Closing the gap: prognostic and predictive biomarker validation for personalized care in a Latin American hormone-dependent breast cancer cohort.

BACKGROUND: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. METHODS: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. RESULTS: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively). CONCLUSION: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

Opportunities for personalised follow-up in breast cancer: the gap between daily practice and recurrence risk.

PURPOSE: Follow-up guidelines barely diverge from a one-size-fits-all approach, even though the risk of recurrence differs per patient. However, the personalization of breast cancer care improves outcomes for patients. This study explores the variation in follow-up pathways in the Netherlands using real-world data to determine guideline adherence and the gap between daily practice and risk-based surveillance, to demonstrate the benefits of personalized risk-based surveillance compared with usual care. METHODS: Patients with stage I-III invasive breast cancer who received surgical treatment in a general hospital between 2005 and 2020 were selected from the Netherlands Cancer Registry and included all imaging activities during follow-up from hospital-based electronic health records. Process analysis techniques were used to map patients and activities to investigate the real-world utilisation of resources and identify the opportunities for improvement. The INFLUENCE 2.0 nomogram was used for risk prediction of recurrence. RESULTS: In the period between 2005 and 2020, 3478 patients were included with a mean follow-up of 4.9 years. In the first 12 months following treatment, patients visited the hospital between 1 and 5 times (mean 1.3, IQR 1-1) and received between 1 and 9 imaging activities (mean 1.7, IQR 1-2). Mammogram was the prevailing imaging modality, accounting for 70% of imaging activities. Patients with a low predicted risk of recurrence visited the hospital more often. CONCLUSIONS: Deviations from the guideline were not in line with the risk of recurrence and revealed a large gap, indicating that it is hard for clinicians to accurately estimate this risk and therefore objective risk predictions could bridge this gap.

Dynamic risk assessment in patients with differentiated thyroid cancer.

The current approach for patients with differentiated thyroid carcinoma should be individualized according to the risk of recurrence, and this stratification could be used to identify the risk of persistent/recurrent disease in three scenarios: preoperatively, immediately postoperatively, and during long-term follow-up. The initial risk of recurrence will tailor the management of the patient in the preoperative and immediate postoperative settings, while the dynamic risk, which considers the responses to treatment, could guide the decision-making process for remnant ablation and long-term management.This review provides a summary of the existing information regarding the dynamic risk of recurrence and recommended management for patients with differentiated thyroid cancer. The application of this approach is essential to avoid unnecessary treatments for most patients who will have a favorable prognosis. On the other hand, it allows specific therapeutic interventions for those patients at high risk of recurrence. In the future, analysis of tumor biology and prospective studies will surely improve the accuracy of recurrence risk prediction.

The value of endocervical curettage during large loop excision of the transformation zone in combination with endocervical surgical margin in predicting persistent/recurrent dysplasia of the uterine cervix: a retrospective study.

BACKGROUND: Cervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated. METHODS: In this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital's patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy). RESULTS: Patients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p < 0.001). The Fisher's exact test confirmed a statistically significant connection between the resection status together with the result of the ECC and the reoccurrence of dysplasia after surgery (p < 0,001). 40,6% of the patients with re-dysplasia after primary LLETZ had shown cranial R1-resection together with cells of HSIL in the ECC. Investigating the risk for a future abnormal Pap smear, patients with cranial R1-resection together with dysplastic cells in the ECC showed the greatest deviation of statistical normal distribution with SR = 2.6. CONCLUSION: Our results demonstrate that the future risk of re-dysplasia, re-surgery, and abnormal Pap smear for patients after LLETZ due to HSIL is highest within patients who were diagnosed with cranial (endocervical) R1-resection and with cells of HSIL in the ECC in their primary LLETZ. Consequently, the identification of patients, who could benefit of intensified observation or required intervention could be improved.

PAM50 intrinsic subtypes, risk of recurrence score and breast cancer survival in HIV-positive and HIV-negative patients-a South African cohort study.

PURPOSE: Treatment decision making for patients with breast cancer increasingly depends on analysis of markers or systems for estimating risk of breast cancer recurrence. Breast cancer intrinsic subtypes and risk of recurrence (ROR) scores have been found to be valuable in predicting survival and determining optimal treatment for individual patients. We studied the association of breast cancer survival with the PAM50 gene expression assay in HIV-positive and HIV-negative patients. METHOD: RNA was extracted from formalin-fixed paraffin-embedded specimens of histologically confirmed invasive carcinoma and was purified using the AllPrep® DNA/RNA FFPE kit, Qiagen (Hilden, Germany). The NanoString RUO PAM50 algorithm was used to determine the molecular subtype and the risk of recurrence score of each sample. The overall and disease-free survival were determined with comparison made among HIV-positive and -negative patients. We then generated Kaplan-Meier survival curves, calculated p-values and estimated hazard ratios and their 95% confidence intervals using Cox regression models. RESULTS: Of the 384 RNA samples analysed, 98.4% met the required RNA quality standard and the specified QC threshold for the test. Luminal B was the most common PAM50 intrinsic subtype and 82.1% of patients were at high risk for disease recurrence based on ROR score. HIV infection, PAM50-based HER2-enriched and basal-like intrinsic subtypes, and high ROR were associated with poor overall and disease-free survival. HIV-positive patients with luminal A & B subtypes had significantly worse survival outcomes than HIV-negative luminal patents. CONCLUSION: Aggressive tumour biology was common in our cohort. HIV infection, PAM50 HER2-enriched,basal-like intrinsic subtypes and high ROR score were associated with poor overall and disease-free survival. HIV infection impacted survival in patients with luminal subtypes only.

Long-term clinical and radiological outcomes of endoscopic ultrasound-guided radiofrequency ablation of benign insulinomas.

OBJECTIVE: In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative nonsurgical treatment for pancreatic neuroendocrine tumours. The aim of our study was to assess the long-term follow-up of patients treated with EUS-RFA for a sporadic insulinoma in our centre in terms of efficacy, safety and risk of recurrence. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed the data of 11 patients with an insulinoma treated by EUS-RFA in our tertiary centre between June 2018 and April 2022. Clinical and biological, as well as imaging, follow-up was planned at 3, 6, 12 months and then annually. RESULTS: In our series, there were nine women and two men with a median age of 65 years. All tumours were sporadic, with a mean size of 11 mm. The procedure allowed an immediate and complete symptomatic and biological remission in all patients without notable complications. Complete radiological resolution of the tumour after ablation was observed in seven patients, and persistence of an asymptomatic tumour residue was observed in four patients. During the mean follow-up period of 26 months, two patients presented a significant but asymptomatic increase of the tumour residue; a second EUS-RFA session was performed in one patient and the other patient is being closely monitored. CONCLUSIONS: EUS-RFA treatment of benign insulinomas provides a long-term complete clinical resolution of hypoglycaemia. A long-term follow-up is essential if residual tumour persists after initial EUS-RFA treatment.

Personalized surveillance and aftercare for non-metastasized breast cancer: the NABOR study protocol of a multiple interrupted time series design.

BACKGROUND: Follow-up of curatively treated primary breast cancer patients consists of surveillance and aftercare and is currently mostly the same for all patients. A more personalized approach, based on patients' individual risk of recurrence and personal needs and preferences, may reduce patient burden and reduce (healthcare) costs. The NABOR study will examine the (cost-)effectiveness of personalized surveillance (PSP) and personalized aftercare plans (PAP) on patient-reported cancer worry, self-rated and overall quality of life and (cost-)effectiveness. METHODS: A prospective multicenter multiple interrupted time series (MITs) design is being used. In this design, 10 participating hospitals will be observed for a period of eighteen months, while they -stepwise- will transit from care as usual to PSPs and PAPs. The PSP contains decisions on the surveillance trajectory based on individual risks and needs, assessed with the 'Breast Cancer Surveillance Decision Aid' including the INFLUENCE prediction tool. The PAP contains decisions on the aftercare trajectory based on individual needs and preferences and available care resources, which decision-making is supported by a patient decision aid. Patients are non-metastasized female primary breast cancer patients (N = 1040) who are curatively treated and start follow-up care. Patient reported outcomes will be measured at five points in time during two years of follow-up care (starting about one year after treatment and every six months thereafter). In addition, data on diagnostics and hospital visits from patients' Electronical Health Records (EHR) will be gathered. Primary outcomes are patient-reported cancer worry (Cancer Worry Scale) and overall quality of life (as assessed with EQ-VAS score). Secondary outcomes include health care costs and resource use, health-related quality of life (as measured with EQ5D-5L/SF-12/EORTC-QLQ-C30), risk perception, shared decision-making, patient satisfaction, societal participation, and cost-effectiveness. Next, the uptake and appreciation of personalized plans and patients' experiences of their decision-making process will be evaluated. DISCUSSION: This study will contribute to insight in the (cost-)effectiveness of personalized follow-up care and contributes to development of uniform evidence-based guidelines, stimulating sustainable implementation of personalized surveillance and aftercare plans. TRIAL REGISTRATION: Study sponsor: ZonMw. Retrospectively registered at ClinicalTrials.gov (2023), ID: NCT05975437.

Clinicopathological analysis of patients with molecularly confirmed stage I adult granulosa cell tumors and prediction of recurrence.

OBJECTIVE: Adult granulosa cell tumors (AGCTs) are rare malignancies that accounts for approximately 1% of ovarian neoplasms. As there are currently no well-recognized models for predicting relapse-free survival (RFS), we performed a clinicopathological analysis to identify risk factors for AGCT recurrence. METHODS: We investigated 130 patients with pathologically diagnosed AGCT as confirmed by the presence of the characteristic FOXL2 C402G mutation. RESULTS: Most patients had International Federation of Gynecology and Obstetrics stage I disease (n = 122, 95.3%). The 10-year RFS rate was 31.4% (22/70) and mean 10-year RFS was 74.4 (95% CI, 65.2-83.7) months. Ten patients experienced recurrence beyond the 10-year follow-up period. Undergoing fertility sparing surgery, an estrogen receptor-α (ERα) score (>0.25), and a Ki-67 index >15% were independent risk factors for recurrence in patients with stage I disease (bias-corrected C-index: 0.776). We constructed a nomogram with well-fitting calibration plots; the areas under the curve (AUCs) for 5-, and 10-year RFS prediction were 0.883 and 0.906 respectively. A simplified model with 3 predictive factors (ERα score, Ki-67 index, and primary surgical procedure) and 2 risk stratification subgroups (low- and high-risk) was constructed; its AUCs for 5-, and 10-year RFS prediction were 0.825 and 0.850 respectively. Kaplan-Meier survival curves showed significant differences in 10-year RFS between the low- and high-risk groups (p < 0.001). CONCLUSIONS: The type of primary surgical procedure, ERα score, and Ki-67 index are independent predictors of recurrence for patients with stage I AGCT. Our predictive model based on these factors showed good performance.

Prediction of recurrent gestational diabetes mellitus: a retrospective cohort study.

BACKGROUND: Women after gestational diabetes mellitus (GDM) are at increased risk for development of GDM recurrence. It was the aim of our study to evaluate factors for prediction of risk of recurrence. METHODS: In this retrospective cohort study we included 159 women with GDM and a subsequent pregnancy. Putative risk factors for GDM recurrence were analyzed by logistic regression models. Results were compared to a cohort of age-matched women without GDM as controls (n = 318). RESULTS: The overall risk of GDM recurrence was 72.3% (115/159). Risk factors of recurrence were a body mass index (BMI) ≥ 30 kg/m2 before the index pregnancy (odds ratio (OR) 2.8 [95% CI 1.3-6.2], p = 0,008), a BMI ≥ 25 kg/m2 before the subsequent pregnancy (OR 2.7 [95% CI 1.3-5.8]. p = 0.008), a positive family history (OR 4.3 [95% CI 1.2-15.4], p = 0.016) and insulin treatment during the index pregnancy (OR 2.3 [95% CI 1.1-4.6], p = 0.023). Delivery by caesarean section (index pregnancy) was of borderline significance (OR 2.2 [95% CI 0.9-5.2], p = 0.069). Interpregnancy weight gain, excessive weight gain during the index pregnancy and fetal outcome where not predictive for GDM recurrence. Neonates after GDM revealed a higher frequency of transfer to intensive care unit compared to healthy controls (OR 2.3 [95% CI 1.1-4.6], p = 0.0225). The best combined risk model for prediction of GDM recurrence including positive family history and a BMI ≥ 25 kg/m2 before the subsequent pregnancy revealed moderate test characteristics (positive likelihood ratio 7.8 [95% CI 1.1-54.7] and negative likelihood ratio 0.7 [95% CI 0.6-0.9]) with a positive predictive value of 96.6% in our cohort. CONCLUSIONS: A positive family history of diabetes mellitus in combination with overweight or obesity were strongly associated with recurrence of a GDM in the subsequent pregnancy. Normalization of the pregravid BMI should be an effective approach for reducing the risk of GDM recurrence.

Surgical treatment and prognosis values of extranodal extension to recurrent laryngeal nerve in papillary thyroid carcinoma.

PURPOSE: Recurrent laryngeal nerve (RLN) invasion by extranodal extension (ENE) is a rare condition that may occur in papillary thyroid cancer (PTC), and it has never been characterised in the literature.Our research aims to investigate the clinical significance of ENE to RLN including its effect on vocal cord function, relationship with the aggressive behaviour of PTC, and optimal surgical methods. METHODS: A total of 3119 patients, including 2868 patients without RLN invasion, 251 patients with RLN invasion [categorised into the ENE invasion group (n = 55) and extrathyroidal extension (ETE) invasion group (n = 196)] were analyzed retrospectively. Data on clinicopathological characteristics, vocal cord paralysis (VCP), postoperative complications, surgical methods, rates of recurrence and metastasis were collected. Predictive disease-free survival (DFS) was analysed using the Kaplan-Meier method. RESULTS: The ENE invasion group showed a similar rate of VCP and DFS compared with the ETE invasion group (P = 0.15, P = 0.38, respectively). Sharp separation applied on the invaded nerves preserves the visual integrity of the RLN without significantly reducing the DFS (P > 0.05). ETE or ENE to RLN, lymph nodes metastasis (LNM), and T4 stage were independent factors for total recurrence [P = 0.04, hazard ratio (HR), 1.97 (1.04-3.75); P = 0.00, HR, 4.63 (2.24-9.54); P = 0.00, HR, 3.63 (1.94-6.77); P = 0.00, HR, 6.1 (3.24-11.50)]. RLN invasion, both by ETE or ENE, was significantly associated with reduced DFS (P = 0.00; P = 0.00, respectively). CONCLUSIONS: ENE to RLN, while rare, has not previously been well-studied. Our interesting premise and important findings including ENE to RLN has the same poor prognostic impact on recurrence as does invasion of the RLN by ETE and surgical management for the invaded RLN that preserves its visual integrity without compromising DFS. Those novel findings indicate that ENE to RLN could be considered as an additional factor beyond post-operative disease status and risk stratification, and it would be a valuable addition to further individualise treatment/surveillance for PTC.

Prognostic significance of different molecular typing methods and immune status based on RNA sequencing in HR-positive and HER2-negative early-stage breast cancer.

BACKGROUND: This study was conducted to evaluate the prognostic significance of different molecular typing methods and immune status based on RNA sequencing (RNA-seq) in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR + /HER2-) early-stage breast cancer and develop a modified immunohistochemistry (IHC)-based surrogate for intrinsic subtype analysis. METHODS: The gene expression profiles of samples from 87 HR + /HER2- early-stage breast cancer patients were evaluated using the RNA-seq of Oncotype Dx recurrence score (RS), PAM50 risk of recurrence (ROR), and immune score. Intrinsic tumor subtypes were determined using both PAM50- and IHC-based detection of estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor, and cytokeratins 14 and 5/6. Prognostic variables were analyzed through Cox regression analysis of disease-free survival (DFS) and distant metastasis-free survival (DMFS). RESULTS: Survival analysis showed that ROR better predicted recurrence and distant metastasis compared to RS (for DFS: ROR, P = 0.000; RS, P = 0.027; for DMFS, ROR, P = 0.047; RS, P = 0.621). Patients with HR + /HER2- early-stage breast cancer was classified into the luminal A, luminal B, HER2-enriched, and basal-like subtypes by PAM50. Basal-like subgroups showed the shortest DFS and DMFS. A modified IHC-based surrogate for intrinsic subtype analysis improved the concordance with PAM50 from 66.7% to 73.6%, particularly for basal-like subtype identification. High level of TILs and high expression of immune genes predicted poor prognosis. Multi-factor Cox analysis showed that IHC-based basal-like markers were the only independent factors affecting DMFS. CONCLUSIONS: Prognosis is better evaluated by PAM50 ROR in early-stage HR + /HER2- breast cancer and significantly differs among intrinsic subtypes. The modified IHC-based subtype can improve the basal-like subtype identification of PAM50. High immunity status and IHC-based basal-like markers are negative prognostic factors.

Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test.

BACKGROUND: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not. OBJECTIVE: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions. METHODS: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold. RESULTS: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death. LIMITATIONS: Multicenter, retrospective study. CONCLUSION: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone.

Giant Ameloblastoma and the Risk of Recurrence: Experiences from a Tertiary Hospital.

BACKGROUND: Ameloblastoma is an aggressive tumor of odontogenic epithelium that grows slowly with propensity for bone expansion. Sometimes it may grow to very large sizes also known as giant ameloblastoma (GA) which may affect function and even pose a threat to life. OBJECTIVE: To present the pattern of presentation of GAs seen in a tertiary centre in Northern Nigeria. PATIENTS AND METHODS: A retrospective study of patients seen with GA at the Oral and Maxillofacial Clinic of a tertiary health facility of Northern Nigeria between January 2006 to December 2019. All patients with complete documentation in the folder, theatre register and histopathologic records were recruited for the study. Data were analyzed using SPSS version 23. RESULTS: GAs accounted for 30.2% (48) of all the ameloblastomas operated during the period with a male dominance of 62.5% (30), giving a ratio of 1.7:1(M:F). The age range was between 12 and 65 years with a mean age of 35.04years (±14.5) and the mandible was the most affected jaw compared to the maxilla (12.5%). Lesions with lowest and highest weight were found on the mandible (77g and 1640g respectively). The treatment most given was mandibulectomy (unspecified) with 20.0% followed by Rt and Lt mandibulectomies with 14.0% each. CONCLUSION: GA was found to account for 30.2% of all lesions seen within the period under review, while the mandible was the most affected jaw bone.

CONTEXTE: L'améloblastome est une tumeur agressive d'épithélium odontogène qui se développe lentement avec une propension à expansion osseuse. Parfois, il peut atteindre de très grandes tailles aussiconnu sous le nom d'améloblastome géant (GA) qui peut affecter la function et constituent même une menace pour la vie. OBJECTIF: Présenter le modèle de présentation des AGvu dans un centre tertiaire dans le nord du Nigeria. PATIENTS ET METHODES: Une étude rétrospective des patients vu avec GA à la clinique orale et maxillo-faciale d'un tertiaire établissement de santé du nord du Nigéria entre janvier 2006 et Décembre 2019. Tous les patients avec une documentation complète dans le dossier, le registre des théâtres et les dossiers histopathologiques étaient recruté pour l'étude. Les données ont été analysées à l'aide de la version SPSS23. RÉSULTATS: Les AG représentaient 30.2 % (48) de tous les améloblastomes opérés pendant la période avec un home dominance de 62.5% (30), ce qui donne un rapport de 1.7:1 (M:F).la fourchette se situait entre 12 et 65 ans avec un âge moyen de 35.04 ans(±14.5) et la mandibule était la mâchoire la plus touchée comparéeau maxillaire (12.5 %). Lésions de poids le plus faible et le plus élevé ont été trouvés sur la mandibule (77g et 1640g respectivement). Le traitement le plus administré était la mandibulectomie (non spécifiée) avec 20.0 %, suivis des mandibulectomies Rt et Lt avec 14.0 % chacun. CONCLUSION: L'AG représentait 30.2 % de tous les lésions observées au cours de la période considérée, tandis que la mandibule était l'os de la mâchoire le plus touché. Mots-clés: Améloblastome géant, Risque de récidive, Expérience.

Clinical implications of age and excellent response to therapy in patients with high-risk differentiated thyroid carcinoma.

BACKGROUND: Patients with American Thyroid Association (ATA) high-risk differentiated thyroid carcinoma (DTC) have poor clinical outcomes. This study aimed to evaluate the clinical implications of age and response to therapy classification in patients with ATA high-risk DTC. DESIGN AND PATIENTS: This study included 222 patients with high-risk DTC who initially underwent therapy between 2000 and 2010 in a single tertiary center in Korea. We evaluated the prognostic parameters associated with progression-free survival (PFS) and disease-specific survival (DSS) with a focus on age and achieving an excellent response (ER). RESULTS: During the median follow-up period of 11.3 years, disease progression was detected in 77 patients (34.7%), and disease-specific mortality was reported in 31 patients (14.0%). Older age (≥55 years) and not achieving ER (not-ER) were independent risk factors associated with PFS (age, p < .001; not-ER, p < .001) and DSS (age, p < .001; not-ER, p = .015). Of the 74 patients in the ER group, 7 (9.5%) displayed disease progression and 1 (1.4%) died from DTC. There were no significant differences in PFS and DSS according to age in the ER group. However, older patients had significantly worse PFS and DSS than younger patients in the not-ER group (p = .002 and p < .001, respectively). CONCLUSIONS: Response to therapy classification is important for predicting PFS and DSS in patients with high-risk DTC. Patients in the ER group had a relatively good prognosis, but disease progression occurred in 9.5% of patients. Age was a key predictor of both PFS and DSS in high-risk patients who did not achieve ER.

[Diagnosis and treatment of basal cell carcinoma : A question of the risk of recurrence]. / Diagnostik und Therapie des Basalzellkarzinoms : Eine Frage des Rezidivrisikos.

Basal cell carcinoma is the most common type of cancer in Central Europe and has a high medical relevance. Due to its high tendency of recurrence, an important parameter in the planning of therapy is the risk of recurrence. After clinical and histological diagnosis, the majority of tumors are treated surgically, although radiation and topical procedures are also possible therapeutic alternatives in certain constellations. Hedgehog inhibitors, a completely new class of substances, have recently been approved for rare metastatic and locally advanced diseases, thus significantly expanding the range of treatments. This article provides an overview of the current guideline-based diagnosis and therapy of basal cell carcinomas in Germany.

[How Itreat ... extended duration of anticoagulation in lower-limb deep venous thrombosis]. / Comment je traite... par anticoagulants la thrombose veineuse profonde des membres inférieurs après la phase aiguë.

Treatment of lower-limb deep vein thrombosis comprises three phases : the initial phase that includes the first 5 to 21 days, the long-term phase that includes the following 3 to 6 months and a potential extended phase (indefinite duration). After 3 to 6 months of anticoagulation, the treatment must be re-evaluated. Full or reduced dosage or complete cessation of anticoagulants can be proposed according to the individual benefit-risk balance. Risk assessment of recurrence may be challenging in the case of unprovoked venous thrombosis. Similarly, risk assessment of bleeding may be difficult. Consequently, a personalized decision must be made and regularly reassessed. As far as possible, it should also take into account the patient's preferences and lifestyle (dangerous sports, sedentary lifestyle, drug adherence,...). Further studies are still needed in order to better assess the individual risks and adapt the treatment.

Le traitement de la thrombose veineuse profonde des membres inférieurs comprend trois étapes : le traitement initial qui inclut les 5 à 21 premiers jours, le traitement au long cours qui dure 3 à 6 mois et un éventuel traitement prolongé, d'une durée non définie. Après 3 à 6 mois d'anticoagulation, se pose le problème de l'arrêt éventuel du traitement ou de la réduction de posologie. Evaluer le risque de récidive à l'arrêt du traitement est parfois une gageure en cas de maladie thromboembolique non provoquée. De même, l'évaluation du risque hémorragique peut être difficile. La décision doit donc être personnalisée et réévaluée régulièrement. Dans la mesure du possible, elle doit aussi tenir compte des préférences et du mode de vie des patients (sports à risque, sédentarité, observance,...). Des études ultérieures sont nécessaires afin de mieux évaluer les risques individuels et d'adapter la prise en charge.

Talking about risk in the context of genomic tests (TARGET): development and evaluation of an educational program for clinicians.

PURPOSE: Gene expression profiling (GEP) test scores calculate risks of recurrence and likely benefit of adjuvant chemotherapy in ER-positive, HER2-negative, early-stage breast cancer. As health literacy and numeracy skills in the general population are poor, healthcare professionals (HCPs) require a wide repertoire of communication skills to explain clearly risk of recurrence scores (RSs) and uncertainty. We developed and evaluated an educational program for HCPs discussing GEP test results and adjuvant treatment. METHODS: Eight-hour workshops contained elements aimed at improving knowledge, communication skills and self-awareness; these included the science underpinning GEP tests, an interactive risk psychology lecture, exercises and facilitated group discussions regarding seven filmed scenarios involving discussions about high, intermediate and low RSs. Attendees were recorded explaining RSs with patient simulators pre and post workshop. Researchers, blinded to time point, analysed recordings using a study-specific scoring system. Primary objective outcomes were improvements post workshop in HCPs' competence and confidence when communicating 17 pre-specified key information areas. We estimated odds ratios (OR) using conditional logistic regression to compare pre- and post-workshop scores. RESULTS: 65 HCPs attended. Objective analyses revealed significant positive shifts post workshop which included explaining GEP tests (OR 2.98; 95% CI 1.38-6.42; P = .001), recurrence RSs (OR 3.99; 95% CI 1.72-9.25; P < .001), benefits of chemotherapy (OR 3.99; 95% CI 1.82-8.75; P < .001; and harms OR 2.31; 95% CI 1.37-3.92; P < .001) using jargon free language (OR 5.29; 95% CI 2.27-12.35; P < .001). Patient simulator assessments also showed significant improvements as did HCPs' self-assessments and ratings of their self-confidence when discussing different GEP tests with diverse patient types (P < .001). CONCLUSION: These short, intensive, interactive TARGET workshops significantly improved HCPs' communication about GEP results in ways likely to promote more informed decision-making by patients about chemotherapy.

Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence.

OBJECTIVE: Tumor volume and regression after external beam radiotherapy have been shown to be accurate parameters to assess treatment response via magnetic resonance imaging (MRI). The aim of the study was to evaluate the prognostic value of tumor size reduction rate after external beam radiotherapy and chemotherapy prior to brachytherapy. METHODS: Patients with locally advanced cervical cancer treated at two French comprehensive cancer centers between 1998 and 2010 were included. Treatment was pelvic external beam radiotherapy with platinum based chemotherapy followed by brachytherapy. Records were reviewed for demographic, clinical, imaging, treatment, and follow-up data. Anonymized linked data were used to ascertain the association between pre-external and post-external beam radiotherapy MRI results, and survival data. RESULTS: 185 patients were included in the study. Median age at diagnosis was 45 years (range 26-72). 77 patients (41.6%) were International Federation of Gynecology and Obstetrics stage IB2-IIA disease and 108 patients (58.4%) were stage IIB-IVA. Median tumor size after external beam radiotherapy and chemotherapy was 2.0 cm (range 0.0-8.0) and median tumor size reduction rate was 62.4% (range 0.0-100.0%). Tumor size and tumor reduction rate at 45 Gy external beam radiotherapy MRI were significantly associated with local recurrence free survival (P<0.001), disease free survival, and overall survival (P<0.05). Tumor reduction rate ≥60% was significantly associated with a decreased risk of relapse and death (HR (95% CI) 0.21 (0.09 to 0.50), P=0.001 for local recurrence free survival; 0.48 (0.30 to 0.77) P=0.002 for disease free survival; and 0.51 (0.29 to 0.88), P=0.014 for overall survival). CONCLUSIONS: Tumor size reduction rate >60% between pre-therapeutic and post-therapeutic 45 Gy external beam radiotherapy with concurrent chemotherapy was associated with improved survival. Future studies may help to identify patients who may ultimately benefit from completion surgery, adjuvant chemotherapy, and closer follow-up.

Risk of recurrence, prognosis, and follow-up for Danish women with cervical cancer in 2005-2013: A national cohort study.

BACKGROUND: In developed countries, women attend follow-up after treatment for cervical cancer to detect recurrence. The aim of this study was to describe the Danish population of women with early-stage cervical cancer at risk for recurrence and death due to recurrence. METHODS: Data were extracted from 3 nationwide databases to find women diagnosed with stage 1A1 to 1B1 cervical cancer in 2005-2013. Recurrences were determined from data on oncological or surgical treatment more than 3 months after the initial diagnosis and were cross-checked with patient journals. RESULTS: In all, 1523 patients were diagnosed with stage 1A1 to 1B1 cervical cancer. Eighty women experienced recurrences: 8 at International Federation of Gynecology and Obstetrics (FIGO) stage 1A1, 0 at FIGO stage 1A2, and 72 at FIGO stage 1B1. The 5-year recurrence rate was 6.4%; 67.5% of the women had symptomatic recurrences, and 28.8% had asymptomatic recurrences. At significantly greater risk for recurrence were women at stage 1B1, regardless of their lymph node (LN) status at diagnosis (hazard ratio with a positive LN, 5.10; 95% confidence interval [CI], 1.65-15.76; P = .0047; hazard ratio with a negative LN, 3.14; 95% CI, 1.25-7.93; P = .0153; hazard ratio with LN data missing, 6.33; 95% CI, 1.80-22.26; P = .004), women older than 50 years (hazard ratio, 1.81; 95% CI, 1.12-2.94; P = .0158), and women with lymphatic and lymphovascular space invasion (LVSI; hazard ratio, 1.92; 95% CI, 1.11-3.30; P = .0188). In a multivariate analysis, significantly inferior survival was found after recurrence for patients with lymphatic LVSI (hazard ratio, 2.23; 95% CI, 1.04-4.80; P = .0401), a symptomatic diagnosis of recurrence (hazard ratio, 2.52; 95% CI, 1.08-5.90; P = .0332), and multiple sites of recurrence (hazard ratio, 2.72; 95% CI, 1.32-5.61; P = .0066). CONCLUSIONS: This study has identified a group of women at FIGO stage 1A1 in no need of specialized, hospital-based follow-up. Many of the recurrences at FIGO stage 1B1 are asymptomatic, and this may show a need for follow-up in this group. Further prospective investigation is needed. Cancer 2018;124:943-51. © 2017 American Cancer Society.

Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.

BACKGROUND: The aim of this study was to investigate the prognostic value of the PAM50 intrinsic subtypes and risk of recurrence (ROR) score in patients with early breast cancer and long-term follow-up. A special focus was placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 patients not treated with chemotherapy. METHODS: Patients with early breast cancer (n = 653) enrolled in the observational Oslo1 study (1995-1998) were followed for distant recurrence and breast cancer death. Clinicopathological parameters were collected from hospital records. The primary tumors were analyzed using the Prosigna® PAM50 assay to determine the prognostic value of the intrinsic subtypes and ROR score in comparison with pathological characteristics. The primary endpoints were distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS). RESULTS: Of 653 tumors, 52.2% were classified as luminal A, 26.5% as luminal B, 10.6% as HER2-enriched, and 10.7% as basal-like. Among the HR+/HER2- patients (n = 476), 37.8% were categorized as low risk by ROR score, 22.7% as intermediate risk, and 39.5% as high risk. Median follow-up durations for BCSS and DDFS were 16.6 and 7.1 years, respectively. Multivariate analysis showed that intrinsic subtypes (all patients) and ROR risk classification (HR+/HER2- patients) yielded strong prognostic information. Among the HR+/HER2- pN0 patients with no adjuvant treatment (n = 231), 53.7% of patients had a low ROR, and their prognosis at 15 years was excellent (15-year BCSS 96.3%). Patients with intermediate risk had reduced survival compared with those with low risk (p = 0.005). In contrast, no difference in survival between the low- and intermediate-risk groups was seen for HR+/HER2- pN0 patients who received tamoxifen only. Ki-67 protein, grade, and ROR score were analyzed in the unselected, untreated pT1pN0 HR+/HER2- population (n = 171). In multivariate analysis, ROR score outperformed both Ki-67 and grade. Furthermore, 55% of patients who according to the PREDICT tool ( http://www.predict.nhs.uk/ ) would be considered chemotherapy candidates were ROR low risk (33%) or luminal A ROR intermediate risk (22%). CONCLUSIONS: The PAM50 intrinsic subtype classification and ROR score improve classification of patients with breast cancer into prognostic groups, allowing for a more precise identification of future recurrence risk and providing an improved basis for adjuvant treatment decisions. Node-negative patients with low ROR scores had an excellent outcome at 15 years even in the absence of adjuvant therapy.