Demand for integrative medicine among women with breast and gynecological cancer: a multicenter cross-sectional study in Southern and Northern Germany.

PURPOSE: The aim of this multicenter cross-sectional study was to analyze a cohort of breast (BC) and gynecological cancer (GC) patients regarding their interest in, perception of and demand for integrative therapeutic health approaches. METHODS: BC and GC patients were surveyed at their first integrative clinic visit using validated standardized questionnaires. Treatment goals and potential differences between the two groups were evaluated. RESULTS: 340 patients (272 BC, 68 GC) participated in the study. The overall interest in IM was 95.3% and correlated with older age, recent chemotherapy, and higher education. A total of 89.4% were using integrative methods at the time of enrolment, primarily exercise therapy (57.5%), and vitamin supplementation (51.4%). The major short-term goal of the BC patients was a side-effects reduction of conventional therapy (70.4%); the major long-term goal was the delay of a potential tumor progression (69.3%). In the GC group, major short-term and long-term goals were slowing tumor progression (73.1% and 79.1%) and prolonging survival (70.1% and 80.6%). GC patients were significantly more impaired by the side-effects of conventional treatment than BC patients [pain (p = 0.006), obstipation (< 0.005)]. CONCLUSION: Our data demonstrate a high overall interest in and use of IM in BC and GC patients. This supports the need for specialized IM counseling and the implementation of integrative treatments into conventional oncological treatment regimes in both patient groups. Primary tumor site, cancer diagnosis, treatment phase, and side effects had a relevant impact on the demand for IM in our study population.

Gynecologists' attitudes toward and use of complementary and integrative medicine approaches: results of a national survey in Germany.

PURPOSE: Despite patients' widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals' current implementation of it in clinical routine. A national survey was conducted to assess gynecologists' attitudes to and implementation of complementary and integrative treatment approaches. METHODS: The Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019. A 29-item survey was sent to all DGGG members by email. RESULTS: Questionnaires from 180 gynecologists were analyzed, of whom 61 were working office-based in private practice and 95 were employed in hospitals. Seventy percent stated that IM concepts are implemented in their routine clinical work. Most physicians reported using IM methods in gynecological oncology. The main indications for IM therapies were fatigue (n = 98), nausea and vomiting (n = 89), climacteric symptoms (n = 87), and sleep disturbances (n = 86). The most commonly recommended methods were exercise therapy (n = 86), mistletoe therapy (n = 78), and phytotherapy (n = 74). Gynecologists offering IM were more often female (P = 0.001), more often had qualifications in anthroposophic medicine (P = 0.005) or naturopathy (P = 0.019), and were more often based in large cities (P = 0.016). CONCLUSIONS: There is strong interest in IM among gynecologists. The availability of evidence-based training in IM is increasing. Integrative therapy approaches are being implemented in clinical routine more and more, and integrative counseling services are present all over Germany. Efforts should focus on extending evidence-based knowledge of IM in both gynecology and gynecological oncology.

Course of cervical intraepithelial neoplasia diagnosed during pregnancy.

PURPOSE: Management of high-grade cervical intraepithelial neoplasia [CIN grade 2 or 3 (CIN2-3)] diagnosed during pregnancy is controversial. Monitoring with colposcopy and cytology every 8-12 weeks is advised by the most current guidelines. STUDY DESIGN: This study analyzes the course of disease in pregnant women with abnormal cytologies or clinically suspicious cervixes. RESULTS: In total, 139 pregnant women, at a median age of 31 years (range 19-49), treated at the Colposcopy Unit of the University Medical Center Hamburg-Eppendorf between 2011 and 2017 were identified. During pregnancy, at least one biopsy was performed on 70.5% of patients. In 84.7% of cases, CIN2-3 (CIN2 n = 14 (14.3%), CIN3 n = 69 (70.4%)) was detected, 7.1% (n = 7) of women were diagnosed with CIN1, while no dysplasia was found in 8.2% (n = 8) of cases. No interventions were necessary during pregnancy. Despite explicit invitation, only 72.3% of women with CIN2-3 attended postpartal consultations. While 61.7% showed persistent lesions, 5% were diagnosed with CIN1 and 33.3% with complete remission. During pregnancy, 68.7% of women with prepartal CIN2-3 were tested for HPV infection. Later, 49.1% were followed up postpartally by means of HPV testing and histology. HPV clearance was observed in 36.4% of women with complete histological remission. Postpartum conization was performed on 44.6% of patients with prepartal CIN2-3 diagnosis. CIN2-3 was histologically confirmed in 97.3% cases. Progression from persistent CIN3 to microinvasive carcinoma was observed in a single case. CONCLUSIONS: High-grade CIN lesions, diagnosed during pregnancy, show a high rate of regression postpartum; whereas, progression to carcinoma is rare. Close and continuous monitoring rarely has any therapeutic consequences. Compliance for postpartal follow-up needs to be improved.

Cerebral metastasis in recurrent squamous cell carcinoma of the vulva: case report and review of the literature.

BACKGROUND: Distant metastases from squamous cell cancer of the vulva (VSCC) are encountered rarely and are associated with a poor prognosis. Cerebral metastases have only been described anecdotally. CASE HISTORY: A 51-year old woman was diagnosed with hepatic metastases due to VSCC. Initial therapy comprised wide local excision of the primary tumor with inguino-femoral lymphadenectomy (LAE) followed by stereotactic radiation of the singular hepatic metastasis while adjuvant chemoradiation of the vulva and lymphatics was declined. 3 years later, she subsequently developed lung and cerebral metastases. CONCLUSION: The course of metastatic disease in VSCC is poorly understood. Further knowledge of the metastatic patterns in vulvar cancer is required for guidance of future therapeutic interventions.

Superficially invasive stage IA vulvar squamous cell carcinoma-therapy and prognosis.

OBJECTIVES: Superficially invasive stage IA squamous vulvar cancer (VSCC) is defined as a single lesion measuring ≤2 cm with a depth of invasion of ≤1.0 mm (FIGO stage IA). This article examines the natural course and prognosis of superficially invasive VSCC. METHODS: This is a retrospective case series of 46 patients (median age 58 years) with superficially invasive stage IA VSCC receiving wide local excision between January 1996 and November 2014 in the University Medical Center Hamburg-Eppendorf. RESULTS: Median tumor size was 4 mm. In 39/46 (84.8%) patients peri-tumoral high-grade intraepithelial neoplasia (HSIL) and/or lichen sclerosus (LS) of the vulva were histologically detected: 34 (74.0%) usual type high-grade vulvar intraepithelial neoplasia (uVIN, HSIL), 4 (8.7%) LS with simultaneous VIN (3 uVIN, 1 differentiated VIN (dVIN)), 1 (2.2%) with LS only. 37/46 (80.4%) patients had a R0 resection; in 2 (4.3%) a high-grade VIN was detected in the margin and in 7 (15.2%) the resection status was unknown. The mean follow-up was 58 (range 10-185) months. Four patients (8.7%) suffered from an invasive recurrence after 4, 17, 40, and 54 months, three in the vulva and one in the groin. All local recurrences occurred in women with LS in a combination with high-grade VIN (3 uVIN, 1 dVIN). Two were treated surgically again including inguino-femoral lymphadenectomy (ifLAE) (no regional lymph node metastasis histologically) as invasion depth exceeded 1 mm. The third patient refused treatment. Inguinal recurrence was treated with a bilateral ifLAE, revealing one positive lymph node, followed by adjuvant radiotherapy (groins, pelvis). None of these patients had experienced further recurrences at last follow-up. CONCLUSIONS: Superficially invasive VSCC is characterized by having a very good prognosis. Sole surgical therapy is highly effective. Patients with LS might benefit additionally from intensified surveillance and adequate maintenance therapy in specialized centers.

Sexual activity and quality of life in patients after treatment for breast and ovarian cancer.

OBJECTIVE: Sexual activity (SA) and functioning (SF) are important factors influencing quality of life (QoL). Anticancer treatment can cause or promote sexual dysfunctions. In this study we analyzed the SA, SF and QoL in patients after completion of treatment for breast cancer (BC) and ovarian cancer (OC). METHODS: In this retrospective multicenter study 396 BC patients and 93 OC patients aged between 18 and 70 years were surveyed at least 24 months after cancer diagnosis and compared to 60 healthy women. Data were collected through validated questionnaires (Sexual Activity Questionnaire, Female Sexual Function Index-d, EORTC Quality of Life Questionnaire-C30). RESULTS: 45.9% of BC patients and 56.5% of OC patients reported SA. SF and well-being of sexually active BC patients were not influenced by the type and radicality of surgery or the administration of chemotherapy. Patients who received antihormonal therapy at the time of evaluation showed a lower frequency of SA (p = 0.007), less satisfaction (p = 0.003) and more discomfort during SA (p = < 0.001) compared to healthy controls but no differences in experiencing orgasms, health status, QoL and global health status. In contrast, BC patients without antihormonal therapy showed only a higher discomfort score (p = 0.028) than healthy controls and estimated their health status and QoL significantly better than patients who received antihormonal therapy (p = 0006). In general, SA was associated with a better health status (p = 0.007), a better QoL (p = 0.004) and a better global health status (p = 0.004) in BC patients. Sexually active OC patients showed no significant differences in SF, QoL and health status compared to healthy controls. CONCLUSIONS: Compared to healthy controls BC patients showed limitations in SF with a lower SA rate and more discomfort. Antihormonal therapy was an important factor influencing SF and well-being. Breast and OC survivors reported good physical and psychical health without differences in QoL and health status compared to controls. This might be explained by a change of perspective on life difficulties and altered priorities through a life threatening disease.

Correlation of Isotope Count With Sentinel Node Positivity in Vulvar Cancer.

OBJECTIVE: Sentinel node biopsy (SNB) has become standard of care in early stage vulvar cancer. As the correlation of isotope count with the presence of metastases remains unclear, often several active nodes are excised per groin. This can result in increased morbidity in node-negative disease despite of SNB. In the current analysis, we assess whether resection of the hottest node could be sufficient to detect sentinel lymph node (SLN) metastasis. METHODS: Patients with primary vulvar cancer receiving an SNB with radioactive tracer at the University Medical Center Hamburg-Eppendorf between 2008 and 2015 were evaluated. RESULTS: A total of 145 patients with SNB were analyzed; thereof, 144 underwent bilateral SNB, resulting in 289 analyzed groins. A median of 2 SLNs (range, 1-7) per groin were removed. From 94 (32.5%) of 289 groins, more than 2 SLNs were excised. Median overall SLN isotope count was 1400 cps. In 50 groins, a positive SLN was detected (unilateral in 38 patients, bilateral in 6). The median number of positive SLN per groin was 1 (range, 1-4). The SLN with the highest isotope count carried metastases in 36 (78.3%) of 46 groins (in 4 cases, the highest count was unknown). In 10 (21.7%) of 46 positive groins, the SLN with the highest count was not the metastatic SLN (9/10 second highest count). Median count of these 10 SLN was 60% of the highest count with a range from 11.0% to 74.0%. CONCLUSIONS: The highest isotope count does not reliably detect the positive SLN in vulvar cancer. To prevent mostly fatal groin recurrences, surgeons should continue to remove all SLN accumulating relevant radioactive tracer over background activity.

Participation of elderly gynecological cancer patients in clinical trials.

BACKGROUND: Elderly patients are underrepresented in clinical trials in gynecological cancer, even though they are disproportionally often affected. This study aimed to evaluate the disposition and apprehension of elderly patients toward study participation. METHODS: 112 elderly gynecological cancer patients (median age 70) were surveyed in a multicenter cross-sectional study. Besides fitness, state of disease, education and domestic situation, questions aimed at the general willingness to participate in a clinical trial. Personal reasons for refusal and anticipated advantages/disadvantages that might evolve from participation were inquired. RESULTS: Willingness to participate in a clinical study was generally high (72%, 74/102). Reasons for potential study participation were: 'better monitoring of the disease' (67.1%), 'better medical care' (46.1%), 'to help medical research' (44.7%), 'better medication' (35.5%) and 'because of my doctor's recommendation' (22.4%). Reasons for potential refusal were: 'too time consuming' (24.4%), 'fear of side effects' (21.8%), 'misuse as experimental animal' (18%), 'long distance to clinic' (14.1%) and 'too little or unclear information' (10.3%). 37.2% (29/78) of the patients stated that they had 'no objection' at all against study participation. The question if patients anticipated having a longer life due to study participation was answered with 'yes' or 'rather yes' in 42% (38/90); 28.9% answered 'no' or 'rather no' (29% undecided). No statistical significant relation between willingness to participate in a study and general fitness (p = 0.133), education (p = 0.122), age (p = 0.474) or domestic situation (p = 0.123) could be observed in a multivariate logistic regression model. CONCLUSIONS: Elderly patients are generally willing to participate in clinical studies, in our cohort regardless of their fitness. Benefits of participation seem to be unclear among a majority of potential study participants. Therefore, it might be decisive to provide more general information regarding benefits and safety for elderly patients in a clinical trial.

Oral Human Papillomavirus in Women With High-Grade Cervical Intraepithelial Neoplasia.

OBJECTIVE: This study was designed to investigate the co-prevalence of cervical and oropharyngeal human papillomavirus (HPV) infection in patients with HPV-related high-grade disease of the uterine cervix (high-grade squamous intraepithelial lesion [HSIL]). MATERIALS AND METHODS: In a prospective cohort study, women with abnormal cervical cytology admitted to our colposcopy units received HPV testing of the uterine cervix and the oropharynx via smear. From a subset of patients, oral lavage was collected to compare detection rates of HPV DNA between lavage and swab. Patients with confirmed high-risk HPV (HR-HPV)-positive HSIL of the cervix were further investigated. Sexual behavior and lifestyle factors were documented with a standardized questionnaire. RESULTS: Two hundred thirty-five women were included in the study. Of the 235 women, 135 (57.5%) were cervically HR-HPV positive with histologically confirmed high-grade cervical intraepithelial lesion (median [range] age = 30 [21-45] years). Of these, only 6 (4.4%) also had a positive oral specimen. In 3 (50%) of the 6 cases, the same HPV type was detected in oral and cervical samples (HPV 16, 35, and 45). Oral HPV detection was not higher when combining swab and lavage compared with swab alone. A relation between sexual behavior and oral HPV detection could not be demonstrated. CONCLUSIONS: Oral HPV prevalence in women with cervical HPV infection and HSIL is low. Simultaneous testing of oropharyngeal and cervical HPV infection does not seem promising as future screening strategy.

The Risk of Contralateral Non-sentinel Metastasis in Patients with Primary Vulvar Cancer and Unilaterally Positive Sentinel Node.

BACKGROUND: In patients with primary vulvar cancer and bilateral sentinel lymph node (SLN) biopsy, bilateral complete inguino-femoral lymphadenectomy (LAE) is recommended, even in cases with only unilaterally positive SLN by most guidelines. The risk of contralateral non-SLN metastasis is unclear. METHODS: All patients with primary vulvar cancer receiving an SLN dissection with radioactive tracer ± blue dye at the University Medical Center Hamburg-Eppendorf between 2001 and 2013 were retrospectively evaluated. Median follow-up was 33 months. RESULTS: A total of 140 patients were included; 124 with bilateral and 16 with unilateral SLN dissection. A median number of two SLNs (range 1-7) per groin were dissected. Overall, 53 (53/140, 37.9 %) patients received a complete inguino-femoral LAE, 41 of whom (77.4 %) had previously presented with a positive SLN (33 unilaterally, 8 bilaterally). Of the 33 patients with unilaterally positive SLN, 28 (84.9 %) underwent complete bilateral inguino-femoral LAE despite a contralateral negative SLN. Of these patients, none presented a contralateral non-SLN metastasis (0/28, 0 %) in full dissection; however, one developed groin recurrence in the initially SLN-negative, fully dissected groin after 19 months (1/28, 3.6 %). CONCLUSION: In case of bilateral SLN biopsy for clinically node-negative disease and only unilaterally positive SLN, the risk for contralateral non-SLN metastases appears to be low. These data support the omission of contralateral LAE to reduce surgical morbidity.

Patterns of distant metastases in vulvar cancer.

OBJECTIVE: Metastatic vulvar cancer is a rare disease. Information on metastatic patterns and corresponding prognosis or therapeutic approaches is scarce. We therefore analyzed pattern and course of metastatic disease in a large single center cohort. METHODS: All patients with primary squamous-cell cancer of the vulvar [n=391, median age: 60years (range 20-94)] treated at the Gynecological Cancer Center Hamburg-Eppendorf 1996-2013 were retrospectively evaluated for occurrence of distant metastasis. Furthermore, a systematic Medline database search was performed using the terms: 'vulvar cancer' AND 'metastasis', 'chemotherapy', 'patterns of recurrence', or 'prognosis'. RESULTS: Out of 391 patients with primary squamous cell vulvar cancer, 20 patients (5.1%) eventually presented with distant metastases. In these 20 patients, median time to first diagnosis of metastasis after primary diagnosis was 13.4months (range 4-104). Often patients experienced one or more local recurrences before distant spread (12/20, 60.0%). Documented metastatic sites were lung (n=9), liver (n=7), bone (n=5), skin (n=4) and lymph-nodes (axillary/thoracic/paraaortic, n=3). The majority of patients presented with unilocal metastases (13/20, 65.0%). In univariate analysis tumor diameter, invasion depth, nodal status and number of metastatic lymph-nodes were identified predictive for occurrence of distant metastases. 2-year-overall-survival-rate after metastases of all metastatic patients was 11.3%; median survival from first diagnosis of metastases was 5.6months. CONCLUSION: The occurrence of distant metastasis from vulvar cancer is a rare event with very limited prognosis. Further efforts, especially translational research will be crucial to identify prognostic markers as well as therapeutic targets to improve survival in these patients.

Sexual activity and function after surgical treatment in patients with (pre)invasive vulvar lesions.

PURPOSE: Sexual activity (SA) and sexual function (SF) are central outcome measures in women affected by preinvasive (vulvar intraepithelial neoplasia, VIN) and invasive (vulvar cancer, VC) vulvar lesions. Data on sexuality after treatment are scarce. METHODS: Validated questionnaires including the female sexual function index (FSFI-d) were provided to 166 women with a history of VIN and VC who attended the colposcopy units of the University Medical Center Hamburg-Eppendorf and Asklepios Medical Clinic Altona for follow-up between March 2011 and June 2012. Additional patients (n = 14) assessed the questionnaires online through the website of the German Vulvar Cancer Support Group (VulvaKarzinom SHG e.V.) during the same time period. RESULTS: Twenty-four patients with VIN and 34 with VC were evaluable. Median age was 51.5 years, with 34 (58.6%) of the patients being postmenopausal. Median time since completion of treatment was 17 months. All women had undergone vulvar surgery (laser/cold knife/combination). Overall, 14 (24.1%) women reported no SA during the last 4 weeks. SF was clearly impaired compared with previously described normal cohorts. SA and SF of active patients did not differ significantly between those with VIN and VC. Analyses contrasting surgical treatment methods yielded no significant associations; likewise, time since diagnosis did not affect SA and SF significantly. Increasing age was negatively associated with most dimensions of the FSFI-d [desire (p = 0.011), arousal (p = 0.004), lubrication (p = 0.003), orgasm (p = 0.013), satisfaction (p = 0.345), pain (p < 0.001)]. CONCLUSION: Women with VIN and VC after surgical treatment are at high risk to suffer from persistent sexual dysfunction especially at higher age.

Sexual Activity and Function in Patients With Gynecological Malignancies After Completed Treatment.

OBJECTIVE: Sexual activity (SA) and sexual function (SF) after completion of treatment are central for quality of life (QoL) in women affected by gynecological cancer (GC). The aim of this study was to analyze the sexual outcome and overall QoL of women after treatment for primary GC compared with a healthy control group (CG). METHODS: In a multicenter cross-sectional study, 77 women aged 28 to 67 years were surveyed at least 12 months after completion of primary therapy for cervical, endometrial, or vulvar cancer [gynecological cancer group (GCG)]. Data were collected through validated questionnaires (Female Sexual Function Index-d, EORTC Quality of Life Questionnaire-C30, and Sexual Activity Questionnaire) and compared to a control of 60 healthy women (CG). RESULTS: In the GCG, 41.3% were sexually active compared to 78.0% in the CG. Twelve women of the CG and 42 women of the GCG indicated the reasons for their sexual inactivity. The most common reason for sexual inactivity in the GCG was "the-presence-of-a-physical-problem" [18/42 (42.9%) vs 2/12 (16.7%) in the CG], whereas in the CG, "because-I-do-not-have-a-partner" was most common [6/12 (50.0%) vs 11/42 (26.2%) in the GCG]. Sexually active patients in the GCG had an SF comparable to the CG. In multivariate analysis of the total cohort (n = 137), relationship status [solid partnership vs living alone; odds ratio (OR), 33.82; 95% confidence interval (CI), 4.83-236.70], smoking (OR, 0.25; 95% CI, 0.06-1.03), and age (OR, 0.87; 95% CI, 0.79-0.94) influenced SA significantly. The probability of SA thereby decreased with increasing age. Quality of life and subjective general health status were not significantly different between the GCG and the CG (EORTC Quality of Life Questionnaire-C30 score 68.25 vs 69.67). CONCLUSIONS: A high number of patients with GC remain sexually inactive after treatment, indicating that women experience persistent functional problems. However, women who regain SA after completed treatment have a good overall SF and vice versa.

Secondary sentinel node biopsy after previous excision of the primary tumor in squamous cell carcinoma of the vulva.

BACKGROUND: To reduce morbidity of radical groin dissection, the sentinel-node (SLN) procedure was implemented for the treatment of vulvar cancer. It has been proven to be a safe alternative in early-stage disease. Feasibility and safety of the procedure after previous vulvar surgery remain unclear. METHODS: A total of 106 patients with primary vulvar cancer undergoing the SLN procedure were analyzed. Seventy-four patients received the SLN procedure concomitant to vulvar surgery [primary-sentinel group (PSG)], whereas 32 patients had vulvar surgery before secondary SLN [secondary-sentinel group (SSG)]. RESULTS: SLN detection was possible in all patients. Three (9.4 %) patients in the SSG and 30 (40.5 %) in the PSG had metastatic spread to the SLN and underwent radical groin dissection. Median interval between vulva surgery and secondary sentinel was 34 days (range, 7-98). In the SSG tumor, stages were earlier with smaller tumor size (median 19 mm in the PSG vs. 9 mm in the SSG) and lesser invasion depth (4 vs. 2 mm; p < 0.001). There were no groin recurrences in the SSG and 5.4 % in the PSG. No significant difference regarding disease-free survival (DFS) could be detected (3-year DFS of 72.5 % in the PSG compared with 92.5 % in the SSG (median DFS not reached, p = 0.114)). Adjusting for potential confounders (tumor stage, nodal status, tumor size, invasion depth) did not alter the results with regards to DFS. CONCLUSIONS: Our results suggest that a secondary SLN procedure after previous vulvar surgery is feasible and can accurately reflect the groin status of selected patients. Ideally, prospective trials should be conducted to verify accuracy and oncologic safety of the procedure.

Impact of taste and smell training on taste disorders during chemotherapy - TASTE trial.

PURPOSE: Two-thirds of cancer patients report taste disorders during and after chemotherapy. Taste disorders impact on nutritional status which is highly relevant for treatment efficacy and overall prognosis. Improvement of taste disorder is of particular importance for cancer patients' outcomes, thus the TASTE trial was conducted to improve taste disorders with a taste and smell training. METHODS: In this trial, patients undergoing chemotherapy were screened for taste disorders. Subsequently, patients were allocated based on the detection of taste disorders (≤8 taste strips points) to an intervention group with a taste and smell training at baseline and week 3-5 or were only followed up, if no taste disorder was detected (≥9 taste strips points) (non-intervention group). At baseline, all patients received a nutritional counseling. The primary endpoint was the minimal clinically relevant improvement of taste strips score by 2 taste strips points in at least 50% of the patients with taste disorders. RESULTS: The trial included 62 patients (48 women [77%], 14 male [23%], age 54.5±11.6 years) who had gastrointestinal (n=29), breast (n=31), or lung cancer (n=2). Taste disorders were more frequent in gastrointestinal than in breast cancer patients. Out of 62 patients screened, 30 patients showed taste disorders. The primary endpoint was met with 92% (n=23 of 25) of the patients completing the intervention. In the intervention group, the patients' taste significantly improved from baseline (median taste strips: 7.0 points) to week 12 (median taste strips: 10.0 points) (P≤0.001). Patients of the non-intervention group who completed the reassessment (n=27 of 32) experienced no change in taste perception in the 3-month follow-up (P=0.897). CONCLUSION: Intensified nutritional counseling with taste and smell training may improve taste perception of patients undergoing chemotherapy. A confirmatory randomized trial is planned.

Comparison of PapilloCheck and Linear Array to Detect and Differentiate Human Papillomaviruses in Cervical and Tonsillar Smears from Females with Cervical Intraepithelial Lesions.

A subgroup of oropharyngeal squamous cell carcinomas (OSCCs) are causally linked to infection with high-risk human papillomaviruses (HR-HPVs). To evaluate the prevalence of simultaneous oral HPV infection in females with cervical high-grade squamous intraepithelial lesions (HSIL), tonsillar- and cervical smears were collected simultaneously from 73 patients and analyzed for HPV using two commercial assays, PapilloCheck (Greiner-Bio-One) and Linear Array (Roche). Only 3/73 (4.1%) tonsillar smears were HPV positive (HPV+), with HPV types 16, 35, and 45, respectively, detected by both assays (100% agreement). Concordant results were also found in 60/66 (91%) evaluable cervical smears. Of specimens, positive by both assays, typing results completely coincide in 71% (all types are identical) and partially coincide in 27% (at least one type is identical). Taken together, results of HPV detection and typing by PapilloCheck and Linear Array are highly congruent and confirm the low prevalence of HR-HPV in tonsillar smears of patients with HSIL of the uterine cervix. Our data indicate low prevalence of oropharyngeal HPV infection in patients with high-grade cervical dysplasia. The low detection rate was confirmed by using two different commercial assays with largely consistent results of HPV detection and typing, but with some variation for particular HPV types. Comparative testing of larger numbers is required to identify the HPV types prone to escape detection with particular assays.

Loss of BRCA1 promotor hypermethylation in recurrent high-grade ovarian cancer.

BACKGROUND: Approximately 20-25% of ovarian cancers are attributable to germline or somatic BRCA1/2 mutations, resulting in defects in the homologous recombination pathway. Inactivation of these genes can also be mediated by epigenetic changes, e.g., hypermethylation of CpG islands in the promoter regions. In such homologous recombination deficient tumors, platinum based chemotherapy is in general effective, however, loss of hypermethylation might lead to refractory disease. The aim of this study was to evaluate the stability of BRCA1 promoter hypermethylation in recurrent disease after platinum based chemotherapy. METHODS: Tumor tissue from 76 patients with primary and 48 patients with platinum-sensitive recurrent high-grade ovarian cancer was collected. In a subgroup of 12 patients, 'paired' tumor tissue from primary and recurrent surgery was available. BRCA1 promoter methylation status was assessed using methylation specific polymerase chain reaction and was verified by Sanger Sequencing. RESULTS: 73.7% (56/76) of primary and 20.8% (10/48) of recurrent tumors displayed BRCA1 promoter hypermethylation. BRCA1 promoter methylation status was not associated with progression-free- or overall survival. In the paired subgroup 83.3% (10/12) of the primary vs. 16.7% (2/12) of the recurrent tumors showed hypermethylation. In eight patients loss of BRCA1 hypermethylation was observed, whereas two patients had stable methylation status. CONCLUSIONS: Loss of BRCA1 promoter methylation may be a mechanism to restore BRCA1 function in recurrent disease. However, currently the clinical significance is still unclear and should be evaluated in prospective clinical trials.

Beyond Bevacizumab: An Outlook to New Anti-Angiogenics for the Treatment of Ovarian Cancer.

In addition to the monoclonal vascular endothelial growth factor (VEGF) antibody bevacizumab, several alternative anti-angiogenic treatment strategies for ovarian cancer patients have been evaluated in clinical trials. Apart from targeting extracellular receptors by the antibody aflibercept or the peptibody trebananib, the multikinase inhibitors pazopanib, nintedanib, cediranib, sunitinib, and sorafenib were developed to interfere with VEGF receptors and multiple additional intracellular pathways. Nintedanib and pazopanib significantly improved progression-free survival in two positive phase III trials for first-line therapy. A reliable effect on overall survival could, however, not be observed for any anti-angiogenic first-line therapies so far. In terms of recurrent disease, two positive phase III trials revealed that trebananib and cediranib are effective anti-angiogenic agents for this indication. Patient selection and biomarker guided prediction of response seems to be a central aspect for future studies. Combining anti-angiogenics with other targeted therapies to possibly spare chemotherapy in certain constellations represents another very interesting future perspective for clinical trials. This short review gives an overview of current clinical trials for anti-angiogenic treatment strategies beyond bevacizumab. In this context, possible future perspectives combining anti-angiogenics with other targeted therapies and the need for specific biomarkers predicting response are elucidated.

Systemic treatment of vulvar cancer.

Squamous cell carcinoma of the vulva is a rare disease, accounting for approximately 5% of cancers of the female genital tract. Standard therapy for early-stage vulvar cancer mainly comprises of surgery of the vulva and groins. In locally advanced or metastatic vulvar cancer, neoadjuvant or definitive chemoradiation is often considered as an alternative treatment option. Given its rarity, the level of evidence for different treatment modalities is poor and few clinical trials have been performed on this disease. Therefore indication criteria for systemic treatment in advanced stage vulvar cancer vary widely among countries and institutions. This review focuses on the different systemic treatment options for patients with locally advanced, recurrent or metastatic vulvar cancer, and highlights the need for an international multicenter approach to identify the most effective therapeutic options.

Clinical management of epithelial ovarian cancer during pregnancy.

UNLABELLED: Epithelial ovarian cancer (EOC) in pregnancy is a rare situation. Due to its low incidence with a consecutive lack of clinical trials many questions regarding indication of different treatment approaches are unanswered. This article discusses the current literature to elaborate recommendations for the management of EOC during pregnancy. A literature search of diagnostic approaches and treatment strategies for EOC complicated by pregnancy was performed. We reviewed the available information with emphasis on surgery as well as chemotherapeutical treatment options. EOC in pregnancy is often diagnosed at early stage and no data support that concurrent pregnancy influences the growth rate or propensity for spread of EOC. Radical cytoreduction of all visible tumour followed by subsequent systemic chemotherapy is the standard treatment of EOC in most non-pregnant women. In pregnant women, however, chemotherapy as well as radical surgery should be avoided in the first trimester because of teratogenesis and high abortion rates. Besides induced abortion followed by classic management of EOC, pregnancy preserving surgery, followed by chemotherapy in the second or third trimester, timely delivery as well as neo-adjuvant chemotherapy with subsequent completing surgery appear to be viable treatment options. CONCLUSIONS: Since there is only very limited information regarding the optimal therapeutic approach to EOC during pregnancy, each case needs to be addressed individually. Treatment in specialised centres should be intended especially in this rare and challenging situation.