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/m2) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg per m2 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.
Summary 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.
The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis (NMA) to synthesize evidence of ...their comparative effectiveness for improving overall survival (OS) among EOC patients. We searched six databases for randomized controlled trials (RCTs) from their inception to February 2021. We performed an NMA with hazard ratios (HRs) and 95%-confidence intervals (CIs) to evaluate comparative effectiveness among different AAAs in chemotherapy-naïve and recurrent EOC. P-score was used to provide an effectiveness hierarchy ranking. Sensitivity NMA was carried out by focusing on studies that reported high-risk chemotherapy-naïve, platinum-resistant, and platinum-sensitive EOC. The primary outcome was OS. We identified 23 RCTs that assessed the effectiveness of AAAs. In recurrent EOC, concurrent use of trebananib (10 mg/kg) with chemotherapy was likely to be the best option (P-score: 0.88, HR 1.67, 95% CI 0.94; 2.94). The NMA indicated that bevacizumab plus chemotherapy followed by maintenance bevacizumab (P-score: 0.99) and pazopanib combined with chemotherapy (P-score: 0.79) both had the highest probability of being the best intervention for improving OS in high-risk chemotherapy-naïve and platinum-resistant EOC, respectively. AAAs may not play a significant clinical role in non-high-risk chemotherapy-naïve and platinum-sensitive EOC.
Abstract Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with ...cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 95% CI = 0.35–0.68) and all-cause mortality (HR: 0.67 95% CI = 0.61–0.74), with no significant difference in major bleeding (HR: 1.04 95% CI = 0.83–1.31) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.
•Treatment outcomes of 3328 NPC patient treated with IMRT in Hong Kong.•8 year local/regional control remained promising.•Confirmed benefits of concurrent chemotherapy with IMRT.•Additional ...chemotherapy onto backbone of concurrent chemo-irradiation warrants further investigation.•Various severe symptomatic complications after IMRT remained low.
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.
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.
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.
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.
The standard of care for newly diagnosed advanced ovarian cancer is surgical cytoreduction plus platinum-based chemotherapy; however, recurrent disease frequently occurs after treatment. ...Poly(ADP-ribose) polymerase (PARP) inhibitors as first-line maintenance therapy have been demonstrated to significantly reduce the risk of disease progression or death in patients with advanced ovarian cancer who have a complete or partial response to first-line platinum-based chemotherapy. Niraparib is the only PARP inhibitor that offers a significant progression-free survival benefit compared with placebo in this patient population regardless of the homologous recombination status. However, predictive factors for treatment responses and approaches to dose optimization remain to be investigated. In this study, two Chinese patients with newly diagnosed advanced ovarian cancer exhibited long-term responses to niraparib treatment, and hematological toxicity was successfully managed by dose adjustment. The literature on clinical trials and real-world experience on the efficacy, tolerability, and dose individualization of niraparib treatment in Western and Chinese patients was also reviewed. Future research is warranted to identify the characteristics of ‘long responders’ to niraparib treatment.
The cyclin-dependent kinase 4/6 inhibitor palbociclib has demonstrated efficacy and a manageable safety profile in combination with endocrine therapy in women with oestrogen receptor–positive ...(ER+)/human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) in international phase 3 trials. The phase 3 PALOMA-4 trial evaluated the efficacy and safety of palbociclib plus letrozole versus placebo plus letrozole in Asian women with ER+/HER2– ABC.
Postmenopausal women (n = 340) with no prior systemic treatment for advanced disease were randomised 1:1 to palbociclib (125 mg/d orally; 3 weeks on, 1 week off) plus letrozole (2.5 mg/d orally; continuously) or placebo plus letrozole. The primary end-point was investigator-assessed progression-free survival (PFS). Secondary end-points included tumour response and safety.
Median (95% CI) PFS was 21.5 (16.6–24.9) months with palbociclib plus letrozole and 13.9 (13.7–16.6) months with placebo plus letrozole (hazard ratio, 0.68 95% CI, 0.53–0.87; P = 0.0012). Consistent with the established safety profile, the most common adverse events (AEs) with palbociclib plus letrozole were neutropenia, leukopenia, thrombocytopaenia, and anaemia. Grade 3/4 neutropenia was reported in 84.5% of patients in the palbociclib arm versus 1.2% in the placebo arm. One serious AE of febrile neutropenia in the palbociclib group was reported.
Findings from PALOMA-4 support the efficacy and safety of first-line palbociclib plus letrozole in postmenopausal Asian women with ER+/HER2– ABC. No new safety concerns of palbociclib plus letrozole were identified.
Clinicaltrials. gov, NCT02297438.
•Addition of palbociclib to letrozole prolonged PFS in Asian women with ER+/HER2– ABC.•No new safety concerns of palbociclib plus letrozole were identified in Asian women.•Findings support first-line palbociclib in postmenopausal Asians with ER+/HER2– ABC.
Cancer outcomes vary widely among different countries. However, comparisons of cost-effectiveness and cost-efficiency of different systems are complex because the incidences of different cancers vary ...across countries and their chances of cure also differ substantially. We aim to propose a new standardized method for global comparison and to explore its relationship with economic indicators.
Cancer statistics from all 184 countries and 27 cancers listed in GLOBOCAN 2012 were analyzed. The complement of age-standardized mortality/incidence ratio 1 - (ASM/ASI) was taken as the proxy relative survival (RS). Accounting for various country-specific cancer patterns, the cancer site-standardized proxy RS (proxy SS-RS) of individual countries were calculated by weighting the proportion of specific cancer sites as compared with the global pattern of incidence. Economic indicators of different countries listed by the World Bank were correlated with corresponding proxy SS-RS.
Substantial variation in site-specific survival and new case distribution supported the use of proxy SS-RS, which ranged from 0.124 to 0.622 (median 0.359). The median total health expenditure per capita (HEpc) increased from US$44 for countries with proxy SS-RS < 0.25, to US$4643 for countries with proxy SS-RS ≥0.55. Results from logarithmic regression model showed exponential increase in total HEpc for better outcome. The expenditure varied widely among different strata, with the widest difference observed among countries with SS-RS ≥0.55 (total HEpc US$1412-$9361).
Similar to age-standardization, cancer site-standardization adjusted for variation in pattern of cancer incidence provides the best available and feasible strategies for comparing cancer survivals across countries globally. Furthermore, cancer outcome correlated significantly with economic indicators and the amount of HEpc escalated exponentially. Our findings call for more in-depth studies applying cancer-site standardization to provide essential data for sharing of experience and urgent actions by policy makers to develop comprehensive and financially sustainable cancer plan for greater equity.
Abstract 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.
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