Diakovere

IntroductionThe influence of patient age on the clinical outcome of surgically treated osteochondral lesions of the talus (OCT) is controversial. Aim of this study was to evaluate the 24 months follow-up data of the German Cartilage Registry (KnorpelRegister DGOU, GCR) regarding the influence of patient age on clinical outcomes after surgical OCT treatment.Materials and methods303 patients met the inclusion criteria and were divided into patients < 40 years (27.1 ± 5.8 years, n = 177) and patients ≥ 40 years (50.8 ± 7.4 years, n = 126). Pre- and postoperative FAOS total scores, subscores and ΔFAOS for most frequent surgical techniques (bone marrow stimulation, matrix-augmented bone marrow stimulation, matrix-augmented bone marrow stimulation with additional bone grafting) and lesion size characteristics were evaluated for both groups. ANOVA analysis with post hoc Duncan test was applied for statistical analysis.ResultsBoth patients < 40 years and patients ≥ 40 years benefit from surgical treatment of OCT showing significant changes from pre- to postoperative FAOS total score (63.8 ± 20.3 to 81.5 ± 17.8 in patients < 40 years, p < 0.001; 57.3 ± 20.1 to 74.9 ± 21.6 in patients ≥ 40 years, p < 0.001) and subscores. Younger patient group tended to higher pre- and postoperative scores. ΔFAOS was not different between both groups. Older patient group had significantly higher lesion size area and volume; proportion of additional bone grafting was increased.ConclusionResults of surgical therapy of OCTs are independent from patient age. There is no superiority of a specific surgical technique depending on patient age.

223Ra, a targeted α-therapy, is approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have bone metastases. In the phase 3 ALSYMPCA study, 223Ra prolonged survival and improved quality of life versus placebo. Our real-world study, PARABO, investigated pain and bone pain-related quality of life in patients with mCRPC and symptomatic bone metastases receiving 223Ra in clinical practice. Methods: PARABO was a prospective, observational, noninterventional single-arm study conducted in nuclear medicine centers across Germany (NCT02398526). The primary endpoint was a clinically meaningful pain response (≥2-point improvement from baseline for the worst-pain item score in the Brief Pain Inventory-Short Form). Results: The analysis included 354 patients, who received a median of 6 223Ra injections (range, 1-6). Sixty-seven percent (236/354) received 5-6 injections, and 33% (118/354) received 1-4 injections. Of 216 patients with a baseline worst-pain score of more than 1, 59% (128) had a clinically meaningful pain response during treatment. Corresponding rates were 67% (range, 98/146) with 5-6 223Ra injections versus 43% (range, 30/70) with 1-4 injections, 60% (range, 60/100) in patients with no more than 20 lesions versus 59% (range, 65/111) in those with more than 20 lesions, and 65% (range, 69/106) in patients without prior or concomitant opioid use versus 54% (range, 59/110) in those with prior or concomitant opioid use. Mean subscale scores (pain severity and pain interference) on the Brief Pain Inventory-Short Form improved during treatment. Conclusion: 223Ra reduced pain in patients with mCRPC and symptomatic bone metastases, particularly in patients who received 5-6 injections. The extent of metastatic disease did not impact pain response.

Despite ongoing discussions for the previous few decades, there is still no consensus regarding the optimal surgical technique for acromioclavicular joint instabilities. The purpose of this study was to determine the impact of various implant materials following arthroscopically assisted stabilization of acromioclavicular joint instabilities on tunnel widening and implant migration. We hypothesized an implant-dependent behavior for tunnel widening and implant migration with differences when comparing acute and chronic acromioclavicular joint instabilities. This study compared 105 patients with acromioclavicular joint instabilities that were managed operatively with coracoclavicular double button constructs. Two of the groups containing acute cases were treated with either a double button construct with a wire (TR) or a tape (D) as a central pillar. The two groups with chronic cases were either treated with a wire (T+) or tape D+ as a central pillar and additional hamstring tendon augmentation (+). One central transclavicular-transcoracoidal drill channel was made in the acute cases, while additional medial and lateral drill channels to augment the central pillar with the hamstring tendon were made. The central drill channel in all cases and the medial/lateral drill channels in chronic cases were subsequently radiologically analyzed immediately postoperatively and at follow-up. Following this, additional radiological analysis of the implant migration of the clavicular button took place. All groups showed significant tunnel widening of the central drill channel at follow-up (p ≤ 0.001). The TR+ technique demonstrated significant widening in both the medial (p ≤ 0.001) and lateral (p ≤ 0.001) drill channels. The D and D+ group displayed significant higher rates of clavicular button migration to a cortical and intraosseous level (p ≤ 0.002). Tunnel widening and implant migration following arthroscopically assisted management of acromioclavicular joint instabilities are dependent on the chosen implant. The stable tape showed a significantly increased degree of tunnel widening with respect to the central drill channel in comparison with the wire. In contrast, a higher degree of load capacity of the tape ultimately favors a protected intraosseous graft healing for chronic cases, which leads to less tunnel widening of the medial and lateral drill channel. Finally, the D/D+ implant groups showed higher rates of implant migration due to lower contact surface area of the implant at the upper clavicular cortex.

There is a great need for fully automated plasma assays that can measure amyloid beta (Aβ) pathology and predict future Alzheimer's disease (AD) dementia. Two cohorts (n=920) were examined: Panel A+ (n=32 cognitively unimpaired [CU], n=106 mild cognitive impairment [MCI], and n=89 AD) and BioFINDER-1 (n=461 CU, n =232 MCI). Plasma Aβ42/Aβ40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. The best biomarker for discriminating Aβ-positive versus Aβ-negative participants was Aβ42/Aβ40 (are under the curve [AUC] 0.83-0.87). Combining Aβ42/Aβ40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P<0.01). Adding additional biomarkers had marginal effects (ΔAUC ≤0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and Aβ42/Aβ40 in MCI (AUC 0.87). The high accuracies for Aβ pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.

Abstract Background: De-escalating strategies seem promising in HER2-positive early breast cancer (EBC) and chemo-free regimens are thus of key interest. Recent data have underlined the role of tumor immunogenicity in response to de-escalated neoadjuvant anti-HER2 therapy. Therefore, the prospective single arm hypothesis-generating phase II KEYRICHED-1 trial (NCT03988036) investigates the pCR-rate in patients with HER2-enriched EBC receiving four cycles of the dual anti-HER2 blockade in combination with the checkpoint inhibitor pembrolizumab. Initial studies with dual antibody-based HER2 blockade alone were able to achieve pCR-rates of 20-40%, which did not quite match the pCR-rates obtained with concurrent chemotherapy. KEYRICHED-1 aims at achieving pCR-rates comparable to standard chemotherapy-containing regimens by incorporating appropriate molecular selection and immune oncology.. Methods: A total of 48 pre- and postmenopausal patients with newly diagnosed HER2 2+ or 3+ EBC (stage I-III) and HER2-enriched (HER2-E) subtype by PAM50 were enrolled in this single-arm study. All patients received four cycles of study treatment with pembrolizumab (200mg), trastuzumab biosimilar (Trazimera®, loading dose 8mg/kg bodyweight (BW), maintenance dose 6mg/kg BW), and pertuzumab (loading dose 840mg/kg BW, maintenance dose 420mg/kg BW) q21d. Primary endpoint was centrally confirmed pCR (ypT0/is, ypN0). The trial was planned as a Simon's two-stage design (null and alternative pCR were 40% and 60%); interim analysis after 16 patients had to show a pCR rate of at least 50% to continue recruitment.. Results: Between 05/2020 and 03/2021, 98 patients were screened. N=52 (55%) had HER2-E subtype, of whom 48 patients entered the treatment phase. Median patient age was 57 years (28-83). 65% had tumors &amp;gt; 2 cm and 30% positive lymph node status. Centrally confirmed pCR-rate in surgical specimens was 46% (95% CI 0.31-0.62) in the 43 patients of the per-protocol-population, and 52% (95%CI 0.37-0.67) in all 46 evaluable patients (local assessment; two pCRs verified only by core biopsy) (p=0.22 and p=0.06 for null hypothesis, respectively). Despite HER2-E subtype, no pCR was observed in the four patients with immunohistochemical (IHC) HER2 2+/ISH-positive status in contrast to 20/39 (51.2%) pCR in IHC HER2 3+ tumors. Centrally confirmed pCR-rate in HR+/HER2+ tumors was 38.5% compared to 58.5% in HR-/HER2+ tumors. No new safety signals were observed.. Conclusions: These are the first results of a neoadjuvant chemotherapy-free 12-week de-escalation anti-HER2-regimen with trastuzumab and pertuzumab in combination with the PD-1 inhibitor pembrolizumab in patients with a HER2-E EBC. In the context of the WSG ADAPT HER2+ de-escalation trials the observed pCR-rates compare favorably in HR+ as well as HR- HER2+ EBC. Moreover, KEYRICHED-1 demonstrates that with appropriate molecular patient selection clinically meaningful pCR-rates in the range of those obtained with longer, more toxic chemotherapy-containing regimens can be achieved. Citation Format: Sherko Kuemmel, Oleg Gluz, Mattea Reinisch, Athina Kostara, Iris Scheffen, Monika Graeser, Rachel Wuerstlein, Ulrike Nitz, Kerstin Luedtke-Heckenkamp, Andreas Hartkopf, Felix Hilpert, Angela Kentsch, Carsten Ziske, Reinhard Depenbusch, Michael Braun, Jens Blohmer, Christine zu Eulenburg, Matthias Christgen, Stephan Bartels, Hans Kreipe, Enrico Pelz, Peter Schmid, Nadia Harbeck. Keyriched-1- A prospective, multicenter, open label, neoadjuvant phase ii single arm study with pembrolizumab in combination with dual anti-HER2 blockade with trastuzumab and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD10-11.

Simple SummaryThe extent of axillary surgery has been reduced in recent years to minimize side effects. However, a negative impact of reduced surgery on outcome must be avoided. We investigated for whom the extent of surgery can be safely reduced by examining early-stage breast cancer patients converting from lymph node (LN)-positive to LN-negative disease after neoadjuvant systemic treatment (NAST). Of 242 initially LN-positive patients treated within the GeparOcto trial, 54.5% were classified as LN-negative after NAST, 31.8% as LN-positive, and for 13.6% data were missing. Overall, 92.1% of patients underwent complete axillary LN dissection, with 6.6% undergoing sentinel LN dissection only. At surgery, 55.4% of patients had no signs of cancer in the LN, 45.0% had no signs of cancer in the breast (of those 8.3% had involved LN), and 41.3% had no signs of cancer at all. Patients with involved LN still had a bad prognosis. Conversion from LN-positive to LN-negative after NAST is of highest prognostic value. Surgical axillary staging after NAST is essential in these patients to offer tailored treatment.Background: The conversion of initially histologically confirmed axillary lymph node-positive (pN+) to ypN0 after neoadjuvant systemic treatment (NAST) is an important prognostic factor in breast cancer (BC) patients and may influence surgical de-escalation strategies. We aimed to determine pCR rates in lymph nodes (pCR-LN), the breast (pCR-B), and both (tpCR) in women who present with pN+ BC, to assess predictors for response and the impact of pCR-LN, pCR-B, and tpCR on invasive disease-free survival (iDFS). Methods: Retrospective, exploratory analysis of 242 patients with pN+ at diagnosis from the multicentric, randomized GeparOcto trial. Results: Of 242 patients with initially pN+ disease, 134 (55.4%) had a pCR-LN, and 109 (45.0%) a pCR-B. Of the 109 pCR-B patients, 9 (8.3%) patients had involved LN, and 100 (41.3%) patients had tpCR. Those with involved LN still had a bad prognosis. As expected, pCR-B and intrinsic subtypes (TNBC and HER2+) were identified as independent predictors of pCR-LN. pCR-LN (ypN0; hazard ratio 0.42; 95%, CI 0.23–0.75; p = 0.0028 for iDFS) was the strongest independent prognostic factor. Conclusions: In initially pN+ patients undergoing NAST, the conversion to ypN0 is of high prognostic value. Surgical axillary staging after NAST is still essential in these patients to offer tailored treatment.

Background:Matrix-associated autologous chondrocyte implantation (ACI) is awell-established treatment for cartilage defects. High-level evidence atmidterm follow-up is limited, especially for ACI using spheroids (sphericalaggregates of ex vivo expanded human autologous chondrocytes andself-synthesized extracellular matrix).Purpose:To assess the safety and efficacy of 3-dimensional matrix-associated ACIusing spheroids to treat medium to large cartilage defects on differentlocations in the knee joint (patella, trochlea, and femoral condyle) at5-year follow-up.Study Design:Cohort study; Level of evidence, 2.Methods:A total of 75 patients aged 18 to 50 years with medium to large (4-10cm2), isolated, single cartilage defects, InternationalCartilage Repair Society grade 3 or 4, were randomized on a single-blindbasis to treatment with ACI at 1 of 3 dose levels: 3 to 7, 10 to 30, or 40to 70 spheroids/cm2 of defect size. Outcomes were assessed viachanges from baseline Knee injury and Osteoarthritis Outcome Score (KOOS),International Knee Documentation Committee score, and modified Lysholmassessments at 1- and 5-year follow-up. Structural repair was evaluatedusing MOCART (magnetic resonance observation of cartilage repair tissue)score. Treatment-related adverse events were assessed up to 5 years for allpatients. The overall KOOS at 12 months was assessed for superiority versusbaseline in a 1-sample, 2-sided t test.Results:A total of 73 patients were treated: 24 in the low-dose group, 25 in themedium-dose group, and 24 in the high-dose group. The overall KOOS improvedfrom 57.0 ± 15.2 at baseline to 73.4 ± 17.3 at 1-year follow-up(P < .0001) and 76.9 ± 19.3 at 5-year follow-up(P < .0001), independent of the applied dose. Thedifferent defect locations (patella, trochlea, and weightbearing part of thefemoral condyles; P = .2216) and defect sizes(P = .8706) showed comparable clinical improvement. Nodifferences between the various doses were observed. The overall treatmentfailure rate until 5 years was 4%. Most treatment-related adverse eventsoccurred within the first 12 months after implantation, with the mostfrequent adverse reactions being joint effusion (n = 71), arthralgia (n =14), and joint swelling (n = 9).Conclusion:ACI using spheroids was safe and effective for defect sizes up to 10cm2 and showed maintenance of efficacy up to 5 years for all3 doses that were investigated.Registration:NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCTnumber).