Neoadjuvant Endocrine Research Articles

Comparing Black and White Patients in Treatment of Advanced Prostate Cancer and Survival in an Equal Access Health System.

Racial disparities in prostate cancer treatment and survival in the U.S. have been attributed to differences in access to care and medical insurance. We aimed to compare treatment and survival of advanced prostate cancers between White and Black men in the equal access Military Health System (MHS). We accessed the MilCanEpi database to study a cohort of non-Hispanic White and Black men diagnosed with stage III or IV prostate cancer between 1998 and 2014 in the MHS. The racial groups were compared in receiving curative treatment of radical prostatectomy (RP) only, RP with (neo)adjuvant radiation or hormone therapy, radiation only, or combination radiation and hormone therapy; and overall survival using multivariable regression models. The study included 1476 White and 531 Black men. Overall, there was no racial difference in receiving any curative treatment (AOR = 0.85, 95% CI = 0.67, 1.08 for Black vs. White). By treatment type, Black men were statistically as likely to receive RP only (AOR = 0.87, 95% CI = 0.67, 1.14), radiation only (AOR = 0.81, 95% CI = 0.49, 1.34), or combination radiation and hormone therapy (AOR = 1.12, 95% CI = 0.71, 1.78) but statistically less likely to receive RP with (neo)adjuvant treatment (AOR = 0.56, 95% CI = 0.37, 0.86) relative to no curative treatment compared to White men. The difference in RP with (neo)adjuvant treatment was also statistically significant among patients with stage III tumors, but not stage IV. Survival was similar overall (AHR = 1.12, 95% CI = 0.88, 1.42 for Black vs. White) and when evaluated by tumor stage. In the MHS, the overall likelihood to receive any treatment for advanced prostate cancers and survival was similar between races, which might result from universal health care. Racial differences in receipt of RP with (neo)adjuvant treatment, especially for patients with stage III prostate cancer, may be related to factors other than access to care and warrants further research.

The use of neoadjuvant hormone therapy in locally advanced luminal breast cancer

Neoadjuvant endocrine therapy, luminal breast cancer

Abstract PO5-26-04: The value of skin involvement in achieving of pCR in patients with locally advanced breast cancer

Abstract Objective: The management of patients with locally advanced breast cancer (LABC) with skin involvement (edema or thickening) continues to be one of the most controversial topics in mammology. The most recommended conventional treatment strategies include systemic therapy (chemotherapy/hormone therapy/biological agents) followed by local therapy (surgery and/or radiation therapy). However, approximately 1/3 of patients with locally advanced breast cancer are “resistant” to neoadjuvant chemotherapy (which is manifested by the persistence of skin involvement/edema/thickening). In this study, we aimed to identify the relationship between skin involvement and clinicopathological features of LABC patients. In particular, we sought to develop the algorithm for skin involvement measurement and examine the impact of skin involvement on the rate of pCR. Materials and methods: We performed a retrospective analysis of 182 patients diagnosed with LABC from 2010 to 2018 at N.N. Blokhin National Cancer Research Center. All patients were treated with neoadjuvant hormone- or chemotherapy and were considered as borderline for surgical resection because of partial skin edema. Ninety one women received surgery with consecutive radiotherapy (first group) and 50 women (second group) received radiotherapy (total dose 50 Gy) with consecutive surgery after systemic treatment. We developed the algorithm for skin involvement measurement, using a series of formulas. We further interrogated the impact of skin involvement on the rate of breast and lymph node pathological response in every group. Results: The median percentage of skin edema before systemic therapy was 76.3% in the first group and 70.1% in the second group. The median percentage of skin edema after systemic therapy was 62.3% in the first group and 69.1% in the second group. There wasn`t a statistically significant difference between the two groups (р=0,675 and р = 0,286, respectively). Breast pCR was seen in 19,7% (n=18) of the first group patients and partial response was seen in 72.6% (n=66). Breast pCR was seen in 30% (n=15) of the second group patients and partial response was seen in 70% (n=35). Results showed no significant differences between groups, р=0,342 and р = 0,12, respectively. Nodal pCR was reported in 23,9% (n=16) and partial response in 50,8% (n=34) of the 67 node-positive patients. Nodal pCR was reported in 31,6% (n=12) and partial response in 65,8% (n=29) of the 38 node-positive patients of the second group. There was no statistical difference in the groups, p >0,05. Conclusion: Increasing attention has been paid to LABC patients due to the clinical commonness and the complexity of treatment. Our study showed that LABC patients with incomplete clinical response to neoadjuvant systemic therapy can achieve pCR or partial response of tumor despite partial skin edema. In this study we developed the algorithm for skin involvement measurement. We hope that knowledge about volume of skin involvement revealed by this study might shed light on individualized therapies for these patients. In future, it allows to evaluate criteria of tumor resectability to improve patient selection. Therefore, prospective randomized trials are needed to improve optimization of the local treatment. Citation Format: Viktory Amosova, Alexander Petrovskiy, Oxana Trofimova, Mona Frolova, Alexey Rumyantsev. The value of skin involvement in achieving of pCR in patients with locally advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-04.

Abstract PO1-26-04: Patient-derived organotypic tissue cultures for organoid isolation and probing unique metabolic features of individual breast cancer patients

Abstract Patient-derived organotypic tissue cultures (PD-OTC) are unique models for probing how individual patient’s tumor microenvironment (TME) influences cancer development and treatment responses. They retain the patient tumor architecture and TME, that are difficult to recapitulate in other models, while affording flexible treatment options and comparison of cancer (CA) versus matched non-cancer (NC) tissue responses to treatments. We have developed a culturing method for establishing PD-OTC of breast cancer patients that exhibit CA tissue growth and extensive metabolic reprogramming between CA versus matched NC tissues while enabling patient-derived organoids (PDO) and fibroblasts to be isolated. Pairs of CA and NC tissues freshly resected from six patients bearing early-stage estrogen receptor/progesterone receptor positive ductal carcinoma were sliced at 750 µm, embedded in Matrigel, and cultured in a 6-well plate with a Biopore membrane insert and custom medium at 37°C/5% CO2 with gentle rocking (16-40 mg wet weight; n=3). Excess tissue slices were cryopreserved and kept at -196 °C. Culture media were sampled periodically for metabolite analysis by NMR. Microscopic examination revealed significant tissue, organoid-like, and fibroblast outgrowth after 1-1.5 month of culturing. Two to three days prior to the harvest of two patients’ (CZ16 and 17) OTC, the culture medium was replaced with [U-2H]-glucose + [U-13C,15N]-glutamine-containing medium to allow the two stable isotope tracers to be metabolized, followed by Stable Isotope-Resolved Metabolomic (SIRM) analysis by NMR and ion chromatography coupled with ultra high-resolution Fourier transform mass spectrometry (IC-UHRFTMS). Two separate pieces of the OTC were cut and each was assayed for glucose uptake and mitochondrial membrane potential by live fluorescence spectroscopy via a portable custom-built fluorescence microscope, and by histochemical analysis. Histological analysis showed that both CA and NC OTC of all patients maintained their structural integrity. SIRM analysis of two patients’ OTC revealed active catabolic and anabolic metabolism including glucose uptake/glycolysis, the Krebs cycle/mitochondrial membrane potential, the pentose phosphate pathway (PPP), gluconeogenesis, glycogen synthesis, and purine/pyrimidine/sugar nucleotides synthesis. The CA OTC of both patients showed enhanced glucose uptake, glycolysis, mitochondrial membrane potential/Krebs cycle, PPP, glycogen synthesis, and purine nucleotide synthesis, when compared with the matched NC OTC. Treatment-naïve CA OTC of CZ16 showed much more significant metabolic reprogramming (NAD+ metabolism, in particular) than CA OTC of CZ17 who has undergone neoadjuvant treatment, chemotherapy, and hormone therapy prior to surgery. Distinct metabolic features of breast CA tissues can be exploited as therapeutic targets. Organoids and fibroblasts were isolated from CA and/or NC OTC cultures and their characterization is in progress. When revived, cryopreserved OTC exhibited active metabolism and tissue/organoid/fibroblast outgrowth similarly to fresh OTC. In conclusion, our culturing method enables PD-OTC models to be established efficiently for early-stage breast cancer patients for downstream functional studies including live cell imaging and SIRM analysis. Organoids and fibroblasts can also be derived from < 20 mg of tissues for further studies. Future direction includes therapeutic studies on these patient-derived models to better understand and predict individual patient’s responses to therapy. Citation Format: Teresa Fan, Carlos Goncalves, Jing Yan, Jahid Islam, Penghui Lin, Mohamed Kaddah, Richard Higashi, Andrew Lane, Caigang Zhu. Patient-derived organotypic tissue cultures for organoid isolation and probing unique metabolic features of individual breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-26-04.

Long-term outcomes of neoadjuvant endocrine therapy versus chemotherapy in luminal HER2-breast cancer

Introduction. Neoadjuvant endocrine therapy (NET) is an effective treatment modality that can downsize breast tumors in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. A lack of data regarding efficacy of NET vs neoadjuvant cytotoxic chemotherapy (NCT) leads to limited usage of NET despite its favorable toxicity profile. Perioperative endocrine therapy is mainly used for the elderly or patients with comorbidities that limit their access to NCT. The COVID-19 pandemic led to increased data of NET efficacy. Nevertheless, long-term outcomes of NET application are underrepresented in literature. Objective. Assessment of long-term outcomes in patients treated with neoadjuvant endocrine therapy (NAT) versus neoadjuvant cytotoxic chemotherapy in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. Materials and methods. We retrospectively evaluated the results of treatment of 154postmenopausal patients with luminal HER2-breast cancer who were treated with neoadjuvant systemic therapy (NET or NCT) at the State Medical Institution «St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)» from 01.01.2019 to 31.11.2020. We analyzed data on radiological, pathomorphological and long-term treatment outcomes (rate of locoregional and overall recurrence) in two groups.Results. 154 patients received neoadjuvant hormone therapy (n=78) or neoadjuvant chemotherapy (n=76). The clinical response was evaluated according to the RECIST criteria after 12 weeks and after study treatment using MMG. Partial or complete radiological response was achieved in 41.0% (n=32) in the NET group vs 69.7% (n=53) in the NCT group (p<0.001). All patients included in the study underwent surgery. A complete pathologic response was observed in 9.2% (n=7) of patients in the chemotherapy group, and in 0% of patients in the endocrine therapy group (p=0.006). Median follow-up was 46.2 months. Progression was recorded in 23.2% (n=29) of participants, with no significant benefit of NCT over NET in the frequency of locoregional relapses (NET n=8 (10.3%) vs NCT n=4 (5.3%)) (p= 0.369) or the occurrence of distant metastases NAT n=8 (10.3%) vs NCT n=13 (17.1%)) (p=0.216). Multivariate analysis showed that only pathologic lymph node status (ypN2–3) was an independent predictor of progression (p=0.007, OR=3.2; 95%CI: 1.380-7.422). Conclusions. Long-term outcomes after neoadjuvant hormone therapy are comparable with chemotherapy in the group of postmenopausal women with luminal HER2-breast cancer. The small sample size and limited follow-up period are significant limitations of our work.

Abstract 7568: Molecular effects of neo-adjuvant hormone therapy for locally advanced prostate cancer: An ancillary study of the ARNEO phase 2 trial

Abstract Intensified hormone therapy in combination with radiotherapy improves outcome for very high-risk locally advanced prostate cancer. The impact of hormone therapy with surgery, however, is uncertain. In order to understand this better, we ran an ancillary translational study on ARNEO (NCT03080116), a Phase 2 clinical trial, which randomized 89 locally-advanced prostate cancer patients to 12 weeks LHRHa +/- apalutamide (APA) followed by prostatectomy. We performed clinical-grade transcriptome-wide expression array analysis (Veracyte, Inc. San Diego, CA) of FFPE diagnostic core biopsies (N=89) and tumors removed at prostatectomy (N=32 LHRHa, N=23 LHRHa + APA). We also performed RNASeq on fresh frozen biopsies of prostatectomy tumors (N=42 LHRHa, N=45 LHRHa + apalutamide) and LHRHa-naive control cases (N=61) matched for clinical and pathological risk factors. Pre-surgery serum PSA decreased by a median of 98% (IQR:90.2-99.3) after hormone treatment. This decrease was better associated with tumor AR signaling (r2=0.11) versus pre-treatment serum PSA (r2=0.0005), or between pre-treatment serum PSA with diagnostic biopsies (r2=0.008). We confirmed APA more potently suppressed AR signaling than LHRHa alone, with no detectable difference in direction of effect for differentially regulated genes/pathways. LHRHa + APA had less residual tumor (median Residual Cancer Burden, RCB=0.48cm3) than in LHRHa (median RCB=1.7cm3) but in cases with sufficient tumor, we observed residual active AR signaling pathways at prostatectomy in both treatment arms. To orthogonally confirm this, we selected 28 ERG positive cases (by IHC pre-treatment) and found retained ERG expression in 12/13 on LHRHa and 10/15 on LHRHa + APA. Using pathway analysis in the RNAseq data, we identified LHRHa +/- APA induced down-regulation of AR, metabolic pathways, as well as DNA repair, and up-regulation of hallmark NOTCH, Hedgehog, TGF-beta, WNT and immune signaling (adjusted p-value cutoff=0.001). Comparing differentially expressed genes on RNASeq between treatment-naïve versus LHRHa +/- APA treated tumors, we observed STING1 as significantly higher in LHRHa +/- APA vs control (Wilcoxon rank sum test p-value <0.001). We found that expression of STING1 was positively correlated with hallmark interferon alpha response (r=0.7, rs=0.6) that was correlated with apoptosis (r=0.5, rs=0.5). Whilst we show that adding APA to LHRHa increases suppression of AR activity and ERG expression, we find that 12 weeks is insufficient to abrogate AR signaling in most tumors, despite ~98% decrease in serum PSA. We identify novel processes modulated in humans by potent suppression of androgen activity, including upregulation of STING1-type 1 interferon response as a potential key modulator of treatment effect. Citation Format: Mazlina Ismail, Wout Devlies, Marina Parry, Gaetan Devos, Stefanie Friedrich, Charles Parker, Larissa Mendes, Elai Davicioni, Mark Linch, Frank Claessens, Steven Joniau, Gerhardt Attard. Molecular effects of neo-adjuvant hormone therapy for locally advanced prostate cancer: An ancillary study of the ARNEO phase 2 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7568.

PET/CT with <sup>18</sup>F-Fluoroestradiol in First Diagnosed Breast Cancer. A Pilot Study

Purpose: To evaluate the informativity of PET/CT with 18F-FES in determining estrogen receptor (ER) positivity in breast tumor tissue, as well as in regional lymph nodes or distant metastatic foci. Material and methods: The data of 30 patients who underwent PET/CT with 18F-FES performed at the stage of primary diagnosis were retrospectively analyzed. The study included patients before the start of specific treatment or on the background of neoadjuvant hormone therapy, with previously determined expression of ER according to the results of IGC. 14 patients underwent 18F-FDG PET/CT with 2–7 days difference between both PET/CT. Results: In our study, the mean SUVmax value in the primary tumor focus was 4.8, the lowest SUVmax = 1.61, and the highest SUVmax = 18.86. 18F-FES accumulation considered suspicious for metastatic lesion in axillary lymph nodes on the affected side was detected in 16 patients (56 %), mean SUVmax = 5.2, lowest SUVmax = 0.99, highest SUVmax = 11.54. On subsequent histological examination, tumor changes in axillary lymph nodes were confirmed in 16/16 patients. Conclusion: PET/CT with 18F-FES is a diagnostic method for noninvasive evaluation of ER expression in tumor foci, which can complement the data of traditional diagnostic methods and has a significant clinical potential. In our study, the results of PET/CT with 18F-FES coincided with the data of immunohistochemical study in 100 % of cases.

Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial

ObjectiveTo assess the efficacy and safety of pyrotinib (an irreversible pan-HER (human epidermal growth factor receptor) inhibitor), trastuzumab, and docetaxel compared with placebo, trastuzumab, and docetaxel for untreated HER2 positive...

Omission of Axillary Dissection in Node Positive Breast Cancer After Neoadjuvant Systemic Therapy

IntroductionGuidelines recommend axillary lymph node dissection (ALND) for ypN + positive patients as patients receiving neoadjuvant systemic therapy (NST) were excluded from trials omitting ALND in pN + patients. We sought to characterize trends in omission of ALND in patients with ypN + disease. MethodsAdult women with invasive breast carcinoma in the National Cancer Database between 2012 and 2019 who received NST (chemotherapy or endocrine) and had ypN + disease were included. Patients were excluded if they did not have definitive surgery within eight months of diagnosis. The primary study outcome was completion of ALND versus omission. Differences in demographics, tumor characteristics, and treatment were identified using bivariate and multivariate logistic regression models. ResultsIn total, 103,121 women were included. Most had cT1 (26%) or cT2 (45%) tumors, cN + disease (71%), and ductal histology (83%). 69% of patients received neoadjuvant chemotherapy and 31% neoadjuvant endocrine without chemotherapy (30% both). ALND was performed in 77% of patients. Omission of ALND became more prevalent each year from 2012 (14%) to 2019 (34%). On multivariate modeling, year of diagnosis, black race, cN status, higher grade, estrogen receptor+/HER2-receptor subtype, and mastectomy were associated with increased prevalence of ALND. Age, Charlson/Deyo comorbidity index score, endocrine versus chemotherapy, and adjuvant radiation were not associated with receipt of ALND. ConclusionsDespite guidelines recommending ALND, omission is common in patients with ypN + breast cancer after NST. Omission of ALND increased significantly over time and is associated with clinical and demographic factors. Future study is needed to determine the oncologic safety of this approach.

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks

Reports of radiation therapy for prostate cancer using dose fractions between moderate hypofractionation and ultrahypofractionation are limited. This pilot study involved the application of highly hypofractionated intensity modulated radiation therapy (IMRT) in 15 fractions for 3 weeks and the number of fractions was intermediate between the 2 previously mentioned dose fractions. The long-term outcomes are reported. From April 2014 to September 2015, patients with low- to intermediate-risk prostate cancer received 54 Gy in 15 fractions (3.6 Gy per fraction) for 3 weeks using IMRT without intraprostatic fiducial markers or a rectal hydrogel spacer. Neoadjuvant hormone therapy (HT) was administered for 4 to 8 months. Adjuvant HT was not administered to any patients. Rates of biochemical relapse-free survival, clinical relapse-free survival, overall survival, and the cumulative incidence of late grade ≥2 toxicities were analyzed. Twenty-five patients were enrolled in this prospective study; 24 of them were treated with highly hypofractionated IMRT (17% had low-risk and 83% had intermediate-risk disease). The median neoadjuvant HT duration was 5.3 months. The median follow-up period was 77 months (range, 57-87 months). Biochemical relapse-free survival, clinical relapse-free survival, and overall survival rates were 91.7%, 95.8%, and 95.8% at 5 years, and 87.5%, 86.3%, and 95.8% at 7 years, respectively. Neither grade ≥2 late gastrointestinal toxicity nor grade ≥3 late genitourinary toxicity was observed. The cumulative incidence rates of grade 2 genitourinary toxicity were 8.5% and 18.3% at 5 and 7 years, respectively. Highly hypofractionated IMRT delivering 54 Gy in 15 fractions for 3 weeks for prostate cancer without intraprostatic fiducial markers facilitated favorable oncological outcomes without severe complications. This treatment approach may be a possible alternative to moderate hypofractionation, but further validation is needed.

Radiation Therapy of Patients with Regional Risk Group of Prostate Cancer

Relevance: Radiation therapy is one of the main local method of treatment for patients with prostate
 cancer and regional metastases of pelvic lymph nodes. However, unfortunately, some patients can be
 subject to development progression of disease as emergence regional lymph node’s metastasis of
 retroperitoneal space.
 Purpose: To develop a new more effective radical method of radiation therapy for patients with metastases in the regional lymph nodes.
 Material and methods: The radiotherapy department has developed a new method of radiation therapy
 for patients with prostate cancer and metastases in the regional lymph nodes, which includes prophylactic irradiation of retroperitoneal lymph nodes.
 Results: 20 patients with prostate cancer and metastases to the regional lymph nodes were treated
 from June 2020 to December 2022. The median follow-up was 17 months. In all patients, radiation
 therapy was carried out in combination with neoadjuvant, concomitant and adjuvant hormone therapy
 with analogues of luteinizing hormone releasing hormone. All patients received a course of radiation
 therapy without interruption. At the time of analysis, all patients are alive and stay by under active surveillance with no signs of progression. At the end of radiation therapy, all patients noted manifestations
 of toxicity of the I-II degree genitourinary and gastrointestinal systems. There is a gradual recovery of
 patients in the form of a decrease and relief of radiation reactions in 3-6 months after the end of radiation therapy.
 Conclusion: The first data evaluating the safety of the new developed method of radiation therapy by
 hypofraction mode with additional prophylactic irradiation of the retroperitoneal lymph nodes demonstrate good tolerability. However, further study and conducting the 3rd phase of randomized trial are required to determine clinical efficacy.

Long-term clinical outcomes of cancers diagnosed following detection by a blood-based multi-cancer early detection (MCED) test.

3037 Background: Less than 20% of cancers are diagnosed as a result of standard-of-care (SOC) screening in the US. MCED tests may expand screening to more cancers, but the long-term outcomes of MCED test-detected cancers are unknown. DETECT-A was the first large prospective interventional clinical trial to evaluate an MCED blood test. The test used was an early version of CancerSEEK and was evaluated in 9,911 women without history of cancer ( Science 369:6499, 2020). CancerSEEK, coupled with diagnostic PET-CT, safely identified cancers including those not detected by SOC screening, the majority of which were localized or regional. This follow-up observational study evaluated longitudinal clinical outcomes of cancers diagnosed as a result of an abnormal CancerSEEK test with a median follow up of 4.4 (IQR:4.1-4.6) years from initial CancerSEEK testing. Methods: Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnosis, treatment, treatment response, remission status, recurrence, secondary cancer diagnoses, and mortality (cancer-related and all-cause) was extracted from electronic medical records through November 2022. Data collection for living participants took place a median of 3.7 years following cancer diagnosis (IQR: 3.3-3.9) and a median of 4.3 years (IQR: 4.1-4.7) following initial CancerSEEK screen. Results: Fourteen (53.8%) participants underwent surgery; 5 had surgery alone, 9 had surgery with adjuvant and/or neoadjuvant chemotherapy, radiation, or hormone therapy. Twelve of 14 (85.7%) surgically treated participants were in remission as of November 2022, including 10 with localized or regional disease at diagnosis. Among patients whose treatment was non-surgical (11) or unknown (1), 1 (8.3%) was in remission (stage I at diagnosis), 9 (75.0%) were deceased (all stage III or IV at diagnosis), and 2 (16.7%) were in surveillance or ongoing treatment (stage II and stage III at diagnosis). Overall, 13 of 26 (50%) participants were in remission [ovarian (4), thyroid (1), uterus (2), breast (1), colorectal (2), and lung (3)]; 7 of these 13 (54%) had cancers without recommended SOC screening modalities. Eleven of 17 (64.7%) participants with localized or regional disease (stage I, II, or III) were in remission, whereas 2 of 9 (22.2%) with stage IV disease at diagnosis were in remission. Conclusions: CancerSEEK detected cancers earlier in patients who, when treated subsequently with conventional methods, achieved long-term survival. Half of all patients with a CancerSEEK-detected cancer remain cancer-free after treatment >4 years (median) after their initial CancerSEEK test. This includes 7 patients with cancer types for which no SOC screening option exists. Additional biomarkers, new analytic methods and algorithms are being incorporated in the development of the next generation of the MCED test.

Combined treatment of high and very high risk prostate cancer: results of neoadjuvant treatment

Purpose of the study. Assessment of safety and short‑term effectiveness of high and very high‑risk prostate cancer neoadjuvant chemo‑ hormonal treatment without distant metastases.Patients and methods. Combined hormone chemo‑ radiation treatment of 33 patients with prostate cancer of high and very high risk of progression without distant metastases was performed. Metastases to regional lymph nodes were found in 9 patients according to the examination data (MRI, MSCT), no metastases were detected in 24 patients. All patients underwent combined chemohormonal therapy in the amount of 4 courses of docetaxel intravenously at a dose of 75 mg/m2 every 3 weeks as the first stage of treatment. in combination with androgen deprivation therapy with agonists or antagonists of GnRH before performing radical radiation therapy (combined or remote). All patients underwent neoadjuvant hormone therapy: 16 patients – with the use of GnRH antagonists (Degarelix), 17 – with the use of GnRH agonists (Gozerelin/Leuprorelin/Triptorelin). The toxicity of the presented treatment regimen and its immediate effectiveness – the effect on the level of prostate‑s pecific antigen (PSA), prostate volume, and the quality of urination – were evaluated.Results. Treatment regimen was highly effective concerning PSA decrease (from initial median level 79,67 ng/ml to 1,45 ng/ml after neoadjuvant treatment), all subjects responded well, no non‑responders observed. Median prostate volume decreased from 44 cm3 to 25 cm3 after treatment, which guaranteed availability and safety of further radical radiation treatment. Urinary function was restored in all subject with initial urinary retention.Conclusion. Neoadjuvant chemo‑h ormonal treatment was highly effective in PSA level, prostate volume decrease and functional results improvement which secured further radical radiation treatment in one of its types. Toxicity was acceptable, adverse events did not exceed grade II in most cases and did not lead to treatment discontinuation in any cases, while quality of life remained high enough.

Efficacy and Safety of Neoadjuvant Luteinizing Hormone-Releasing Hormone Antagonist and Tegafur-Uracil Chemohormonal Therapy for High-Risk Prostate Cancer.

This retrospective single-center cohort study evaluated the efficacy and safety of a combination of neoadjuvant luteinizing hormone-releasing hormone (LHRH) antagonist and tegafur-uracil (UFT) therapy (NCHT) and investigated the medical records of patients with high-risk PCa who underwent robot-assisted radical prostatectomy (RARP). The therapy was followed by RARP for high-risk PCa. The enrolled patients were divided into two groups: low-intermediate-risk PCa patients who underwent RARP without neoadjuvant therapy (non-high-risk) and those who underwent NCHT followed by RARP (high-risk group). This study enrolled 227 patients (126: non-high-risk and 101: high-risk group). Patients in the high-risk-group had high-grade cancer compared to those in the non-high-risk-group. At the median follow-up period of 12.0 months, there were no PCa deaths; two patients (0.9%) died of other causes. Twenty patients developed biochemical recurrence (BCR); the median time until BCR was 9.9 months after surgery. The 2-year biochemical recurrence-free survival rates were 94.2% and 91.1% in the non-high-risk and high-risk-group, respectively (p = 0.465). Grade ≥3 NCHT-related adverse events developed in nine patients (8.9%). This study indicates that combining neoadjuvant LHRH antagonists and UFT followed by RARP may improve oncological outcomes in patients with high-risk PCa.

Single-arm phase 2 clinical trial evaluating neoadjuvant abiraterone and gonadotrophin-releasing hormone agonist in high-risk localised prostate carcinoma: CTRIAL-IE (ICORG) 13-23.

360 Background: Our aim was to evaluate the clinical, radiological and biochemical response achieved by 4 months of neo-adjuvant (NA) combination hormone therapy (HT) comprising abiraterone acetate (AA), prednisolone and gonadotrophin-releasing hormone (GnRH) agonist in treatment-naïve high-risk localised prostate carcinoma (HRLPC) prior to radical radiotherapy (RRT). Methods: This single-arm phase II clinical trial recruited 45 patients between 07/15 and 02/2020. Patients presenting with RTOG HRLPC, planned for RRT combined with short or long-term HT, were eligible. Patients completed 4 months of NA combined AA and GnRH agonist. The primary outcomes assessed at 4 months were 1) the mean percentage reduction at 99 days in prostate gland volume (PGV) via transrectal ultrasound, 2) the change in PSA levels, and 3) the percentage of patients achieving a complete clinical and biochemical response as defined by normalisation of DRE and PSA <0.1ng/ml. The secondary endpoints included the decrease in testosterone level, PSA kinetics and change in urinary symptoms. Adverse events (AE) in the form of HT-related symptoms and sexual function were also assessed. Results: The mean percentage reduction in PGV from baseline at day 99 was 42.4 % [CI 38.6-46.2]. Of 11 patients, who may have been deemed unsuitable for brachytherapy due to large PGV (>50cm3) at initial assessment, 9 patients achieved PGV reduction. The median reduction in PSA from baseline at 4 months was 13.7 ng/mL (3 – 146). A total of 33 patients (80.5%) achieved a PSA value of <0.1ng/ml at day 126. The median reduction from baseline reached 13.6ng/mL (range 3-144) at day 43 and remained unchanged up to 2 months post radiotherapy. A total of 16 patients (48.5% of 33 patients with day 126 assessment) had a complete clinical and biochemical response. By day 43, every patient had a testosterone level of <0.5nmol/L. The median International Prostate Symptom Score at baseline was 9 (range 0-32). The median change from baseline at day 126 was -1 (range -30-10), indicating minimal improvement. 95.6% of patients experienced an AE related to AA. There was no grade 4 or grade 5 AE. A total of 18 patients (40%) experienced, the most common of which was hypertension or elevated liver enzymes. 5 patients (11.1%) discontinued AA secondary to AE. The percentage of patients with normal erectile function and normal intercourse satisfaction decreased from 44.4% and 46.7% respectively at baseline to 2.3% by day 126. The percentage of patients with normal overall satisfaction decreased from 72.5% at baseline to 50% at day 126. Conclusions: NA HT with AA and GnRH agonist achieved a very high rate of undetectable PSA for HRLPC and substantial PGV reduction which may lead to improved eligibility for brachytherapy. Sexual function and satisfaction were significantly impacted. Clinical trial information: NCT02160353 .

Cardiovascular and thromboembolic events associated with intense neoadjuvant androgen deprivation therapy followed by prostatectomy in patients with localized prostate cancer: A meta-analysis of clinical trials.

341 Background: Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients (pts). However, data regarding complications of the intense hormone therapy and surgical complications are scarce. The phase III trial PROTEUS testing ARSIs plus ADT added an amendment for thrombotic prophylaxis in the perioperative setting. We conducted a systematic review and meta-analysis to evaluate cardiovascular (CV) and thromboembolic (TE) adverse events (AEs) during neoadjuvant and perioperative intervals. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42022344104). A comprehensive search of PubMed, Embase, and Scopus databases and conference abstracts was performed from January 2010 to June 2022. Eligible studies include randomized and single-arm trials testing ARSIs prior to prostatectomy which adequately reported safety data regarding TE and CV AEs, peri-operative complications, and mortality during therapy. DerSimon and Laird method for random effects model was performed to estimate the pooled incidence (PI) of events with 95% confidence interval (95% CI). Heterogeneity was tested with I2 value. Results: 8 RCTs and 3 single-arm phase II trials comprising 674 pts were included (674 pts for CV and TE AEs and 499 for perioperative complications). Neoadjuvant regimen was classified as monotherapy with ADT (21 pts), ARSIs (100 pts), combination therapy with ADT + ARSI (338 pts), or ADT + ARSI + ARSI (215 pts). PI of all grade TE was 3.2% (95% CI, 1.6% – 4.8%, I2 = 0.0%, p = 0.92); TE incidence during perioperative period was 3.9% (95% CI, 1.6 – 6.1%, I2 = 0.0%, p = 0.67). 7 deaths were reported, with a PI of 3.0% (95% CI, 0.7–5.3%, I2 = 0.0%, p = 0.98). 2 of the mortality AE were considered treatment-related within perioperative interval. Incidence of hypertension grade 3-5 was 8.9% (95% CI, 5.2–12.7%, I2= 51.6%, p = 0.02). Incidence measures per regimen are described. Conclusions: CV and TE events associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 3.9% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting. [Table: see text]

Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. Of the 354 patients enrolled, 253 initiallyresponded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

The Impact of Breast Cancer Type, Staging, and Treatment on Vascular Complications of Immediate Free-Flap Breast Reconstruction.

Patients with advanced cancer staging have a greater risk of developing venous thromboembolism than noncancer patients. The impact of breast cancer stage and treatment on outcomes after autologous free-flap breast reconstruction (ABR) is not well-established. The objective of this retrospective study is to determine the impact of breast cancer characteristics, such as cancer stage, hormone receptor status, and neoadjuvant treatments, on vascular complications of ABR. A retrospective review was conducted examining patients who underwent ABR from 2009 to 2018. Breast cancer stage, cancer types, hormone receptor status, and treatments were collected in addition to demographic data. Intraoperative vascular concerns, postoperative vascular concerns, and flap loss were analyzed. Univariate analysis and fixed-effects models were used to associate breast cancer characteristics with outcomes. Neoadjuvant hormone therapy was associated with increased risk for intraoperative vascular concern (odds ratio, 1.059 [ P = 0.0441]). Neoadjuvant trastuzumab was associated with decreased risk of postoperative vascular concern (odds ratio, 0.941 [ P = 0.018]). Breast cancer stage, somatic genetic mutation, receptor types, neoadjuvant chemotherapy, and neoadjuvant radiation had no effect on any vascular complications of ABR. Autologous free-flap breast reconstruction is a reliable reconstructive option for patients with all stages and types of breast cancer. There is potentially increased risk of intraoperative microvascular compromise in patients who have neoadjuvant hormone therapy. Trastuzumab is potentially protective against postoperative microvascular compromise. Patients should feel confident that, despite higher stage cancer, they can pursue their desired reconstructive option without fear of vascular compromise.

Clinical Analysis of Perioperative Outcomes on Neoadjuvant Hormone Therapy before Laparoscopic and Robot-Assisted Surgery for Localized High-Risk Prostate Cancer in a Chinese Cohort.

To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort. The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively. In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05). NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible.

Preoperative Hormone Therapy in the Treatment of Breast Cancer: What Do We Know So Far?

Breast cancer is the most common malignant disease in the world. One of the methods of treating breast cancer is neoadjuvant chemotherapy. Neoadjuvant chemotherapy (NCT) is now the standard of care for locally advanced breast cancer. Patients with HER2-positive and triple-negative breast cancer subtypes benefi t the most from NCT, with a 50–60 % chance of achieving pCR, while patients with hormone-sensitive, HER2-negative breast cancer subtypes have an average chance of achieving pCR of 10–20 %. For patients with locally advanced, hormone-sensitive Her2neu-negative breast cancer, neoadjuvant hormone therapy contributes to a tumor downstaging and an increasing rate of organ-preserving surgery. However, neoadjuvant hormone therapy is still not used routinely. There are a limited number of clinical guidelines that describe the choice of the optimal drugs, the optimal duration of hormone therapy and the criteria for selecting patients for preoperative hormone therapy. This is the first literature review in Russia that includes a systematization of the evidence regarding the effectiveness of neoadjuvant hormone therapy, a comparison of hormone therapy with neoadjuvant chemotherapy, comparison of hormonal drug groups, optimal duration of hormone therapy, attempts to combine hormone therapy with drugs of the group of selective CDK4/6 cyclin-dependent kinase inhibitors and phosphatidylinositol 3-kinase inhibitors for women with locally advanced hormone-sensitive Her2neu-negative breast cancer. The possibilities of using modern commercial multigene panels to assess the feasibility of identifying the cohort of patients for whom neoadjuvant hormone therapy would be most effective are also considered.