ABSTRACT
Case report of a HER2-expressed ovarian clear cell carcinoma with exceptional response to trastuzumab deruxtecan.
Subject(s)
Neoplasm Recurrence, Local , Ovarian Neoplasms , Receptor, ErbB-2 , Trastuzumab , Humans , Female , Trastuzumab/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Receptor, ErbB-2/genetics , Neoplasm Recurrence, Local/drug therapy , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/genetics , Antineoplastic Agents, Immunological/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Middle Aged , Immunoconjugates/therapeutic useABSTRACT
Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells and extrinsic microenvironmental influences change during treatment. To support the development of methods for identifying these mechanisms in individual people, here we present an omic and multidimensional spatial (OMS) atlas generated from four serial biopsies of an individual with metastatic breast cancer during 3.5 years of therapy. This resource links detailed, longitudinal clinical metadata that includes treatment times and doses, anatomic imaging, and blood-based response measurements to clinical and exploratory analyses, which includes comprehensive DNA, RNA, and protein profiles; images of multiplexed immunostaining; and 2- and 3-dimensional scanning electron micrographs. These data report aspects of heterogeneity and evolution of the cancer genome, signaling pathways, immune microenvironment, cellular composition and organization, and ultrastructure. We present illustrative examples of how integrative analyses of these data reveal potential mechanisms of response and resistance and suggest novel therapeutic vulnerabilities.
Subject(s)
Breast Neoplasms , Biopsy , Breast Neoplasms/genetics , Female , Humans , Tumor Microenvironment/geneticsSubject(s)
Melanoma , Skin Neoplasms , CTLA-4 Antigen , Humans , Ipilimumab , Programmed Cell Death 1 ReceptorABSTRACT
OBJECTIVE: To compare the acute effects of acupuncture with sham acupuncture on knee pain, range of motion and ambulation in patients with knee osteoarthritis undergoing bilateral total knee arthroplasty, when added to a standard postoperative physiotherapy programme. DESIGN: Prospective patient- and assessor-blinded randomized controlled trial. SETTING: Acute inpatient physiotherapy department. PATIENTS: Thirty patients (24 women and 6 men) undergoing bilateral total knee arthroplasty were included for final analysis in the study. INTERVENTIONS: Both groups received a standard postoperative physiotherapy programme. Each patient was also given either 10 sessions of acupuncture or sham acupuncture within two weeks. MAIN OUTCOME MEASURES: The primary outcome measures were the levels of pain at rest and at maximum after exercise measured by the numeric pain rating scale. Other outcome measures included active and passive ranges of knee motion measured by standard goniometer, and ambulation measured by the timed up-and-go test. RESULTS: Thirty-six patients were recruited at the start of the study with 18 patients allocated to the acupuncture group and another 18 patients to the sham acupuncture group. On postoperative day 15, there were 30 patients with complete data; three patients in each group dropped out from the study. The mean differences (95% confidence interval (CI)) in overall averages of postoperative mean pain levels were 0.4 (-0.6 to 1.3) and -0.8 (-2.0 to 0.4) at rest and at maximum respectively. There were no significant differences in the active and passive ranges of knee motion and the time for the timed up-and-go test between the two groups. CONCLUSION: There is no difference between the acute effects of acupuncture and sham acupuncture in addition to standard postoperative physiotherapy programme in patients with knee osteoarthritis undergoing bilateral total knee arthroplasty.
