Metastatic pituitary neuroendocrine neoplasms: A case report of a malignant prolactinoma.

We report a rare clinical case of a malignant prolactinoma in which the exponential increase of prolactin levels with minimal tumor growth and no response to treatment led to diagnosis of abdominal, thoracic, and vertebral metastases.

Epidemiology, Management, and Survival Outcomes of Germ Cell Cancer in Southern Portugal: A Population-Based Study (2008-2012).

INTRODUCTION: Building on previous suboptimal survival results, we aimed to perform a study of the epidemiological status, management, and outcomes of germ cell tumors (GCT) in the Portuguese population. MATERIALS AND METHODS: Retrospective populational study of GCT cases diagnosed between 2008 and 2012 in southern Portugal. Joinpoint regression was used to compute average annual percentage change (AAPC) in incidence rate. ESMO/EAU guidelines served as references to evaluate compliance. Association between compliance with guidelines and hospital GCT case load was performed by generalized estimating equation. Survival was calculated by Kaplan-Meier and prognostic factors by Cox models. RESULTS: The study included 401 GCT male cases. The AAPC was 5.4% (IC 95% 3.3-7.4, P < .001) from 1999 (an earlier cohort published) to 2012. The median time to diagnosis was 63 days (Q25 = 33 days; Q75 = 114 days; IQR = 81 days). For stage II/III the median time to start chemotherapy was 34 days (Q25 = 22 days; Q75 = 56 days; IQR = 22 days). In 86% cases there was noncompliance with guidelines for the orchiectomy report, 6% for staging, 38% for tumor markers evaluation, 20% for treatment and 25% for chemotherapy dose intensity. The 5-year overall survival was 93.8% (95% CI, 91.3%-96.4%). Hospitals that managed ≤ 3 GCT cases/ year had higher odds for noncompliance with guidelines of blood markers, treatment and dose intensity. None of GCT healthcare access and management factors studied were associated with prognosis. CONCLUSIONS: The burden of GCT is rising in Portugal. Although survival has improved, efforts must be made to nationally enhance training and expertise in GCT and support region adapted models of centralization of care.

A method to detect fulvestrant interference in estradiol in breast cancer patients.

Background: Fulvestrant resembles estradiol in its structure. Reports have been published concerning fulvestrant measured as estradiol by the immunoassays. This may induce falsely elevated estradiol results and wrongly impact medical decisions. Our aim was to confirm the interference of fulvestrant on estradiol concentration and test a method to identify the false results. Methods: Four serum samples with low estradiol levels were spiked with fulvestrant at various concentrations. Estradiol was then measured directly on serum (Dir), after a 1:5 dilution (Dil), and a ratio Dil/Dir was estimated. On the second part of the study, estradiol results (Dir, Dil and ratio Dil/Dir) from 14 women treated with fulvestrant were analysed, as well as from 14 patients not under this treatment. Results: The addition of exogenous fulvestrant to the serum samples induced a gradual rise on estradiol concentration with a mean ratio for the Dil/Dir samples of 2.1 ± 0.4 (range 1.7-2.9). Patients on fulvestrant treatment experienced a mean ratio for the Dil/Dir estradiol sample of 2.4 ± 0.4 (range 1.6-3.0). In the control group, a mean estradiol ratio Dil/Dir of 1.1 ± 0.1 was observed (range 0.8-1.3). No correlation between the number of days after fulvestrant injection and estradiol result (r = 0.531) was observed. Conclusion: Our study confirmed the interference of fulvestrant in the estradiol measurement by immunoassay. When fulvestrant was present, the estradiol ratio for Dil/Dir sample was about 2. In the control group, the ratio was around 1. The estradiol Dil/Dir ratio is a simple tool which can be used to identify fulvestrant false immunoassay estradiol results.

Adjuvant Chemotherapy De-Escalation with Genomic Assay Protocol in Patients with Early Breast Cancer: A Single-Centre Prospective Cohort Study.

INTRODUCTION: Genomic assays are useful tools for tailoring adjuvant treatment in early breast cancer. We aimed to analyse the role of an institutional protocol of a genomic assay for chemotherapy de-escalation. MATERIAL AND METHODS: Prospective cohort study of all consecutive women diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-negative early breast cancer, tested with the 21-gene Recurrence Score (RS) assay from August 2015 to July 2018 at a Portuguese cancer centre. For being tested, patients should meet at least one of the pre-defined inclusion criteria: i) luminal A-like, pT2pN0; ii) luminal A-like, 1 - 3 positive nodes and comorbidities with higher risk of chemotherapy-induced toxicity; iii) pT1-2pN0, progesterone receptor ≤ 20% and/or Ki67 14% - 40%. Adjuvant treatment was de-escalated to isolated endocrine therapy if RS was less than 18. We measured the reduction in chemotherapy prescribing and its clinical impact, the RS association with pathologic features, and the protocol feasibility. RESULTS: We tested 154 women with a median age of 61 years old (range: 25 - 79), 69% postmenopausal. Tumours were mainly pT1 (55%), pN0 (82%), invasive ductal (73%), G2 (86%), luminal B-like (69%) and stage IA (85%). We obtained a RS less than 18 in 60% of women, with an overall adjuvant chemotherapy reduction of 65%. Seven (95% confidence interval: 5 - 10) patients needed to be screened with the 21-gene RS assay to prevent one clinically relevant adverse event during the first six months of adjuvant treatment. Considering the currently used RS cut-off, only 9% of node-negative and 11% of node-positive patients had RS over 25. We found no relevant associations between RS and pathologic features. The protocol was feasible and did not compromise the adequate timing for adjuvant treatment. CONCLUSION: These criteria allowed the de-escalation of adjuvant systemic treatment in at least six out of ten women.

Valorization of Vegetable Waste from Leek, Lettuce, and Artichoke to Produce Highly Concentrated Lignocellulose Micro- and Nanofibril Suspensions.

Vegetable supply in the world is more than double than vegetable intake, which supposes a significant waste of vegetables, in addition to the agricultural residues produced. As sensitive food products, the reasons for this waste vary from the use of only a part of the vegetable due to its different properties to the product appearance and market image. An alternative high-added-value application for these wastes rich in cellulose could be the reduction in size to produce lignocellulose micro- and nanofibrils (LCMNF). In this sense, a direct treatment of greengrocery waste (leek, lettuce, and artichoke) to produce LCMNFs without the extraction of cellulose has been studied, obtaining highly concentrated suspensions, without using chemicals. After drying the wastes, these suspensions were produced by milling and blending at high shear followed by several passes in the high-pressure homogenizer (up to six passes). The presence of more extractives and shorter fiber lengths allowed the obtention of 5-5.5% leek LCMNF suspensions and 3.5-4% lettuce LCMNF suspensions, whereas for artichoke, only suspensions of under 1% were obtained. The main novelty of the work was the obtention of a high concentration of micro- and nanofiber suspension from the total waste without any pretreatment. These high concentrations are not obtained from other raw materials (wood or annual plants) due to the clogging of the homogenizer, requiring the dilution of the sample up to 1% or the use of chemical pretreatments.

Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical Oncologists.

INTRODUCTION: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer. METHODS: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents' regions, case volumes, and practice type were explored. RESULTS: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents' region and case volume were noted. CONCLUSION: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.

This study was an online survey of Portuguese medical oncologists to determine how they managed patients with breast cancer during the COVID-19 pandemic. Forty-two questions covered topics such as how COVID testing was done, the types of cancer treatments used, and how this compared to before the pandemic. It also examined whether the geographic region, the number of patients each doctor was responsible for (caseload), and the type of medical institution influenced how patients with breast cancer were managed. One hundred and twenty-nine oncologists completed the survey, of whom 108 worked in the public health system, making this survey representative of breast cancer management during the COVID-19 pandemic across Portugal. Most (71%) said there were fewer visits for new cases of breast cancer during lockdown. The use of telemedicine increased, as did the use of pre-surgery hormone therapy or chemotherapy when access to surgery was difficult, and the use of anticancer medications taken orally or metronomically (low doses given frequently over a long time period). Chemotherapy given very frequently (dose-dense) was used less often, and fewer patients participated in clinical trials. Treatment decisions for patients with aggressive breast cancer types (e.g., triple-negative breast cancer) were largely unchanged, except for greater use of cyclin-dependent kinase 4/6 inhibitors­drugs targeting the cell cycle and cell division control. Geographic region and caseload influenced treatment decisions. All of these changes in breast cancer treatment during the COVID-19 pandemic were logical and reasonable for the circumstances, but their long-term impact is not yet known.

Peritoneal carcinosis in male germ cell tumor patients: a registry study compiled by the German Testicular Cancer Study Group (GTCSG).

PURPOSE: To report on the clinical characteristics, outcome, and frequency of peritoneal carcinosis (PC) in patients with advanced germ cell tumors (GCT), a multicenter registry analysis was carried out. METHODS: A multicenter registry analysis was conducted by the German Testicular Cancer Study Group (GTCSG) with international collaborators. Data was collected and analyzed retrospectively. Patients were eligible for inclusion if PC was diagnosed either by radiologic or histopathologic finding during the course of disease. Descriptive and explorative statistical analysis was carried out with cancer-specific survival (CSS) as primary study endpoint. RESULTS: Collaborators from ten GCT expert centers identified 28 GCT (0.77%) patients with PC after screening approximately 3767 GCT patient files and one case was contributed from a cancer registry request. Patients were diagnosed from 1997 to 2019 at a median age of 37 years (interquartile range, 13). Two patients (7%) presented with stage I and 27 patients (93%) with synchronous metastatic disease at first diagnosis. The primary histology was seminoma in seven (27%) and non-seminoma in 21 patients (72%). PC was detected after a median of 15.3 months from primary diagnosis (range 0-177) and two consecutive treatment lines (range 0-5), respectively. The median CSS from the time of detection of PC was 10.5 months (95%Confidence Interval 0.47-1.30) associated with an overall 2-year CSS rate of 30%. CONCLUSION: PC represents a rare tumor manifestation in GCT patients and was primarily associated with the occurrence of advanced cisplatin-refractory disease conferring to a dismal prognosis.

Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study.

BACKGROUND: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). METHODS: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). RESULTS: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. CONCLUSIONS: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. LAY SUMMARY: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.

Safety and health risks for workers exposed to cold thermal environments: A frozen food processing industry perspective.

BACKGROUND: Environmental temperatures in the fresh food industry vary from 0°C to 10°C, and go below -20°C for the frozen food industry, representing risk for the health and safety of workers involved. OBJECTIVE: The aim of this work was to evaluate the cold thermal stress risks for workers working in a frozen food industry. METHODS: A total of 27 acclimatized workers (13 male and 14 female) participated in a study which was conducted during 11 working days. The thermal sensation questionnaire and the cold work health questionnaire (CWHQ) were applied to all participants. Additionally, 4 workers were chosen to be fully monitored with a thermometer telemetry capsule for measuring the intra-abdominal temperature and 8 skin temperature sensors. RESULTS: The lowest recorded hand temperature was 14.09°C, lowest forehead 18.55°C, mean skin temperature had variations of 1.10 to 3.20°C along the working period. Highest and most frequent fluctuations were found in the hand and forehead skin temperatures, small changes were found in mean skin temperature. CONCLUSIONS: Answers to the CWHQ increase concern on clinical forms of "a frigore", and in two cases the mean body temperature decreased below 35.0°C, which is defined in the current literature as a mild form of hypothermia.

Polyphasic characterization of carbapenem-resistant Klebsiella pneumoniae clinical isolates suggests vertical transmission of the blaKPC-3 gene.

Carbapenem-resistant Klebsiella pneumoniae are a major global threat in healthcare facilities. The propagation of carbapenem resistance determinants can occur through vertical transmission, with genetic elements being transmitted by the host bacterium, or by horizontal transmission, with the same genetic elements being transferred among distinct bacterial hosts. This work aimed to track carbapenem resistance transmission by K. pneumoniae in a healthcare facility. The study involved a polyphasic approach based on conjugation assays, resistance phenotype and genotype analyses, whole genome sequencing, and plasmid characterization by pulsed field gel electrophoresis and optical DNA mapping. Out of 40 K. pneumoniae clinical isolates recovered over two years, five were carbapenem- and multidrug-resistant and belonged to multilocus sequence type ST147. These isolates harboured the carbapenemase encoding blaKPC-3 gene, integrated in conjugative plasmids of 140 kbp or 55 kbp, belonging to replicon types incFIA/incFIIK or incN/incFIIK, respectively. The two distinct plasmids encoding the blaKPC-3 gene were associated with distinct genetic lineages, as confirmed by optical DNA mapping and whole genome sequence analyses. These results suggested vertical (bacterial strain-based) transmission of the carbapenem-resistance genetic elements. Determination of the mode of transmission of antibiotic resistance in healthcare facilities, only possible based on polyphasic approaches as described here, is essential to control resistance propagation.

A Risk-benefit Analysis of Prophylactic Anticoagulation for Patients with Metastatic Germ Cell Tumours Undergoing First-line Chemotherapy.

BACKGROUND: It remains unclear which patients with metastatic germ cell tumours (mGCTs) need prophylactic anticoagulation to prevent venous thromboembolic events (VTEs). OBJECTIVE: To assess the risk and onset of VTEs stratified by risk factors. DESIGN, SETTING, AND PARTICIPANTS: This multi-institutional retrospective dataset included mGCT patients treated with first-line platinum-based chemotherapy. INTERVENTION: Patients with prophylactic anticoagulation were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A regression analysis was performed to select risk factors for VTEs. The simulated number needed to treat (NNT) and the number needed to harm (NNH) with prophylactic anticoagulation were calculated based on the cumulative incidences retrieved from this study and hazard rates of recently published trials describing the efficacy of prophylactic anticoagulation to prevent VTEs and the risk of bleeding events. RESULTS AND LIMITATIONS: From 1120 patients, 121 (11%) had a VTE, which occurred prior to chemotherapy in 49 (4%) and on or after chemotherapy in 72 (6%). Six patients (<1%) had a bleeding event without anticoagulation. After backward regression, the one risk factor for a VTE during or after chemotherapy was the use of a venous access device. The simulated cumulative VTE incidence from prophylactic anticoagulation for patients on or after chemotherapy would translate into an NNT of 45 (95% confidence interval [CI] 36-56) and an NNH of 186 (95% CI 87-506). Limitations are mainly related to the retrospective nature of the study. CONCLUSIONS: The mGCTs associated VTEs are most common before and during, but not after, chemotherapy. Avoiding venous access device and/or prophylactic anticoagulation with an acceptable risk-benefit profile may decrease VTE occurring on chemotherapy. PATIENT SUMMARY: We found that venous thromboembolic events (VTEs) occur rarely after chemotherapy. Based on experience of prophylactic anticoagulation in other cancers, we conclude that the risk of VTE in men undergoing chemotherapy for metastatic germ cell tumours can be decreased by thromboprophylaxis with a reasonable risk-benefit profile and by avoidance of venous access devices.

Author Correction: Challenges in the serological evaluation of dogs clinically suspect for canine leishmaniasis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Human chorionic gonadotropin-positive seminoma patients: A registry compiled by the global germ cell tumor collaborative group (G3).

BACKGROUND: The prognostic role of human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH) serum levels in seminoma patients remains uncertain. This observational study evaluates the prognostic impact of tumour marker levels, and other clinicopathological findings, in hCG-positive seminoma patients. METHODS: Seminoma patients with serum hCG levels above normal at first diagnosis were eligible for recruitment. Statistical analysis, including multivariate regression, was performed to identify risk factors. Primary end-points were overall survival (OS) and recurrence-free survival (RFS). RESULTS: We recruited 1031 hCG-positive patients (stage I: n = 586; stage II + III: n = 427) diagnosed between 1981 and 2018. In metastatic disease, LDH levels ≥3 above upper normal limit (UNL) pre- (n = 109) or post-orchiectomy (n = 73) and patients aged ≥40 years (n = 187) were associated with poor prognosis: 5-year OS rates of 84% (LDH ≥3 UNL pre-orchiectomy) versus 92% (<3 UNL pre-orchiectomy) (hazard ratio [HR]: 3.155, [95% confidence interval {CI}: 1.28-7.75], P = 0.012), 82% (≥3 UNL post-orchiectomy) versus 92% (<3 UNL post-orchiectomy) (HR: 6.877, [95% CI: 1.61-29.34]; P = 0.009) and 86% (≥40 years) versus 91% (<40 years) (HR: 6.870, [95% CI: 1.45-13.37], P = 0.009), respectively. A subset of patients with hCG levels ≥2000 IU/l pre-orchiectomy (n = 17) exhibited a poor prognosis, with 5-year OS rates of 73% (≥2000 IU/l) versus 94% (<2000 IU/l) (HR: 3.936, [95% CI: 1.02-12.61], P = 0.047). CONCLUSIONS: Age and LDH levels are significantly associated with poor prognosis in hCG-positive seminoma patients. A small number of patients, with levels of hCG ≥2000 IU/l, may represent a separate prognostic subgroup associated with impaired survival rates.

Challenges in the serological evaluation of dogs clinically suspect for canine leishmaniasis.

Canine leishmaniasis is a major veterinary issue and also a public health challenge due to its zoonotic potential. In this context, serological evaluation is essential for Canine leishmaniasis management. Several serological alternatives, such as rapid diagnostic tests, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence antibody test (IFAT), are well established. In fact, the capacity of distinct tests and antigens, evaluated by their sensitivity and specificity, to detect disease is normally considered sufficient for diagnosing Canine leishmaniasis. In this context, we evaluated the seropositivity using 8 different serological tests (ELISA with Leishmania recombinant proteins (rK39, LicTXNPx); soluble promastigote Leishmania antigens (SPLA); commercial ELISA test) in 82 clinically suspect animals from Northern Portugal. The obtained serological data originated 50% of inconclusive serological information with a mixture of seropositive and seronegative results for individual animals. Cut-off independent risk groups were then generated from the serological data to evaluate the clustering of the samples. This analysis originated risk groups that correlated with the most seropositive samples, suggesting that this method might be used, in a cut-off independent manner, to improve conventional serological evaluation. Ultimately, given that no test prioritization exists, the use of any single serological test increases the potential for misdiagnosis, along with all associated risks for the dog as well as public health. The use of a cut-off independent analysis has the potential to improve the predictive values of these tests, enabling a more accurate evaluation of the dog's condition.

Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first-line chemotherapy for metastatic germ cell tumors: A study by the global germ cell cancer group (G3).

BACKGROUND: Metastatic germ cell tumor (mGCT) patients receiving chemotherapy have increased risk of life-threatening venous thromboembolism (VTE). Identifying VTE risk factors may guide thromboprophylaxis in this highly curable population. METHODS: Data were collected from mGCT patients receiving first-line platinum-based chemotherapy at 22 centers. Predefined variables included International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, long-axis diameter of largest retroperitoneal lymph node (RPLN), Khorana score, and use of indwelling vascular access device (VAD). VTE occurring at baseline, during chemotherapy and within 90 days, was analyzed. RESULTS: Data from 1135 patients were collected. Median age was 31 years (range 10-74). IGCCCG risk was 64% good, 20% intermediate, and 16% poor. VTE occurred in 150 (13%) patients. RPLN >3.5 cm demonstrated highest discriminatory accuracy for VTE (AUC 0.632, P < .001) and was associated with significantly higher risk of VTE in univariable analysis (22% vs 8%, OR 3.0, P < .001) and multivariable analysis (OR 1.8, P = .02). Other significant risk factors included, Khorana score ≥3 (OR 2.6, P = .008) and VAD use (OR 2.7, P < .001). CONCLUSIONS: Large RPLN and VAD use are independent risk factors for VTE in mGCT patients receiving chemotherapy. VAD use should be minimized in this population and thromboprophylaxis might be considered for large RPLN.

Loss of HER2 and disease prognosis after neoadjuvant treatment of HER2+ breast cancer.

INTRODUCTION: HER2 overexpression/amplification occurs in 15-20% breast cancers (BC) and is associated with worse prognosis. The addition of anti-HER2 treatment to neoadjuvant chemotherapy significantly improves the pathological complete response (pCR) rate. Changes in HER2 status after neoadjuvant treatment (NAT) have been reported and may affect prognosis. The aim of this study was to assess the efficacy of NAT in patients with HER2+ BC and its influence on HER2 status and associated prognostic impact. METHODS: Retrospective chart review and pathologic evaluation of all consecutive patients with HER2+ BC (defined as IHC 3+ or IHC 2+ confirmed by SISH) submitted to NAT between 2010-2015 in three Portuguese Hospitals. RESULTS: One hundred eight female patients were included; 40 with stage II, 68 with stage III. Hormone receptors were positive in 70. pCR (ypT0/isN0) was achieved in 48 patients (44%). With a median follow-up of 52 months, there were 5 disease free survival (DFS) events among pCR patients and 19 among non-pCR (P = 0.02). Of the 60 patients with residual disease at surgery, 52 remained HER2+ and 8 (13%) lost HER2 overexpression/amplification. 5y-DFS and 5y-OS was 70% and 84%, respectively, for patients whose residual tumors remained HER2+, and 21% and 50% for patients whose residual tumors became HER2 negative (P = 0.02 and < 0.001). DISCUSSION: We confirmed the negative prognostic impact of NAT-induced HER2 loss on residual tumor leading to worse DFS and OS. Despite the retrospective design and small sample size, these results suggest that it is important to retest HER2 after NAT, to better refine patient outcome.

The prognostic impact of different tumor marker levels in nonseminomatous germ cell tumor patients with intermediate prognosis: A registry of the International Global Germ Cell Tumor Collaborative Group (G3).

BACKGROUND: Germ cell tumor patients with intermediate prognosis (IPGCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification represent a heterogeneous group with different clinical features. This analysis was performed to investigate the prognostic impact of different tumor marker levels prior to first line chemotherapy within IPGCT. METHODS: For this study an international registry for IPGCT was established. Eligibility criteria were intermediate prognosis according to IGCCCG criteria, nonseminomatous histology, male sex, and age ≥ 16 years. Uni- and multivariate analysis were conducted to identify characteristics associated with survival outcomes. Receiver-Operating-Characteristic curve analysis was applied to find cut-off parameters. Five-year overall survival (OS) rate was the primary and 5-year progression-free survival rate the secondary endpoint. RESULTS: This database included 634 IPGCT with a median follow-up of 9.0 years (interquartile range: 14.35). Patients received first line treatment with platinum based chemotherapy, associated with a 5-year OS rate of 87%. The stratification of patients according to AFP levels revealed a correlation between AFP levels and outcome, associated with 5-year OS rates of 88% for AFP levels <1,000 IU/ml (n = 303), 89% for 1,000 to 2,000 IU/ml (n = 82), 87% for >2,000 to 6,000 IU/ml (n = 121), and 82% for >6,000 IU/ml (n = 57) prior first course of chemotherapy, respectively (P= 0.013). LDH levels prior fist course of chemotherapy also correlated with outcome associated with 5-year OS rates of 92% for <2 UNL (n = 271), 89% for ≥2 to 3 UNL (n = 85), 78% for >3 to 4 UNL (n = 34), and 77% for >4 UNL (n = 79), respectively (P= 0.03). Different HCG levels prior chemotherapy were not associated with outcome. In multivariable analysis AFP levels >6,000 IU/ml (P= 0.023; hazard ratio HR 2.263) or >1,982 IU/ml (P= 0.031; HR 1.722), and LDH levels >3 UNL (P< 0.001; HR 2.616) were independent prognosticators for OS. CONCLUSIONS: Prognostication according to LDH and AFP levels prior chemotherapy could offer a new approach to stratify patients within the intermediate prognosis cohort. According to our findings, patients with AFP values above 6,000 IU/ml or/and LDH > 3 UNL represent an independent high risk cohort. Our results need to be confirmed in the upcoming IGCCCG reclassification.

High-Risk human papillomavirus genotype distribution in the Northern region of Portugal: Data from regional cervical cancer screening program.

High-Risk Human papillomavirus (HR-HPV) full genotyping methods have been described as of great potential use in epidemiology and preventive strategies, including cervical cancer screening and HPV vaccination. We characterized the prevalence and distribution of HR-HPV genotypes in cervico-vaginal samples obtained from the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. HR-HPV genotyping was performed using Anyplex™ II HPV-HR Detection kit in 105,458 women enrolled between August 2016 and December 2017. HR-HPVs were detected in 10,665 women (10.2%) with a prevalence ranging from 6.2 to 17.1% depending on age, and from 8.7 to 10.7% depending on geographical location. Multiple infections with two or more HR-HPVs were detected in 2736 (25.7%) of HR-HPV women ranging from 16.5 to 31.0% depending on age. Amongst HR-HPV positive women, HPV-16 (17.5%), HPV-39 (16.7%), HPV-31 (15.0%), HPV-68 (13.2%), HPV-52 (10.7%) and HPV-51 (10.6%) were the most common genotypes in our population, being HPV-16 more frequent in women aged from 30 to 45 years and HPV-39 in 50-65 years. Results also show that HPV16/18 are present in 22.1% and HPV16/18/31/33/45/52/58 in 47.6% of HR-HPV positive women. This is the largest study on HR-HPV genotyping for Cervical Cancer Screening in European populations and provides critical data for program management and vaccine policy.

Effectiveness of Adjuvant Ovarian Function Suppression in Premenopausal Women With Early Breast Cancer: A Multicenter Cohort Study.

BACKGROUND: Ovarian function suppression (OFS) with tamoxifen or aromatase inhibitors (AIs) improves disease-free survival in premenopausal women with breast cancer, mostly in those at higher risk of recurrence. However, its real-world use and impact remain poorly understood. PATIENTS AND METHODS: This is a multicenter retrospective cohort study of premenopausal women with stage I to III hormone receptor-positive breast cancer diagnosed from 2006 to 2015 that aimed to look at the uptake and effectiveness of the addition of OFS to backbone endocrine therapy (tamoxifen or AI). To deal with confounding, we used both multivariate modeling and propensity score matching. RESULTS: Of 1717 eligible patients, 17.1% were treated with OFS. There was a substantial increase of use of OFS over time, especially from 2014 onward (16% vs. 25% after 2014), particularly for the combination with AI (0.4% vs. 8% after 2014). In a multivariate model, only younger age and year of diagnosis ≥ 2014 were associated with OFS utilization (both P < .001). With a median follow-up of 38 months (P25-P75, 19.6-66.4 months), patients receiving OFS had a better overall survival than those not receiving OFS (adjusted hazard ratio, 0.44; 95% confidence interval, 0.19-0.96; absolute benefit at 5 years, 2.1% [95.3% vs. 93.2% in those not receiving OFS]). A similar benefit was identified using propensity score matching. CONCLUSIONS: In the real-world setting, there was an increase in the use of OFS after 2014. After 2014, one-quarter of premenopausal women received adjuvant OFS, of which more than 30% received it in combination with an AI. In this study, the use of adjuvant OFS was associated with an overall survival benefit.

Rectal and anal canal neuroendocrine tumours.

Neuroendocrine tumors (NETs) are rare, representing 0.5% of all newly diagnosed malignancies. Rectal and anal canal (AC) NETs account for less than 1% of all rectal and AC cancers. Review our institutional experience on NET of the rectum and AC, with emphasis on demographic, histological and treatment features and oncologic outcomes. The study group was identified from the Portuguese Regional South Oncological Registry. From 2000 to 2014, 22 patients with rectal or AC NETs were treated at our institution. Medical records were retrospectively reviewed. There were 12 males (54.5%) and 10 females (45.5%) and the median age at diagnosis was 59.5 years. The majority had rectal NET (81.8%). All 4 patients with AC NETs had neuroendocrine carcinoid (NEC) tumors. Of the patients with rectal NETs, 3 had NEC and 15 had NET, mainly G1. Different approaches to treatment were made according to histological and staging features. After an average follow-up of 39.1 months, 16 patients were alive and only one with evidence of disease. The median time to progression was 12.4 months and the liver was the most frequent site of metastasis. The European and North American Neuroendocrine Societies offer guidelines for the treatment of rectal NETs. However, for AC NETs there are only small series and not prospective studies due to their rarity, hence the importance to report institutional experience. Our practice demonstrated that primary excisional treatment, regardless the histology, provides a favorable prognosis and long survival.