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Spina bifida (SB) is a congenital neural tube defect that often presents with neurological disability and decubitus ulcers. A 66-year-old woman with SB presented to our hospital with decubitus ulcers and was treated by a plastic surgeon. She was referred to our department because of a mass measuring 5 × 4 cm in the superolateral quadrant of the right breast. The size of the right axillary lymph node (LN) was 2 × 1 cm. A core-needle biopsy revealed an invasive ductal carcinoma. Total mastectomy and axillary LN dissection were planned. However, 2 days prior to surgery, the size of the mass and the LN rapidly increased to 7 × 4 cm and 3 × 2 cm, respectively. Furthermore, the enlarged LN was close to the thoracodorsal artery. Since complete resection was difficult, neoadjuvant chemotherapy was also administered. On day 11 of neoadjuvant chemotherapy, the patient was febrile and developed a decubitus ulcer infection at the buttock. The neutrophil count was within normal limits; thus, she was not diagnosed with febrile neutropenia. Follow-up computed tomography revealed a shrinking of the mass to 5 × 4 cm after the first cycle of neoadjuvant chemotherapy. After 17 days of antibiotic therapy and drainage, total mastectomy and axillary LN dissection were performed. Due to the risk of recurrence of infection, adjuvant chemotherapy was discontinued and hormone therapy was initiated. In conclusion, indications for chemotherapy should be carefully evaluated in SB patients with lower limb paralysis and decubitus ulcers. [ABSTRACT FROM AUTHOR]

The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the current status of reproductive disorders and provision of information on oncofertility to female adolescent and young adult (AYA) cancer patients in Japan. Methods: A national survey of AYA cancer survivors was conducted. Children were <15 years old, and AYAs were 15‐39 years old. Results from the survivors of other than gynecological disease who underwent chemotherapy were analyzed. Results: Among the survivors, 41.4% were concerned about their reproductive function and infertility, and 36.2% were aware of menstrual cycle abnormalities. Among them, 15.5% (n = 20) of all and 21.2% (n = 17) of the AYA‐onset survivors suffered infertility due to chemo‐ or radiotherapy and gave up childbearing. These rates were significantly higher than those of healthy AYAs. Although 80.8% of AYA‐onset survivors answered that they had received information on reproductive function and infertility, only 55.8% had received information on fertility preservation methods. Furthermore, only 22.4% of all and 42.3% of AYA‐onset survivors had received pretreatment information on fertility preservation methods. Conclusions: Not a few AYA cancer survivors reported reproductive dysfunction. These findings indicate that information provided on therapy‐related problems before cancer treatment in Japan was insufficient and highlight the need to improve patient decision‐making and support systems for fertility preservation. This the first report to discuss the current status of oncofertility in Japanese AYA cancer patients and survivors and to clarify the importance of the correct and timely provision of information on oncofertility to these patients in order to enlighten health care providers of its importance. [ABSTRACT FROM AUTHOR]

Background: Cancer is rare among adolescents and young adults (AYA). Affected persons need generation-specific attention and care; however, no nationwide study has investigated the medical care structure for AYA cancer treatment in Japan.Methods: We conducted a nationwide survey of AYA cancer for frequency of AYA patients, type of cancer, medical facilities, and certified cancer professionals. Data were collected from 14,713 patients at 218 Core Cancer Treatment Hospitals.Results: The average proportion of AYA cancer patients to all cancer patients was 3.6%. The median number of patients aged 15 to 24 years per hospital was small (n = 5, range 1-51). The most frequent primary site of AYA cancer was the cervix uteri, but when cancer in situ was excluded, the hematopoietic malignancies were the most frequent cancer in males and females aged 15-24 years. In the age group 25-39 years, testicular and breast cancers were the most frequent cancers in males and females, respectively. Certified cancer professionals and facilities are necessary for appropriate care of AYA cancer patients, but the availability of such professionals varied greatly among hospitals. Hospitals with few AYA cancer patients were less likely to employ such physicians.Conclusions: The present findings suggest that medical care for AYA cancer in Japan requires further refinement and a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Since breast cancers in young women are generally aggressive, young patients tend to be intensively treated with anti-cancer drugs. To optimize the strategy for treatment, particularly in young women, prognostic biomarkers are urgently required. The objective of this study was to identify a tissue microRNA (miRNA) signature that predicts prognosis in young breast cancer patients. Total RNA from 45 breast cancer patients aged <35 years was extracted from formalin-fixed paraffin-embedded (FFPE) tissues and analyzed using miRNA microarrays. Patients were categorized into two groups according to recurrence status within the 5 year period after surgery: recurrence (n = 11) and non-recurrent (n = 34). Histological parameters of hormone receptors and Ki-67 were statistically compared between the two groups. Differentially expressed miRNAs were identified, and their associations with overall survival (OS) were evaluated by log-rank test. The median observation period was 5.8 years for the recurrent group, and 9.1 years for the non-recurrent group. Nine miRNAs were significantly differentially expressed between the recurrent and non-recurrent groups. Receiver Operating Characteristic curve analysis was performed to evaluate the prediction accuracy of the identified miRNAs, and the resultant area under the curve was >0.7. Five of the miRNAs were validated by qRT-PCR, and the expression levels of three of those five (miR-183-5p, miR-194-5p, and miR-1285-5p), both alone and in combination, were associated with OS. In conclusion, we identified three candidate miRNAs that could be used separately or in combination as prognostic biomarkers in young breast cancer patients. This miRNA signature may enable selection of better treatment choices for young women with this disease. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to describe physicians' clinical practice of discussing fertility issues with cancer patients and determine the factors associated with such discussion.Methods: In this cross-sectional study, a nationwide Internet survey was conducted among physicians who provided daily medical care to cancer patients at hospitals or clinics. Participants answered a questionnaire assessing characteristics, discussion practices, attitudes, and barriers regarding fertility preservation.Results: Among the 180 participants, 42% discussed fertility issues with patients daily, and 30% had experience in referring patients to fertility preservation specialists. A multivariate logistic regression analysis showed that those who agreed or strongly agreed with the statements "physicians are responsible for discussing fertility preservation" (OR = 2.04, 95% CI 1.14-3.63, p < 0.05) and "patients who have an exceedingly aggressive disease and need immediate cancer treatment should not be told about fertility issues" (OR =1.84, 95% CI 1.09-3.10, p < 0.05) were nearly twice as likely to discuss fertility issues with patients.Conclusions: Compared to Western countries, fertility issues are less likely to be discussed in Japan. To increase opportunities for patients to discuss fertility issues, the ASCO guidelines should be widely understood. Additionally, these results suggest that physicians who are more likely to discuss fertility issues might feel more conflicted about whether they in fact should discuss such issues with patients with poor prognosis or insufficient time for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Information regarding hematological toxicities in breast cancer chemotherapy patients with hepatitis B (HBV) or C virus (HCV) infection is limited. Methods: We retrospectively reviewed the presence of hepatotoxicities (i.e. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin elevation) and hematotoxicities (i.e. leukopenia and thrombocytopenia) among breast cancer patients with HBV or HCV infection who received chemotherapy from 1999 to 2010. All of the patients included in this analysis were classified as Child-Pugh A. Results: Among 32 patients with HBV infection who underwent chemotherapy (total cycles, 378), 3 experienced grade 3/4 hepatotoxicities, requiring 2 treatment delays and 1 treatment revision. Further, 9 patients experienced grade 3/4 hematotoxicities; of these, 2 required treatment delays and 3 required treatment revisions. Fifty-two HCV patients underwent a total of 570 cycles of chemotherapy. Five patients experienced grade 3/4 hepatotoxicities and required treatment delays, whereas 10 patients experienced grade 3 hematotoxicities; 3 of these patients required treatment delays. Conclusion: Hematotoxicities requiring chemotherapy dose or treatment revision were not highly prevalent among breast cancer chemotherapy patients with HBV or HCV infection and a normal range of liver function. Under careful monitoring, chemotherapy dosage or schedule adjustments may not be necessary in similar patients positive for HBV or HCV. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to analyze the prognostic impact of suboptimal treatment in patients with mediastinal primary nonseminomatous germ cell tumor (MNSGCT). Methods: We retrospectively reviewed the clinical data of 23 consecutive MNSGCT patients who were referred to the National Cancer Center Hospital between 1999 and 2007. Optimal treatment was defined as a primary chemotherapy regimen comprising a standard dosage of bleomycin + etoposide + cisplatin or etoposide + ifosfamide + cisplatin with sufficient dose intensity according to the guidelines of the European Germ Cell Cancer Consensus Group. Results: Ten and 13 patients received optimal and suboptimal treatment, respectively. The progression-free survival was statistically different between the patients who received optimal and suboptimal treatment (p = 0.01), and the hazard ratio of the optimal treatment group relative to the suboptimal treatment group was 0.19 (95% CI, 0.04–0.89). Although the overall survival was not statistically different between the 2 patient groups (p = 0.12), the hazard ratio in this regard was 0.36 (95% CI, 0.10–1.38). Conclusions: Patients who receive suboptimal treatment have poor clinical outcomes. Providing treatment after considering evidence-based guidelines may be important for improving the clinical outcomes of MNSGCT patients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Significant achievements in the systemic treatment of advanced breast cancer over the past years have led to a growing number of possible drugs, combinations and sequences to be tested in clinical trials. The definition and choice of end points for such trials have thus become a critical issue and have generated increasing interest in the recent literature. Nearly two-thirds of recent randomized trials in advanced breast cancer have used progression-free survival (PFS) or time to tumor progression (TTP) as the primary end point. PFS and TTP are attractive end points because they are available earlier than overall survival (OS) and are not influenced by treatments administered in subsequent lines. Therefore, PFS and TTP have been used and accepted by regulatory agencies as surrogates for OS. However, the formal process for validation of surrogate end points is complex and has produced controversial results in advanced breast cancer. Also, the question of whether PFS and TTP can be considered acceptable end points depends not only on formal validation but also on standardized definition and unbiased ascertainment of disease progression in clinical trials. On the other hand, the availability of effective subsequent-line therapies questions the validity of OS as the end point of interest in clinical trials in breast cancer, although gain in OS clearly remains the ultimate goal of therapy for patients in clinical practice. Thus, a pressing question is whether PFS or TTP sufficiently reflect clinical benefit to be considered as true, rather than surrogate end points in and of themselves. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NC) is standard therapy for patients with locally advanced breast cancer and is increasingly used for early-stage operable disease. Clinical and pathological responses are important prognostic parameters for NC, which aims to achieve a pathological complete response or tumor reduction to reduce the volume of subsequent breast resection. Clinicopathological markers that predict patient response to NC are needed to individualize treatment. From 1998 to 2006, 368 patients with primary breast cancer underwent curative surgical treatment after NC (anthracycline and/or taxane without trastuzumab). We retrospectively evaluated the clinicopathological features and classification of the tumors using computed tomography (CT) before NC and analyzed the correlation with the pathological complete response (pCR) and reduction of tumor size after treatment. The overall response and pCR rates in these patients were 86% and 17%, respectively. In multivariate analysis, classification as a scirrhous-type tumor was an independent predictor of reduced likelihood of pCR ( p = 0.0115; odds ratio 0.21). For tumor reduction, histological grade 3 ( p = 0.0002; odds ratio 3.3) and localized tumors identified by using CT imaging ( p = 0.0126; odds ratio 2.4) were independent predictors in multivariate analysis. In this study, NC often did not result in pCR for breast cancers classified as scirrhous. Furthermore, tumor type classification using CT imaging and histological grading was effective to predict tumor reduction in response to NC that included an anthracycline and/or a taxane. [ABSTRACT FROM AUTHOR]

A 60-year-old woman with a history of ovarian carcinoma and complaining of gait instability, dizziness, nausea, and a right temporal headache visited a neurologist. A diagnosis of leptomeningeal metastasis was made, based on the results of a cerebrospinal fluid examination. After the administration of intrathecal methotrexate, her neurological complaints disappeared. An Ommaya intraventricular reservoir was inserted, and methotrexate administration was continued for 11 months, until another recurrence was found in her pelvis. Although uncommon, the possibility of leptomeningeal metastasis from ovarian carcinoma should be considered; in such cases, treatment with intraventricular methotrexate may be effective and feasible and should be considered as a treatment strategy. [ABSTRACT FROM AUTHOR]

Cancer of unknown primary (CUP) is not a rare clinical entity, accounting for 3%–5% of all solid malignancies. We retrospectively reviewed 86 (38 male/48 female) patients with a diagnosis of CUP (exclusive of female patients with adenocarcinoma involving the axillary lymph nodes alone and patients with squamous cell carcinoma of the cervical lymph nodes) who were referred to the National Cancer Center Hospital between April 1996 and October 2002. The median interval between the first visit to a local community hospital and referral to our hospital was 1 month (range, 1 to 45 months). The histological diagnosis was adenocarcinoma in 61 patients (71%), poorly differentiated carcinoma in 18 patients (21%), and squamous cell carcinoma in 4 patients (5%). Twenty-three female patients had peritoneal carcinomatosis of adenocarcinoma. Seventy-eight patients (91%) received platinum-containing chemotherapy. Sixty-one of the 86 patients (71%) were categorized as a subgroup of CUP without a specific therapy, and 55 of these 61 patients (90%) received platinum-containing regimens. The median survivals of all 86 patients and the 61 patients in the subgroup without a specific therapy in this series were 13 months and 11 months, respectively. In this series, the survival of the patients in the CUP subgroup without a specific therapy did not seem worse than that in previous reports. Empirical chemotherapy with platinum-containing regimens may benefit some CUP patients in a subgroup without a specific chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : Irinotecan is one of the drugs that might be effective against platinum- and taxanes-resistant epithelial ovarian cancer. We investigated efficacy and safety of the weekly dosing schedule of irinotecan. Methods. : From September 2001 to March 2003, 28 eligible patients who have histologically confirmed epithelial ovarian cancer, which was resistant or refractory to both platinum and taxanes, were consecutively treated at the National Cancer Center Hospital. Irinotecan (100 mg/m2) was administered intravenously over 90 min on days 1, 8, and 15. The chemotherapy was repeated every 4 weeks, up to 6 cycles. Results. : A total of 107 treatment cycles of irinotecan were administered to 28 patients. The median number of prior chemotherapy regimen was 3. Among 28 patients, 8 (29%) responded to irinotecan (2 complete responses and 6 partial responses). The median time to progression was 17 weeks. Three patients experienced hematological toxicities of Grade 4. Five patients experienced non-hematological toxicities Grade 3 or 4. No treatment-related death occurred. Conclusion. : The weekly dosing schedule of irinotecan seems to be effective and safe salvage chemotherapy regimen for platinum- and taxanes-resistant or refractory epithelial ovarian cancer. Gastrointestinal toxicities, especially diarrhea, were moderate and manageable in an outpatient setting. [Copyright &y& Elsevier]