Publications by authors named "Dominik Berthold"

Aim: Addition of abiraterone acetate plus prednisone (AAP) to androgen deprivation therapy (ADT) with or without docetaxel (D) improved overall survival in patients with de novo metastatic castration sensitive prostate cancer in the PEACE-1 trial. The protocol was amended during the course of the study to assess whether addition of AAP increases bone loss.

Methods: Patients were randomized to receive either ADT + D with or without AAP.

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Background: The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population.

Methods: We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe.

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Adjuvant immunotherapy has been recently recommended for patients with metastatic clear cell renal cell carcinoma (ccRCC), but there are no tissue biomarkers to predict treatment response in ccRCC. Potential predictive biomarkers are mainly assessed in primary tumor tissue, whereas metastases (METs) remain understudied. To explore potential differences between genomic alterations and immune phenotypes in primary tumors and their matched METs, we analyzed primary tumors (PTs) of 47 ccRCC patients and their matched distant METs by comprehensive targeted parallel sequencing, whole-genome copy number variation analysis, determination of microsatellite instability, and tumor mutational burden.

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We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (Ga-PSMA-PET/CT) images.

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The oncology field continues its remarkable evolution over the years, with promising advances leading to innovative and individualized treatments. The development of new molecules, the identification of new therapeutic targets and the search for new sequences or combinations promise to revolutionize cancer treatments and contribute to improving survival rates, patients' quality of life and to open new perspective in oncology research. In this article, the newest data released in 2023 are reviewed.

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The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the available options is of the utmost importance.

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Purpose: The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab.

Patients And Methods: SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC.

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Precision medicine is playing an increasingly crucial role in the treatment of prostate cancer. By tailoring treatments to the unique characteristics of patients and their tumors, this approach enables more targeted and personalized care, ultimately improving patient survival. In this article, we discuss the targeted therapies that have recently changed the management of this cancer.

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Article Synopsis
  • A study was done to see if a new treatment for prostate cancer is safe and doesn't hurt the patient's quality of life.
  • The treatment involved giving higher doses of radiation directly to the most important part of the tumor while using a special balloon to protect the nearby area.
  • Results showed that the treatment worked well without causing serious side effects, and patients mostly felt okay afterward.
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The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers.

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Background: OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949.

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Prostate cancer is the second most common cancer in men and represents a significant healthcare burden worldwide. Therapeutic options in the metastatic castration-resistant setting remain limited, despite advances in androgen deprivation therapy, precision medicine and targeted therapies. In this review, we summarize the role of immunotherapy in prostate cancer and offer perspectives on opportunities for future development, based on current knowledge of the immunosuppressive tumor microenvironment.

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Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy.

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Background: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care.

Methods: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland.

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Article Synopsis
  • Medical oncology specialists are continuing their research for new treatments to enhance life expectancy and quality of life for patients, despite the ongoing impact of COVID-19 on global health and the economy.
  • In 2021, immunotherapy has been proven effective, either alone or combined with other treatments, across various cancer types.
  • The focus this year includes new therapeutic strategies in lung, breast, melanoma, gynecological, digestive, urological, and ENT cancers.
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The University Hospital of Lausanne has heavily invested in the development of interdisciplinary oncology centers to improve the quality of care, and structure research and training. By integrating specialist nurses, it follows international recommendations. These specialists' nurses rephrase the information given by the doctor and ensure patients' understanding.

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Approximately 420 men are diagnosed with germ-cell cancer (GCC) in Switzerland each year. Recent international guidelines outline management issues, but many aspects remain controversial in an area of highly individualised treatments. Even more than in other tumour types, in GCC the challenge is to choose exactly the correct treatment for an individual patient.

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Article Synopsis
  • Low-dose radiotherapy (LDRT) enhances T-cell infiltration in tumors, increasing their response to immunotherapy through an interferon (IFN)-dependent mechanism.
  • The treatment effectively engages both adaptive and innate immunity, particularly involving cytotoxic CD4 and CD8 T cells, with LDRT mainly promoting CD4 cells that show characteristics of exhausted cytotoxic T cells.
  • A phase I clinical trial confirmed that combining LDRT with low-dose cyclophosphamide and immune checkpoint blockade resulted in T-cell infiltration in patients with immune-desert tumors, primarily featuring CD4 Th1 cells, suggesting a promising strategy for treating low T cell-infiltrated tumors.
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Article Synopsis
  • The study aimed to evaluate the clinical outcomes of men with low-risk and favorable intermediate-risk prostate cancer under a structured active surveillance protocol.
  • Participants underwent thorough initial assessments and regular follow-ups over an average of 36 months, with findings showing that a significant number from the expanded criteria group transitioned to active treatment compared to those under strict criteria.
  • Conclusions suggest that while broader criteria increase treatment transitions, well-selected patients with favorable intermediate-risk prostate cancer can still benefit from active surveillance without losing the chance for effective treatment.
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This article describes a ureter-sparing procedure used to treat lymph node metastases with SBRT. We delivered 35 Gy in 5 fractions of 7 Gy to patients with lesions located less than 7 mm from the ureters using a urography CT scan for planification. Two dosimetry plans were created, one using a CT scan urography-based contour and the other using the native phase.

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Intravesical immunotherapy with Calmette-Guerin bacillus (BCG) have been used since decades for the treatment of non-muscle invasive bladder cancer and is a proof of principle that immunotherapy works for this malignancy. Since 2016, immune checkpoint inhibitors (ICI) demonstrated clinical benefits in locally advanced or metastatic bladder cancer, providing potentially durable tumor control in first line therapy or upon relapse after standard treatments. Ongoing clinical trials aim to demonstrate the efficiency of ICI for the treatment of localized disease.

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Article Synopsis
  • - The COVID-19 pandemic has significantly altered daily practices and habits in healthcare since early 2020.
  • - In 2020, new therapeutic approaches and combinations have emerged, enhancing patient outcomes and quality of life in oncology.
  • - The article highlights recent advances in cancer treatments across various tumor types, including lung, breast, digestive, gynecological, urological, and ENT cancers.
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The therapy of advanced (clear-cell) renal cell carcinoma (RCC) has recently experienced tremendous changes. Several new treatments have been developed, with PD-1 immune-checkpoint inhibition being the backbone of therapy. Diverse immunotherapy combinations change current first-line standards.

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Article Synopsis
  • In 2019, oncology experienced significant advancements due to specialized medicine and personalized treatments.
  • Key treatments gained importance and expanded their uses, while new innovative therapies in research raised hopes for future developments.
  • Biomarkers like PD-L1, MSI, TMB, BRCA1/2 mutations, and HRD improved the selection and customization of available cancer treatments.
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