Real-world study on microsatellite instability and mismatch repair deficiency testing patterns among patients with metastatic colorectal cancer in Spain / Estudio en el mundo real sobre patrones de prueba de inestabilidad de microsatélites y deficiencia de reparación de desajustes en pacientes con cáncer colorrectal metastásico en España

Purpose: Clinical practice guidelines recommend that all patients with metastatic colorectal cancer (mCRC) should be tested for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). We aimed to describe the dMMR/MSI-H testing practice in patients with mCRC in Spanish centers.Methods: Multicenter, observational retrospective study that included patients newly diagnosed with mCRC or who progressed to a metastatic stage from early/localized stages. Results: Three hundred patients were included in the study from May 2020 through May 2021, with a median age of 68 years, and two hundred twenty-five (75%) had stage IV disease at initial diagnosis; two hundred eighty-four patients received first-line treatment, and dMMR/MSI-H testing was performed in two hundred fifty-one (84%) patients. The results of the dMMR/MSI-H tests were available in 61 (24%) of 251 patients before the diagnosis of metastatic disease and in 191 (81%) of 236 evaluable patients for this outcome before the initiation of first-line treatment. Among the 244 patients who were tested for dMMR/MSI-H with IHC or PCR, 14 (6%) were MMR deficient. The most frequent type of first-line treatment was the combination of chemotherapy and biological agent, that was received by 71% and 50% of patients with MMR proficient and deficient tumors, respectively, followed by chemotherapy alone, received in over 20% of patients in each subgroup. Only 29% of dMMR/MSI-H tumors received first-line immunotherapy. Conclusion: Our study suggests that a high proportion of patients with mCRC are currently tested for dMMR/MSI-H in tertiary hospitals across Spain. However, there is still room for improvement until universal testing is achieved.(AU)

The trend of dental check-up and prevalence of dental complications following the use of bone modifying agents in patients with metastatic breast and prostate cancer: analysis of data from the Korean National Health Insurance Service.

BACKGROUND: Bone-modifying agents (BMA) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMA is associated with dental adverse events (AEs) including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the frequency of dental surveillance before BMA treatment and the prevalence of dental AEs including MRONJ, after BMA treatment in patients with bone metastasis from breast and prostate cancer using data from the national health insurance system. METHODS: Data, including age, cancer diagnosis, administered BMA, and dental AEs during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. RESULTS: Of the 15,357 patients who received BMA, 1,706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-up increased from 4.4% in 2007 to 16.7% in 2019. Referral to dentists for a dental check-up was more active in clinics/primary hospitals than general/tertiary hospitals, and medical doctors and urologists actively consulted to dentists than general surgeons, regardless of the patient's health insurance status. After BMA treatment, 508 patients (3.8%) developed dental AEs, including abscess (42.9%), acute periodontitis (29.7%), acute pericoronitis (14.9%), and MRONJ (12.5% of dental AEs cases, 0.5% of total BMA treated patients). CONCLUSIONS: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental management before the initiation of BMA.

Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression (CREATINE-52): a protocol for a double-blind randomized controlled trial.

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

Primary Intrathoracic Ectopic Papillary Thyroid Carcinoma, Presenting With Thoracic Spine Metastasis: A Case Presentation and Literature Review.

Thyroid cancer in ectopic thyroid tissue is a very rare entity. We report a patient with papillary thyroid cancer arising from upper mediastinal ectopic thyroid tissue. The patient presented with thoracic spine metastasis with cord compression. The patient was a 67-year-old woman, who presented with upper back pain. Magnetic resonance imaging (MRI) showed suspected metastatic disease in the second and third thoracic vertebrae (T2 and T3). She underwent laminectomy and decompression surgery at the T1-T3 level. The final pathology report showed metastatic thyroid carcinoma with papillary features. She underwent external beam radiation to the affected spine. Computerized tomography (CT) scan of the chest, abdomen, and pelvis showed a 3.0 × 2.8 × 2.3 cm soft-tissue mass in the left superior mediastinum extending into the supraclavicular region. Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed hypermetabolic foci in the upper mediastinum. Fine needle aspiration (FNA) of the upper mediastinal mass was consistent with papillary thyroid cancer. Molecular testing from the FNA sample using Thyroseq V3 showed SQSTM1NTRK3 chromosomal rearrangement. A total thyroidectomy was performed. Pathology of the resected thyroid was benign. Pathology of the mediastinal mass showed a papillary thyroid carcinoma with focal tall cell features, forming a 4 × 2.5 × 2.5 cm mass. Surgery was followed by ablation with 100 millicuries (mci) of radioactive iodine (I-131) and external beam radiation. This case highlights the presentation of primary intrathoracic papillary thyroid cancer with SQSTM1-NTRK3 chromosomal rearrangement and the challenges in the diagnosis and management of this unique case. This patient had a very aggressive disease presentation that required multimodal treatment, including thoracic spine decompression, total thyroidectomy, primary intrathoracic goiter resection, high-dose radioactive iodine treatment, and external beam radiation to the affected spine area. SQSTM1-NTRK3 chromosomal rearrangement can be targeted by medications such as larotrectinib and endtrectinib.

Epiberberine inhibits bone metastatic breast cancer-induced osteolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The anti-tumor related diseases of Coptidis Rhizoma (Huanglian) were correlated with its traditional use of removing damp-heat, clearing internal fire, and counteracting toxicity. In the recent years, Coptidis Rhizoma and its components have drawn extensive attention toward their anti-tumor related diseases. Besides, Coptidis Rhizoma is traditionally used as an anti-inflammatory herb. Epiberberine (EPI) is a significant alkaloid isolated from Coptidis Rhizoma, and exhibits multiple pharmacological activities including anti-inflammatory. However, the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis has not been demonstrated clearly. AIM OF THE STUDY: Bone metastatic breast cancer can lead to osteolysis via inflammatory factors-induced osteoclast differentiation and function. In this study, we try to analyze the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis. METHODS: To evaluate whether epiberberine could suppress bone metastatic breast cancer-induced osteolytic damage, healthy female Balb/c mice were intratibially injected with murine triple-negative breast cancer 4T1 cells. Then, we examined the inhibitory effect and underlying mechanism of epiberberine on breast cancer-induced osteoclastogenesis in vitro. Xenograft assay was used to study the effect of epiberberine on breast cancer cells in vivo. Moreover, we also studied the inhibitory effects and underlying mechanisms of epiberberine on RANKL-induced osteoclast differentiation and function in vitro. RESULTS: The results show that epiberberine displayed potential therapeutic effects on breast cancer-induced osteolytic damage. Besides, our results show that epiberberine inhibited breast cancer cells-induced osteoclast differentiation and function by inhibiting secreted inflammatory cytokines such as IL-8. Importantly, we found that epiberberine directly inhibited RANKL-induced differentiation and function of osteoclast without cytotoxicity. Mechanistically, epiberberine inhibited RANKL-induced osteoclastogensis via Akt/c-Fos signaling pathway. Furthermore, epiberberine combined with docetaxel effectively protected against bone loss induced by metastatic breast cancer cells. CONCLUSIONS: Our findings suggested that epiberberine may be a promising natural compound for treating bone metastatic breast cancer-induced osteolytic damage by inhibiting IL-8 and is worthy of further exploration in preclinical and clinical trials.

Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study.

PURPOSE: To evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. MATERIALS & METHODS: Bony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. RESULTS: Based on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. CONCLUSIONS: WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.

Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS: The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

[Palliative surgery for metastatic prostate cancer]. / Palliative Chirurgie des metastasierten Prostatakarzinoms.

Androgen deprivation in combination with novel hormonal agents, docetaxel, or in combination with abiraterone/prednisone plus docetaxel or darolutamid plus docetaxel represent the standard therapeutic approach in metastatic hormone-sensitive prostate cancer (mHSPC). Patients with low-risk prostate cancer also benefit from additional radiation therapy or radical prostatectomy in terms of progression-free and overall survival. Despite favorable response rates, basically all patients will develop castration resistant prostate cancer (CRPC) within 2.5 to 4 years. In addition to systemic chemotherapy, second-line hormonal treatment of systemic application of radionuclides such as radium223 or 177Lu-PSMA represent salvage management options. However, nowadays about 50-65% of patients will develop symptoms due to local progression of prostate cancer which is the result of improved oncological outcomes with significantly prolonged survival times due to the new medical treatment options. Management of such symptomatic local progression will become more important in upcoming years so that all uro-oncologists need to be aware of the various surgical management options. Complications of the lower urogenital tract such as recurrent gross hematuria ± bladder clotting and with the necessity for red blood cell transfusions, subvesical obstruction and acute urinary retention, rectourethral or rectovesical fistulas might be managed by palliative surgery such as palliative transurethral resection of the prostate (TURP), radical cystectomy, radical cystoprostatectomy with urinary diversion, and pelvic exenteration. Symptomatic or asymptomatic obstruction of the upper urinary tract might be managed by endoluminal or percutaneous urinary diversion, ureteral reimplantation, ileal ureter replacement, or implantation of the Detour® system (Coloplast GmbH, Hamburg, Germany).

Making the unbearable, bearable: Qualitative examination of patient, family and nurses' perspectives on the role and value of specialist metastatic breast care nurses.

PURPOSE: To examine the role and value of specialist metastatic breast care nurses in Australia from the perspective of metastatic breast care nurses, patients, and family members. Metastatic breast cancer (mBC) is treatable yet incurable, with distinct supportive care needs, yet many of these needs are unmet. METHOD: Diverse sampling methods were used to recruit 10 people with mBC, 5 family members and 10 metastatic breast care nurses. Semi-structured interviews were conducted online or by telephone during August-December 2020, and analysed thematically. RESULTS: The role of the specialist nurse was strongly valued within and across participant groups, with close alignment regarding what was highly valued. Three themes were identified. First, nurses played a vital role in giving voice and visibility to patients with mBC in a healthcare system in which they often felt invisible. Second, nurses combined their clinical and psychosocial skills with a sense of authentic engagement to create a safe space for those with mBC to discuss their feelings, experiences, and topics, especially those that were unlikely to be discussed in their other social and clinical interactions. Finally, nurses supported patients in living as well as possible while managing symptoms, ongoing treatment, and attendant psychosocial impacts of an incurable and life-limiting condition. CONCLUSIONS: This study underscores the central importance of metastatic breast care nurses in enhancing patient well-being, bridging gaps in care, and offering much-needed support. By addressing patients' emotional, clinical, and social needs, these specialist nurses contribute to a more holistic and compassionate approach to managing mBC.

Palliative Care Interventions and End-of-Life Care for Patients with Metastatic Breast Cancer: A Multicentre Analysis.

BACKGROUND: The aim of this study was to describe the implementation of integrated palliative care (PC) and the intensity of care in the last 3 months before death for patients with metastatic breast cancer. MATERIALS AND METHODS: We conducted a multicentric study of all adult patients with metastatic breast cancer who died over a 4-month period. Complete data were collected and checked from clinical records, including PC interventions and criteria regarding EOL care aggressiveness. RESULTS: A total of 340 decedent patients from 12 comprehensive cancer centres in France were included in the study. Sixty-five percent met the PC team with a median time of 39 days between the first intervention and death. In the last month before death, 11.5% received chemotherapy, the frequency of admission to intensive care unit was 2.4%, and 83% experienced acute hospitalization. The place of death was home for 16.7%, hospitalization for 63.3%, PC unit for 20%. Univariate and multivariate analyses showed factors independently associated with a higher frequency of chemotherapy in the last month before death: having a dependent person at home, meeting for the first time with a PC team < 30 days before death, and time between the first metastasis and death below the median. CONCLUSION: PC team integration was frequent and late for patients with metastatic breast cancer. However, PC intervention > 30 days is associated with less chemotherapy in the last month before death. Further studies are needed to better understand how to implement a more effective mode of PC integration for patients with metastatic breast cancer.

Study protocol: phase II study to evaluate the effect of cetuximab monotherapy after immunotherapy with PD-1 inhibitors in patients with head and neck squamous cell cancer.

Background: Immunotherapy with programmed death receptor-1 (PD-1) inhibitors, as a single agent or in combination with chemotherapy, is the standard first-line treatment for recurrent or metastatic head and neck squamous cell cancer (R/M HNSCC). Unfortunately, there is no established second-line treatment for the many patients who fail immunotherapy. Cetuximab is the only targeted therapy approved in HNSCC but historically has a low response rate of 13%. Objectives: We hypothesize that cetuximab monotherapy following an immune checkpoint inhibitor (ICI) will lead to increased efficacy due to a potential synergistic effect on the antitumor immune response, as a result of activation effects of both treatments on innate and adaptative immune responses. To the authors' knowledge, this is the only ongoing prospective clinical study that evaluates the combination of cetuximab and ICIs administered sequentially. Methods and analysis: In this non-randomized, open-label, phase II trial, 30 patients with R/M HNSCC who have previously failed or could not tolerate a PD-1 inhibitor as a single agent or in combination with chemotherapy will subsequently be treated with cetuximab monotherapy. Outcomes of interest include overall response rate, duration of response, progression-free survival, overall survival, and treatment toxicity, as well as treatment outcome measured by a patient-reported outcome questionnaire. Saliva and blood will be collected for correlative studies to investigate the immune response status at the end of therapy with an ICI and the effect of cetuximab on the antitumor immune response. The results will be correlated with the response to cetuximab and the time window between the last administration of an ICI and the loading dose of cetuximab. The clinical study is actively recruiting. Ethics: This study was approved by the Wake Forest Comprehensive Cancer Center Institutional Review Board: IRB00065239. Clinical trial registration: This study is registered on ClinicalTrials.gov: NCT04375384.

Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis.

BACKGROUND: Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis. METHODS: Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot. RESULTS: Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21-1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13-1.70) for patients with lower VD levels, as indicated by fixed-effects models. CONCLUSIONS: Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes.

Multifunctional hydrogel for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer recurrence and wound infection.

Metastatic recurrence and postoperative wound infection are two major challenges for breast cancer patients. In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer and wound infection. The hydrogel system was obtained by cross-linking Prussian blue-modified N-carboxyethyl chitosan (PBCEC) and oxidized sodium alginate using the amino and aldehyde groups on the polysaccharides, resulting in the formation of responsive dynamic imine bonds. Conditioned stimulation (e.g., acid microenvironment) enabled the controlled swelling of hydrogels as well as subsequent slow release of loaded doxorubicin (DOX). Additionally, this hydrogel system decomposed endogenous reactive oxygen species into oxygen to relieve the hypoxic tumor microenvironment and promote the healing of infected-wounds. Both in vitro and in vivo experiments demonstrated the synergistic reoxygenation and chemo/photothermal effects of the PB/DOX hydrogel system against metastatic breast cancer and its recurrence, as well as postoperative wound infection. Thus, the combination of reoxygenation and chemo/photothermal therapy represents a novel strategy for treating and preventing tumor recurrence and associated wound infection.

First-line real-world treatment patterns and survival outcomes in women younger or older than 40 years with metastatic breast cancer in the real-life multicenter French ESME cohort.

AIM: To describe first-line treatment patterns, overall survival (OS) and real-world progression-free survival (rwPFS) in young women (<40) with metastatic breast cancer (mBC), as compared to women aged 40-69. MATERIALS AND METHODS: Data on adult women diagnosed with mBC (2008-2017) were extracted from the ESME mBC database (NCT03275311) which includes consecutive patients starting first-line metastatic treatment in one of the 18 French Comprehensive cancer centers. We reported first-line therapeutic strategy and prognostic factors of OS and rwPFS for women aged < 40 and 40-69. RESULTS: In total, 14,897 mBC women were included (1512 aged <40). HR+ /HER2- mBC was the most frequent subtype. First-line treatment differed between young patients and older ones for HR+ /HER2- and Triple Negative (TN) mBC. Median OS for women aged < 40 and 40-69, respectively, was 46.9 and 46.2 months for HR+ /HER2- mBC; 13.5 and 15.2 for TN mBC; and, 60.7 and 55.1 for HER2 + mBC. Median rwPFS under first line treatment was 11.6 and 11.9 months for HR+ /HER2- in women aged < 40 and 40-69, respectively; 5.5 and 5.9 for TN, and, 13.3 and 12.9 for HER2 + . Factors associated with shorter OS and rwPFS were similar for both women aged < 40 and 40-69 and included ≥ 3 metastatic sites, visceral metastases, and longer MFI, with time-varying effects observed for several prognostic factors. CONCLUSION: Young women presented more frequently with TN and HER2 + subtypes and aggressive mBC than women aged 40-69 did. Prognostic factors of OS and rwPFS were quite similar between age groups and mBC subtypes.

Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study.

INTRODUCTION: Historically, stage IV adrenocortical carcinoma (mACC) has a poor prognosis with a median overall survival (OS) of only 5 months. Based on the FIRM-ACT trial published in 2012, guidelines now advise first line systemic treatment with etoposide, cisplatin, doxorubicin and mitotane (EDP-M). The effect of EDP-M on patient survival in clinical practice in the Netherlands is unknown. METHODS: The data of all patients with mACC (2005-2020) were obtained from the Netherlands comprehensive cancer organization (IKNL). The effect of EDP-M on patient survival was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis including clinical, therapy and tumor characteristics. RESULTS: In total 167 patients with mACC were included. For patients diagnosed from 2014 onwards, EDP-M (in 22 patients (22%)) lead to a numerically but not statistically significant improved OS compared to those not receiving EDP-M (11.8 vs 5.6 months, p = 0.525). For systemic treatments, patients treated with mitotane only had the best 5-year OS (11.4%, p = 0.006) regardless of year of diagnosis. In multivariate Cox regression analysis EPD-M was not associated with OS; palliative adrenalectomy (HR: 0.26, p = <.001) and local treatment of metastases (HR: 0.35, p = 0.001) were associated with a better OS and a primary tumor Ki-67 index > 20% (HR: 2.67, p = 0.003) with a worse OS from 2014 onwards. Patients diagnosed before 2014 had a significantly poorer OS compared to from 2014 onwards (5-yr: 4.5 vs 8.4%, OS: 6.8 vs 8.3 months, p = 0.032). CONCLUSION: OS for mACC in the Netherlands has improved in the last decade. Receiving EDP-M did not significantly improve OS for patients with mACC. The use of multimodality treatment including palliative adrenalectomy, mitotane and local treatment of (oligo-)metastases in appropriately selected patients has improved the OS for mACC patients since 2014.

Re-imagining metastatic breast cancer care delivery: a patient-partnered qualitative study.

PURPOSE: While significant progress in metastatic breast cancer (MBC) treatment has prolonged survival and improved prognosis, there remain substantial gaps in providing patient-centered supportive care. The specific care delivery needs for metastatic cancer differ from that of early-stage cancer due to the incurable nature and lifelong duration of the condition. The objective of this study was to assess how patients living with MBC would re-imagine cancer care delivery. METHODS: This qualitative study was conducted in partnership with patient-led organizations Guiding Researchers and Advocates to Scientific Partnerships (GRASP) and Project Life, a nonprofit, online wellness community founded by patients with MBC for patients living with MBC. Virtual semi-structured interviews (n = 36) were conducted with Project Life members purposively sampled from the groups' overall membership. The interview guide contained items surrounding patients' lived experiences of MBC, greatest unmet needs related to care, and perspectives on virtual wellness community involvement. Interviews were coded using two-stage deductive and inductive analysis. RESULTS: Three major themes for re-imagining cancer care delivery were identified, including holistic care, information needs, and conceptual shifts. Within these several subthemes emerged with patients re-imagining referrals to non-oncological services, caregiver support, acceptance of integrative medicine, streamlined clinical trial enrollment, curated quality patient resources, MBC-specific terminology and approaches, long-term life and goal-of-care planning, and patient-centered voice throughout. CONCLUSION: People living with metastatic cancers have specific supportive care needs. These findings highlight patient-driven areas for re-imagination that are most salient for individuals with MBC.

Management of melanoma: can we use gene expression profiling to help guide treatment and surveillance?

Although the incidence of cutaneous melanoma (CM) has been increasing annually, the mortality rate has been decreasing, likely due to better prevention, earlier detection, improved surveillance, and the development of new therapies. Current clinical management guidelines by the National Comprehensive Cancer Network (NCCN) are based on patient risk assignment using staging criteria established by the American Joint Committee on Cancer (AJCC). However, some patients with localized disease (stage I-II), generally considered to have a good prognosis, will develop metastatic disease and die, whereas some patients with later stage disease (stage III-IV) will be cured by surgery, adjuvant therapy, and/or systemic therapy. These results emphasize the importance of identifying patients whose risk may be over or underestimated with standard staging. Gene expression profile (GEP) tests are noninvasive molecular tests that assess the expression levels of a panel of validated genes, providing information about tumor prognosis, including the risk of recurrence, metastasis, and cancer-specific death. GEP tests can provide prognostic information beyond standard staging that may aid clinicians and patients in treatment and surveillance management decisions. This review describes how combining clinicopathologic staging with a robust assessment of tumor biology may provide information that will allow more refined intervention and long-term management.

PERSIAN trial (NCT05717660): an ongoing randomized trial testing androgen deprivation therapy, apalutamide and stereotactic body radiotherapy. An alternative "triplet" for oligometastatic hormone sensitive prostate cancer patients.

Earlier treatment intensification with systemic potent androgen receptor inhibition has been shown to improve clinical outcomes in metastatic hormone sensitive prostate cancer. Nonetheless, oligometastatic patients may benefit from local treatment approaches such as stereotactic body radiotherapy (SBRT). Aiming to explore the benefit of SBRT in this scenario, we designed this trial to specifically test the hypothesis that SBRT will improve clinical outcomes in select population affected by metachronous oligometastatic HSPC treated with androgen deprivation therapy + apalutamide. Enrolled patients will be randomized to receive the standard systemic treatment alone or in combination with SBRT on all metastatic sites of disease. Here we report the protocol design and an overview of the ongoing trials testing different integration strategies between RT and systemic therapies.

Metastatic Colon Cancer - An Effective Treatment Protocol of Integrative Therapies Including Electromagnetic Field Frequencies: A Case Report.

Introduction: Colorectal cancer is the third most common cancer worldwide, with 25% of patients being diagnosed with metastatic disease, mostly in the liver, resulting in poor survival. Standard treatment of stage-IV colorectal cancer consists of primary tumour resection followed by chemotherapy. Case Presentation: Here, we report on the treatment effectiveness using integrative therapies in a 52-year-old male with metastatic colon cancer and liver lesions to achieve stable partial remission with an overall high level of wellbeing. After surgical removal of the primary tumour, the 8-month integrative treatment regime consisted of standard anti-angiogenesis treatment, as well as multiple non-standard but evidence-based therapies, including high-dose intravenous nutrients and herbal therapies, oral intake of repurposed medication and nutritional supplements, and a 4-month targeted electromagnetic field/Rife frequency therapy. Conclusion: The integrative therapies used in this case study were highly tolerable and effective in the treatment of metastatic colon cancer with liver lesions, achieving substantial tumour response and stable partial remission with a high level of wellbeing.

Plasma Androstenedione Concentration Can Discriminate Frail versus Non-Frail Men with Prostate Cancer under Androgen Deprivation Therapy.

BACKGROUND: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH). METHODS: The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions. RESULTS: The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups (p = 0.018; odds ratio = 4.66, 95% confidence interval [1.30-16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione (p = 0.01), but not the concentration of testosterone (p = 0.60) or DHEA (p = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione (p = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group (p = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group (p = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55-0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome. CONCLUSIONS: Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.