Knowledge, attitudes and intention on fertility preservation among breast cancer patients.

Breast cancer is the most common cancer in reproductive age women. The aim of this study is to assess the knowledge, attitude and intention on fertility preservation among women diagnosed to have breast cancer. This is a multi-centre cross-sectional questionnaire study. Reproductive age women diagnosed with breast cancer attending Oncology, Breast Surgery and Gynaecology Clinics and support groups were invited to participate. Women filled in paper or electronic form of the questionnaire. 461 women were recruited and 421 women returned the questionnaire. Overall, 181/410 (44.1%) women had heard of fertility preservation. Younger age and higher education level were significantly associated with increased awareness of fertility preservation. Awareness and acceptance of the different fertility preservation methods in reproductive age women with breast cancer was suboptimal. However, 46.1% women felt that their fertility concerns affected their decision for cancer treatment in some way.

Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens.

PURPOSE: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. METHODS: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. RESULTS: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. CONCLUSION: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. CLINICAL TRIAL REGISTRATION: NCT01808573.

Trastuzumab emtansine (T-DM1) versus trastuzumab in Chinese patients with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy for HER2-positive breast cancer in the phase 3 KATHERINE study.

PURPOSE: In the KATHERINE study (NCT01772472), patients with HER2-positive early breast cancer (EBC) and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy who were treated with adjuvant trastuzumab emtansine (T-DM1) had a 50% reduction in the risk of an invasive disease-free survival (IDFS) event compared to patients treated with adjuvant trastuzumab. In metastatic disease, T-DM1 has resulted in higher rates of thrombocytopenia in Asian versus non-Asian patients. Here, we report safety and efficacy in Chinese patients from KATHERINE. METHODS: Patients with HER2-positive EBC and residual invasive disease after taxane- and trastuzumab-containing neoadjuvant chemotherapy followed by surgery were randomized 1:1 to 14 cycles of adjuvant T-DM1 or trastuzumab. The primary endpoint was time to an IDFS event. RESULTS: Among Chinese patients (T-DM1 n = 51, trastuzumab n = 50), T-DM1 treatment resulted in a 43% reduction in risk of an IDFS event compared to trastuzumab (HR = 0.57; 95% CI 0.25-1.31), with similar results for secondary endpoints. As in the global population, Chinese patients receiving T-DM1 versus trastuzumab had more grade ≥ 3 adverse events (AEs; 39.2% versus 4.1%) and AEs leading to treatment discontinuation (27.5% versus 0%). The most common grade ≥ 3 AE with T-DM1 was thrombocytopenia (21.6%), a frequency higher than the frequency in the global population (5.7%). Grade ≥ 3 hemorrhage was reported in 1 patient (T-DM1 arm). CONCLUSIONS: In the KATHERINE study, T-DM1 demonstrated increased efficacy compared to trastuzumab in Chinese patients. Consistent with previous data in Asian patients, T-DM1 was associated with more grade ≥ 3 AEs, and AEs leading to discontinuation, which was driven by an increase in thrombocytopenia.

BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy.

PURPOSE: BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. MATERIALS AND METHODS: Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored. RESULTS: p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib. CONCLUSION: The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Prognostic value of lymphocyte-monocyte ratio at diagnosis in Hodgkin lymphoma: a meta-analysis.

BACKGROUND: Prognoses of most adult Hodgkin lymphoma (HL) patients are excellent; most of them can achieve permanent remission that can be considered cured. However, many are under-treated or over-treated by standard modern therapies. An accurate determination of prognosis may allow clinicians to design personalised treatment according to individual risk of disease progression and survival. Lymphocyte monocyte ratio (LMR) at diagnosis has been investigated as a prognostic biomarker in patients with HL. Our objective with this meta-analysis was to explore the prognostic value of the LMR at diagnosis in adult HL, by investigating the association between LMR and survival outcomes. METHODS: PUBMED and EMBASE were searched for relevant articles. Survival outcomes that we investigated included overall survival (OS), progression-free survival (PFS), event-free survival (EFS), lymphoma-specific survival (LSS), and time to progression (TTP). No restriction to the language, date, study country, or sample size was applied. Final search of databases was performed on 2 April 2018. We performed random-effects meta-analysis to aggregate and summarise the results from included studies, where four or more studies on a particular outcome were available. RESULTS: A total of eight studies (all retrospective cohort studies) involving 3319 HL patients were selected for analysis. All studies except one reported the effect of LMR on OS; five reported on PFS, three reported on TTP and LSS, respectively, and one reported on EFS. The pooled estimates showed low LMR was associated with poor OS (hazard ratio [HR] 2.67, 95% CI 1.67, 4.26) and PFS (HR 2.19, 95% CI 1.46, 3.29). Subgroup analyses of OS stratified by LMR cut-off values and sample sizes both indicated that low baseline LMR was associated with poorer prognosis. CONCLUSIONS: Low LMR at diagnosis was associated with poor OS and PFS in HL. LMR is easy and cheap to determine and has a potential role in daily clinical management. More studies are needed to validate this biomarker and explore its interaction with known prognostic factors.

The Value of Prognostic Nutritional Index in Follicular Lymphoma.

OBJECTIVES: Previous studies reported that prognostic nutritional index (PNI), a marker of host inflammatory and nutritional status, is associated with prognoses in a number of cancer types. Thus, we investigated PNI at diagnosis as a prognostic factor in FL. METHODS: We reviewed FL patients in Tuen Mun Hospital, Hong Kong from 2000 to 2014 (n=88). PNI was calculated by serum albumin (g/L)+5×absolute lymphocyte count (10/L). We determined the best PNI cut-off value using receiver-operating characteristic curves. The extent to which progression-free survival (PFS) and overall survival differed by PNI cut-off was assessed using Kaplan-Meier and log-rank tests. Cox proportional hazards model was utilized to adjust for covariates. RESULTS: The best cut-off value for PNI was determined to be 45. Patients with high PNI (>45) had a higher complete response (CR) rate after primary treatment, 46 of 61 (75.4%) patients with high PNI had CR, compared with 10 of 23 (43.5%) for low PNI (2-sample test of proportions P-value=0.006). Further, higher PNI at relapse as a continuous variable was associated with superior postprogression survival with a hazard ratio (HR) 0.88 (95% confidence interval [CI], 0.81-0.96). In multivariate analysis, high PNI at diagnosis had superior PFS (adjusted HR of 0.37; 95% CI, 0.15-0.93). CONCLUSIONS: PNI was shown to be independent prognostic factor of PFS in FL. It is a cheap and widely available biomarker. Future study is needed to validate its prognostic value and clinical utility in a prospective cohort.

The Role of Radiotherapy in Early-stage Primary Diffuse Large B-Cell Lymphoma of the Waldeyer Ring: A Retrospective Cohort Study.

OBJECTIVES: The role of radiotherapy (RT) in improving survival of patients with diffuse large B-cell lymphoma (DLBCL) of the Waldeyer ring (WR) remains controversial. Therefore, this retrospective cohort study aimed to determine the role of RT in the treatment of DLBCL of the WR as well as the effects of associated covariates. MATERIALS AND METHODS: Patients (n=35) with stage I to II DLBCL of the WR who underwent treatment at our center between 1994 and 2010 were retrospectively investigated. All patients had histologic diagnosis and staging workup completed. Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were analyzed. Variables with a P-value of <0.1 were subjected to multivariate Cox proportional hazards model analyses. RESULTS: The median OS was 8.1 years. The 5-year OS, DFS, and EFS rates were 59.4%, 53.8%, and 70.7%, respectively; the corresponding 10-year rates were 34.9%, 29.5%, and 51.0%, respectively. The 5-year OS rate was significantly higher in the RT group than in the non-RT group (65.4% vs. 36.4%, respectively; P=0.008). On multivariate analysis, RT was associated with improved OS (hazard ratio=0.15; 95% confidence interval [CI], 0.04-0.50; P=0.002) and EFS (hazard ratio=0.29; 95% CI, 0.095-0.86; P=0.026). An Eastern Cooperative Oncology Group performance status >1 and age above 60 years were also found to negatively influence OS and EFS. CONCLUSIONS: RT was associated with improved OS and EFS in stage I to II DLBCL of the WR. Future prospective studies are required to confirm these findings.

Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1.

BACKGROUND: The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial. METHODS: Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR-) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety. RESULTS: In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61-1.11)). In the HR- subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29-0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm. CONCLUSIONS: The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00876395 . Registered on 2 April 2009.

Aspirin and risk of multiple myeloma in adults: A systematic review and meta-analysis.

Multiple myeloma is a relatively uncommon plasma cell malignancy. Preclinical and clinical studies have suggested that aspirin might modify the risk of multiple myeloma. We performed a systematic review and meta-analysis of studies to examine the association between regular aspirin use and risk of multiple myeloma. Five observational studies including 332,660 adults were evaluated. The pooled estimate had a hazard ratio of 0.90 (95% confidence interval =0.58-1.39; P=0.638). Odds ratios from the two case-control studies were similar. The findings demonstrated that there was no significant association between aspirin use and the risk of multiple myeloma.

Clinical features and treatment outcomes of Hodgkin's lymphoma in Hong Kong Chinese.

INTRODUCTION: Little information is available on the outcomes of Hodgkin's lymphoma in Chinese patients. We analyzed the clinical and histopathological characteristics, treatment types, clinical course and treatment outcomes of Hong Kong Chinese patients. MATERIAL AND METHODS: Patients with Hodgkin's lymphoma diagnosed from January 1991 to December 2010 were recruited. A retrospective analysis of these patients was performed. RESULTS: Sixty-seven Chinese patients (38 males and 29 females) were identified and the median age was 36 (range 16-80). Nodular sclerosis was the most common histology (54%), followed by mixed cellularity (36%). Twenty-four patients had early favorable, 20 patients had early unfavorable and 23 patients had advanced-stage diseases. The most common presentation was palpable lymph node or mass (85%) followed by fever, weight loss, night sweating and mediastinal mass. Ninety percent of patients received chemotherapy and 40% received radiotherapy as consolidation. Seven patients with stage I lymphoma received radiotherapy alone. ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) was the most commonly used chemotherapeutic regimen. Following treatment, 87% of patients achieved complete remission. Six patients relapsed after first remission and 3 achieved second remission after re-induction therapy. The 5-year overall survival of the entire cohort was 89% and the freedom from treatment failure (FFTF) at 5 years was 82%. The 5-year overall survival rate for early favorable, early unfavorable and advanced stages was 95.7%, 95.0% and 74.7%, respectively. CONCLUSIONS: Despite the relatively low incidence of Hodgkin's lymphoma in Hong Kong Chinese, the treatment outcomes are comparable to Caucasian patients.

Concurrent celecoxib with 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel for stages II - III invasive breast cancer: the OOTR-N001 study.

OBJECTIVES: This prospective study aimed at investigating the efficacy and safety of the concurrent use of celecoxib (CXB) with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), followed by docetaxel (T) in the neoadjuvant setting. PATIENTS AND METHODS: A total of 64 invasive breast cancer patients were recruited in the N001 Phase II, multicenter, open-label, single-arm study to receive four cycles of FEC (500, 100, 500 mg/m(2)) followed by four cycles of T (100 mg/m(2)) with concurrent CXB (200 mg b.i.d.) as neoadjuvant therapy (NAT). The combined chemotherapies were administered on day 1 of each cycle every 3 weeks. Primary endpoints were pathologic complete response (pCR) rate and objective response rate (ORR). Quasi-pCR (QpCR), pCR and near pCR (npCR) were discussed considering their similar survival outcomes. ORR included clinical complete response (cCR) and clinical partial response (cPR). Secondary endpoints included safety, breast conservation rate and disease-free survival. RESULTS: Between February 2006 and January 2010, 57 of 64 evaluable patients with luminal A (n = 35, 61.4%), luminal B (n = 12, 21.1%), HER-2 positive (n = 8, 14%) and triple-negative (n = 2, 3.5%) breast cancer completed NAT and surgery. QpCR rate was observed in 18 (31.6%) patients. Exclusive of triple-negative subtype, pCR (p = 0.761) did not differ compared to other subtypes, while npCR (p = 0.043) exhibited a difference. Patients with HER-2 overexpression had a significantly higher QpCR than those of the disease attribute (10/20 vs 8/37, p = 0.029). After NAT, 43 (75.4%) and 13 (22.8%) patients achieved cCR and cPR, respectively. Patients responding to FEC were more likely to achieve a better ORR after subsequent T (p = 0.004). Over 80% of all patients received breast-conserving therapy (BCT) after receiving NAT, and 11 of 14 (78.6%) patients with T3 tumor at diagnosis became eligible for BCT after NAT. A total of 60 patients completed ≥ 6 cycles of NAT, followed by surgery; at a median follow-up of 50 months, 80% of the patients are disease-free. Neither drug-induced life-threatening toxicity nor cardiotoxicity was observed. CONCLUSIONS: Neoadjuvant use of FEC-T with concurrent CXB is active and safe for treatment of operable invasive breast cancer. The ORR was higher, but QpCR was comparable to other studies. Most patients are still disease-free, and BCT became an option for the females. Further clinical and translational studies on the use of cyclooxygenase-2 inhibitors with neoadjuvant chemotherapy are warranted.

Treatment results of 1070 patients with nasopharyngeal carcinoma: an analysis of survival and failure patterns.

BACKGROUND: The aim of this analysis was to evaluate the outcomes of patients with nasopharyngeal carcinoma (NPC) treated primarily by external beam irradiation (ERT) and to explore for possible ways to improve the treatment results. METHODS: One thousand seventy patients with nonmetastatic NPC treated from 1990 to 1998 were retrospectively analyzed. The distribution according to the Union Internationale Contre le Cancer (UICC) (1997 edition) staging system at initial diagnosis was as follows: stage I, n = 113; stage IIA, n = 38; stage IIB, n = 360; stage III, n = 306; stage IVA, n = 136; stage IVB, n = 117; T1, n = 284; T2a, n = 88; T2b, n = 398; T3, n = 149; T4, n = 151; N0, n = 321; N1, n = 393; N2, n = 238; N3a, n = 29; N3b, n = 89. Two hundred eight patients were given neoadjuvant chemotherapy. Ninety-seven patients were diagnosed with locally persistent disease and were salvaged with high dose rate intracavitary brachytherapy. Multivariate analysis was performed with the Cox regression proportional hazards model. RESULTS: The 5-year actuarial local failure-free survival, regional failure-free survival, distant metastasis-free survival, progression-free survival, cancer-specific survival, and overall survival rates were 80.9%, 93.3%, 77.2%, 62.7%, 71.4%, and 66.5%, respectively. Isolated distant metastasis occurred in 191 patients (18%). The distributions were as follow: stage I, 2.1% (two of 95); stage IIA, 5.7% (two of 35); stage IIB, 14.9% (45 of 302); stage III, 26.4% (62 of 235); stage IVA, 40% (40 of 100); stage IVB, 47.1% (40 of 85). Results of the multivariate analysis of various clinical endpoints were discussed. By studying these failure patterns, it is hoped that we could refine future treatments according to the failure patterns of patients with different risks of locoregional and distant failure. CONCLUSIONS: The 18% incidence of isolated distant metastasis is too high to be ignored. Maximizing the local control and minimizing the risk of distant metastasis and late complications should be the key objectives in designing future clinical trials.

High dose rate brachytherapy for early stage oral tongue cancer.

BACKGROUND: High dose rate (HDR) interstitial brachytherapy of the oral tongue is a new treatment modality. Our study evaluates the outcomes of patients with early stage oral tongue cancer as treated by HDR interstitial implant. METHODS: We reviewed the records of 19 patients who were seen between 1994 and 2000 with carcinoma of the oral tongue and whose primary tumors were treated solely with interstitial implant using HDR remote afterloading technique. Ten patients had T1 N0 disease, and the remaining 9 had T2 N0 disease. Elective neck treatment was withheld for 12 patients. The remaining seven patients had ipsilateral elective neck dissection. The male-female ratio was 1:0.9, and the median age was 60 years (range, 32-81 years). The median follow-up time was 43 months (range, 6-78 months). The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Fifteen patients had single planar implants, and the remaining four had double planar implants. The median number of catheters inserted was 5 (range, 4-9). The median dose given was 55 Gy in 10 fractions over 6 days. The minimal interfraction interval was 7 hours for the first 7 patients and was extended to 8 hours for the other 12. Mandibular shields were inserted before treatment. RESULTS: The mucositis lasted for 6 to 20 weeks (median, 9 weeks). One patient had local failure, and the 4-year local failure-free survival rate was 94.7%. Three of the 12 patients without elective neck treatment had ipsilateral regional failure develop. They were salvaged by neck node dissection and regionally remained in control. One patient with multiple nodal metastases and extracapsular spread had biopsy-proven liver metastases and died 6 months after implant. One of the seven patients who were treated with elective neck dissection had multiple nodal metastases and extracapsular spread. She was treated with postoperative radiotherapy to the neck. She died 30 months after implant with evidence of regional and distant failure. One patient treated with double planar implant had grade II necrosis of the soft tissue and bone develop. The necrosis resolved with conservative treatment. Another four patients had small area of soft tissue deficit of the tongue attributed to aggressive debulking or biopsy before brachytherapy. CONCLUSIONS: Our experience in treating early stage tongue cancer with HDR remote afterloading technique is encouraging, because it gives a local control rate of 94.7% at 4 years with acceptable morbidity. Further studies are eagerly awaited to delineate the optimum schedule for this new treatment modality.