Management Of Cancer Patients Research Articles

Key points of anti-tumor treatment in breast cancer patients with SARS-CoV-2 infection.

Internationally, the outbreak of coronavirus disease 2019 (COVID-19) has become the most serious public health emergency. With the adjustment of the prevention and control policies, China downgraded the management of COVID-19 from Class A to Class B, causing new challenges in the clinical management of patients with breast cancer. It is necessary to formulate clinical strategies for timely and reasonable anti-tumor treatment after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. By combing the relevant evidence and summarizing the anti-tumor treatment experience for breast cancer patients with SARS-CoV-2 infection in various regions, the expert panel of the Breast Cancer Professional Committee of the Chinese Society of Clinical Oncology (CSCO-BC) discussed and voted on hot and difficult issues of this situation timely. Based on the vote results, combined with domestic and foreign guidelines and consensus, the key points of treatment and management of breast cancer patients who were infected with COVID-19 have been established to provide suggestions and recommendations for clinical practice, such as restart time of anti-tumor treatment, application of anti-tumor drugs and other considerations. In the formulation of this key point, we mainly focus on mild to moderate and asymptomatic infection patients who account for the largest proportion of COVID-19 patients, and propose diagnosis and treatment recommendations for breast cancer patients with different infections and after SARS-CoV-2 infection, aiming to provide a reference for clinical diagnosis and treatment.

Impact of COVID-19 on Breast Cancer Management in a Multiethnic Middle-Income Asian Country Setting.

Coronavirus disease-2019 (COVID-19) has caused hospitals to suspend routine procedures. As the world recovers, there is concern that the outcome of many diseases has been impaired. This study aimed to assess the impact of the pandemic on breast cancer demography, clinicopathological characteristics and patient management at a teaching hospital in Kuala Lumpur, Malaysia. Pre-COVID data were collected between January 1, 2019, to March 18, 2020, when a national lockdown was implemented, which caused the suspension of services at the breast clinic of University Malaya Medical Centre (UMMC). COVID data was obtained from March 2020 until June 2021. This study compared 374 breast cancer patients in the COVID-19 period with 382 patients in the pre-COVID period. There was no significant difference in the median (range) time to surgery between pre-COVID [45 (26.50-153.50) days] and COVID [44 (24.75-156.25) days] periods. The clinicopathological features of breast cancer showed reduction in in situ carcinoma and increase in Stage 4 diagnoses during the COVID period. There was a reduction in screening-detected carcinoma (9% vs. 12.3%), mastectomy followed by immediate reconstruction (5.6% vs. 14.5%) and adjuvant chemotherapy (25.8% vs. 32.9%) in the COVID period. In this center COVID-19 caused operational changes in breast cancer management, including a reduction in reconstructive procedures and adjuvant treatment. Healthcare disruption and fear of COVID may have caused delayed diagnosis, resulting in a higher frequency of Stage 4 disease and lower proportion of in situ carcinoma during the pandemic. However, there was no delay in the time to surgery, reduction in surgical volume, or change in surgery types.

Management of pain in children with cancer admitted to the pediatric department of university hospital center

Pain management in pediatric cancer patients is a significant concern among caregivers, as it is the most prevalent symptom and often undertreated. This study conducted a review of the literature on pain management protocols for hospitalized cancer children, and also conducted a case report on pain management practices at a Central Hospital Pharmacy and Pediatric Oncology Ward. The study found that the majority of patients admitted to the pediatric oncology ward were diagnosed with lymphocytic leukemia, and that pain in children with cancer was not only caused by the cancer itself, but also by medical procedures such as myelograms and venipunctures. Abdominal pain and lower limb pain were the most common pain locations reported. The study revealed that pain management was not optimal, with only pharmacological tools being used and a limited number of antalgic and analgesic medications being available due to drug shortages. The majority of patients (65%) still experienced pain even after receiving pain medication, indicating a need for improved pain management protocols in pediatric oncology.

A Case of Imatinib Induced Nephrotic Syndrome in a Child with Chronic Myeloid Leukaemia

Background:Tyrosin kinase inhibitors (TKI) are used as a targeted therapy for the treatment of chronic myeloid leukaemia and Philadelphia chromosome positive acute lymphoblastic leukaemia. Increasing use of TKI has been associated with hypertension, proteinuria and acute kidney injury. There are only afew reports of adults with TK -inhibitor associated nephrotic syndrome.But TK inhibitor associated Nephrotic syndrome is very rare in paediatric age group. Case:A -6- year old boy presented with fever, anaemia, splenomegaly, leucocytosis and finally diagnosed as accelerated phase of chronic myeloid leukaemia (CML) by bone marrow study.He achieved clinical and haematological remission with Imatinib. But developed generalized oedema and was found to have massive proteinuria and microscopic haematuria after three and half months. Renal biopsy revealed focal segmental glomerulosclerosis. Imatinib along with Prednisolone, 60 mg/m2/ day was added to treat nephrotic syndrome. Imatinib discontinued as the patient did not achieve complete remission. After one week of Imatinib withdrawal and five weeks of daily prednisolone the boy attained complete remission of nephrotic syndrome. Conclusion:Tyrosine Kinase inhibitors are important therapies in paediatric cancer and their use is expanding. Timely recognition of renal adverse effectsfor TK inhibitors can aid in the proper management of cancer patients. J Bangladesh Coll Phys Surg 2023; 41: 170-172

The association between postvoid residual and response to standard therapy in male and female patients with non-muscle-invasive bladder cancer.

The urinary retention is recognized as a promoting factor for bladder cancer, but its role as prognostic factor of therapeutic response has not yet been widely considered. To correlate bladder outlet characteristics with short-term response to treatment in non-muscle-invasive bladder cancer. We carried out a case-control study on 600 consecutive patients with a first diagnosis of non-muscle-invasive bladder cancer, recruited at the first endoscopic follow-up visit after standard treatment: 200 patients were not tumor-free (cases) and 400 were tumor-free (controls). Patients were compared based on baseline and bladder-outlet characteristics ("functional parameters": postvoid residual volume [PVR], International Prostatic Symptoms Score, perceived quality of bladder outlet). t Test, χ2 test, receiver operating characteristic curves, logistic correlations, and multivariate analysis were applied. The cases had higher statistically significant PVR values compared with controls. We reported a linear correlation of no-tumor-free status with PVR (R2 = 0.087, p < 0.005); the receiver operating characteristic curves revealed an area under the curve of 0.824 (95%confidence interval, 0.783-0.865; optimal PVR cutoff, 50 mL). In the multivariate analysis, age, American Society of Anesthesiologists score ≥2, risk category ≥intermediate, and all functional parameters represented independent factors for no-tumor-free status. Urinary retention could represent a prognostic factor of treatment response, and its active treatment should be considered as an important therapeutic step into the clinical management of bladder cancer patients.

Liquid Biopsy in the Management of Breast Cancer Patients: Where Are We Now and Where Are We Going

Liquid biopsy (LB) is an emerging diagnostic tool that analyzes biomarkers in the blood (and possibly in other body fluids) to provide information about tumor genetics and response to therapy. This review article provides an overview of LB applications in human cancer with a focus on breast cancer patients. LB methods include circulating tumor cells and cell-free tumor products, such as circulating tumor DNA. LB has shown potential in detecting cancer at an early stage, monitoring tumor progression and recurrence, and predicting patient response to therapy. Several studies have demonstrated its clinical utility in breast cancer patients. However, there are limitations to LB, including the lack of standardized assays and the need for further validation. Future potential applications of LB include identifying the minimal residual disease, early detection of recurrence, and monitoring treatment response in various cancer types. LB represents a promising non-invasive diagnostic tool with potential applications in breast cancer diagnosis, treatment, and management. Further research is necessary to fully understand its clinical utility and overcome its current limitations.

Rapid estimation of patient-specific organ doses using a deep learning network.

Patient-specific organ-dose estimation in diagnostic CT examinations can provide useful insights on individualized secondary cancer risks, protocol optimization and patient management. Current dose estimation techniques mainly rely on time-consuming Monte Carlo methods or/and generalized anthropomorphic phantoms. We proposed a proof-of-concept rapid workflow based on deep learning networks to estimate organ doses for individuals following thorax Computed Tomography (CT) examinations METHODS: CT scan data from 95 individuals undergoing thorax CT examinations were used. Monte Carlo simulations were performed and three-dimensional (3D) dose distributions for each patient were obtained. A fully connected sequential deep learning network model was constructed and trained for each organ considered in this study. Water-equivalent diameter (WED), scan length and tube current were the independent variables. Organ doses for heart, lungs, esophagus, and bones were calculated from the Monte Carlo 3D distribution and used to train the deep learning networks. Organ dose predictions from each network were evaluated using an independent data set of 19 patients. The trained networks provided organ dose predictions within a second. There was very good agreement between the deep learning network predictions and reference organ dose values calculated from Monte Carlo simulations. The average difference was -1.5% for heart, -1.6% for esophagus, -1.0% for lungs, and -0.4% for bones in the 95 patients dataset, and -5.1%, 4.3%, 0.9%, and 1.4% respectively in the 19 patients test dataset. The proposed workflow demonstrated that patient specific organ-doses can be estimated in nearly real-time using deep learning networks. The workflow can be readily implemented and requires a small set of representative data for training. This article is protected by copyright. All rights reserved.

Microbial composition of tumorous and adjacent gastric tissue is associated with prognosis of gastric cancer

Helicobacter pylori (H. pylori) infection has been considered as the main causal factor in gastric carcinogenesis, but other bacterial species may also play an important role in pathophysiology of gastric cancer. The aim of the study was to explore the link between gastric cancer prognosis and the mucosal microbial community in tumorous and adjacent gastric tissue. The bacterial profile was analysed using 16S sequencing (V1–V2 region). Microbial differences were mostly characterized by lower relative abundances of H. pylori in tumorous gastric tissues. Bacterial community and outcome data analysis revealed the genus Fusobacterium and Prevotella significantly associated with worse overall survival in gastric cancer patients. In particular, Fusobacterium was associated with significant increase in hazard ratio in both univariable and multivariable analysis and independently validated using TCMA data. Phylogenetic biodiversity of Fusobacterium species in the stomach revealed F. periodonticum as the most prevalent in healthy subjects, while F. nucleatum was most abundant in patients with gastric cancer. Bacterial community network analysis in gastric cancer suggests substantial complexity and a strong interplay between F. nucleatum and Prevotella. In summary, mucosal microbial community in the stomach was associated with worse overall survival in gastric cancer patients. Strongest negative impact on prognosis was linked to the abundance of F. nucleatum in tumorous specimens, suggesting its translational relevance in management of gastric cancer patients.

Immune Checkpoint Inhibitors and the Kidney: A Focus on Diagnosis and Management for Personalised Medicine

Immunity plays a crucial role in fighting cancer, but tumours can evade the immune system and proliferate and metastasize. Enhancing immune responses is a new challenge in anticancer therapies. In this context, efficacy data are accumulating on immune checkpoint inhibitors and adjuvant therapies for various types of advanced-stage solid tumours. Unfortunately, immune-related adverse events are common. Although infrequent, renal toxicity may occur via several mechanisms and may require temporary or permanent drug suspension, renal biopsy, and/or immunosuppressive treatment. This short review aims to provide a practical approach to the multidisciplinary management of cancer patients with renal toxicity during treatment with immune checkpoint inhibitors.

The Economic Cost of Thyroid Cancer in France and the Corresponding Share Associated With Treatment of Overdiagnosed Cases

ObjectivesThyroid cancer incidence in France has increased rapidly in recent decades. Most of this increase has been attributed to overdiagnosis, the major consequence of which is overtreatment. We aimed to estimate the cost of thyroid cancer management in France and the corresponding cost proportion attributable to the treatment of overdiagnosed cases. MethodsMultiple data sources were integrated: the mean cost per patient with thyroid cancer was estimated by using the Echantillon Généraliste des Bénéficiaires data set; thyroid cancer cases attributable to overdiagnosis were estimated for 21 departments using data from the French network of cancer registries and extrapolated to the whole country; medical records from 6 departments were used to refine the diagnosis and care pathway. ResultsBetween 2011 and 2015, 33 911 women and 10 846 men in France were estimated to be diagnosed of thyroid cancer, with mean cost per capita of €6248. Among those treated, 8114 to 14 925 women and 1465 to 3626 men were due to overdiagnosis. The total cost of thyroid cancer patient management was €203.5 million (€154.3 million for women and €49.3 million for men), of which between €59.9 million (or 29.4% of the total cost, lower bound) and €115.9 million (or 56.9% of the total cost, upper bound) attributable to treatment of overdiagnosed cases. ConclusionsThe management of thyroid cancer represents not only a relevant clinical and public health problem in France but also a potentially important economic burden. Overdiagnosis and corresponding associated treatments play an important role on the total costs of thyroid cancer management.

Effect of Psychosocial, Behavioral, and Disease Characteristics on Health-Related Quality of Life (HRQoL) After Breast Cancer Surgery: A Cross-Sectional Study of a Regional Australian Population.

Increasing long-term breast cancer survivorship has highlighted the importance of patient-reported outcomes such as health-related quality of life (HRQoL) in addition to traditional outcomes that were used to define successful operative management. This study aimed to describe HRQoL in patients who underwent breast cancer resection in a regional Australian setting and identify the psychosocial, demographic, and operative characteristics associated with poor HRQoL. Consecutive patients who underwent breast cancer resection between 2015 and 2022 were included. Patients were asked to complete a survey instrument that included validated measures of HRQoL, emotional distress, fear of cancer recurrence (FCR), and social support. Demographic, disease, and operative data were collected from the medical record of the respondents. Forty-six patients completed the survey (100% female, mean age = 62.68 years). Most HRQoL domains were significantly lower than an Australian reference population. HRQoL was more strongly associated with psychosocial factors (emotional distress, FCR, and social support) but was also associated with socioeconomic status, stage of cancer at presentation, and surgical complications. HRQoL was not related to breast conservation, management of the Axilla, or time since operation. Long-term changes in HRQoL should be considered during the management and surveillance of breast cancer patients in regional Australia.

Acute heart failure presentation, management and outcomes in cancer patients: a national longitudinal study.

Currently, little evidence exists on survival and quality of care in cancer patients presenting with acute heart failure (HF). To investigate the presentation and outcomes of hospital admission with acute HF in a national cohort of patients with prior cancer. This retrospective, population-based cohort study, identified 221,953 patients admitted to hospital in England for HF during 2012-2018 (12,867 with a breast, prostate, colorectal or lung cancer diagnosis in the previous 10 years). We examined the impact of cancer on 1) HF presentation and in-hospital mortality, 2) place of care, 3) HF medication prescribing, and 4) post-discharge survival, using propensity score weighting and model-based adjustment. HF presentation was similar between cancer and non-cancer patients. A lower percentage of patients with prior cancer were cared for in a cardiology ward (-2.4 percentage point difference [ppd] [95% CI -3.3, -1.6]) or were prescribed ACEi/ARB for HFrEF (-2.1 ppd [-3.3, -0.9]) than non-cancer patients. Survival after HF discharge was poor with median survival of 1.6 years in prior cancer and 2.6 years in non-cancer patients. Mortality in prior cancer patients was driven primarily by non-cancer causes (68% of post-discharge deaths). Survival in prior cancer patients presenting with acute HF was poor, with a significant proportion due to non-cancer causes of death. Despite this, cardiologists were less likely to manage cancer patients with HF. Cancer patients who develop HF were less likely to be prescribed guideline-based HF medications compared with non-cancer patients. This was particularly driven by patients with a poorer cancer prognosis.

Differences between zoledronic acid and denosumab for breast cancer treatment.

Zoledronic acid and denosumab are bone-modifying agents that are clinically important in multiple aspects of bone management for breast cancer patients. These aspects include the prevention of osteoporosis induced by cancer-treatment bone loss, treatment and prevention of bone metastasis, and improvement of survival directly or indirectly by maintaining bone health. Interestingly, zoledronic acid and denosumab have different anticancer activities, and they may be associated with the improvement of survival of breast cancer patients under different mechanisms. Zoledronic acid is the most potent bisphosphonate. It provides significant benefits for improving breast cancer mortality in patients with suppressed estrogen level such as in postmenopausal or ovarian suppression condition. Although denosumab's anticancer activity has not been clearly proven compared with zoledronic acid's anticancer activity, denosumab is promising in preventing BRCA1 mutant breast cancer because RANKL is a targetable pathway in BRCA1-associated tumorigenesis. Further studies and more effective clinical use of these agents are anticipated to contribute to the improvement of the clinical outcome of breast cancer patients.

The innovative model based on artificial intelligence algorithms to predict recurrence risk of patients with postoperative breast cancer.

This study aimed to develop a machine learning model to retrospectively study and predict the recurrence risk of breast cancer patients after surgery by extracting the clinicopathological features of tumors from unstructured clinical electronic health record (EHR) data. This retrospective cohort included 1,841 breast cancer patients who underwent surgical treatment. To extract the principal features associated with recurrence risk, the clinical notes and histopathology reports of patients were collected and feature engineering was used. Predictive models were next conducted based on this important information. All algorithms were implemented using Python software. The accuracy of prediction models was further verified in the test cohort. The area under the curve (AUC), precision, recall, and F1 score were adopted to evaluate the performance of each model. A training cohort with 1,289 patients and a test cohort with 552 patients were recruited. From 2011 to 2019, a total of 1,841 textual reports were included. For the prediction of recurrence risk, both LSTM, XGBoost, and SVM had favorable accuracies of 0.89, 0.86, and 0.78. The AUC values of the micro-average ROC curve corresponding to LSTM, XGBoost, and SVM were 0.98 ± 0.01, 0.97 ± 0.03, and 0.92 ± 0.06. Especially the LSTM model achieved superior execution than other models. The accuracy, F1 score, macro-avg F1 score (0.87), and weighted-avg F1 score (0.89) of the LSTM model produced higher values. All P values were statistically significant. Patients in the high-risk group predicted by our model performed more resistant to DNA damage and microtubule targeting drugs than those in the intermediate-risk group. The predicted low-risk patients were not statistically significant compared with intermediate- or high-risk patients due to the small sample size (188 low-risk patients were predicted via our model, and only two of them were administered chemotherapy alone after surgery). The prognosis of patients predicted by our model was consistent with the actual follow-up records. The constructed model accurately predicted the recurrence risk of breast cancer patients from EHR data and certainly evaluated the chemoresistance and prognosis of patients. Therefore, our model can help clinicians to formulate the individualized management of breast cancer patients.

Integration of longitudinal deep-radiomics and clinical data improves the prediction of durable benefits to anti-PD-1/PD-L1 immunotherapy in advanced NSCLC patients

BackgroundIdentifying predictive non-invasive biomarkers of immunotherapy response is crucial to avoid premature treatment interruptions or ineffective prolongation. Our aim was to develop a non-invasive biomarker for predicting immunotherapy clinical durable benefit, based on the integration of radiomics and clinical data monitored through early anti-PD-1/PD-L1 monoclonal antibodies treatment in patients with advanced non-small cell lung cancer (NSCLC).MethodsIn this study, 264 patients with pathologically confirmed stage IV NSCLC treated with immunotherapy were retrospectively collected from two institutions. The cohort was randomly divided into a training (n = 221) and an independent test set (n = 43), ensuring the balanced availability of baseline and follow-up data for each patient. Clinical data corresponding to the start of treatment was retrieved from electronic patient records, and blood test variables after the first and third cycles of immunotherapy were also collected. Additionally, traditional radiomics and deep-radiomics features were extracted from the primary tumors of the computed tomography (CT) scans before treatment and during patient follow-up. Random Forest was used to implementing baseline and longitudinal models using clinical and radiomics data separately, and then an ensemble model was built integrating both sources of information.ResultsThe integration of longitudinal clinical and deep-radiomics data significantly improved clinical durable benefit prediction at 6 and 9 months after treatment in the independent test set, achieving an area under the receiver operating characteristic curve of 0.824 (95% CI: [0.658,0.953]) and 0.753 (95% CI: [0.549,0.931]). The Kaplan-Meier survival analysis showed that, for both endpoints, the signatures significantly stratified high- and low-risk patients (p-value< 0.05) and were significantly correlated with progression-free survival (PFS6 model: C-index 0.723, p-value = 0.004; PFS9 model: C-index 0.685, p-value = 0.030) and overall survival (PFS6 models: C-index 0.768, p-value = 0.002; PFS9 model: C-index 0.736, p-value = 0.023).ConclusionsIntegrating multidimensional and longitudinal data improved clinical durable benefit prediction to immunotherapy treatment of advanced non-small cell lung cancer patients. The selection of effective treatment and the appropriate evaluation of clinical benefit are important for better managing cancer patients with prolonged survival and preserving quality of life.

Management of Acute Cancer Pain in Asia: An Expert Opinion on the Role of Tramadol/Dexketoprofen Fixed-Dose Combination.

Most patients experience acute cancer pain at some stage throughout their cancer journey. When inadequately managed, cancer pain has devastating consequences for the patient's quality of life. The suboptimal management of cancer pain in Asia is mainly driven by over-regulation and limited access to opioids. Concerns about adverse events and addiction have resulted in a negative perception of this group of drugs among physicians, as well as patients. There is a need to optimize the management of cancer pain across the region, through the provision of an alternative treatment option that is simple to prescribe, convenient to administer and well tolerated by patients, which will increase patients' compliance and good results. As recommended in many international guidelines, starting by the WHO analgesic ladder, cancer pain can be effectively managed with multimodal analgesia. Fixed-dose combinations (FDCs), in which two or more analgesic agents act synergistically to deliver a broad spectrum of pain relief, represent an effective and convenient option for delivering multimodal analgesia to patients with cancer pain. This is extremely well accepted by patients for several reasons. Any multimodal pharmacological approach to pain management should be based on the potentiality to block pain at different levelsand to reduce the dosages of single analgesics, reducing their side effects. Hence, the use of NSAIDs, combined with other analgesics, is the general basis of multimodal pain management. If NSAIDs are combined with tramadol, a weak opioid that has per se a multimodal analgesic efficacy, it may beideal. The tramadol/dexketoprofen FDC combines the centrally acting weak opioid with a peripherally acting NSAID to deliver rapid-onset, long-lasting analgesia, which has been proven efficacious and safe in the management of moderate-to-severe acute pain in the postoperative setting. This expert opinion explores the role oftramadol/dexketoprofen FDC in the management of patients with moderate-to-severe acute cancer pain. It is essentially based on the incredibly high amount of existing data on the use of the drug, and on the long-lasting experience of the experts in pain management of cancer patients participating in the advisory panel.

Management of Cancer Patients with Opioid-Induced Constipation (OIC): The Experience of Three Italian Centres

Objectives: To present the Training on the field about OIC undertaken by three Italian oncological centres involving professionals of different sub-specialties. Methods: Four on-site interactive meetings of multidisciplinary hospital teams; interactive presentation and discussion, questionnaires administration at the baseline and at the end of the field programme over two years (2019-2021). Outcomes evaluated by estimated increase of OIC diagnosis and OIC treatments. Results: Shared principles about OIC prevention and management in all the steps (from laxatives to PAMORAs), and use of PROMs. Participants were asked about their initial awareness at the inception of the Training on the field programme and their final experiences at the end. Discussion: The experience of this Training on the field underlined the cardinal role of a constant teamwork in the Onco-ematology and Palliative Care Departments and the territory with a shared and tested algorithm. The proposed platform of activities is a call to action to mitigate the burden of pain and OIC if specialists act in concert during all the steps of the trajectory of cancer patients requiring opioid treatment. Multidisciplinary teamwork may help redefine and optimize doses and time schedules tailored to each patient and can contribute to designing controlled studies of OIC

Liquid Biopsies, Novel Approaches and Future Directions.

Cancer is among the leading causes of death worldwide. Early diagnosis and prognosis are vital to improve patients' outcomes. The gold standard of tumor characterization leading to tumor diagnosis and prognosis is tissue biopsy. Amongst the constraints of tissue biopsy collection is the sampling frequency and the incomplete representation of the entire tumor bulk. Liquid biopsy approaches, including the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor-derived extracellular vesicles (EVs), as well as certain protein signatures that are released in the circulation from primary tumors and their metastatic sites, present a promising and more potent candidate for patient diagnosis and follow up monitoring. The minimally invasive nature of liquid biopsies, allowing frequent collection, can be used in the monitoring of therapy response in real time, allowing the development of novel approaches in the therapeutic management of cancer patients. In this review we will describe recent advances in the field of liquid biopsy markers focusing on their advantages and disadvantages.

Abstract P5-02-50: Do thymidine kinase 1 (TK1) plasma concentration and activity play a role in therapy management of metastatic breast cancer patients treated with CDK4/6 inhibitors?

Abstract Introduction: CDK4/6 is a checkpoint kinase, regulating the transition of the S into the G2 phase of the cell cycle. As a cell transverses through the cell cycle, thymidine kinase 1 (TK1) is expressed and represents a direct marker of proliferative activity.which might indicate therapy efficiency of CDK4/6 inhibitors (CDK4/6i), the first choice of therapy in case no sign of visceral crisis is detected in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC) patients. We here determined whether the activity and/or concentration of TK1 in plasma samples of MBC patients treated with CDK4/6i harbours predictive, monitoring or prognostic value. Methods: Blood of 90 HR+/HER2-MBC patients drawn at baseline of CDK4/6i (Ribociclib/Palbociclib) plus endocrine treatment and 18 HR+/HER2-MBC patients drawn before initiation of endocrine monotherapy (control), as well as available matched blood samples of these patients after six months under TX (n=90), 12/24 months before progression (n=72/24) and at the time of progression (n=52) are available. TK1 concentration in plasma samples was measured by competitive ELISA (ABIN809094, Shanghai BlueGene Biotech Co., LTD, China) and TK1 activity of matched plasma samples by competitive, two-step chemiluminescence immunoassay (REF 310960, Diasorin, Stillwater, US). Statistical analysis was conducted via log-rank test and univariate or multivariate Cox regression. Results: Currently, baseline samples were evaluated for TK1 concentration (n=106) and activity (n=90). The mean value for TK1 activity was 12.69 U/L and the median value was 8.37 U/L in the entire cohort. Values ranged from 0.89 to 79.50 U/L and the standard deviation was determined to be 12.64 U/L, which is similar to the mean value. In contrast to the control group, high TK1 activity (Cut-off: mean or determined by ROC analysis and maximal Youden’s Index for PFS &amp;lt; six months) was significantly correlated with decreased progression free survival (PFS) in the CDK4/6i cohort (p-value &amp;lt; 0.05 in log rank test and univariate Cox regression). In addition, using multivariate Cox regression analysis including clinical parameters (e.g. therapy line, prior chemo- or endocrine therapies, type of CDK4/6i accompanying endocrine therapy, number of sites of metastases, visceral metastases, menopausal status), TK1 activity was found to be an independent marker for PFS.High TK1 activity (Cut-off: mean or determined by ROC analysis and maximal Youden’s Index for PFS &amp;lt; six months or already deceased patients) at baseline was significantly correlated with shorter time from baseline to death in the CDK4/6i cohort (p-value &amp;lt; 0.05 in log rank test and univariate Cox regression) but not in the control cohort. For TK1 concentration analysis, the mean value was 21.76 ng/ml and the median value was 18.57 ng/ml in the entire cohort. Values ranged from 7.35 ng/ml to 46.66 ng/ml and the standard deviation was determined to be 11.16 ng/ml, which is half of the mean value. In contrast to TK1 activity measurements, no significant association of TK1 concentration with PFS or overall survival (OS) was detected in the CDK4/6i cohort. Currently, all remaining samples during the course of treatment are evaluated for TK1 activity and concentration and final statistical analysis of the complete data set will be available at the meeting. Conclusion: Our preliminary results indicate that TK1 activity, in contrast to TK1 concentration, determined before starting CDK4/6 inhibtion could be a suitable predictive and prognostic biomarker for estimating response to treatment. Our final analysis will clarify, whether TK1 could also serve as a monitoring marker during treatment. Citation Format: Stefanos Moukas, Merle Dohn, Rainer Kimmig, Mitra Tewes, Hans-Christian Kolberg, Sabine Kasimir-Bauer, Corinna Keup. Do thymidine kinase 1 (TK1) plasma concentration and activity play a role in therapy management of metastatic breast cancer patients treated with CDK4/6 inhibitors? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-50.

Axillary management of breast cancer patients with isolated chest wall recurrence after mastectomy.

National Comprehensive Cancer Network (NCCN) guidelines on the axillary management of breast cancer patients with isolated chest wall recurrence after mastectomy are unclear. Though sentinel lymph node biopsy (SLNB) is possible and may be considered, there is limited data on its usefulness. We aimed to determine if axillary restaging surgery was required in this cohort of patients who developed operable isolated chest wall recurrences after mastectomy. Breast cancer patients treated at a tertiary institution from 1st September 2005 to 31st October 2017 and developed isolated chest wall invasive recurrences after mastectomy were retrospectively reviewed. We excluded patients with bilateral cancers, concurrent regional or distant metastases, patients without surgery for their chest wall recurrences and patients who were lost to follow-up. The demographics, pathological data and second recurrences were collected from a prospectively maintained database and compared between patients with axillary lymph node dissection (ALND), SLNB and no axillary operation. Of the 1,841 patients who underwent mastectomy, 26 (1.4%) patients developed isolated chest wall recurrences. Twenty two eligible patients were analysed. The mean age at diagnosis of the recurrence was 54.7 years (range, 37-84 years). 1, 2 and 19 patients had ALND, SLNB and no axillary operation respectively. On mean follow-up of 38.3 months, no axillary recurrences were noted. In breast cancer patients with isolated chest wall recurrences after mastectomy, axillary restaging surgery can be safely omitted with no increased axillary recurrences on medium term follow-up. This finding could refine existing guidelines in the management of the axilla for patients with chest wall recurrences after mastectomy.