Multicentre phase II trial of cabozantinib in patients with hepatocellular carcinoma after immune checkpoint inhibitor treatment.

BACKGROUND & AIMS: Prospective data on treatment after immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC) are lacking. We conducted a phase II multicentre study on cabozantinib after ICI treatment in HCC. METHODS: This is an investigator-initiated, single-arm, clinical trial involving academic centres in Hong Kong and Korea. Key eligibility criteria included diagnosis of HCC, refractoriness to prior ICI-based treatment, and Child-Pugh A liver function. A maximum of two prior lines of therapy were allowed. All patients were commenced on cabozantinib at 60 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were recruited from Oct 2020 to May 2022; 27 and 20 patients had received one and two prior therapies, respectively. Median follow-up was 11.2 months. The median PFS was 4.1 months (95% CI 3.3-5.3). The median overall survival (OS) was 9.9 months (95% CI 7.3-14.4), and the 1-year OS rate was 45.3%. Partial response and stable disease occurred in 3 (6.4%) and 36 (76.6%) patients, respectively. When used as a second-line treatment (n = 27), cabozantinib was associated with a median PFS and OS of 4.3 (95% CI 3.3-6.7) and 14.3 (95% CI 8.9-NR) months, respectively. The corresponding median PFS and OS were 4.3 (95% CI 3.3-11.0) and 14.3 (95% CI 9.0-NR) months, respectively, for those receiving ICI-based regimens with proven benefits (n = 17). The most common grade 3-4 treatment-related adverse event was thrombocytopenia (6.4%). The median dose of cabozantinib was 40 mg/day. The number of prior therapies was an independent prognosticator (one vs. two; hazard ratio = 0.37; p = 0.03). CONCLUSIONS: Cabozantinib demonstrated efficacy in patients who had received prior ICI regimens; survival data for second-line cabozantinib following first-line ICI regimens provide a reference for future clinical trial design. The number of prior lines of treatment may be considered a stratification factor in randomised studies. IMPACT AND IMPLICATIONS: Prospective data on systemic treatment following prior immune checkpoint inhibitor (ICI) therapy for hepatocellular carcinoma (HCC) are lacking. This phase II clinical trial provides efficacy and safety data on cabozantinib in patients who had received prior ICI-based treatment. Exploratory analyses showed that the performance of cabozantinib differed significantly when used as a second- or third-line treatment. The above data could be used as a reference for clinical practice and the design of future clinical trials on subsequent treatment lines following ICIs. GOV IDENTIFIER: NCT04588051.

Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Radiologic extranodal extension for nodal staging in nasopharyngeal carcinoma.

PURPOSE: Extranodal extension (ENE) has the potential to add value to the current nodal staging system (N8th) for predicting outcome in nasopharyngeal carcinoma (NPC). This study aimed to incorporate ENE, as well as cervical nodal necrosis (CNN) to the current stage N3 and evaluated their impact on outcome prediction. The findings were validated on an external cohort. METHODS & MATERIALS: Pre-treatment MRI of 750 patients from the internal cohort were retrospectively reviewed. Predictive values of six modified nodal staging systems that incorporated four patterns of ENE and two patterns of CNN to the current stage N3 for disease-free survival (DFS) were compared with that of N8th using multivariate cox-regression and concordance statistics in the internal cohort. Performance of stage N3 for predicting disease recurrence was calculated. An external cohort of 179 patients was used to validate the findings. RESULTS: Incorporation of advanced ENE, which infiltrates into adjacent muscle/skin/salivary glands outperformed the other five modifications for predicting outcomes (p < 0.01) and achieved a significantly higher c-index for 5-year DFS (0.69 vs 0.72) (p < 0.01) when compared with that of N8th staging system. By adding advanced ENE to the current N3 increased the sensitivity for predicting disease recurrence from 22.4 % to 47.1 %. The finding was validated in the external cohort (5-year DFS 0.65 vs. 0.72, p < 0.01; sensitivity of stage N3 increased from 14.0 % to 41.9 % for disease recurrence). CONCLUSION: Results from two centre cohorts confirmed that the radiological advanced ENE should be considered as a criterion for stage N3 disease in NPC.

Discriminating between benign and malignant salivary gland tumors using diffusion-weighted imaging and intravoxel incoherent motion at 3 Tesla.

PURPOSE: The purpose of this study was to retrospectively evaluate the diagnostic performances of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) for discriminating between benign and malignant salivary gland tumors (SGTs). MATERIALS AND METHODS: Sixty-seven patients with 71 SGTs who underwent MRI examination at 3 Tesla were included. There were 34 men and 37 women with a mean age of 57 ± 17 (SD) years (age range: 20-90 years). SGTs included 21 malignant tumors (MTs) and 50 benign SGTs (33 pleomorphic adenomas [PAs] and 17 Warthin's tumors [WTs]). For each SGT, DWI and IVIM parameters, mean, skewness, and kurtosis of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion volume fraction (f) were calculated and further compared between SGTs using univariable analysis. Areas under the curves (AUC) of receiver operating characteristic of significant parameters were compared using the Delong test. RESULTS: Significant differences in ADCmean, Dmean and D*mean were found between SGTs (P < 0.001). The highest AUC values were obtained for ADCmean (0.949) for identifying PAs and D*mean (0.985) for identifying WTs and skewness and kurtosis did not outperform mean. To discriminate benign from malignant SGTs with thresholds set to maximize Youden index, IVIM and DWI produced accuracies of 85.9% (61/71; 95% CI: 75.6-93.0) and 77.5% (55/71; 95% CI: 66.0-86.5) but misdiagnosed MTs as benign in 28.6% (6/21) and 61.9% (13/21) of SGTs, respectively. After maximizing specificity to 100% for benign SGTs, the accuracies of IVIM and DWI decreased to 76.1% (54/71; 95% CI: 64.5-85.4) and 64.8% (46/71; 95% CI: 52.5-75.8) but no MTs were misdiagnosed as benign. IVIM and DWI correctly diagnosed 66.0% (33/50) and 50.0% (25/50) of benign SGTs and 46.5% (33/71) and 35.2% (25/71) of all SGTs, respectively. CONCLUSION: IVIM is more accurate than DWI for discriminating between benign and malignant SGTs because of its advantage in detecting WTs. Thresholds set by maximizing specificity for benign SGTs may be advantageous in a clinical setting.

Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial.

Introduction: This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC). Methods: A phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy. Results: Total 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1-8). The median OS was 13.6 months (95% CI: 5.4-21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3-25.2) and the median PFS was 9 months (95% CI: 3.2-13.1). The response rate was 25% (95% CI: 3.8-46.2%), and the disease control rate was 75% (95% CI: 53.8-96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7-42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n = 4), underlying treatment unrelated comorbidities (n = 2), and withdrawal of consent due to personal reasons (n = 2). Conclusions: Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.

Radiomics for Discrimination between Early-Stage Nasopharyngeal Carcinoma and Benign Hyperplasia with Stable Feature Selection on MRI.

Discriminating early-stage nasopharyngeal carcinoma (NPC) from benign hyperplasia (BH) on MRI is a challenging but important task for the early detection of NPC in screening programs. Radiomics models have the potential to meet this challenge, but instability in the feature selection step may reduce their reliability. Therefore, in this study, we aim to discriminate between early-stage T1 NPC and BH on MRI using radiomics and propose a method to improve the stability of the feature selection step in the radiomics pipeline. A radiomics model was trained using data from 442 patients (221 early-stage T1 NPC and 221 with BH) scanned at 3T and tested on 213 patients (99 early-stage T1 NPC and 114 BH) scanned at 1.5T. To verify the improvement in feature selection stability, we compared our proposed ensemble technique, which uses a combination of bagging and boosting (BB-RENT), with the well-established elastic net. The proposed radiomics model achieved an area under the curve of 0.85 (95% confidence interval (CI): 0.82−0.89) and 0.80 (95% CI: 0.74−0.86) in discriminating NPC and BH in the 3T training and 1.5T testing cohort, respectively, using 17 features selected from a pool of 422 features by the proposed feature selection technique. BB-RENT showed a better feature selection stability compared to the elastic net (Jaccard index = 0.39 ± 0.14 and 0.24 ± 0.06, respectively; p < 0.001).

Prognostic value of cervical nodal necrosis on staging imaging of nasopharyngeal carcinoma in era of intensity-modulated radiotherapy: a systematic review and meta-analysis.

PURPOSES: To systematically review and perform meta-analysis to evaluate the prognostic value of cervical nodal necrosis (CNN) on the staging computed tomography/magnetic resonance imaging (MRI) of nasopharyngeal carcinoma (NPC) in era of intensity-modulated radiotherapy. METHODS: Literature search through PubMed, EMBASE, and Cochrane Library was conducted. The hazard ratios (HRs) with 95% confidence intervals (CIs) of CNN for distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were extracted from the eligible studies and meta-analysis was performed to evaluate the pooled HRs with 95%CI. RESULTS: Nine studies, which investigated the prognostic values of 6 CNN patterns on MRI were included. Six/9 studies were eligible for meta-analysis, which investigated the CNN presence/absence in any nodal group among 4359 patients. The pooled unadjusted HRs showed that the CNN presence predicted poor DMFS (HR =1.89, 95%CI =1.72-2.08), DFS (HR =1.57, 95%CI =1.08-2.26), and OS (HR =1.87, 95%CI =1.69-2.06). The pooled adjusted HRs also showed the consistent results for DMFS (HR =1.34, 95%CI =1.17-1.54), DFS (HR =1.30, 95%CI =1.08-1.56), and OS (HR =1.61, 95%CI =1.27-2.04). Results shown in the other studies analysing different CNN patterns indicated the high grade of CNN predicted poor outcome, but meta-analysis was unable to perform because of the heterogeneity of the analysed CNN patterns. CONCLUSION: The CNN observed on the staging MRI is a negative factor for NPC outcome, suggesting that the inclusion of CNN is important in the future survival analysis. However, whether and how should CNN be included in the staging system warrant further evaluation.

Association of high adherence to vegetables and fruits dietary pattern with quality of life among Chinese women with early-stage breast cancer.

PURPOSE: Dietary intake and patients' quality of life (QoL) are important supportive care issues in breast cancer survivorship. This study aimed to identify dietary pattern before and after breast cancer diagnosis. In addition, the association between dietary patterns and QoL were cross-sectionally and longitudinally investigated. METHODS: A breast cancer cohort which included 1462 Chinese women were longitudinally interviewed at four time-points, namely baseline, 18-, 36-, and 60 months after diagnosis. At each follow-up, validated food frequency questionnaires (FFQ) were used to assess patients' dietary intake, and factor analysis was used to derive dietary patterns. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) were used to measure QoL at each follow-up. This study included 1368, 1226, 1079 and 1095 patients with invasive disease who completed assessment at baseline, 18-, 36- and 60-month follow-up and had detailed data of dietary intake and QoL. RESULTS: Based on data obtained at 18-month follow-up, two major dietary patterns were identified: "grain and animal food pattern" and "vegetables and fruits pattern". Similar dietary patterns were obtained at baseline, 36- and 60- month follow-up. Generalized Estimating Equations (GEE) were used to analyze the longitudinal associations between dietary patterns and QoL over the four follow-ups. High intake of grain and animal food was inversely associated with scores for role functioning (B = - 0.744; 95%CI - 0.147 to - 0.017), dyspnea (B = - 0.092; 95%CI - 0.092 to - 0.092) and constipation (B = - 1.355; 95%CI - 2.174 to - 0.536). Vegetables and fruits intake were positively associated with scores for global health status/QoL (B = 1.282; 95%CI 0.545-2.019), physical functioning (B = 0.545; 95%CI: 0.037-1.053), emotional functioning (B = 1.426; 95%CI 0.653-2.200) and cognitive functioning (B = 0.822; 95%CI 0.007-1.637), while inversely associated with scores for nausea and vomiting (B = - 0.382; 95%CI - 0.694 to - 0.071), dyspnea (B = - 0.570; 95%CI - 0.570 to - 0.570), insomnia (B = - 1.412; 95%CI - 2.647 to - 0.177), loss of appetite (B = - 0.722; 95%CI - 1.311 to - 0.132), constipation (B = - 2.028; 95%CI - 2.775 to - 1.281) and diarrhea (B = - 0.929; 95%CI - 1.481 to - 0.377). CONCLUSION: This study suggested that high adherence to "grain and animal food pattern" or "vegetables and fruits pattern" was significantly associated with several aspects of QoL. For instance, vegetables and fruits pattern appears to have beneficial effect on global health status/QoL among Chinese breast cancer patients. Prospective follow-up data could further confirm whether a specific dietary pattern has impact on cancer outcomes.

NEPA efficacy and tolerability during (neo)adjuvant breast cancer chemotherapy with cyclophosphamide and doxorubicin.

OBJECTIVES: This is a prospective study evaluating NEPA in patients with breast cancer (the NEPA group), who received (neo)adjuvant AC chemotherapy (consisting of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). The primary objectives were to assess the efficacy and safety of NEPA in controlling chemotherapy-induced nausea and vomiting (CINV). The secondary objectives were to compare CINV between the NEPA group and historical controls (the APR group) who received aprepitant in an earlier prospective randomised study. PATIENTS AND METHODS: 60 patients participated in the NEPA group; 62 were in the APR group. Eligibility criteria of both groups were similar, that is, Chinese patients with breast cancer who were treated with (neo)adjuvant AC. NEPA group received NEPA and dexamethasone; APR group received aprepitant, ondansetron and dexamethasone. Individuals filled in self-reported diary, visual analogue scale for nausea and Functional Living Index-Emesis questionnaire. RESULTS: Within the NEPA group, 70.0%, 85.7% and 60.0%, respectively reported complete response in the acute, delayed and overall phases in cycle 1 AC. When compared with the historical APR group during cycle 1 AC, NEPA group achieved significantly higher rates of complete response, complete protection, total control, 'no significant nausea' and 'no nausea' in the delayed phase; similar findings were noted in the overall phase with significantly better quality of life. Superior efficacy of NEPA was maintained over multiple cycles. Both antiemetic regimens were well tolerated. CONCLUSION: In this study on Chinese patients with breast cancer who were uniformly receiving AC, NEPA was effective in controlling CINV. TRIAL REGISTRATION NUMBER: NCT03386617.

Higher Level of Sports Activities Participation during Five-Year Survival Is Associated with Better Quality of Life among Chinese Breast Cancer Survivors.

Evidence about the association between the level of sports activities participation post-diagnosis and quality of life (QoL) among Chinese women with early-stage breast cancer is limited. A validated modified Chinese Baecke questionnaire was used to prospectively measure sports activities among a breast cancer cohort at four time-points: baseline and 18, 36, and 60 months after diagnosis (sports activities during the previous 12 months before each interview); QoL was measured at the same time. In total, 1289, 1125, and 1116 patients were included in the analyses at 18-, 36- and 60-month follow-up, respectively. The percentages of patients who belonged to no (0 metabolic equivalent of task (MET)-hours per week), low-level (<10 MET-hours/week), and high-level (≥10 MET-hours/week) sports activities group were 20.7%, 45.5%, and 33.8% at 18-month follow-up, respectively; the corresponding figures at 36 and 60 months differed slightly. Using data from the three follow-ups, generalized estimating equation (GEE) analyses showed that higher levels of sports activities participation were associated with better QoL in several items as well as fewer symptoms. The present findings in Chinese women with breast cancer provide important evidence on the beneficial effect of regular participation in sports activities following cancer diagnosis on patients' QoL.

Quality of Life Associated with Nausea and Vomiting from Anthracycline-Based Chemotherapy: A Pooled Data Analysis from Three Prospective Trials.

BACKGROUND: There is limited work on the impact of chemotherapy-induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin-cyclophosphamide (AC)-treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients' QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. MATERIALS AND METHODS: This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index-emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included "no significant nausea" (NSN), "significant nausea" (SN), "no vomiting" (NoV), "vomiting" (V), and complete response (CR). RESULTS: Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p < .0001), with lower scores indicating better QoL; the mean scores for the FLIE vomiting domain for patients who experienced NoV versus V were 1.44 versus 19.11, respectively (p < .0001), with similar results across subsequent cycles. Analysis of the effect of the QoL in cycle 1 on the QoL of subsequent cycles revealed the following: for the nausea domain, among patients who had cycle 1 FLIE scores ≥ versus < the mean, the corresponding scores in cycle 2 were 6.87 versus 36.71 (p < .0001); whereas those for cycle 3 were 7.07 versus 36.87 (p < .0001); and those for cycle 4 were 5.92 versus 21.48 (p < .0001). Similar findings were observed for the vomiting domain. Netupitant + palonosetron- or aprepitant/olanzapine-based antiemetics had significantly better QoL outcomes. CONCLUSION: CINV had a significant impact on the QoL of patients with breast cancer treated with AC over multiple cycles. IMPLICATIONS FOR PRACTICE: In this post-hoc analysis of three prospective studies on chemotherapy-induced nausea and vomiting (CINV), quality of life (QoL) using contemporary antiemetic regimens in Chinese breast cancer patients receiving doxorubicin-cyclophosphamide (AC) was evaluated. During the first and subsequent AC cycles, QoL was significantly better for patients who did not experience vomiting or significant nausea. QoL in an earlier cycle affected the QoL in subsequent AC cycles. Furthermore, recent regimens involving olanzapine/aprepitant or netupitant-palonosetron were associated with a positive impact in QoL. Antiemetic guideline-consistent practice and higher clinician awareness of the impact of CINV on QoL can further mitigate the negative effects of CINV on QoL.

Weight and waist-to-hip ratio change pattern during the first five years of survival: data from a longitudinal observational Chinese breast cancer cohort.

BACKGROUND: Body weight management was an important component in breast cancer survivorship care. The present study described the change patterns of body weight and waist-to-hip ratio (WHR) during the first 5 years of survival, and investigated potential factors associated with very substantial changes. PATIENTS AND METHODS: Based on a longitudinal cohort with 1462 Chinese women with breast cancer, anthropometric measurements including body weight, height, waist and hip circumferences were measured by trained interviewers following standard protocol at four time-points: baseline at study entry, 18-, 36- and 60-months follow up assessments (termed as T0, T1, T2 and T3, respectively). Body height was measured at baseline and body weight at cancer diagnosis were retrieved from medical record. RESULTS: Compared to weight at breast cancer diagnosis, the median weight change was - 0.5 kg, 0 kg, + 0.5 kg, and + 1 kg at T0, T1, T2 and T3, respectively. During the first 5 years of survival, the proportion of women who were obese have slightly increased. At 60-months after diagnosis, only 14.3% of women had weight gain by > 5 kg; and the percentage of women who had weight gain by > 10% was 10.7%. Nearly half of patients had abdominal obesity at study entry, and this proportion were gradually increased to nearly 70% at 60-months follow-up. Multivariate analysis indicated that older age, and frequent sports participation during the first 5 years of survival were related to lower risk of very substantial weight gain (> 10%) at 60-month follow-up; patients aged 40-49 years, having ≥2 comorbidities and ER negative were associated with less likelihood of very substantial WHR substantial increase (> 10%) at 60-month follow-up. CONCLUSION: Weight gain was modest in Chinese breast cancer survivors during the first 5 years of survival, while central adiposity has become a contemporary public health issue. The incorporation of healthy weight and abdominal circumference patient education and management has a potential to improve cancer survivorship.

Menopausal symptoms inversely associated with quality of life: findings from a 5-year longitudinal cohort in Chinese breast cancer survivors.

OBJECTIVE: This study assessed menopausal symptoms (MPS) after breast cancer in relation to quality of life (QoL) during the first 5 years of survival. METHODS: An ongoing prospective study enrolled 1,462 Chinese women with early-stage breast cancer. They were longitudinally followed up at four time-points, namely baseline, 18-, 36-, and 60-month after diagnosis. At each follow-up, Menopause Rating Scale (MRS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were used to assess MPS and QoL, respectively. RESULTS: In total, 1,462, 1,289, 1,125, and 1,116 patients were included into the analyses at baseline, 18-, 36-, and 60-months, respectively. The percentages of patients with no or little, mild, moderate, and severe MPS at baseline were 31.8%, 30.0%, 30.4%, and 7.7%, respectively; the corresponding figures at 18-, 36-, and 60-month follow-up were similar. Using data from four follow-ups, Generalized Estimating Equations analyses showed that MPS was inversely associated with QoL. Higher MRS scores were related to lower QoL scores. For instance, every 1 point increase in MRS score was associated with a 1.5 point decrease in global health status/QoL score (P < 0.01). In terms of symptoms, higher MRS scores were related to more severe symptoms. CONCLUSIONS: This study highlighted patients with more severe MPS tend to have worse QoL. Future investigation should be conducted to assess different means of alleviating MPS to improve patient's QoL.

Dynamic Changes of Post-Radiotherapy Plasma Epstein-Barr Virus DNA in a Randomized Trial of Adjuvant Chemotherapy Versus Observation in Nasopharyngeal Cancer.

PURPOSE: To study the dynamic changes in plasma Epstein-Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC). EXPERIMENTAL DESIGN: We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS). RESULTS: We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy (n = 52) versus observation (n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation. CONCLUSIONS: Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.

Identification of optimal contemporary antiemetic prophylaxis for doxorubicin-cyclophosphamide chemotherapy in Chinese cancer patients: post-hoc analysis of 3 prospective studies.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis. METHODS: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1-3); Group 4, aprepitant/ondansetron/dexamethasone (D1-3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1-3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared. RESULTS: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% (P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% (P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% (P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively (P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively (P = 0.3459); Group 3 had a worse QOL. CONCLUSIONS: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit.

Durability of the parotid-sparing effect of intensity-modulated radiotherapy (IMRT) in early stage nasopharyngeal carcinoma: A 15-year follow-up of a randomized prospective study of IMRT versus two-dimensional radiotherapy.

BACKGROUND: The durability of improved xerostomia with intensity-modulated radiotherapy (IMRT) in patients with early stage nasopharyngeal carcinoma (NPC) is uncertain. We conducted a long-term prospective assessment of participants treated with IMRT or two-dimensional radiotherapy (2DRT) in a prior randomized study. METHODS: Parent study participants (IMRT, n = 28; 2DRT, n = 28) who were free of second malignancy or recurrence were eligible. Long-term radiotherapy-related toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Long-term patient-reported outcomes were assessed by the six-item xerostomia (XQ) and two European Organisation for Research and Treatment of Cancer (EORTC) questionnaires (QLQ-C30, QLQ-H&N35). Overall survival (OS), locoregional relapse-free survival (LRFS), distant relapse-free survival (DRFS), and the rate of symptomatic late complications (SLCs) were estimated for the entire cohort (n = 56). RESULTS: Totally, 21 (IMRT, n = 10; 2DRT, n = 11) patients gave consent and were assessed for an overall median follow-up of 15.5 years. There was significantly less RTOG ≥grade 2 xerostomia with IMRT versus 2DRT (20% vs. 90%; p = 0.001), but no significant difference in XQ scores. Patients in the IMRT arm reported lower mean scores for the "dry mouth" domain of EORTC QLQ-H&N35 (p = 0.02) and showed trends toward better 15-year OS (81.5% vs. 53.8%, p = 0.06), LRFS (70.6% vs. 53.8%, p = 0.38), and DRFS (81.5% vs. 53.8%, p = 0.07). SLCs were more frequent in the 2DRT arm. CONCLUSIONS: The parotid-sparing effect of IMRT in NPC treatment is durable, with significantly less physician- and patient-scored xerostomia at 15 years. IMRT results in better long-term survival and fewer SLCs.

Convolutional neural network in nasopharyngeal carcinoma: how good is automatic delineation for primary tumor on a non-contrast-enhanced fat-suppressed T2-weighted MRI?

PURPOSE: Convolutional neural networks (CNNs) show potential for delineating cancers on contrast-enhanced MRI (ce-MRI) but there are clinical scenarios in which administration of contrast is not desirable. We investigated performance of the CNN for delineating primary nasopharyngeal carcinoma (NPC) on non-contrast-enhanced images and compared the performance to that on ce-MRI. MATERIALS AND METHODS: We retrospectively analyzed primary NPC in 195 patients using a well-established CNN, U-Net, for tumor delineation on the non-contrast-enhanced fat-suppressed (fs)-T2W, ce-T1W and ce-fs-T1W images. The CNN-derived delineations were compared to manual delineations to obtain Dice similarity coefficient (DSC) and average surface distance (ASD). The DSC and ASD on fs-T2W were compared to those on ce-MRI. Primary tumor volumes (PTVs) of CNN-derived delineations were compared to that of manual delineations. RESULTS: The CNN for NPC delineation on fs-T2W images showed similar DSC (0.71 ± 0.09) and ASD (0.21 ± 0.48 cm) to those on ce-T1W images (0.71 ± 0.09 and 0.17 ± 0.19 cm, respectively) (p > 0.05), and lower DSC but similar ASD to ce-fs-T1W images (0.73 ± 0.09, p < 0.001; and 0.17 ± 0.20 cm, p > 0.05). The CNN overestimated PTVs on all sequences (p < 0.001). CONCLUSION: The CNN showed promise for NPC delineation on fs-T2W images in cases where it is desirable to avoid contrast agent injection. The CNN overestimated PTVs on all sequences.

Test-retest repeatability of T1rho (T1ρ) MR imaging in the head and neck.

PURPOSE: T1rho imaging is a new quantitative MRI sequence for head and neck cancer and the repeatability for this region is unknown. This study aimed to evaluate the repeatability of quantitative T1rho imaging in the head and neck. MATERIALS AND METHODS: T1rho imaging of the head and neck was prospectively performed in 15 healthy participants on three occasions. Scan 1 and 2 were performed with a time interval of 30 minutes (intra-session) and scan 3 was performed 14 days later (inter-session). T1rho values for normal tissues (parotid glands, palatine tonsils, pterygoid muscles, and tongue) were obtained on each scan. Intra-class coefficients (ICCs), within-subject coefficient of variances (wCoVs), and repeatability coefficient (RCs) of the intra-session scan (scan 1 vs 2) and inter-session scan (scan 1 vs 3) for the normal tissues were calculated. RESULTS: The ICCs of T1rho values for normal tissues were almost perfect (0.83-0.97) for intra-session scans and were substantial (0.71-0.80) for inter-session scans. The wCoVs showed a small range (2.46%-3.30%) for intra-session scans, and slightly greater range (3.27%-6.51%) for inter-session scan. The greatest and lowest wCoVs of T1rho were found in the parotid gland and muscles, respectively. The T1rho RCs varied for all tissues between intra- and inter- sessions, and the greatest RC of 10.07 msec was observed for parotid gland on inter-session scan. CONCLUSION: T1rho imaging is a repeatable quantitative MRI sequence in the head and neck but variances of T1rho values among tissues should be take into account during analysis.

Prospective Randomized Phase II Study of Stereotactic Body Radiotherapy (SBRT) vs. Conventional Fractionated Radiotherapy (CFRT) for Chinese Patients with Early-Stage Localized Prostate Cancer.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has potential radiobiologic and economic advantages over conventional fractionated radiotherapy (CFRT) in localized prostate cancer (PC). This study aimed to compare the effects of these two distinct fractionations on patient-reported quality of life (PRQOL) and tolerability. METHODS: In this prospective phase II study, patients with low- and intermediate-risk localized PC were randomly assigned in a 1:1 ratio to the SBRT (36.25 Gy/5 fractions/2 weeks) or CFRT (76 Gy/38 fractions/7.5 weeks) treatment groups. The primary endpoint of variation in PRQOL at 1 year was assessed by changes in the Expanded Prostate Cancer Index Composite (EPIC) questionnaire scores and analysed by z-tests and t-tests. RESULTS: Sixty-four eligible Chinese men were treated (SBRT, n = 31; CFRT, n = 33) with a median follow-up of 2.3 years. At 1 year, 40.0%/46.9% of SBRT/CFRT patients had a >5-point decrease in bowel score (p = 0.08/0.28), respectively, and 53.3%/46.9% had a >2-point decrease in urinary score (p = 0.21/0.07). There were no significant differences in EPIC score changes between the arms at 3, 6, 9 and 12 months, but SBRT was associated with significantly fewer grade ≥ 1 acute and 1-year late gastrointestinal toxicities (acute: 35% vs. 87%, p < 0.0001; 1-year late: 64% vs. 84%, p = 0.03), and grade ≥ 2 acute genitourinary toxicities (3% vs. 24%, p = 0.04) compared with CFRT. CONCLUSION: SBRT offered similar PRQOL and less toxicity compared with CFRT in Chinese men with localized PC.

Convolutional neural network for discriminating nasopharyngeal carcinoma and benign hyperplasia on MRI.

OBJECTIVES: A convolutional neural network (CNN) was adapted to automatically detect early-stage nasopharyngeal carcinoma (NPC) and discriminate it from benign hyperplasia on a non-contrast-enhanced MRI sequence for potential use in NPC screening programs. METHODS: We retrospectively analyzed 412 patients who underwent T2-weighted MRI, 203 of whom had biopsy-proven primary NPC confined to the nasopharynx (stage T1) and 209 had benign hyperplasia without NPC. Thirteen patients were sampled randomly to monitor the training process. We applied the Residual Attention Network architecture, adapted for three-dimensional MR images, and incorporated a slice-attention mechanism, to produce a CNN score of 0-1 for NPC probability. Threefold cross-validation was performed in 399 patients. CNN scores between the NPC and benign hyperplasia groups were compared using Student's t test. Receiver operating characteristic with the area under the curve (AUC) was performed to identify the optimal CNN score threshold. RESULTS: In each fold, significant differences were observed in the CNN scores between the NPC and benign hyperplasia groups (p < .01). The AUCs ranged from 0.95 to 0.97 with no significant differences between the folds (p = .35 to .92). The combined AUC from all three folds (n = 399) was 0.96, with an optimal CNN score threshold of > 0.71, producing a sensitivity, specificity, and accuracy of 92.4%, 90.6%, and 91.5%, respectively, for NPC detection. CONCLUSION: Our CNN method applied to T2-weighted MRI could discriminate between malignant and benign tissues in the nasopharynx, suggesting that it as a promising approach for the automated detection of early-stage NPC. KEY POINTS: • The convolutional neural network (CNN)-based algorithm could automatically discriminate between malignant and benign diseases using T2-weighted fat-suppressed MR images. • The CNN-based algorithm had an accuracy of 91.5% with an area under the receiver operator characteristic curve of 0.96 for discriminating early-stage T1 nasopharyngeal carcinoma from benign hyperplasia. • The CNN-based algorithm had a sensitivity of 92.4% and specificity of 90.6% for detecting early-stage nasopharyngeal carcinoma.