Clinical Consultation During a Trauma-Focused Cognitive Behavioral Therapy Community-Based Learning Collaborative: Examination of Consultation Content, Consultative Strategies, and Provider Engagement.

Consultation following evidence-based practice (EBP) training enhances the uptake of EBPs. Yet, little is known about what occurs during consultation, and it is often difficult for providers to engage in consultation. This study examined provider engagement in consultation and the content and strategies used during consultation following training in Trauma-focused Cognitive Behavioral Therapy (TF-CBT) as part of a community-based learning collaborative (CBLC). Minute-to-minute live coding of consultation calls revealed most content was clinically-oriented and the most common strategies used by consultants were didactic in nature. Providers with more years of professional experience and those with greater TF-CBT knowledge attended significantly more consultation calls. Providers with a greater average weekly caseload and providers who were supervisors presented significantly more cases on calls. Providers with greater TF-CBT knowledge spoke significantly more minutes on calls. Consistent with previous work, findings highlight difficulties with provider engagement in consultation and that providers with more baseline expertise are most likely to be engaged. Findings suggest tailoring EBP training efforts to better engage providers at greatest risk for low engagement.

Altered Epigenetic Marks and Gene Expression in Fetal Brain, and Postnatal Behavioural Disorders, Following Prenatal Exposure of Ogg1 Knockout Mice to Saline or Ethanol.

Oxoguanine glycosylase 1 (OGG1) is widely known to repair the reactive oxygen species (ROS)-initiated DNA lesion 8-oxoguanine (8-oxoG), and more recently was shown to act as an epigenetic modifier. We have previously shown that saline-exposed Ogg1 -/- knockout progeny exhibited learning and memory deficits, which were enhanced by in utero exposure to a single low dose of ethanol (EtOH) in both Ogg1 +/+ and -/- progeny, but more so in Ogg1 -/- progeny. Herein, OGG1-deficient progeny exposed in utero to a single low dose of EtOH or its saline vehicle exhibited OGG1- and/or EtOH-dependent alterations in global histone methylation and acetylation, DNA methylation and gene expression (Tet1 (Tet Methylcytosine Dioxygenase 1), Nlgn3 (Neuroligin 3), Hdac2 (Histone Deacetylase 2), Reln (Reelin) and Esr1 (Estrogen Receptor 1)) in fetal brains, and behavioural changes in open field activity, social interaction and ultrasonic vocalization, but not prepulse inhibition. OGG1- and EtOH-dependent changes in Esr1 and Esr2 mRNA and protein levels were sex-dependent, as was the association of Esr1 gene expression with gene activation mark histone H3 lysine 4 trimethylation (H3K4me3) and gene repression mark histone H3 lysine 27 trimethylation (H3K27me3) measured via ChIP-qPCR. The OGG1-dependent changes in global epigenetic marks and gene/protein expression in fetal brains, and postnatal behavioural changes, observed in both saline- and EtOH-exposed progeny, suggest the involvement of epigenetic mechanisms in developmental disorders mediated by 8-oxoG and/or OGG1. Epigenetic effects of OGG1 may be involved in ESR1-mediated gene regulation, which may be altered by physiological and EtOH-enhanced levels of ROS formation, possibly contributing to sex-dependent developmental disorders observed in Ogg1 knockout mice. The OGG1- and EtOH-dependent associations provide a basis for more comprehensive mechanistic studies to determine the causal involvement of oxidative DNA damage and epigenetic changes in ROS-mediated neurodevelopmental disorders.

Breast cancer 1 (BRCA1) protection in altered gene expression and neurodevelopmental disorders due to physiological and ethanol-enhanced reactive oxygen species formation.

The breast cancer 1 (Brca1) susceptibility gene regulates the repair of reactive oxygen species (ROS)-mediated DNA damage, which is implicated in neurodevelopmental disorders. Alcohol (ethanol, EtOH) exposure during pregnancy causes fetal alcohol spectrum disorders (FASD), including abnormal brain function, associated with enhanced ROS-initiated DNA damage. Herein, oxidative DNA damage in fetal brains and neurodevelopmental disorders were enhanced in saline-exposed +/- vs. +/+ Brca1 littermates. A single EtOH exposure during gestation further enhanced oxidative DNA damage, altered the expression of developmental/DNA damage response genes in fetal brains, and resulted in neurodevelopmental disorders, all of which were BRCA1-dependent. Pretreatment with the ROS inhibitor phenylbutylnitrone (PBN) blocked DNA damage and some neurodevelopmental disorders in both saline- and EtOH-exposed progeny, corroborating a ROS-dependent mechanism. Fetal BRCA1 protects against altered gene expression and neurodevelopmental disorders caused by both physiological and EtOH-enhanced levels of ROS formation. BRCA1 deficiencies may enhance the risk for FASD.

Evaluation of drug-free methods for the detection of gene silencing in Saccharomyces cerevisiae.

Multiple studies in Saccharomyces cerevisiae have measured the levels of gene silencing by inserting the URA3 gene at various loci and selecting against URA3-expressing cells by 5-flouroorotic acid (5-FOA). However, 5-FOA affects the cellular pools of dNTPs and can produce side effects. To circumvent this issue, we and others have introduced drug-free techniques to detect silent and active gene states. In this study, we compared three drug-free methods based on the expression of fluorescent reporters in the VIIL telomere of S. cerevisiae. Our results point out that only one of these methods is suitable for large-scale drug-free analyses of gene silencing.

Exploratory Study of NPC-0501 Trial: Optimal Cisplatin Dose of Concurrent and Induction/Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. EXPERIMENTAL DESIGN: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases was studied. RESULTS: Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (stage III: 90% vs. 75%; stage IVA-B: 80% vs. 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases versus suboptimal dose in each phase are significant independent factors for OS, with HR of 0.61 [95% confidence interval (CI), 0.41-0.91] and 0.67 (95% CI, 0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. CONCLUSIONS: Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at ≥160 mg/m2 when coupled with adequate induction/adjuvant dosage at ≥260 mg/m2 (or at least ≥240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.

Prognostic significance of abdominal obesity and its post-diagnosis change in a Chinese breast cancer cohort.

PURPOSE: It is well-known that obesity has an adverse impact on breast cancer prognosis; nonetheless, the prognostic role of abdominal obesity, especially its post-diagnosis change, has been understudied. This study aims to examine the prospective associations of general and abdominal obesity and their post-diagnosis changes with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence in Chinese breast cancer patients. METHODS: From 2011 to 2014, 1460 Chinese breast cancer patients were recruited and followed up at 18, 36, and 60 months after diagnosis. Body mass index (BMI), waist-to-hip ratio (WHR), and their changes between baseline and 18-month follow-up were derived. Clinical records on diagnosis, treatment, and death were also obtained. In total, 1309 women who completed the 18-month follow-up were included for Cox regression analyses, stratified by follow-up periods. RESULTS: Within 18-48 months post-diagnosis, substantial WHR loss (5% or above) had reduced risk of all-cause (HR = 0.21 [95% CI 0.06-0.75]) and breast cancer-specific mortality (0.21 [0.06-0.77]) relative to stable WHR; whereas after 48 months post-diagnosis, substantial WHR gain showed elevated risks of all-cause mortality (2.67 [1.22-5.85])). Higher baseline WHR was also associated with both mortality outcomes. Nonetheless, no such associations were observed for BMI measures. Also, the effects of obesity measures on breast recurrence were less apparent. CONCLUSION: Abdominal obesity, rather than general obesity, was linked to worse survival in Chinese breast cancer patients. Prevention on abdominal obesity and waist gain following breast cancer diagnosis may have a beneficial effect on longer-term survival over and above conventional weight management. Waist assessment and abdominal obesity control should therefore be incorporated as a vital component of the evaluation and interventions of breast cancer prognosis.

Induction chemotherapy followed by radical chemoradiotherapy for patients with stage IV non-metastatic nasopharyngeal carcinoma: 11-Year Experience in a tertiary centre.

INTRODUCTION: T4 nasopharyngeal carcinoma (NPC) with close proximity to critical organs at risk (OARs) is usually underdosed during radiotherapy in order to respect radiation constraints. N3 disease has high risk of distant metastasis. Induction chemotherapy (IC) provides advantages of sparing of OARs during subsequent chemoradiotherapy (CCRT) and early eradication of micrometastasis. However, factors predicting successes of IC in this patient group are not well-studied. METHODS: 104 T4 or N3 NPC patients were retrospectively reviewed during 2007-2018. They were planned for IC followed by CCRT using intensity-modulated radiotherapy. RESULTS: In the whole group, five-year failure-free survival (FFS), locoregional failure-free survival (LRFS), distant failure-free survival (DFFS) and overall survival (OS) were 40.9%, 45.7%, 46.9% and 53.6% respectively. Isolated marginal failure rate was 5% (4/80) among patients with primary tumours located close to critical OARs. Pre-IC gross tumour volume primary (GTVp) total volume > 110 cm3 correlated with worse five-year LRFS (OR 6.37, P = 0.008), DFFS (OR 8.89, P = 0.003) and OS (OR 50.12, P < 0.001). In the T4 subgroup, IC improved D100% GTVp from 61.39 Gy to 64.71 Gy (P < 0.001) and V100% GTVp from 98.78% to 99.28% (P < 0.001). CONCLUSION: Our study demonstrated improved dosimetric parameters and low isolated marginal failure rate. It supported the use of IC and CCRT for tumours located close to critical OARs. Further research is warranted to compare predictive roles of pre- and post-IC tumour volumes. For high-risk patients being defined by pre-IC volume or other prognostic models, treatment escalation should be considered.

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.

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.

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.

Dietary Pattern at 18-Month Post-Diagnosis and Outcomes of Breast Cancer Among Chinese Women with Early-Stage Breast Cancer.

BACKGROUND: Evidence of the association between dietary pattern and outcomes of breast cancer was limited in Asian women, including Chinese. PATIENTS AND METHODS: A prospective cohort study was initiated among Chinese breast cancer patients to investigate lifestyle habits and outcomes of breast cancer. At each follow-up, validated food frequency questionnaires (FFQ) were used to assess patients' dietary intake. This study included 1226 patients with invasive early-stage breast cancer with detailed data at 18-month follow-up after cancer diagnosis. Factor analysis was used to derive dietary patterns, whereby two dietary patterns were identified. Cox proportional hazards models were used to investigate associations between dietary patterns and time to outcome, including breast cancer recurrence, overall mortality and breast cancer-specific mortality. RESULTS: With a median follow-up time of 54.1 months, 165 patients had breast cancer recurrence and 98 deaths occurred. Two dietary patterns were identified: "Western dietary pattern" characterized by high intake of refined grains and cakes, red and processed meat and oil; "healthy dietary pattern" characterized by high consumption of vegetables and fruits. Participants in the highest tertile of "Western dietary pattern" did not have a higher risk of breast cancer recurrence (P trend = 0.89), overall mortality (P trend = 0.48) and breast cancer-specific mortality (P trend = 0.75). Similarly, a null association existed between "healthy dietary pattern" and outcomes of breast cancer. CONCLUSION: Neither dietary pattern was associated with risk of breast cancer recurrence, all-causes death or death from breast cancer. Prospective follow-up is still needed to further confirm the association between specific dietary pattern and outcomes of breast cancer.

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.

Pre-diagnosis and early post-diagnosis dietary soy isoflavone intake and survival outcomes: A prospective cohort study of early stage breast cancer survivors.

BACKGROUND: There is concern that the estrogen-like effects of soy isoflavones may stimulate mammary tumor growth and interfere with the efficacy of breast cancer treatment. This study aimed to examine prospectively the associations of dietary soy isoflavone intake with all-cause mortality and breast cancer (BC) specific mortality and recurrence among BC survivors. DESIGN: The study included 1460 Chinese women with early-stage incident BC. Pre-diagnosis and early post-diagnosis soy food intakes were assessed at study entry, and at 18-month follow-up using validated soy food frequency questionnaire. Associations of soy isoflavone intake with prognostic outcomes within 48 months were examined using multivariable adjusted Cox proportional hazards models. RESULTS: We observed increasing pre-diagnosis and early post-diagnosis soy isoflavone intakes up to the third quartile (Q3) were associated with reductions for adverse prognostic outcomes. Relative to the lowest quartile (Q1), the hazard ratios (HRs) for all-cause mortality for pre-diagnosis and post-diagnosis Q3 intake were respectively 0.34 (95% CI, 0.16-0.74), and 0.44 (95% CI, 0.22-0.89). A similar risk reduction was observed for pre- and post-diagnosis intakes and BC-specific mortality when comparing Q3 versus Q1 with the respective HRs 0.36 (95% CI, 0.16-0.82), and 0.49 (95% CI, 0.23-1.01). Subgroup analyses showed more favourable prognostic outcomes in association with moderate soy intake among premenopausal women, those with triple negative cancer and recipients of tamoxifen treatment. CONCLUSION: Moderate soy isoflavone intake was associated with favourable prognostic outcomes in Chinese early stage BC survivors.

Longitudinal change of quality of life in the first five years of survival among disease-free Chinese breast cancer survivors.

PURPOSE: This study aimed to investigate changes of QoL during the first 5 years of survival among disease-free Chinese breast cancer survivors. METHODS: A prospective cohort study enrolled 1462 Chinese women with early-stage breast cancer, and longitudinally visited those patients at four time-points, namely baseline (T0), 18- (T1), 36- (T2), and 60-month (T3) after diagnosis. This study included 992 patients who were disease-free during the first 5 years of survival and who had completed QoL assessments at all four time-points. RESULTS: The score of global health status/QoL improved gradually (T1, T2, T3 > T0; P < 0.001 for overall comparisons). Social functioning score significantly improved when compared to that of T0 (T1, T2, T3 > T0; P < 0.001 for overall comparisons). In contrast, cognitive functioning score decreased (T0 > T1, T2, T3; P < 0.001 for overall comparisons). Scores of physical functioning, role functioning and emotional functioning showed a fluctuated picture, with the highest score achieved at T1. In symptoms profile, most of them scored lowest at T1 (best QoL). Multivariate analysis showed that several characteristics significantly correlated to changes in QoL from T0 to T3. For instance, patients with higher education had better recovery of physical functioning, role functioning, and social functioning. CONCLUSION: During the first 5 years of survival, patients' global health status/QoL improved over time, social functioning consistently improved, but cognitive functioning steadily deteriorated. Most of functioning domains and symptoms improved at 18-month follow-up, but such improvements were not maintained and even deteriorated at 36- and 60-month post-diagnosis. This study suggested that some interventions should be investigated during such period.

Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci.

Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC-associated signals and provides mechanistic insight for disrupted transcription factor binding, altering target gene transcription. Two novel protective variants, rs2517664 (Trs2517664 = 4.6%, P = 6.38 × 10-21) and rs117495548 (Grs117495548 = 3.0%, P = 4.53 × 10-13), map near TRIM31 and TRIM39/TRIM39-RPP21; multiple independent protective signals map near HLA-B including a previously unreported variant, rs2523589 (P = 1.77 × 10-36). The rare HLA-B*07:05 allele (OR < 0.015, P = 5.83 × 10-21) is absent in NPC, but present in controls. The most prevalent haplotype lacks seven independent protective alleles (OR = 1.56) and the one with additional Asian-specific susceptibility rs9391681 allele (OR = 2.66) significantly increased NPC risk. Importantly, this study provides new evidence implicating two non-human leukocyte antigen (HLA) genes, E3 ubiquitin ligases, TRIM31 and TRIM39, impacting innate immune responses, with NPC risk reduction, independent of classical HLA class I/II alleles.

Longitudinal changes in sports activity from pre-diagnosis to first five years post-diagnosis: a prospective Chinese breast cancer cohort study.

BACKGROUND: To compare change in level of physical activity between pre-and post- diagnosis of breast cancer in Chinese women. METHODS: Based on an on-going prospective study consisting of a sample of Chinese women with breast cancer, a validated modified Chinese Baecke questionnaire was used to measure physical activity at baseline (12 months before cancer diagnosis), 18-, 36- and 60-months after diagnosis (over the previous 12 months before each interview). RESULTS: In our cohort of 1462 Chinese women with a mean age of 52 years, the mean level of physical activity at post-diagnosis was 9.6 metabolic equivalent of task (MET)-hours/week, which was significantly higher than that at pre-diagnosis with mean level of 5.9 MET-hours/week (P < 0.001). The mean levels of physical activity at 18-, 36- and 60-months follow-up were 9.9, 9.8 and 9.3 MET-hours/week, respectively. There was no significant difference between any two of the three follow-ups at post-diagnosis. The proportions of participant who met World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR) recommendation before and after cancer diagnosis were both low, being 20.7 and 35.1%, respectively. Compared to pre-diagnosis, most of the patients improved or had no change on level of physical activity at post-diagnosis, with the respective proportion being 48.2 and 43.8%. CONCLUSIONS: Adherence to current lifestyle recommendation for cancer survivors, Chinese women with breast cancer significantly increased level of physical activity level after cancer diagnosis, and such improvement was sustained to 5 years post-diagnosis. The proportion of patients who met the exercise recommendation for cancer survivors was still low. Encouraging patients on the importance of durable high level of physical activity in breast cancer survivorship is warranted.

NPC-0501 trial on the value of changing chemoradiotherapy sequence, replacing 5-fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma.

BACKGROUND: A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy (RT) with concurrent cisplatin followed by adjuvant cisplatin and 5-fluorouracil (PF). This randomized NPC-0501 trial evaluated the therapeutic effect of changing to an induction-concurrent sequence or accelerated-fractionation sequence, and/or replacing 5-fluorouracil with capecitabine (X). METHODS: Patients with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC initially were randomly allocated to 1 of 6 treatment arms (6-arm full-randomization cohort). The protocol was amended in 2009 to permit centers to opt out of randomization regarding fractionation (3-arm chemotherapy cohort). RESULTS: A total of 803 patients were accrued (1 of whom was nonevaluable) from 2006 to 2012. Based on the overall comparisons, neither changing the chemotherapy sequence nor accelerated fractionation improved treatment outcome. However, secondary analyses demonstrated that when adjusted for RT parameters and other significant factors, the induction-concurrent sequence, especially the induction-PX regimen, achieved significant improvements in progression-free survival (PFS) and overall survival. Efficacy varied among different RT groups: although no impact was observed in the accelerated-fractionation group and the 3-arm chemotherapy cohort, a comparison of the induction-concurrent versus concurrent-adjuvant sequence in the conventional-fractionation group demonstrated a significant benefit in PFS (78% vs 62% at 5 years; P = .015) and a marginal benefit in overall survival (84% vs 72%; P = .042) after adjusting for multiple comparisons. Comparison of the induction-PX versus the adjuvant-PF regimen demonstrated better PFS (78% vs 62%; P = .027) without an increase in overall late toxicity. CONCLUSIONS: For patients irradiated using conventional fractionation, changing the chemotherapy sequence from a concurrent-adjuvant to an induction-concurrent sequence, particularly using induction cisplatin and capecitabine, potentially could improve efficacy without an adverse impact on late toxicity. However, further validation is needed for confirmation of these findings.

The association between soy isoflavone intake and menopausal symptoms after breast cancer diagnosis: a prospective longitudinal cohort study on Chinese breast cancer patients.

PURPOSE: This study investigated the association between soy isoflavone intake and menopausal symptoms (MPS) among Chinese women with early stage breast cancer in a prospective cohort study. METHODS: In an on-going prospective cohort study that involved 1462 Chinese women with early stage breast cancer, MPS were assessed at 18, 36 and 60 months after cancer diagnosis using the validated menopausal rating scale (MRS) questionnaire. Daily soy food intake for the previous 12 months was assessed at the same time using a validated food frequency questionnaire. The associations between MPS and soy isoflavone intake were evaluated in multivariable logistic regression analyses. RESULTS: The prevalence of MPS was almost the same during the first 60 months after cancer diagnosis, which were 64.5%, 65.2%, and 63.9% at 18, 36, and 60 months, respectively. Patients with MPS tended to be younger than those without MPS. The intake of soy isoflavones was not associated with the total score of MRS at 18-month follow-up [highest vs lowest tertile, odds ratio (OR) = 1.00, 95% CI 0.75-1.34]. Similarly, no significant association was noted at 36-month (OR = 1.25, 95% CI 0.92-1.69) and 60-month (OR = 1.21, 95% CI 0.84-1.74) follow-up. With regards to specific domain within MRS, the risk of symptoms presenting in somatic domain was higher among breast cancer patients who were in the highest tertile of soy isoflavone intake at 36 months post-diagnosis (OR = 1.44, 95% CI 1.07-1.94, P-trend = 0.02), compared with the lowest tertile, where a stronger significant association was noted among patients who were younger than 60 years (OR = 1.52, 95% CI 1.05-2.20, P-trend = 0.03) and pre-menopausal (OR = 3.81, 95% CI 1.85-8.11, P-trend < 0.01). CONCLUSION: The present study provided further evidence that soy isoflavone consumption was not associated with MPS among Chinese breast cancer patients. In fact, patients with higher intake of soy isoflavone have increased risk of experiencing somatic symptoms.

A dosimetric comparison of the use of equally spaced beam (ESB), beam angle optimization (BAO), and volumetric modulated arc therapy (VMAT) in head and neck cancers treated by intensity modulated radiotherapy.

INTRODUCTION: Previous studies have shown that the beam arrangement had significant influence on plan quality in intensity modulated radiotherapy (IMRT). This study aimed to evaluate the dosimetric performance of beam arrangement methods by employing equally spaced beams (ESB), beam angle optimization (BAO), and volumetric modulated arc therapy (VMAT) in the planning of five types of head and neck (H&N) cancers treated by IMRT. METHODS: Five plans of different beam arrangement methods were optimized for 119 H&N cancer patients with the prescription of 66-70 Gy for high-risk planning target volume (PTV), 60 Gy for intermediate risk PTV, 54 Gy for low-risk PTV using a simultaneously integrated boost method. The five-beam arrangement methods were: ESB, coplanar BAO (BAOc), noncoplanar BAO (BAOnc), two-arc VMAT (VMAT2), and three-arc VMAT (VMAT3). The H&N cancers included cancers of nasopharynx, oral cavity, larynx, maxillary sinus, and parotid. Although the partial arc VMAT could be used in cases where the PTVs were situated at one side of the head such as the parotid, this arrangement was not included because it was intended to include only the beam arrangements that were applicable to all the types of head and neck cancers in the study. The plans were evaluated using a "figure-of-merit" known as uncomplicated target conformity index (UTCI). In addition, PTV conformation number and homogeneity index, normal tissue integral dose, and organ at risk (OAR) doses were also used. The mean values of these parameters were compared among the five plans. RESULTS: All treatment plans met the preset dose requirements for the target volumes and OARs. For nasopharyngeal cancer, VMAT3 and BAOnc demonstrated significantly higher UTCI. For cancer of oral cavity, most beam arrangement showed similar UTCI except ESB, which was relatively lower. For cancer of larynx, there was no significant difference in UTCI among the five-beam arrangement methods. For cancers of maxillary sinus and parotid gland, the two BAO methods showed marginally higher UTCI among all the five methods. CONCLUSION: Individual methods showed dosimetric advantages on certain aspects, and the UTCI of the BAO treatment plans are marginally greater in the case of maxillary sinus and parotid gland. However, if treatment time was included into consideration, VMAT plans would be recommended for cancers of the nasopharynx, oral cavity, and larynx.

Dysfunctional CAF-I reveals its role in cell cycle progression and differential regulation of gene silencing.

Chromatin Assembly Factor I (CAF-I) plays a central role in the reassembly of H3/H4 histones during DNA replication. In S. cerevisiae CAF-I is not essential and its loss is associated with reduced gene silencing at telomeres and increased sensitivity to DNA damage. Two kinases, Cyclin Dependent Kinase (CDK) and Dbf4-Dependent Kinase (DDK), are known to phosphorylate the Cac1p subunit of CAF-I, but their role in the regulation of CAF-I activity is not well understood. In this study we systematically mutated the phosphorylation target sites of these kinases. We show that concomitant mutations of the CDK and DDK target sites of Cac1p lead to growth retardation and significant cell cycle defects, altered cell morphology and increased sensitivity to DNA damage. Surprisingly, some mutations also produced flocculation, a phenotype that is lost in most laboratory strains, and displayed elevated expression of FLO genes. None of these effects is observed upon the destruction of CAF-I. In contrast, the mutations that caused flocculation did not affect gene silencing at the mating type and subtelomeric loci. We conclude that dysfunctional CAF-I produces severe phenotypes, which reveal a possible role of CAF-I in the coordination of DNA replication, chromatin reassembly and cell cycle progression. Our study highlights the role of phosphorylation of Cac1p by CDK and a putative role for DDK in the transmission and re-assembly of chromatin during DNA replication.