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Nasopharyngeal carcinoma (NPC) is rare in Western countries, but its incidence in China and Southeast Asia is notably high. NPC shows a high rate of distant metastasis including metachronous metastasis (mmNPC, metastasis after definitive chemo-radiotherapy) and synchronous metastasis (smNPC, metastasis at initial diagnosis). 4-10% of patients would be diagnosed as smNPC annually, and the survival outcomes of these patients are quite poor. As with few clinical trials exclusively focusing on this population, treatment on smNPC is not unified and many problems remain unsolved. To date, systematic chemotherapy (CT) still remains a fundamental treatment in smNPC. Although no randomized trial has been conducted to compare different CT regimens in smNPC, gemcitabine and taxanes in combination with platinum seem optimal in first-line setting. In second-line CT, there is no consensus: mono-chemotherapy with drugs such as gemcitabine, taxanes or capecitabine could be taken into consideration. Immunotherapy based on checkpoint inhibitors shows promising efficacy both in first-line and in the following lines of therapy. In addition to CT, local therapy in smNPC is also very important. Locoregional radiotherapy (RT) for primary tumor in combination with CT could strikingly increase OS with acceptable toxicities. And local treatment, such as surgery and RT, for metastatic lesions could bring extra survival benefit in patients with solitary or limited metastases. Overall, the present study provides an overview of the literature on the various studies of smNPC.

Purpose Ribociclib has provided significant improvements in progression-free survival (PFS) and overall survival (OS) of postmenopausal patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). However, given the high cost of ribociclib, its value must be evaluated based on cost-effectiveness. Thus, we aimed to explore the cost-effectiveness of ribociclib for postmenopausal patients with HR-positive and HER2-negative ABC. Methods A comprehensive Markov model was developed to estimate the cost-effectiveness of ribociclib plus fulvestrant versus placebo plus fulvestrant as first-line treatment for HR-positive, HER2-negative ABC. Variables were estimated based on data from the randomized Phase III MONALEESA-3 trial. Ten-year values were estimated for quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Direct treatment costs were estimated from the perspective of a United States payer. One-way and probabilistic sensitivity analyses were conducted to confirm the model’s robustness. Results Ribociclib plus fulvestrant increased the treatment cost by $382,172 and provided 0.47 QALYs, relative to fulvestrant alone, which corresponded to an ICER of $813,132 per QALY. Sensitivity analyses revealed that ribociclib was unlikely to be cost-effective even under the most favorable assumptions. When the cost of ribociclib was <$1,384, there was a >50% chance of cost-effectiveness at a willingness-to-pay threshold of $150,000/QALY. Subgroup analyses also confirmed that ribociclib was not cost-effective. Conclusion At current drug prices in the United States, ribociclib is unlikely to be cost-effective for treating postmenopausal patients with HR-positive HER2-negative ABC. Despite the clinical benefits of ribociclib, its cost would need to decrease to provide more favorable economic outcomes.

Background To develop a risk model based on dosimetric metrics to predict local recurrence in nasopharyngeal carcinoma (NPC) patients treated with intensive modulated radiation therapy (IMRT). Methods 493 consecutive patients were included, among whom 44 were with local recurrence. One-to-two propensity score matching (PSM) was used to balance variables between recurrent and non-recurrent groups. Dosimetric metrics were extracted, and critical dosimetric predictors of local recurrence were identified by Cox regression model. Moreover, recurrent sites and patterns were examined by transferring the recurrent tumor to the pretreatment planning computed tomography. Results After PSM, 44 recurrent and 88 non-recurrent patients were used for dosimetric analysis. The univariate analysis showed that eight dosimetric metrics and homogeneity index were significantly associated with local recurrence. The risk model integrating D5 and D95 achieved a C-index of 0.706 for predicting 3-year local recurrence free survival (LRFS). By grouping patients using median value of risk score, patients with risk score ˃ 0.885 had significantly lower 3-year LRFS (66.2% vs. 86.4%, p = 0.023). As for recurrent features, the proportion of relapse in nasopharynx cavity, clivus, and pterygopalatine fossa was 61.4%, 52.3%, and 40.9%, respectively; and in field, marginal, and outside field recurrence constituted 68.2%, 20.5% and 11.3% of total recurrence, respectively. Conclusions The current study developed a novel risk model that could effectively predict the LRFS in NPC patients. Additionally, nasopharynx cavity, clivus, and pterygopalatine fossa were common recurrent sites and in field recurrence remained the major failure pattern of NPC in the IMRT era.

e13046 Background: There is some tumor defined HER2 1+ or 2+ by IHC and negative in FISH as HER2 low expression in common triple-negative breast cancer (TNBC). This subset is considered to be a new subtype of HER2-low BC, which might benefit from HER2-targeted antibody drug conjugate (ADC). Therefore, it could preliminarily understand on treatment status and treatment needs of HER2-low BC by analysis of the distribution, treatment patterns and prognosis of HER2-low BC in advanced TNBC. Methods: This was a retrospective study which included HR-negative, HER2 IHC 0/1+/2+ and FISH negative ABC patients (pts) diagnosed from June 2006 to September 2020, with recurrence and de novo metastatic cancer at a single institution in China. The cut-off date of follow-up was 31 December 2020. The baseline characteristics, first- and second-line therapies and the clinical outcomes were reported. Results: In total of 195 pts with complete follow-up data were included into final analysis. HR-negative, HER2 IHC 0 pts (triple negative, TN pts) were 61.5% (n = 120), and HR- negative, HER2 IHC 1 + / 2 + and FISH negative pts (HER2-low pts) were 38.5% (n = 75). The baseline characteristics and treatment patterns of HER2-low pts and TN pts were similar. The median age of pts at diagnosis was 48 years old while 54.4% pts were premenopausal. About 80% pts were recurrence, and 27.6% of them received neoadjuvant chemotherapy. The median disease-free interval (DFI) in early stage was 15.5 months, with 66.0% pts for DFI≥12 months. 56.4% of the pts presented with visceral metastasis. The most common sites of metastasis were lung (35.4%), lymph node (27.7%), soft tissue (24.1%), liver (20.5%), bone (20.5%), and brain (6.2%). The most commonly used regimens for first- and second-line were combination chemotherapy, which were 74.7% and 65.3%, respectively; paclitaxel (55.6%) and platinum (43.8%) were the most commonly used drugs for the first-line treatment. Only 14.4% and 3.6% pts received targeted combination therapy and immunotherapy in advanced setting, respectively. In TN and HER2-low ABC pts, the median PFS of first-line treatment were both 7.2 months, and the median OS was 17.2 months and 17.0 months, respectively. In DFI≥12 months and DFI<12 months subgroup, the median PFS was 8.4 months vs. 4.7 months, with a median OS of 17.8 months vs. 14.4 months, respectively. No significant different was observed between HER2-low pts and TN pts. Conclusions: Based on this observational cohort study, there is no significant difference in the current treatment patterns and prognosis between HER2-low pts and TN pts. However, with the emergence of HER2-targeted ADC therapy, HER2-low ABC pts which were commonly defined as TNBC may benefit from these novel therapies. The recurrence subgroup with DFI≥12 months presented a trend of longer OS, suggesting the therapy mode and response in early stage should be considered in advanced TNBC treatment.