cooperative Oncology Group [ECOG]2) was shown to be a significant favorable factor for DFS (p = 0.011), whereas good performance status (ECOG2) and Ann Arbor Stage I(E) disease were shown to be significant favorable factors for OS (p = 0.001 and p = 0.013, respectively). The type of intended treatment was not a significant factor for DFS (5-year DFS CMT vs. RT = 35.8% vs. 30.5%, p = 0.795) or OS (5-year OS CMT vs. RT = 40.3% vs. 29.8%, p = 0.693) though only 2 of the 16 Stage II(E) patients were intended for RT alone. Resistance to treatment, especially to chemotherapy, was common. Of 61 patients intended to be given CMT, 31 showed disease progression while receiving chemotherapy, of whom 17 progressed locoregionally. Nine of the latter group were rendered CR by salvage radiotherapy.The overall outcome in early stage nasal NK/T-cell lymphoma is poor. Performance status and Ann Arbor stage are significant factors influencing DFS and OS. The addition of anthracycline-containing chemotherapy to radiotherapy does not appear to confer any survival benefit in Stage I(E) patients. Therefore, radiation therapy remains the mainstay of treatment for this lymphoma type.

6002 Background: The benefit of adjuvant CT in NPC is unclear. Post-RT EBV DNA predicts poor survival and may be a biomarker of subclinical residual disease. We conducted a biomarker driven RCT using post-RT EBV DNA to select high risk NPC patients (pts) for adjuvant CT while sparing low risk pts from unnecessary toxicity. Methods: Eligible pts had biopsy proven NPC of AJCC (6th Ed) stage IIB-IVB, detectable EBV DNA ( > 0 copy/ml) at 6-8 weeks post-RT, no persistent locoregional disease or distant metastasis, ECOG 0 or 1, and adequate organ function. Pts were randomized with stratification for primary therapy (RT Vs CRT) and tumor stage (II/III Vs IV) to arm A (adjuvant cisplatin 40 mg/m2 and gemcitabine 1000 mg/m2, both given on D1+8 q3w x 6 cycles) or arm B (clinical follow-up). Primary endpoint was relapse free survival (RFS). With a hazard ratio (HR) of 2, 100 pts were required with a power of 0.8 and an alpha at 0.05. Results: From 9/2006 to 7/2015, 789 pts consented for EBV DNA screening, 218 (27.6%) pts had detectable EBV DNA, and 104 (13.2%) pts were randomized (arm A: 52; arm B: 52). The two arms were well balanced in baseline characteristics. 84.6% received prior neoadjuvant and/or concurrent CT and all received curative RT. Staging distribution: IIB 27.9%, III 37.5%, IVA 19.2%, IVB 15.4%. 8 pts refused adjuvant CT after randomization. Overall 69% and 50% completed 3 and 6 cycles of adjuvant CT respectively. After median follow up of 6.5 years (yr), the 3-yr and 5-yr survival outcomes were summarized in Table. Conclusions: In NPC pts who had residual EBV DNA after curative RT/CRT, adjuvant CT with cisplatin-gemcitabine did not improve survival. Clinical trial information: NCT00370890. [Table: see text]

BACKGROUND Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients. Cancer 1998;83:2284-2292. © 1998 American Cancer Society.

The stage IVC nasopharyngeal carcinoma is a catch-all entity covering minute solitary metastasis to bulky disseminated disease. Prognosis varies greatly within this stage group. A subset of patients with oligometastases may benefit from aggressive local ablative therapy. Meanwhile, in multiple metastatic diseases, customizing conventional cytotoxics basing on individual tumor characteristics and previous chemotherapy responses can be a new direction to improve therapeutic results. Prognostic models built on clinical features and genomic profiles can be utilized to stratify different risk groups and tailor therapy schemes.

To investigate the dosimetric difference amongst TomoTherapy, sliding-window intensity-modulated radiotherapy (IMRT), and RapidArc radiotherapy in the treatment of late-stage nasopharyngeal carcinoma (NPC). Ten patients with late-stage (Stage III or IV) NPC treated with TomoTherapy or IMRT were selected for the study. Treatment plans with these 3 techniques were devised according to departmental protocol. Dosimetric parameters for organ at risk and treatment targets were compared between TomoTherapy and IMRT, TomoTherapy and RapidArc, and IMRT and RapidArc. Comparison amongst the techniques was done by statistical tests on the dosimetric parameters, total monitor unit (MU), and expected delivery time. All 3 techniques achieved similar target dose coverage. TomoTherapy achieved significantly lower doses in lens and mandible amongst the techniques. It also achieved significantly better dose conformity to the treatment targets. RapidArc achieved significantly lower dose to the eye and normal tissue, lower total MU, and less delivery time. The dosimetric advantages of the 3 techniques were identified in the treatment of late-stage NPC. This may serve as a guideline for selection of the proper technique for different clinical cases.

OBJECTIVE. To determine the effectiveness and toxicity of docetaxel for Chinese patients with castrate-resistant prostate cancer in a local Hong Kong hospital. DESIGN. Case series. SETTING. A tertiary cancer centre in Hong Kong. PATIENTS. In all, 39 castrate-resistant prostate cancer patients were treated with 3-weekly docetaxel at 75 mg/m(2) and prednisolone 10 mg daily between January 2006 and December 2011 in Queen Elizabeth Hospital. MAIN OUTCOME MEASURES. Prostate-specific antigen control rate, pain control rate, progression-free survival, overall survival, and complication rates. RESULTS. The prostate-specific antigen response rate was 36%, and 27 (69%) of the patients had improved pain control after chemotherapy. The median progression-free survival, cancer-specific survival, and overall survival was 7.8 (95% confidence interval, 4.9-10.8) months, 13.0 (95% confidence interval, 9.6-16.3) months, and 12.2 (95% confidence interval, 9.3-15.1) months, respectively. The grade 3 anaemia and thrombocytopenia rates were 5%, and the neutropenic fever rate was 8%. CONCLUSIONS. Chemotherapy with docetaxel at a dose of 75 mg/m(2) given once every 3 weeks together with daily prednisolone is well tolerated in Chinese and can offer good symptom palliation in suitable patients with castrate-resistant prostate cancer.

Background and purpose Significant tumor shrinkage and weight loss may occur during Intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aims to evaluate the dosimetric effect of volumetric changes on target volumes and organs at risk (OARs) during IMRT, using reassessment of computed tomography (CT) and magnetic resonance imaging (MRI). Material and methods Nineteen loco-regionally advanced NPC patients treated with IMRT were recruited prospectively. Repeat planning CT and MRI were acquired at 30 and 50Gy intervals. Recontouring of target volumes and OARs was based on the fused CT-MRI images. Hybrid plans with recontouring were generated. The assessment of volumetric and dosimetric changes was performed by comparing the hybrid plans with the original plan. Results There was volume reduction of target volumes and parotid glands over the course of IMRT. Relative to the original plan, the hybrid plans demonstrated significantly higher dose to most of target volumes with greater dose inhomogeneity, higher maximum doses to the spinal cord and brainstem, and higher median doses to the parotid glands. Conclusions Replanning with repeat CT and MRI scans at 30Gy is essential to keep a satisfactory dose to the target volumes and avoid overdosing the OARs.

BACKGROUND Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed. METHODS Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m(2)) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg per m(2) per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided. RESULTS The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015). CONCLUSIONS Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.

Natural killer (NK)-cell lymphomas are aggressive and relapses occur early. Late relapses are exceptional. Ten relapses 17.5 (11-29) years after first complete remission (CR1) were analyzed. Initial diseases were stage-I (nasal, n = 8; tonsil, n =1; ileum, n =1), treated with radiotherapy (n = 6), combined radiotherapy/chemotherapy (n =3), and chemotherapy (n =1). Relapse occurred at the same (nasal, n = 6; tonsil, n = 1), adjacent (initial: nasal, relapse: palate; n =1) or distant (n =2) sites. Five patients died soon afterwards. Four patients remitted with chemotherapy, two remaining in CR2 (3, 14 years). This series documented the rare late relapses in NK-cell lymphomas, which may still respond to salvage therapy.

Background To evaluate the efficacy and toxicity of combination gemcitabine plus cisplatin (GC) chemotherapy in metastatic or recurrent nasopharyngeal carcinoma (NPC). Patients and methods Forty-four patients of Chinese ethnicity with metastatic or recurrent NPC received ambulatory GC chemotherapy every 28 days (gemcitabine 1000 mg/m2 days 1, 8 and 15; cisplatin 50 mg/m2 days 1 and 8). There were 40 male and four female patients with a mean age of 47.4 years. More than half (54.5%) of the patients had received either prior platinum-based chemotherapy and/or radiotherapy to target lesions. Results There were nine complete responses and 23 partial responses in the 44 patients, achieving an overallresponse rate of 73% (78% for the 41 assessable patients). The mean duration of response was 5.3 months. Improved subjective symptom-control scores were found in 78% of patients with pre-existing symptoms, while 64% of patients experienced improved general well-being scores. Toxicity was mainly hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were found in 11, 37 and 16% of cycles, respectively. With a median follow-up of 17.2 months, 62% survived 1 year while 36% were alive and progression free. Conclusions Gemcitabine plus cisplatin chemotherapy offers a satisfactory overall response rate, subjective patient improvement and safety profile for metastatic and recurrent NPC.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho’s N2 or N3 stage or N1 stage with nodal size ≥ 4 cm were randomized to receive cisplatin 40 mg/m2 weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P = .10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho’s stage T3 (P = .0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P = .016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

BACKGROUND Central nervous system (CNS) metastasis from nasopharyngeal carcinoma (NPC) is an extremely rare occurrence, although direct intracranial invasion is not infrequent in patients with NPC at a locally advanced stage. Only five other patients have been reported in detail in the English literature. METHODS The clinical records of two such patients with NPC who were diagnosed with metastasis to the spinal cord (intradural) and to the occipital lobe, respectively, were reviewed. The literature was searched for a review of similar incidents. RESULTS Both patients had locally advanced disease at the time of presentation and were treated with neoadjuvant chemotherapy and radical radiotherapy. The CNS metastases in both patients were accompanied by disease recurrences in multiple sites after a prolonged period of clinical remission. Spread through cerebral spinal fluid was postulated for the patient with spinal cord metastasis, and hematogenous spread was postulated for the patient with brain metastasis. Aggressive surgical resection with or without postoperative radiotherapy conferred reasonable survival and symptom control. The patient with brain metastasis died 6 months later of lung metastasis, whereas the other patient is still alive 40 months from the diagnosis of spinal metastasis. CONCLUSIONS Good symptom control and disease control can be achieved for patients with CNS metastasis after surgery with or without radiotherapy. After aggressive therapy, the ultimate survival depends on control of extracranial disease. Cancer 2002;94:398–405. © 2002 American Cancer Society.

Treatment results of 37 consecutive patients with primary ovarian germ cell tumors (OGCTs) were analyzed. Thirty-three were referred after initial laparotomy and four were first seen at relapse. Four patients with stage I dysgerminoma and grade 1 immature teratoma were observed after operation without recurrence. There was also no relapse in eight patients with dysgerminoma given postoperative irradiation (whole abdomen, median 30 Gy). Twenty-five patients (3 dysgerminomas, 11 immature teratomas, 9 endodermal sinus tumors, and 2 mixed germ cell tumors) received short-term cis -platinum-based chemotherapy. Six out of eight measurable tumors treated by chemotherapy had complete remission. Complete follow-up information was obtained in 35 out of 37 patients. The 4-year actuarial survival rates of the whole group and those referred immediately after initial surgery were 94.1 and 100%, respectively. cis -Platinum was substituted by carboplatin in eight cases but this did not affect treatment result. Nonetheless, deaths occurred in two of four patients referred at relapse with extensive disease and initially treated with suboptimal regimens. Chemotherapy-induced side effects were common but mostly tolerable and were related to cis -platinum and bleomycin. The results of this series show that cis -platinum-based chemotherapy is so effective that nearly 100% cure can be achieved in OGCTs and suggest that it is important to institute optimal chemotherapy from the start. On the other hand, common side effects of treatment and possible late toxicities make it desirable for future studies to see whether chemotherapy intensity could be reduced in patients with good prognosis.

Background and purpose Significant tumor shrinkage and weight loss may occur during Intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aims to evaluate the dosimetric effect of volumetric changes on target volumes and organs at risk (OARs) during IMRT, using reassessment of computed tomography (CT) and magnetic resonance imaging (MRI). Material and methods Nineteen loco-regionally advanced NPC patients treated with IMRT were recruited prospectively. Repeat planning CT and MRI were acquired at 30 and 50Gy intervals. Recontouring of target volumes and OARs was based on the fused CT-MRI images. Hybrid plans with recontouring were generated. The assessment of volumetric and dosimetric changes was performed by comparing the hybrid plans with the original plan. Results There was volume reduction of target volumes and parotid glands over the course of IMRT. Relative to the original plan, the hybrid plans demonstrated significantly higher dose to most of target volumes with greater dose inhomogeneity, higher maximum doses to the spinal cord and brainstem, and higher median doses to the parotid glands. Conclusions Replanning with repeat CT and MRI scans at 30Gy is essential to keep a satisfactory dose to the target volumes and avoid overdosing the OARs.

LBA19684 Background: About 10% cancer patients (pts) are HBV carriers in endemic areas, who have a risk of HBV reactivation with CT preventable by Lamivudine (Lam). Methods: Pts seropositive for HBV surface antigen (HBsAg+) planned to receive ≥ 4 cycles of CT for non-hematological malignancy were randomized to receiving either preemptive Lam during and for 8 weeks after CT (arm I), or observation only and deferred Lam at biochemical hepatitis reactivation (arm II). All pts had normal liver enzymes & clotting profiles, age 18–75 & KPS >50 before entry. Serial clotting profile, liver enzyme and HBV DNA levels were monitored during CT and for 15 weeks post-CT. The endpoints include % of CT interruptions due to HBV reactivation (primary), HBV reactivation %, CT drug dose intensity levels & HBV reactivation-free survival (all secondary). 110 pts are estimated to give a power of 90% to detect the projected difference in the primary endpoint at 2-sided alpha error of 0.05. Results: Pt accrual was completed in 1/07. As at 3/07, 92 (81%) of the 114 pts randomized have completed the study or died, and were included for analysis. Breast & lung cancer constituted 71% of the cancers. There was no statistical difference in pt, cancer, CT, or viral characteristics between the 2 arms. Results are summarized in table . All 4 pts with CT interruptions and 11/14 pts with HBV reactivation had breast cancer. No difference in CT drug dose intensity levels was observed. Steroid used in the anti-emetic regimen was a significant factor in predicting viral reactivation in arm II pts in multivariate analysis. Conclusions: Although the incidence of CT interruptions was low in unselected pts without preemptive Lam, it was much higher in breast cancer pts despite deferred Lam, who also had significant rates of biochemical hepatitis & viral reactivation. Preemptive Lam should be given to breast cancer pts, & considered in other cancer pts receiving CT who are HBsAg+. [Table: see text] No significant financial relationships to disclose.

8075 Background: Nasal NK/T lymphoma is uncommon but prognosis is universally poor even in early stage disease. Chemotherapy is often added to radiation for improving outcome although its role has not been well defined. Methods: Since 1998, an intensive protocol has been introduced for pts with stage I or II disease, which consists of 3 cycles of anthracycline-based (CHOP or ProMACE-CytaBOM) chemotherapy to be followed by cCRT (50–54Gy radiotherapy with weekly cisplatin at 40mg/m2) for pts with adequate renal function, and then consolidation HDCT. Cyclophosphamide, BCNU & Etoposide HDCT was offered to pts No significant financial relationships to disclose.

5523 Background/Objective: NPC is highly radiosensitive and chemosensitive. 3 cycles of 3-weekly chemotherapy concurrent with RT followed by 3 cycles of adjuvant chemotherapy has improved survival over RT alone in a previous randomized study. The regimen was associated with significant toxicities. This randomized phase III study compared concurrent weekly cisplatin-RT with RT alone in patients with locoregionally advanced NPC. Methods: Patients with Ho's N2 or N3 stage or N1 stage with nodal size ≥ 4 cm were randomized to receive cisplatin 40 mg/m2 weekly up to 8 weeks concurrently with RT (CRT) or RT alone. The primary endpoints are progression-free survival (PFS) and overall survival (OS). Results: 350 eligible patients were randomized. Baseline patient characteristics, treatment toxicities and PFS analysis at median follow up of 2.71 years have been published previously. At a median follow up of 5.5 years where 58 and 73 deaths were found out of 174 CRT and 176 RT patients respectively (95th and 5th pe...

Purpose To evaluate the clinical outcome of early glottic cancer (GC) treated by primary radiotherapy (RT) with 6 MV photons. Methods and materials We retrospectively reviewed the medical records of 695 consecutive patients with T1N0 and T2N0 GC treated between 1983 and 2005 by RT in our institution. Clinical outcome in terms of local control (LC), overall survival (OS) and cause- specific survival (CSS) rate were evaluated. Results The median follow-up time was 10.5 years. The 10-year actuarial LC rates were as follows: T1A, 91%; T1B, 87%; T2, 77%. The 10-year OS were as follows: T1, 74.2%; T2, 70.7%. The 10-year CSS were as follows: T1, 97.7%; T2, 97.1%. Poorly differentiated histology and tumor biologically effective dose

Background To evaluate prognostic factors that may influence local control (LC) of T1N0 glottic cancer treated by primary radiotherapy (RT) with 6 MV photons. Methods We retrospectively reviewed the medical records of 433 consecutive patients with T1N0 glottic cancer treated between 1983 and 2005 by RT in our institution. All patients were treated with 6 MV photons. One hundred and seventy seven (41%) patients received 52.5 Gy in 23 fractions with 2.5 Gy/fraction, and 256 (59%) patients received 66 Gy in 33 fractions with 2 Gy/fraction. Results The median follow-up time was 10.5 years. The 10-year LC rates were 91% and 87% for T1a and T1b respectively. Multivariate analysis showed LC rate was adversely affected by poorly differentiated histology (Hazard Ratio [HR]: 7.5, p = 0.035); involvement of anterior commissure (HR: 2.34, p = 0.011); fraction size of 2.0 Gy (HR: 2.17, p = 0.035) and tumor biologically effective dose (BED) < 65 Gy15 (HR: 3.38, p = 0.017). Conclusions The negative impact of anterior commissure involvement could be overcome by delivering a higher tumor BED through using fraction size of > 2.0 Gy. We recommend that fraction size > 2.0 Gy should be utilized, for radiation schedules with five daily fractions each week.