Low-rank tensor methods for Markov chains with applications to tumor progression models.

Cancer progression can be described by continuous-time Markov chains whose state space grows exponentially in the number of somatic mutations. The age of a tumor at diagnosis is typically unknown. Therefore, the quantity of interest is the time-marginal distribution over all possible genotypes of tumors, defined as the transient distribution integrated over an exponentially distributed observation time. It can be obtained as the solution of a large linear system. However, the sheer size of this system renders classical solvers infeasible. We consider Markov chains whose transition rates are separable functions, allowing for an efficient low-rank tensor representation of the linear system's operator. Thus we can reduce the computational complexity from exponential to linear. We derive a convergent iterative method using low-rank formats whose result satisfies the normalization constraint of a distribution. We also perform numerical experiments illustrating that the marginal distribution is well approximated with low rank.

A standardized simulation training program to type 1 loop electrosurgical excision of the transformation zone: a prospective observational study.

PURPOSE: To evaluate a simulation-based standardized training program for type 1 loop electrosurgical excision procedure (LEEP) under direct colposcopic vision in postgraduate teaching. METHODS: Seventeen participants (five experienced and 12 novice surgeons) performed 170 simulated cervical excisional procedures. Each participant performed 10 type 1 (cone length between 8 and 10 mm) excisional procedures under direct colposcopic vision on a low-fidelity simulator. Length of specimen was measured after each excision allowing the surgeons a subsequent resection to ensure a cone length of more than 8 mm. Main outcome measures were cone length, specimen fragmentation, and a self-developed score (LEEP score), which allowed the simultaneous evaluation of both measured parameters. RESULTS: The precision of the excision showed statistically significant improvement in the novice group during the training procedures after five procedures [LEEP score 1.61 (SD 1.34) vs. 0.46 (SD 0.58); p = 0.023], while experts showed consistently high performance. Inexperienced surgeons performed more frequently cuts that were too deep than experienced surgeons (33/120, 27.5% vs. 4/50, 8%; p = 0.003). CONCLUSIONS: Low-fidelity simulation training seems to be an effective method for learning the accurate cone length for a type 1 excision for novice surgeons. As excessive excisions are related with high risk for premature delivery in subsequent pregnancies, in our opinion, LEEP should be practiced in simulation training, especially before performing in woman of reproductive age.

Factors influencing the time to surgery after neoadjuvant chemotherapy in breast cancer patients.

PURPOSE: It is suspected that delayed surgery after neoadjuvant chemotherapy (NACT) leads to a worse outcome in breast cancer patients. We therefore evaluated possible influencing factors of the time interval between the end of NACT and surgery. METHODS: All patients receiving NACT due to newly diagnosed breast cancer from 2015 to 2017 at the Department of Gynecology, Saarland University Medical Center, were included. The time interval between end of NACT and surgery was defined as primary endpoint. Possible delaying factors were investigated: age, study participation, outpatient and inpatient presentations, implants/expander, MRI preoperatively, discontinuation of chemotherapy, and genetic mutations. RESULTS: Data of 139 patients was analyzed. Median age was 53 years (22-78). The time interval between end of NACT and surgery was 28 days (9-57). Additional clinical presentations on outpatient basis added 2 days (p = 0.002) and on inpatient basis added 7 days to time to surgery (p < 0.001). Discontinuation of NACT due to chemotherapy side effects prolonged time to surgery by 8 days (p < 0.001), whereas discontinuation due to disease progress did not delay surgery (p = 0.6). In contrast, a proven genetic mutation shortened time to surgery by 7 days (p < 0.001). Patient's age, participation in clinical studies, oncoplastic surgery, and preoperative MRI scans did not delay surgery. CONCLUSION: Breast care centers should emphasize a reduction of clinical presentations and a good control of chemotherapy side effects for breast cancer patients to avoid delays of surgery after NACT.

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study.

BACKGROUND: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. METHODS: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. RESULTS: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. CONCLUSIONS: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. TRIAL REGISTRATION: Clinical Trials Number: CFEM345DDE19.

Oral etoposide for metastatic choriocarcinoma: a case report and review of guidelines.

BACKGROUND AND PURPOSE: Choriocarcinoma (CCA) is a rare form of malignant trophoblastic disease. Systemic polychemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) is the mainstay of treatment for metastatic disease. Due to the rarity of the condition, however, the evidence basis for this management is small and other chemotherapy regimens may also be effective. The reported case presents anecdotal evidence of an effective etoposide monotherapy treatment. METHOD: CASE PRESENTATION: We report the case of a patient with gestational choriocarcinoma and pulmonary metastases initially treated with methotrexate. Due to local disease progression, she underwent hysterectomy and continued treatment with methotrexate. After pulmonary progression, she was switched to oral etoposide. RESULTS: After four cycles of etoposide monotherapy at a oral dosage of 100 mg d1-7, q28, the patient had no evidence of disease according to human chorionic gonadotropin serum levels and imaging studies. The treatment was well tolerated with World Health Organization (WHO) grade 2 alopecia and hot flushes as the most prominent side effects. The patient has achieved a sustained complete remission with a follow-up of 6 years. CONCLUSION: Oral etoposide may be an effective treatment alternative to EMA/CO in selected patients with oligometastatic CCA.

Preoperative morphological diagnosis of axillary lymph nodes in a breast center consultation service: evaluation of fine-needle aspiration and core biopsy techniques.

PURPOSE: Preoperative routine examination of axillary lymph nodes (ALN) in breast cancer patients is carried out physically and by ultrasound imaging; unsuspicious nodes will lead to a sentinel node (SN) procedure, suspicious ones require axillary dissection (AD). Pre-operative biopsy techniques like fine needle aspiration (FNA) or core biopsy (CB) may reduce the number of false "suspicious" cases and prevent overtreatment. We evaluated the effectiveness of both biopsy techniques. MATERIALS AND METHODS: After physical and ultrasound examination 241 suspicious ALNs were found in 214 patients. Ultrasound-guided FNA and/or CB procedures were chosen randomly, resulting in 138 FNA and 86 CB. In 17 further events both FNA and CB were employed. The samples were examined in our Cytology lab or in the Pathology Department and the findings correlated with post-operative histological lymph node reports. Patients with histologically proven breast cancer underwent sentinel node biopsy, cytologically or histologically positive FNA/CB-findings prompted ALN dissection. RESULTS: Out of 155 FNA samples 34 were not representative (21.9%), 89 showed no tumor cells (57.4%), 30 showed positive tumor cells (19.4%), leaving two missing. All 103 CB showed representative material, positive in 62 (60.2%) and negative in 41 (39.8%) cases. Correlation with histological reports revealed a statistically non-significant advantage for CB over FNA regarding total accuracy (92.9% vs. 78.3%) and sensitivity (92% vs. 73.7%). CONCLUSIONS: Preoperative CB and alternative FNA are valuable complementary methods of predicting ALN involvement in breast cancer patients and may spare the patient unnecessary ALN dissection.

Sec62/Ki67 and p16/Ki67 dual-staining immunocytochemistry in vulvar cytology for the identification of vulvar intraepithelial neoplasia and vulvar cancer: a pilot study.

PURPOSE: The aim of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-staining protocol for the simultaneous expression of SEC62 and Ki67 in vulvar liquid-based cytology specimens for the identification of vulvar intraepithelial neoplasia (VIN) and vulvar cancer. In addition, we investigated the p16/Ki67 dual stain, which has already been established in cervical cytology. MATERIALS AND METHODS: For this pilot study, residual material from liquid-based cytology was collected retrospectively from 45 women. The presence of one or more double-immunoreactive cells was considered as a positive test result for Sec62/Ki67 and p16/Ki67 dual staining. The test results were correlated with the course of histology. RESULTS: All cases of VIN and vulvar cancer were Sec62/Ki67 and p16/Ki67 dual-stain positive, and normal and low-grade squamous intraepithelial lesions were all negative. The sensitivity of cytology for VIN + cases was 100% (22/22), whereas punch biopsy classified one case of vulvar carcinoma as inflammation. All cases with high-intensity (grades 3 and 4) Sec62 staining in Sec62/Ki67-positive cases were carcinomas. CONCLUSIONS: The results of this study demonstrate that Sec62/Ki67 and p16 Ki67 dual-staining cytology could be a promising adjunctive diagnostic tool for VIN and squamous cell carcinoma, in addition to standard histology.

Therapy of isolated locoregional recurrent carcinoma of the breast.

PURPOSE: There is widespread consent that isolated locoregional recurrence (ILRR) in breast cancer should be treated surgically. On searching literature and guidelines most studies include ipsilateral recurrence in breast tissue or on thoracic wall post-mastectomy, recurrence in scar tissue as well as in ipsilateral axillary lymph nodes. Some studies discuss metachronous contralateral breast cancer as ILRR. About 10-35% of women with primary breast cancer suffer from ILRR. The existing data concerning the role of systemic therapy in the treatment of ILRR are insufficient. We investigated the influence of chemotherapy on disease-free- (DFS) and overall-survival (OS). METHODS: Retrospective analysis of all patients with ILRR and without distant metastasis was done, which were treated at the Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University between 2005 and 2013. Data collection used patients' database system and was followed via patient questionnaires. RESULTS: In total, we collected data of 93 patients with locally recurrent breast cancer and observed a 72.6% questionnaire response rate. Average timeline accounted for 99 months between primary diagnosis and local recurrence; average age of patients at diagnosis of local recurrence was 60.6 years. After a median follow-up of 63 months DFS reached 76% with and 73% without chemotherapy, and after 74 months overall survival amounted to 94% and 70%, respectively. CONCLUSION: Almost all patients with ILRR were operated. Especially patients with hormone receptor-negative recurrent breast cancer seemed to show a benefit having been treated with chemotherapy. Most patients were without recurrence after their particular therapies.

A Metastasis of Ovarian Cancer in the Bartholin Gland: A Case Report with Systematic Literature Review.

The metastasis of a gynecological malignancy to the Bartholin gland is rare. We report the case of a 62-year-old patient who had undergone extensive treatment of metastatic ovarian cancer that involved the liver, spleen, and peritoneum. She presented with painful swelling of the left vulva. Clinical and sonographic examinations showed a solid tumor in loco typico of the Bartholin gland. Surgical excision was performed. The patient died 3 months after the diagnosis of this metastasis. We performed a systematic search of PubMed, which yielded 453 entries. We selected those with at least an abstract available in English that described metastatic lesions on the Bartholin gland (n = 5). The review showed that a variety of primary cancers (colorectal, medullary thyroid, breast cancer, and endometrial cancers) metastasize to this location. Some patients showed signs of visceral metastasis. Bartholin gland metastases appeared as initial and metachronous manifestations. Most patients were symptomatic, with painful swelling or abscess. Genetic alterations were mentioned in some cases. The main pathways of metastasis discussed were lymphatic, but the mechanism of such metastasis remains unclear. Surgical resection was the preferred treatment option. The literature review indicated that Bartholin gland metastasis of ovarian cancer is rare and associated with poor prognosis. Oncological reasons for vulvar pathologies should be taken into consideration in patients with metastases.

Phase II study of fulvestrant 250 mg/month in patients with recurrent or metastatic endometrial cancer: a study of the Arbeitsgemeinschaft Gynäkologische Onkologie.

OBJECTIVES: The aim of this study is to evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). METHODS: Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250 mg by IM injection every 4 weeks for at least 12 weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. RESULTS: Thirty-five patients were enrolled in this study and received at least one injection of fulvestrant (intention to treat-population, ITT). Twenty six patients received the intended 3 injections of fulvestrant (per protocol population, PP). There was no complete response but 4 partial responses (11.4% ITT) and 8 stable diseases. The median time to progression was 2.3 months (ITT). Overall survival was 13.2 months (ITT). Treatment was well tolerated. CONCLUSIONS: Fulvestrant at a dose of 250 mg IM every 4 weeks has marginal activity and good tolerability in patients with ER and/or PR positive advanced or recurrent endometrial cancer. A loading dose strategy and the use of 500 mg/4 weeks might improve the efficacy of this treatment.

Allelochemical run-off from the invasive terrestrial plant Impatiens glandulifera decreases defensibility in Daphnia.

Invasive species are a major threat for native ecosystems and organisms living within. They are reducing the biodiversity in invaded ecosystems, by outcompeting native species with e. g. novel substances. Invasive terrestrial plants can release allelochemicals, thereby reducing biodiversity due to the suppression of growth of native plants in invaded habitats. Aside from negative effects on plants, allelochemicals can affect other organisms such as mycorrhiza fungi and invertebrates in terrestrial ecosystems. When invasive plants grow in riparian zones, it is very likely that terrestrial borne allelochemicals can leach into the aquatic ecosystem. There, the often highly reactive compounds may not only elicit toxic effects to aquatic organisms, but they may also interfere with biotic interactions. Here we show that the allelochemical 2-methoxy-1,4-naphthoquinone (2-MNQ), produced by the ubiquitously occurring invasive terrestrial plant Impatiens glandulifera, interferes with the ability of Daphnia to defend itself against predators with morphological defences. Daphnia magna and Daphnia longicephala responded with morphological defences induced by chemical cues released by their corresponding predators, Triops cancriformis or Notonecta sp. However, predator cues in combination with 2-MNQ led to a reduction in the morphological defensive traits, body- and tail-spine length, in D. magna. In D. longicephala all tested inducible defensive traits were not significantly affected by 2-MNQ but indicate similar patterns, highlighting the importance to study different species to assess the risks for aquatic ecosystems. Since it is essential for Daphnia to adapt defences to the current predation risk, a maladaptation in defensive traits when simultaneously exposed to allelochemicals released by I. glandulifera, may therefore have knock-on effects on population dynamics across multiple trophic levels, as Daphnia is a key species in lentic ecosystems.

A risk model for secondary cytoreductive surgery in recurrent ovarian cancer: an evidence-based proposal for patient selection.

BACKGROUND: To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. METHODS: Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR from 7 worldwide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. RESULTS: Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (odds ratio [OR] = 1.32, 95% confidence interval [95% CI]: 0.97-1.80), residual disease after primary cytoreduction (OR = 1.69, 95% CI: 1.26-2.27), progression-free interval (OR = 2.27, 95% CI: 1.71-3.01), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 2.23, 95% CI: 1.45-3.44), CA125 (OR = 1.85, 95% CI: 1.41-2.44), and ascites at recurrence (OR = 2.79, 95% CI: 1.88-4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low-risk group, in which the proportion of complete cytoreduction was 53.4% compared with 20.1% in the high-risk group (OR = 4.55, 95% CI: 3.43-6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiver-operating characteristics for predicting complete SCR was 0.68 (95% CI: 0.60-0.79). CONCLUSIONS: This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with recurrent ovarian cancer should have SCR as part of their management.

Factors Influencing the Onset of Neoadjuvant Therapy in Breast Cancer Patients.

BACKGROUND: Time to treatment onset (TTTO) is critical in breast cancer patients receiving neoadjuvant chemotherapy (NACT). We therefore investigated possible delaying factors of therapy onset. METHODS: All patients were included who qualified for NACT in our hospital from 2015 to 2017. The time interval between core biopsy of tumor and date of therapy onset was defined as primary endpoint. Among other things, age, out- and in-patient presentation, and study or standard treatment were investigated as potentially delaying factors. RESULTS: We analyzed 139 patients scheduled for NACT; 90 (64.7%) received standard NACT, and 49 (35.3%) were recruited for trials. The average age was 53 years (±13.2 years). A time interval of 30.7 days (±11.8 days) was seen between diagnosis and therapy onset. Patients had a mean of 5 (±1.9) pretherapeutic presentations, 4 (±1.8) on outpatient and 1 (±0.5) on inpatient basis, being of significant influence on TTTO. CONCLUSION: Any outpatient presentation extended the time interval by 2 days, inpatient presentation by 4 days. These presentations should be merged in order to minimize TTTO. Neither the site of pathology examinations, additional consultations (genetics, reproductive medicine), nor study participation delayed therapy onset.

Significant improvement of laparoscopic knotting time in medical students through manual training with potential cost savings in laparoscopy - an observational study

Objective: Laparoscopy is a standard procedure in operative gynaecology, but laparoscopic simulator training for novices/junior surgeons is not currently well-established. The aims of this study were to demonstrate that a laparoscopic knot course for trainees can significantly shorten the knotting time and to perform a counter-value calculation for the clinic's costs. Material and Methods: An observational study was performed with exercises on a laparoscopic box trainer as part of the practical clerkship in gynaecology and obstetrics between 07.10.2019-31.01.2020. At the beginning and at the end of the exercises, the participants made a laparoscopic knot and the difference in knotting time, Δt in seconds (s) was measured. Results: Eighty-eight medical students needed an average of 247.1 s for the first laparoscopic knot at the beginning of the course and an average of 45.43 s for the second at the end of the course. Mean shortening of the knotting time was 201.67 s or 81.6% (p=0.02). Calculating costs of an average of €40-50 for an operation minute would mean a cost saving of at least €120-150 for a partial node. Conclusion: Trainees can significantly improve their operative skills in a short time with the aid of surgical simulation training. Such training can be beneficial for clinics by reducing the operating time if the basics, such as sewing and instrument guidance, are learned on a simulator. We therefore suggest that operative simulation training should be mandatory in medical education.

Neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian cancer--a prospective multicenter phase II trial (PRIMOVAR).

Early response criteria and surgical outcome were evaluated in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy. Patients with FIGO stage IIIC or IV ovarian cancer and an ascites volume of >or=500 ml were randomly assigned to receive preoperatively 3 (A1) or 2 (A2) of 6 cycles of carboplatin and docetaxel intravenously. Response was monitored by measuring target lesions, ascites volumes and serum CA 125 levels. The primary outcome measure was the preoperative reduction of ascites volume. Secondary outcome measures were the evaluation of residual tumor and perioperative morbidity and mortality. Eighty-three patients underwent cytoreductive surgery, 40 after 3 cycles and 43 patients after 2 cycles of neoadjuvant chemotherapy. 'Optimal debulking' (or=500 ml. A decrease of the CA 125 level from baseline of less than 50% was observed in 7 (A1) and 9 patients (A2). Computed tomography scan results showed progressive disease in 6 patients (3 A1; 3 A2). Any amount of residual disease after cytoreductive surgery, persistent ascites, and a less pronounced decrease of CA 125 were associated with poor progression-free survival rates. In conclusion, ascites volume reduction and CA 125 decline appear to be appropriate response criteria. A treatment schedule with two preoperative cycles is a reasonable option for neoadjuvant chemotherapy in advanced ovarian cancer. High surgical standards are mandatory, even after neoadjuvant chemotherapy.

Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a rare entity among malignant gynecologic tumors with a very unfavorable prognosis and the highest prevalence in the pre- and peri-menopause. Only early-stage tumors have an acceptable prognosis, provided the patient has been treated without injuring the uterus. uLMS is often diagnosed accidentally and the correct diagnosis ishampered by equivocal features similar to the far more frequent benign uterine fibroids. Surgery is the basis of therapy, and it should be done in order to remove the uterus intact. As vaginal, abdominal, and endoscopic surgery - possibly including morcellation - are the methods of choice for the treatment of uterine fibroids, pre-operatively undiagnosed leiomyosarcoma detected by pathologic examination will have a worsened prognosis. Systemic treatment and radiotherapy are of no proven value in the adjuvant setting. Thus, there is strong need for a reliable pre-operative risk score for leiomyosarcoma in order to justify diagnostic means beyond clinical routine and to choose the correct surgical pathway. The clinical problems in the diagnosis of leiomyosarcoma and treatment are exemplified by a case report of a 30-year-old childless patient. Diagnostic tools as well as treatment options in adjuvant and palliative situations are reviewed.

Neuropsychological assessment in autism spectrum disorder and related conditions.

Neuropsychological assessment provides a profound analysis of cognitive functioning in people with autism spectrum disorder (ASD). Individuals on the autistic spectrum often show a high level of anxiety and are frequently affected by comorbidities that influence their quality of life. Yet, they also have cognitive strengths that should be identified in order to develop effective support strategies. This article presents an overview of five cognitive areas that are essential for neuropsychological evaluation (ie, intelligence, attention, executive function, social cognition, and praxis) and explores the underlying causes of behavioral problems in persons with ASD. Furthermore, it stresses the importance of meticulous neuropsychological testing with regard to cognitive remediation, a method that can help to enhance single cognitive processes in a targeted manner. Objective test results suggest it might be possible to promote an improved sense of coherence. In line with the salutogenic model, this may be fundamental for human health and well-being.

La evaluación neuropsicológica facilita un profundo análisis del funcionamiento cognitivo en las personas con trastorno del espectro autista (TEA). Los sujetos con el espectro autista a menudo muestran un alto nivel de ansiedad y presentan con frecuencia comorbilidades que influyen en su calidad de vida. Sin embargo, ellos también tienen fortalezas cognitivas que deben ser identificadas para desarrollar estrategias de soporte efectivas. Este artículo entrega una panorámica de cinco áreas cognitivas que son esenciales para la evaluación neuropsicológica (como inteligencia, atención, función ejecutiva, cognición social y praxis) y explora las causas subyacentes de los problemas conductuales en personas con TEA. Además, se enfatiza la importancia de una evaluación neuropsicológica rigurosa en relación con la remediación cognitiva, un método que puede ayudar a mejorar los procesos cognitivos individuales de una manera específica. Los resultados de las pruebas objetivas sugieren que podría ser posible fomentar un mejor sentido de coherencia en las personas con TEA. En línea con el modelo salutífero, esto puede ser fundamental para la salud y el bienestar humanos.

L'évaluation neuropsychologique permet une analyse approfondie du fonctionnement cognitif chez les sujets atteints de trouble du spectre de l'autisme (TSA). Ces derniers présentent souvent une anxiété importante et souffrent fréquemment de comorbidités influant sur leur qualité de vie. Ils ont pourtant également des aptitudes cognitives qui devraient être identifiées afin de développer des stratégies de soutien efficaces. Cet article présente une vue d'ensemble des cinq domaines cognitifs essentiels pour l'évaluation neuropsychologique (c'est-à-dire, l'intelligence, l'attention, la fonction exécutive, la cognition et la pratique sociales) et explore les causes sous-jacentes des problèmes comportementaux chez les sujets atteints de TSA. De plus, l'importance d'une évaluation neuropsychologique rigoureuse y est soulignée en ce qui concerne la remédiation cognitive, une méthode qui peut améliorer de façon ciblée des processus cognitifs particuliers. D'après des résultats objectifs, le sens de la cohérence pourrait être amélioré chez les sujets ayant un TSA. Ceci pourrait s'avérer crucial pour la santé et le bien-être chez l'homme dans le cadre d'une démarche basée sur la salutogenèse (promotion de la santé).

Interest in Integrative Medicine Among Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

BACKGROUND: Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. METHODS: The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. RESULTS: Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P < .001) with age (<50 years, 74.1%; 50-60 years, 54.1%; >65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. CONCLUSIONS: This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.

Dose-dense adjuvant chemotherapy for node-positive breast cancer in women 60 years and older: feasibility and tolerability in a subset of patients in a randomized trial.

To evaluate the feasibility and tolerability of dose-dense adjuvant chemotherapy for older patients with node-positive breast cancer, a retrospective subset analysis compared dose delays and dose reductions for women aged > or = 60 years with those of younger women. Patients were randomized to a dose-dense (DD, 14-day cycle) or conventional-schedule (CS, 21-day cycle) regimen. DD patients (n = 104; 25 aged > or = 60 years) received epirubicin 90 mg/m2 plus paclitaxel 175 mg/m2 (four cycles), then cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 (CMF 600/40/600) (three cycles), plus filgrastim 5 microg/kg per day in every cycle. CS patients (n = 107; 27 aged > or = 60 years) received epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 (four cycles), then CMF 600/40/600 (three cycles), plus filgrastim if required. Delays were more common in older patients in both the DD and CS groups (DD, 17% versus 6%; CS, 11% versus 6%), as were Grades 3-4 leukopenia (26% versus 12%) and neutropenia (33% versus 25%). All older DD and 89% of older CS patients received all seven chemotherapy cycles, with 99% of cycles at full dose. This study demonstrates that a dose-dense regimen combining epirubicin and paclitaxel can be administered to patients > or = 60 years of age with a tolerable safety profile.

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

BACKGROUND: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. METHODS: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. RESULTS: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. CONCLUSION: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.