[en] In cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We undertook a randomized trial (ClinicalTrials.gov Identifier: NCT01418859) to compare the efficacy and toxicity of concurrent chemoradiotherapy with topotecan and cisplatin with radiotherapy alone in intermediate-risk cervical cancer patients. Eligible patients were randomly assigned to one of three treatment arms including arm A (radiotherapy only,RT), arm B(concurrent chemoradiotherapy only, CCRT), and arm C (concurrent chemoradiotherapy with following consolidation chemotherapy, CCRT + CT). All eligible patients completed external RT (IMRT or 3D-CRT), receiving 45-50Gy /25f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m² for days 1, 2 and 3, followed by cisplatin 25 mg/m² for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m² for days 1 and 2, and 0.75 mg/m² for day 3; followed by cisplatin 25 mg/m² for days 1, 2 and 3, repeated every 21 days. Adverse events of each group were investigated and compared. Thirty-nine patients enrolled onto the remaining regimens: 14 to RT, 15 to CCRT and 10 to CCRT + CT. Six patients (15.4%) did not complete the protocol treatment. Hematologic toxicity was more frequent and more severe in the CCRT and CCRT + CT arms compared with the RT arm. The incidence of grade 3-4 neutropenia was significantly different statistically between the RT, CCRT and CCRT + RT groups (15.4%, 46.7% and 100%, respectively; P = 0.002). Specially, three patients in CCRT + CT arm of all six patients who did not complete the protocol treatment discontinued planned therapy because of persistent grade 4 neutropenia. However, there were no significant differences in grade 3-4 non-hematologic toxicities between the three groups(all P > 0.05). Recurrence-free survival and overall survival of each group were not analyzed on account of a median follow-up of only 16 months. Concurrent chemoradiotherapy with topotecan and cisplatin showed severe hematologic toxicity in intermediate-risk cervical cancer patients after radical hysterectomy. Thus, the study was closed ahead of schedule. ClinicalTrials.gov Identifier: https://www.clinicaltrials.gov/ct2/show/NCT01418859?term

[en] Highlights: • Penalty cost is introduced for the design of net zero energy building (NZEB). • Three scenarios are conducted to study the impact of penalty cost on system design. • Case studies are conducted on the Hong Kong Zero Carbon Building. • The relationship between total cost (IPOC) and safety factor is investigated. -- Abstract: It is well known that the high cost of installing renewable energy systems (RES) is still a barrier to overcome in the promotion of net-zero energy buildings (NZEB). The current practice in selecting the optimal RES system for NZEB basically involves a consideration of all possible design options, which is usually not a cost-effective process when compared with costs for no or for less RES in buildings. This study, therefore, introduces a penalty cost in the RES design process for NZEB, which aims to ensure that the cost-effective design option is the system which provides for a net-zero/positive energy building. The proposed penalty cost function is investigated in three scenarios (two scenarios with penalty costs and one scenario without a penalty cost) based on the Hong Kong Zero Carbon Building. It is found that the total cost of the building under a safety factor of 0.0 is increased by about 70% when a penalty cost is considered whilst it is reduced by 39% (for penalty cost 1) and 48.9% (for penalty cost 2) for the building under a safety factor of 1.0 (i.e., NZEB), respectively. In addition, three fitting formulas were derived for designers to better understand the relationship between the total cost and safety factor. The idea of developing a penalty cost mechanism provides a progressive perspective to assist the promotion of NZEB in terms of both governments as well as building designers/owners.