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Background HPV-related cervical cancer (CC) is the fourth most frequent cancer in women worldwide. Cell-free tumour DNA is a potent biomarker to detect treatment response, residual disease, and relapse. We investigated the potential use of cell-free circulating HPV-DNA (cfHPV-DNA) in plasma of patients with CC. Methods cfHPV-DNA levels were measured using a highly sensitive next-generation sequencing-based approach targeting a panel of 13 high-risk HPV types. Results Sequencing was performed in 69 blood samples collected from 35 patients, of which 26 were treatment-naive when the first liquid biopsy sample was retrieved. cfHPV-DNA was successfully detected in 22/26 (85%) cases. A significant correlation between tumour burden and cfHPV-DNA levels was observed: cfHPV-DNA was detectable in all treatment-naive patients with advanced-stage disease (17/17, FIGO IB3–IVB) and in 5/9 patients with early-stage disease (FIGO IA–IB2). Sequential samples revealed a decrease of cfHPV-DNA levels in 7 patients corresponding treatment response and an increase in a patient with relapse. Conclusions In this proof-of-concept study we demonstrated the potential of cfHPV-DNA as a biomarker for therapy monitoring in patients with primary and recurrent CC. Our findings facilitate the development of a sensitive and precise, non-invasive, inexpensive, and easily accessible tool in CC diagnosis, therapy monitoring and follow-up.

Zusammenfassung Hintergrund Umfangreiche Daten aus prospektiven klinischen Studien liefern einen hohen Evidenzgrad für den Einsatz von CDK4/6-Hemmern in Kombination mit einer endokrinen Therapie (CDK4/6i + ET) als Standard bei der First-Line-Behandlung von metastatischem HER2-negativen hormonrezeptorpositiven (HER2−/HR+) Brustkrebs. Reale Daten von Patientinnengruppen, die damit in der Praxis behandelt wurden, liefern Erkenntnisse über Veränderungen von Patientenmerkmalen und Prognosen im Laufe der Zeit. Methoden Die Daten wurden dem prospektiven praxisbezogenen PRAEGNANT-Register (NCT02 338 167) entnommen. Die eingeschlossenen Patientinnen hatten fortgeschrittenen primären und metastasierten HER2−/HR+ Brustkrebs. Die gewählten Therapien, das progressionsfreie Überleben und das Gesamtüberleben der jeweiligen Therapie sowie die Zeitspanne, während der die Behandlung erfolgte, werden dargelegt. Ergebnisse Nachdem CDK4/6-Hemmer erstmals im November 2016 eingesetzt wurden, stieg die Häufigkeit ihres Einsatzes schnell an. In den letzten Jahren (2018–2022) wurden ca. 70–80 % aller Patientinnengruppen mit CDK4/6-Hemmern behandelt; eine endokrine Monotherapie wurde rund 10 % und eine Chemotherapie ungefähr 15 % aller Patientinnen verabreicht. Die schlechteste Prognose hatten Patientinnen, die eine Chemotherapie erhielten. Seit Kurzem erhalten hauptsächlich Patientinnen mit guter Prognose eine endokrine Monotherapie; Patientinnen, die eine Chemotherapie erhalten, haben eine ungünstigere Prognose. Das progressionsfreie Überleben und das Gesamtüberleben von mit CDK4/6i + ET behandelten Patientinnen blieb über einen längeren Zeitraum ähnlich, obwohl sich die Patientenmerkmale änderten. Schlussfolgerung Die Behandlung mit CDK4/6i + ET entwickelte sich rasch zum First-Line-Therapiestandard für Patienten mit fortgeschrittenem Mammakarzinom. Seit der Einführung von CDK4/6i + ET wird die endokrine Monotherapie nur bei Patientinnen mit einer sehr günstigen Prognose eingesetzt, während Chemotherapie meist nur an Patientinnen verabreicht wird, die eine eher ungünstige Prognose haben. Veränderungen der Patientenmerkmale scheinen die Prognose von mit CDK4/6i + ET behandelten Patientinnen nicht zu beeinflussen.

Purpose The diagnosis of cervical intraepithelial neoplasia during pregnancy poses a great challenge to the treating clinician and the patient. According to the current guidelines, watchful waiting during pregnancy can be justified. Only in cases of invasion, immediate treatment may be indicated. However, few data are available on the management of cervical dysplasia during pregnancy. Further research is important for counselling affected women. Methods Data of pregnant patients with suspected cervical dysplasia who presented to the University Women’s Hospital Tübingen between 2008 and 2018 were evaluated retrospectively. Colposcopic, cytologic, and histologic assessment was performed for diagnosis. Data on remission, persistence and progression of disease based on histologic and cytologic assessment and the mode of delivery were correlated. Results 142 patients were enrolled. Cytology at first presentation was PAPIII (-p/-g) in 7.0%, PAPIIID (IIID1/IIID2) in 38.7%, PAPIVa (-p/-g) in 50.0%, PAPIVb (-p) in 2.8%, and PAPV (-p) in 1.4%. All cases with suspected invasion were recorded at the initial presentation. Complete histological or cytological remission was observed in 24.4%, partial remission in 10.4%, persistence in 56.3%, and progression in 8.9%. In two cases (1.5%) progression to squamous cell carcinoma occurred. Conclusions Watchful waiting for cervical intraepithelial neoplasia during pregnancy seems to be sufficient and oncologically safe. It is important to exclude invasion during pregnancy, to perform frequent colposcopic, cytologic and histologic examinations and to ensure a postpartum follow-up examination to initiate the treatment of high-grade lesions. Spontaneous delivery seems to be safe in patients with cervical dysplasia, Caesarean section is not indicated.

Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as a standard for the treatment of HER2-negative, hormone receptor-positive (HER2− HR+) breast cancer patients in the first-line advanced therapy setting. Data on patient populations that have been treated in the real-world setting may provide an insight into changes of patient characteristics and prognosis over time. Methods The data were extracted from the prospective real-world registry PRAEGNANT (NCT02338167). Patients had to have HER2− HR+ advanced breast cancer in the first-line metastatic setting. The chosen therapies were described as well as progression-free survival (PFS) and overall survival (OS) in relation to the given therapies and time periods during which they were indicated. Results CDK4/6 inhibitors have been rapidly implemented since their introduction in November 2016. In recent years (2018 – 2022), about 70 – 80% of the patient population have been treated with CDK4/6 inhibitors, while endocrine monotherapy was given to about 10% and chemotherapy to about 15% of all patients. The prognosis was worst in patients treated with chemotherapy. Recently, mainly patients with a good prognosis are being treated with endocrine monotherapy, and patients who are treated with chemotherapy have an unfavorable prognosis. The PFS and OS of patients treated with CDK4/6i + ET have remained similar over time despite changes in patient characteristics. Conclusion A treatment with CDK4/6i + ET has rapidly become the therapy standard for patients in the first-line advanced breast cancer setting. After the implementation of CDK4/6i + ET, endocrine monotherapy is only given to patients with a very favorable prognosis, while chemotherapy is provided to patients with a rather unfavorable prognosis. These changes in patient characteristics did not seem to influence the prognosis of patients treated with CDK4/6i + ET.

Disseminated tumor cells (DTCs) in the bone marrow (BM) are known to be of prognostic value for patients with early breast cancer (EBC). In addition to histopathological features, multigene expression assays, such as the commercially available 21-gene Breast Recurrence Score® assay, have been validated for evaluating prognosis and making decisions concerning adjuvant treatment in EBC. In a previous retrospective study from our group, the 21-gene assay was shown to be associated with DTC-detection. A key endpoint of the prospective IRMA trial was to evaluate the association between Recurrence Score® (RS) result and tumor cell dissemination in patients with EBC. DTC-status and RS result were assessed in patients with ER-positive/HER2-negative EBC with 0–3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women’s Health of Tuebingen University, Germany. Patients with a high RS result (≥ 26) were more frequently DTC-positive (22.6%) than patients with a low RS result (8.6%, p=0.034). The odds for DTC-positivity increased with rising RS values (p= 0.047). We therefore confirm that a high genomic risk is associated with tumor cell dissemination into the BM. Further trials are needed to investigate whether therapeutic decisions could be further individualized by combining DTC-status and prognostic gene signature testing.

BackgroundThe clinical utility of molecular profiling and targeted therapies for neuro-oncology patients outside of clinical trials is not established. We aimed at investigating feasibility and clinical utility of molecular profiling and targeted therapy in adult patients with advanced tumors in the nervous system within a prospective observational study.Methodsmolecular tumor board (MTB)@ZPM (NCT03503149) is a prospective observational precision medicine study for patients with advanced tumors. After inclusion of patients, we performed comprehensive molecular profiling, formulated ranked biomarker-guided therapy recommendations based on consensus by the MTB, and collected prospective clinical outcome data.ResultsHere, we present initial data of 661 adult patients with tumors of the nervous system enrolled by December 31, 2021. Of these, 408 patients were presented at the MTB. Molecular-instructed therapy recommendations could be made in 380/408 (93.1%) cases and were prioritized by evidence levels. Therapies were initiated in 86/380 (22.6%) cases until data cutoff. We observed a progression-free survival ratio >1.3 in 31.3% of patients.ConclusionsOur study supports the clinical utility of biomarker-guided therapies for neuro-oncology patients and indicates clinical benefit in a subset of patients. Our data might inform future clinical trials, translational studies, and even clinical care.

Background ABP 980 is a biosimilar antibody to reference trastuzumab (RTZ). Aim of the following study is to confirm the similarity of ABP 980 and RTZ in terms of clinical efficacy and safety in patients with HER2-positive early breast cancer (EBC) undergoing neoadjuvant trastuzumab-containing chemotherapy in a clinical real-world situation that also includes patients receiving pertuzumab. Methods Patients with HER2-positive EBC, who were treated from 12/2010 to 03/2020 at the Department of Women’s Health at Tuebingen University Hospital, Germany, with at least four cycles of neoadjuvant chemotherapy (+/− pertuzumab) in combination with ABP 980 or RTZ were included in a retrospective analysis. For efficacy analysis patients achieving a pathologic complete remission (pCR = no invasive tumor in breast and lymph nodes) were compared. Safety was evaluated by comparing the number of patients with a decrease in left ventricular function (LVEF) of > 10%. Results 124 patients were included of whom 46 (37.1%) have received ABP 980 and 77 (62.9%) were treated with RTZ. A pCR was found in 77 patients (62.1%). For patients treated with ABP 980 as compared to RTZ, there was no significant difference regarding efficacy (pCR-rates of 60.9% versus 62.8%, p = 0.829) or cardiac safety (LVEF decline in 6.5% versus 2.6%, p = 0.274). Conclusion Similarity of ABP 980 as compared to RTZ was confirmed in a real-world situation, including a large proportion of patients that have also received pertuzumab treatment.

Patients with hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and Ki67) are of limited value to predict chemotherapy efficacy, multigene expression assays such as the Oncotype DXThe RS result was assessed in patients with HR+/HER2- unilateral eBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. Therapy recommendations without knowledge of the RS result were compared to therapy recommendations with awareness of the RS result.In total, 245 patients underwent RS assessment. Without knowledge of the RS result, 92/245 patients (37.6%) would have been advised to receive chemotherapy. After RS assessment, 56/245 patients (22.9%) were advised to undergo chemotherapy. Chemotherapy was waived in 47/92 patients (51.1%) that were initially recommended to receive it. Chemotherapy was added in 11/153 patients (7.2%) that were recommended to not receive it initially.Using the RS result to guide adjuvant treatment decisions in HR+/HER2- breast cancer led to a substantial reduction of chemotherapy. In view of the results achieved in prospective studies, the RS result is among other risk-factors suitable for the individualization of adjuvant systemic therapy.

Purpose This study evaluates the overall treatment indicators and outcomes of patients who underwent loop electrosurgical excision procedure (LEEP) at the Department of Women’s Health Tübingen and the impact of certification as a dysplasia unit on treatment quality. Methods Retrospective data analysis of 1596 patients from 2013 to 2018 who underwent LEEP excision at the Department of Women’s Health Tübingen. Data of cytology, colposcopy, biopsy, LEEP histology, repeat LEEP histology and general characteristics were collected and analyzed descriptively. Results 85.4% (1364) of patients had CIN 2 + and 14.6% (232) had CIN 1 or normal findings on LEEP histology. The proportion of CIN 2 + excisions increased significantly from 82.4% in 2013 to 89% in 2018. The concordance of HSIL biopsy and LEEP histology was 89.1% in 2013 and 92.6% in 2018. In 2018, more biopsies and colposcopies were performed before excision. Complete resection (R0) was achieved in 88.3% of all excisions. R0 rates in patients with CIN 3 increased in 2014–2017 compared to 2013, resulting in fewer Re-LEEP excisions and hysterectomies. Conclusion Certification as a dysplasia unit and the associated requirements have improved the diagnostic quality for patients with cervical dysplasia undergoing LEEP. This was demonstrated by several treatment indicators such as the number of colposcopies and biopsies and treatment outcomes such as an increased proportion of CIN 2 + excisions and R0 resections.

Abemaciclib significantly improves invasive disease-free survival when combined with endocrine therapy in clinical high-risk patients with HR+/Her2− early breast cancer (eBC). The objective of the following study was to model how many patients with eBC would be available for adjuvant treatment with abemaciclib in a real-world setting. Patients that underwent complete surgical treatment for eBC between January 2018 and December 2020 in a large single-center university hospital in Germany were eligible. Descriptive statistics were used to describe the patient population that could benefit from abemaciclib according to the inclusion criteria of monarchE. Of 1474 patients with eBC, 1121 (76.1%) had a HR+/Her2− subtype. Of these, 217 (19.4%) fulfilled the monarchE inclusion criteria. Within patients that fulfilled the monarchE inclusion criteria, 48.9% received no adjuvant or neoadjuvant chemotherapy. Thus, in a real-world situation, fewer patients will be pretreated with chemotherapy than was the case in monarchE. Breast care units are facing a significant patient burden, since the 2-year abemaciclib therapy requires regular monitoring of toxicities. Specific care concepts to strengthen therapy adherence as well as further studies to deescalate adjuvant systemic treatment and individualize CDK 4/6 inhibitor therapy are therefore needed.

Invasive breast cancer (IBC) is the most common malignant disease in women worldwide. In recent years, the landscape of treatment options has rapidly evolved. With the success of checkpoint inhibitors in triple negative IBC, immunotherapy has become standard of care highlighting the strength of T cell-based strategies for anti-tumor therapy. Naturally, the targets of T cell-mediated immune responses are represented by short peptides presented on human leukocyte antigen (HLA) molecules. For several years, huge effort has been made to analyze and characterize HLA-presented tumor antigens to further understand anti-tumor immunity and to identify suitable targets for novel immunotherapy approaches. Aside from membrane-bound HLA molecules, soluble HLA-peptide complexes (sHLA) can be found in a variety of body fluids. These molecules are suggested to impact cellular immune responses, but it is still a matter of debate, whether shifts in sHLA levels contribute to disease outcome or are observed as a consequence of disease. Whereas the role of the non-classical sHLA-G in IBC has been studied showing elevated levels in patients compared to a healthy cohort, data on classical sHLA class I molecules is not yet available. Here, we report on sHLA class I serum levels in patients with IBC after neoadjuvant chemotherapy or combined chemotherapy with antibody treatment (n = 52). We observed higher serum levels of sHLA in neoadjuvant-treated IBC patients without histopathological complete response after neoadjuvant therapy (n = 36) compared to healthy volunteers (n = 84). Patients with locally advanced tumors, according to TNM classification, had a tendency towards lower sHLA levels than patients with small size tumors. Furthermore, sHLA levels were decreased in patients with sentinel node or disseminated axillary lymph node metastases compared to non-metastatic patients. Of note, sHLA levels tended to be elevated in patients with Her2-overexpression (based on immunohistochemistry staining and fluorescence in situ hybridization), whereas for histological hormone receptor expression a tendency towards lower sHLA levels in patients with high expression was observed. Furthermore, sHLA levels were reduced in patients with disseminated tumor cells in bone marrow aspiration. No significant difference in sHLA levels were seen in terms of grading of tumor, prevalence of distant metastasis, menopausal status and elevated tumor markers. Interestingly, we observed a tendency to prolonged progression-free survival in patients with high serum concentrations of sHLA, which will be updated with data from additional patients at the AACR meeting. Taken together, these data provides first insights about sHLA class I in patients with IBC after neoadjuvant treatment suggesting an impact of sHLA and T cell-mediated immune surveillance on survival in patients with IBC. Citation Format: Christian M. Tegeler, Jonas Rieth, André Koch, Dominik Dannehl, Léa L. Volmer, Sabine Matovina, Markus Hahn, Tobias Engler, Andreas D. Hartkopf, Sara Y. Brucker, Juliane S. Walz, Jonas S. Heitmann, Annika Nelde. A correlation of soluble HLA serum levels with clinical data and survival in patients with invasive breast cancer after neoadjuvant treatment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4376.

Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (p < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1–4.4; p < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 106 mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9–26.6; p = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4–12.7; p = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.

Abemaciclib significantly improves invasive disease-free survival when combined with endocrine therapy in clinical high-risk patients with HR+/Her2- early breast cancer (eBC). The objective of the following study was to model how many patients with eBC would be available for adjuvant treatment with abemaciclib in a real-world setting. Patients that underwent complete surgical treatment for eBC between January 2018 and December 2020 in a large single-center university hospital in Germany were eligible. Descriptive statistics were used to describe the patient population that could benefit from abemaciclib according to the inclusion criteria of monarchE. Of 1474 patients with eBC, 1121 (76.1%) had a HR+/Her2- subtype. Of these, 217 (19.4%) fulfilled the monarchE inclusion criteria. Within patients that fulfilled the monarchE inclusion criteria, 48.9% received no adjuvant or neoadjuvant chemotherapy. Thus, in a real-world situation, fewer patients will be pretreated with chemotherapy than was the case in monarchE. Breast care units are facing a significant patient burden, since the 2-year abemaciclib therapy requires regular monitoring of toxicities. Specific care concepts to strengthen therapy adherence as well as further studies to deescalate adjuvant systemic treatment and individualize CDK 4/6 inhibitor therapy are therefore needed.

Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (p < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1–4.4; p < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 106 mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9–26.6; p = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4–12.7; p = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.

Background: Patients with hormone receptor-positive (HR+), HER2-negative (HER2−) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and Ki67) are of limited value to predict chemotherapy efficacy, multigene expression assays such as the Oncotype DX® test were developed to reduce over- and undertreatment. The IRMA trial analyzed the impact of Recurrence Score® (RS) assessment on adjuvant treatment recommendations. Materials and methods: The RS result was assessed in patients with HR+/HER2− unilateral eBC with 0–3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women’s Health of Tuebingen University, Germany. Therapy recommendations without knowledge of the RS result were compared to therapy recommendations with awareness of the RS result. Results: In total, 245 patients underwent RS assessment. Without knowledge of the RS result, 92/245 patients (37.6%) would have been advised to receive chemotherapy. After RS assessment, 56/245 patients (22.9%) were advised to undergo chemotherapy. Chemotherapy was waived in 47/92 patients (51.1%) that were initially recommended to receive it. Chemotherapy was added in 11/153 patients (7.2%) that were recommended to not receive it initially. Summary: Using the RS result to guide adjuvant treatment decisions in HR+/HER2− breast cancer led to a substantial reduction of chemotherapy. In view of the results achieved in prospective studies, the RS result is among other risk-factors suitable for the individualization of adjuvant systemic therapy.

BACKGROUND Health-related quality of life (HRQoL) is used to evaluate the treatment of metastatic breast cancer. In a long-term therapy setting, HRQoL can be used as an important benchmark for treatment success. With the help of digital apps, HRQoL monitoring can be extended to more remote areas and be administered on a more frequent basis. OBJECTIVE This study aims to evaluate 3 common HRQoL questionnaires in metastasized breast cancer in terms of TTD in a digital, web-based setting. We further aim to examine the development of the HRQoL in different systemic treatment groups in each of these evaluation instruments. METHODS A total of 192 patients with metastatic breast cancer were analyzed in this bicentric prospective online cohort study at two German university hospitals. Patients completed questionnaires on HRQoL (EuroQol Visual Analog Scale [EQ-VAS], EuroQol 5 Dimension 5 Level [EQ-5D-5L], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 item [EORTC QLQ-C30]) via an online platform over a 6-month period. Treatment schedules and medical history were retrieved from medical records. Unadjusted Cox regression analysis on treatment-related factors was performed. We conducted subgroup analyses in regard to TTD events between different treatments. RESULTS The EQ-VAS showed a higher rate of deterioration after 8 weeks (84/179, 46.9%) than the EQ-5D-5L (47/163, 28.8%) and EORTC QLQ-C30 (65/176, 36.9%). Unadjusted Cox regression revealed significant connections between known metastases in the liver (P=.03, HR 1.64, 95% CI 1.06-2.52) and pleura (P=.04, HR 0.42, 95% CI 0.18-0.96) in the EQ-VAS. Significant relations between EQ-VAS events and single EQ-5D-5L items and the EQ-5D-5L summary score were demonstrated. All treatment groups significantly differed from the CDK4/6 inhibition subgroup in the EQ-VAS. CONCLUSIONS Compared to the EQ-5D-5L and QLQ-C30, the EQ-VAS showed a higher rate of deterioration after 8 weeks. Significant connections to certain metastatic locations were only detected in the EQ-VAS. The EQ-VAS is capable of reflecting the distinctive HRQoL profiles of different systemic treatments as well as the different aspects of HRQoL presented in the EQ-5D-5L. TTD with the EQ-VAS is an adequate mean of examining longitudinal development of HRQoL among breast cancer patients.

BACKGROUND One in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid. OBJECTIVE The aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors. METHODS Overall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere. RESULTS Patients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app’s evaluation parameters. CONCLUSIONS The results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills.

Eva Katharina Masel, Patrick Huber, Tobias Engler, Herbert Hans WatzkeClinical Division of Palliative Care, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria Background: Decisions on the intensity of analgesic therapy and judgments regarding its efficacy are difficult at the end of life, when many patients are not fully conscious and pain is a very common symptom. In healthy individuals and in postoperative settings, nociception and subsequent pain relief have been shown to induce changes in the autonomic nervous system (ANS), which can be detected by measuring heart rate variability (HRV). Objectives: The changes in the ANS were studied by measuring HRV during opioid therapy for cancer breakthrough pain (CBTP) in palliative-care patients with cancer and compared these changes with patient-reported pain levels on a numeric rating scale (NRS). Patients and methods: The study included ten patients with advanced cancer and baseline opioid therapy. In each patient, a 24-hour peak-to-peak HRV measurement with a sampling rate of 4,000Hz was performed. High frequency (HF), low frequency (LF), total power, pNN50 (indicating parasympathetic activity), and log LF/HF were obtained in two intervals prior to therapy and in four intervals thereafter. Intensity of CBTP was recorded using a patient-reported NRS prior to therapy and 30minutes afterward. Results: CBTP occurred in seven patients (three males and four females; mean age: 62±5.2years) and was treated with opioids. A highly significant positive correlation was found between opioid-induced reduction in patient-reported pain intensity based on NRS and changes in log LF/HF (r>0.700; p2 points on the NRS but remained unchanged in the other patients. Conclusion: Our data suggest that log LF/HF may be a useful surrogate marker for alleviation of CBTP in patients with advanced cancer and might allow detection of pain without active contribution from patients. Keywords: heart rate variability, cancer breakthrough pain, advanced cancer, palliative care