Androgen Deprivation Freezes Hormone-Sensitive Prostate Cancer Cells in a Reversible, Genetically Unstable Quasi-Apoptotic State, Bursting into Full Apoptosis upon Poly(ADP-ribose) Polymerase Inhibition.

Androgen deprivation therapy (ADT) is a powerful treatment for metastatic hormone-sensitive prostate cancer (mHSPC) patients, but eventually and inevitably, cancer relapses, progressing to the fatal castration-resistant (CR)PC stage. Progression implies the emergence of cells proliferating in the absence of androgen through still elusive mechanisms. We show here for the first time that ADT induces LNCaP mHSPC cells to collectively enter a metastable quasi-apoptotic state (QUAPS) consisting of partial mitochondrial permeabilization, limited BAX and caspase activation, and moderate induction of caspase-dependent dsDNA breaks; despite this, cells maintain full viability. QUAPS is destabilized by poly(ADP)-polymerase inhibition (PARPi), breaking off toward overt intrinsic apoptosis and culture extinction. Instead, QUAPS is rapidly and efficiently reverted upon androgen restoration, with mitochondria rapidly recovering integrity and cells collectively resuming normal proliferation. Notably, replication restarts before DNA repair is completed, and implies an increased micronuclei frequency, indicating that ADT promotes genetic instability. The recovered cells re-acquire insensitivity to PARPi (as untreated LNCaP), pointing to specific, context-dependent vulnerability of mHSPC cells to PARPi during ADT. Summarizing, QUAPS is an unstable, pro-mutagenic state developing as a pro-survival pathway stabilized by PARP, and constitutes a novel viewpoint explaining how ADT-treated mHSPC may progress to CRPC, indicating possible preventive countermeasures.

Self-care behaviors in patients with cancer treated with oral anticancer agents: a systematic review.

PURPOSE OF REVIEW: Continuous progress in cancer care has led to its increased use in oral anticancer agents that are easily managed by patients at home with fewer costs and hospitalizations. However, correct self-care behaviors are needed for the safe use of these medications. This review aimed to synthesize studies on self-care behaviors in patients treated with oral anticancer agents. METHODS: This systematic review used a convergent qualitative synthesis design for mixed studies. Studies on adult patients with cancer using any kind of oral anticancer agent and describing self-care maintenance, self-care monitoring, and/or self-care management behaviors were searched on PubMed, EMBASE, and CINAHL. After data extraction, the findings were retained for qualitative synthesis. FINDINGS: Of 3419 records, 19 studies were included in this review. From the qualitative synthesis, all the retrieved behaviors were synthesized in the three self-care dimensions. Five themes and 18 subthemes were identified. Self-care maintenance included "adherence to the medications" and "prevention." Self-care monitoring consisted of "health surveillance and recognition of illness changes." Self-care management included "seeking help" and "autonomous management of side effects." Overall, most of the behaviors described focused only on adherence. CONCLUSION: The findings of this systematic review could guide future studies on self-care and drive future interventions aimed at improving self-care in this vulnerable population. Nurses and other healthcare professionals should provide self-care support to patients taking oral anticancer agents. In particular, they should promote behaviors aimed at improving well-being, preserving health, or managing side effects.

Activity of ALK Inhibitors in Renal Cancer with ALK Alterations: A Systematic Review.

Renal cell carcinoma (RCC) associated with anaplastic lymphoma kinase (ALK) gene rearrangements (ALK-RCC) is currently considered an "emerging or provisional" tumor entity by the last World Health Organization classification published in 2016. Although several studies assessing ALK-RCC's clinical and histological characteristics have been published in recent years, only a few publications have evaluated the activity of ALK inhibitors (ALK-i) in this subgroup of patients. Considering the well-recognized efficacy of this evolving class of targeted therapies in other ALK-positive tumors, we conducted a systematic review to evaluate the reported activity of ALK-i in the ALK-RCC subtype. MEDLINE was searched from its inception to 7 January 2022 for case reports and case series on adult metastatic ALK-RCC patients treated with ALK-i whose therapeutic outcomes were available. A virtual cohort of ALK-RCC patients was created. Our results showed a favorable activity of first- and second-generation ALK-i in pretreated ALK-RCC patients in terms of either radiological response or performance status improvement. We hope that the present work will prompt the creation of large, multi-institutional clinical trials to confirm these promising early data.

Apoptosis as Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer.

Apoptotic cells stimulate compensatory proliferation through the caspase-3-cPLA-2-COX-2-PGE-2-STAT3 Phoenix Rising pathway as a healing process in normal tissues. Phoenix Rising is however usurped in cancer, potentially nullifying pro-apoptotic therapies. Cytotoxic therapies also promote cancer cell plasticity through epigenetic reprogramming, leading to epithelial-to-mesenchymal-transition (EMT), chemo-resistance and tumor progression. We explored the relationship between such scenarios, setting-up an innovative, straightforward one-pot in vitro model of therapy-induced prostate cancer repopulation. Cancer (castration-resistant PC3 and androgen-sensitive LNCaP), or normal (RWPE-1) prostate cells, are treated with etoposide and left recovering for 18 days. After a robust apoptotic phase, PC3 setup a coordinate tissue-like response, repopulating and acquiring EMT and chemo-resistance; repopulation occurs via Phoenix Rising, being dependent on high PGE-2 levels achieved through caspase-3-promoted signaling; epigenetic inhibitors interrupt Phoenix Rising after PGE-2, preventing repopulation. Instead, RWPE-1 repopulate via Phoenix Rising without reprogramming, EMT or chemo-resistance, indicating that only cancer cells require reprogramming to complete Phoenix Rising. Intriguingly, LNCaP stop Phoenix-Rising after PGE-2, failing repopulating, suggesting that the propensity to engage/complete Phoenix Rising may influence the outcome of pro-apoptotic therapies. Concluding, we established a reliable system where to study prostate cancer repopulation, showing that epigenetic reprogramming assists Phoenix Rising to promote post-therapy cancer repopulation and acquired cell-resistance (CRAC).

The Role of Histology-Agnostic Drugs in the Treatment of Metastatic Castration-Resistant Prostate Cancer.

Precision medicine has opened up a new era in the development of anti-cancer agents that is focused on identifying biomarkers predictive of treatment response regardless of tumor histology. Since 2017, the Food and Drug Administration has approved six drugs with histology-agnostic indications: pembrolizumab (both for tumors with the mismatch-repair deficiency (dMMR)/high microsatellite instability (MSI-H) phenotype and for those with the high tumor mutational burden (TMB-H) phenotype), dostarlimab (for dMMR tumors), larotrectinib and entrectinib (for tumors harboring neurotrophic tyrosine receptor kinase (NTRK) fusions), and the combination of dabrafenib plus trametinib (for BRAF V600E-mutated tumors). The genomic alterations targeted by these antineoplastic agents are rare in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, only a small number of mCRPC patients were enrolled in the clinical trials that led to the approval of the above-mentioned drugs. Therefore, we critically reviewed the literature on the efficacy of histology-agnostic drugs in mCRPC patients. Although the available evidence derives from retrospective studies and case reports, our results confirmed the efficacy of pembrolizumab in dMMR/MSI-H mCRPC. In contrast, few data are available for dostarlimab, larotrectinib, entrectinib, and dabrafenib-trametinib in this subset of patients. Large, multi-institutional registries aimed at collecting real-world data are needed to better comprehend the role of tissue-agnostic drugs in mCRPC patients.

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients' quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.

Drug-induced xenogenization of tumors: A possible role in the immune control of malignant cell growth in the brain?

In recent years, immune checkpoint inhibitors (ICpI) have provided the ground to bring tumor immunity back to life thanks to their capacity to afford a real clinical benefit in terms of patient's survival. Essential to ICpI success is the presence of tumor-associated neoantigens generated by non-synonymous mutations, since a direct relationship between mutation load of malignant cells and susceptibility to ICpI has been confidently established. However, it has been also suggested that high intratumor heterogeneity (ITH) associated with subclonal neoantigens could not elicit adequate immune responses. Several years ago we discovered that in vivo treatment of leukemic mice with triazene compounds (TZC) produces a marked increase of leukemia cell immunogenicity [a phenomenon termed Drug-Induced Xenogenization (DIX)] through point mutations able to generate strong tumor neoantigens (Drug-Induced Neoantigens, DIN). Immunogenic mutations are produced by TZC-dependent methylation of O6-guanine of DNA, that is suppressed by the DNA repair protein methyl-guaninemethyltransferase (MGMT). This minireview illustrates preclinical investigations conducted in animal models where DIN-positive murine leukemia cells were inoculated intracerebrally into histocompatible mice. The analysis of the literature indicates that the growth of xenogenized malignant cells is controlled by anti-DIN graft responses and by intra-cerebral or intravenous adoptive transfer of anti-DIN cytotoxic T lymphocytes. This survey reminds also that PARP inhibitors increase substantially the antitumor activity of TZC and can be administered with the intent of suppressing more efficiently tumor load and possibly reducing ITH through downsizing the polyclonality of xenogenized tumor cell population. Finally, the present report illustrates a hypothetical clinical protocol that could be considered as an example of future development of DIXbased tumor immuno-chemotherapy in brain malignancies. The protocol involves oral or intravenous administration of TZC along with loco-regional (i.e. intracerebral "wafer") treatment with agents able to increase tumor cell sensitivity to the cytotoxic and xenogenizing effects of TZC (i.e. MGMT and PARP inhibitors) without enhancing the systemic toxicity of these DNA methylating compounds.

Effects of mutations in Wnt/ß-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer.

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates in an array of critical cellular processes. GSK-3 was first characterized as an enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent studies have revealed that this moon-lighting protein is involved in numerous signaling pathways that regulate not only metabolism but also have roles in: apoptosis, cell cycle progression, cell renewal, differentiation, embryogenesis, migration, regulation of gene transcription, stem cell biology and survival. In this review, we will discuss the roles that GSK-3 plays in various diseases as well as how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and TP53. Mutations that occur in these and other pathways can alter the effects that natural GSK-3 activity has on regulating these signaling circuits that can lead to cancer as well as other diseases. The novel roles that microRNAs play in regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and these other pathways may improve therapy and overcome therapeutic resistance.

Endocrinological side-effects of immune checkpoint inhibitors.

PURPOSE OF REVIEW: Three mAbs targeting immune checkpoint proteins are available for the treatment of patients with melanoma, lung, and kidney cancer, and their use will likely expand in the future to additional tumor types. We here update the literature on the incidence and pathophysiology of endocrine toxicities induced by these agents, and discuss management guidance. RECENT FINDINGS: Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab, whereas the incidence of thyroid dysfunction is higher with nivolumab/pembrolizumab. Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of corticosteroids on the efficacy/activity of immune checkpoint-inhibiting drugs is reported. Hormonal deficiencies are often permanent. SUMMARY: In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.

AMBRA1 and SQSTM1 expression pattern in prostate cancer.

Prostate cancer is among the most commonly diagnosed male diseases and a leading cause of cancer mortality in men. There is emerging evidence that autophagy plays an important role in malignant cell survival and offers protection from the anti-cancer drugs in prostate cancer cells. AMBRA1 and the autophagic protein sequestosome-1 (SQSTM1; p62) expression were evaluated by immunohistochemistry and western blot on tissue samples from both benign and malignant prostatic lesions. The data reported in this pilot study demonstrated an increased expression of AMBRA1 and SQSTM1, which were also associated with an accumulation of LC3II in prostate cancer but not in benign lesion. In the present study we found that: (i) at variance with benign lesion, prostate cancer cells underwent SQSTM1 accumulation, i.e., clearly displayed a defective autophagic process but, also, (ii) prostate cancer accumulated AMBRA1 and (iii) this increase positively correlated with the Gleason score. These results underscore a possible implication of autophagy in prostate cancer phenotype and of AMBRA1 as possible cancer progression biomarker in this malignancy.

Predicting Ovarian Activity in Women Affected by Early Breast Cancer: A Meta-Analysis-Based Nomogram.

BACKGROUND: The assessment of ovarian reserve in premenopausal women requiring anticancer gonadotoxic therapy can help clinicians address some challenging issues, including the probability of future pregnancies after the end of treatment. Anti-Müllerian hormone (AMH) and age can reliably estimate ovarian reserve. A limited number of studies have evaluated AMH and age as predictors of residual ovarian reserve following cytotoxic chemotherapy in breast cancer patients. MATERIALS AND METHODS: To conduct a meta-analysis of published data on this topic, we searched the medical literature using the key MeSH terms "amenorrhea/chemically induced," "ovarian reserve," "anti-Mullerian hormone/blood," and "breast neoplasms/drug therapy." Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements guided the search strategy. U.K. National Health Service guidelines were used in abstracting data and assessing data quality and validity. Area under the receiver operating characteristic curve (ROC/AUC) analysis was used to evaluate the predictive utility of baseline AMH and age model. RESULTS: The meta-analysis of data pooled from the selected studies showed that both age and serum AMH are reliable predictors of post-treatment ovarian activity in breast cancer patients. Importantly, ROC/AUC analysis indicated AMH was a more reliable predictor of post-treatment ovarian activity in patients aged younger than 40 years (0.753; 95% confidence interval [CI]: 0.602-0.904) compared with those older than 40 years (0.678; 95% CI: 0.491-0.866). We generated a nomogram describing the correlations among age, pretreatment AMH serum levels, and ovarian activity at 1 year from the end of chemotherapy. CONCLUSION: After the ongoing validation process, the proposed nomogram may help clinicians discern premenopausal women requiring cytotoxic chemotherapy who should be considered high priority for fertility preservation counseling and procedures.

A rare case of juvenile hypertension: coexistence of type 2 multiple endocrine neoplasia -related bilateral pheochromocytoma and reninoma in a young patient with ACE gene polymorphism.

BACKGROUND: Pheochromocytoma and reninoma represent two rare diseases causing hypertension. We here reported a rare case of association between type 2 multiple endocrine neoplasia related bilateral pheochromocytoma and reninoma. Moreover, polymorphism of ACE gene, which is known to be related to an increase of cardiovascular risk, has been found in the same patient. CASE PRESENTATION: A 24 year old Caucasian man came to our attention for severe hypertension, resistant to anti-hypertensive polytherapy. At the age of twenty he had undergone total thyroidectomy with lymphadenectomy for medullary carcinoma. Genetic testing showed a RET mutation of codon 918 (exon 16) not documented in other family members. During the follow-up, a progressive increase of urinary metanephrines and catecholamines was recorded. Our evaluation confirmed the presence of severe hypertension (220/140 mmHg) and a severe increase of urinary catecholamines and metanephrines. Due to the presence of hypokalemia, other causes of hypertension were researched leading to the discovery of hyperreninemia (236 µUI/ml) with mild hyperaldosteronism, and a mild increase of the renal artery resistance at ultrasound. An abdominal MRI showed multiple adrenal masses and a right kidney nodular lesion of about 2 cm. The patient underwent bilateral adrenalectomy and right nephrectomy, and histology confirmed the presence of bilateral pheochromocytoma and right reninoma. The post-surgery laboratory evaluation showed a rapid reduction of the urinary metanephrines while plasma renin level remained low in spite of the bilateral adrenalectomy without any mineralocorticoid supplementation. To further investigate these unusual feature, we performed genetic testing for the ACE gene, which revealed the presence of ACE I/D polymorphism. CONCLUSION: This unique report describes the association between two rare causes of hypertension in the same patient. Furthermore, the absence of requirement of mineralocorticoid supplementation in spite of bilateral adrenalectomy, represent an uncommon and interest finding.

Testicular and inguinal lymph node metastases of medullary thyroid cancer: a case report and review of the literature.

BACKGROUND: The involvement of the testis by metastatic medullary thyroid carcinoma has never been described before. We describe the first case of metastatic medullary thyroid carcinoma affecting testis and inguinal lymph nodes. CASE PRESENTATION: A 73-year-old Caucasian man was referred to undergo urologic surgery due to a painless nodule in the right testis and an homolateral inguinal lymphoadenomegaly. The patient had a history of medullary thyroid carcinoma with relapsing disease to the spine and lung nodules. Serum calcitonin and CEA levels were 175 pg/ml and 22 ng/ml, respectively. With suspected testicular cancer, the patient underwent radical right orchiectomy with the excision biopsy of the right inguinal lymph node. Histopathology and immunohistochemistry revealed that both the lesions were due to metastases from medullary thyroid carcinoma. CONCLUSION: Metastases to the testis and inguinal lymph nodes may be due to various solid and hematological tumors. This case, despite its rarity, suggests that testis and inguinal lymph nodes should be considered as potential secondary sites of medullary thyroid carcinoma as well.

[Mutuality in caregiving: a literature review]. / La mutualità nel caregiving: una revisione della letteratura.

INTRODUCTION: Mutuality, understood as a feeling of intimacy and positive relationship between caregiver and care receiver, is gaining an increasing interest in the scientific arena in the light of socio-demographic change and the increase in chronic degenerative diseases. The purpose of this article is to carry out a critical analysis of the literature on mutuality in order to identify predictors and outcomes. METHOD: A literature search was carried out the databases PubMed, CINAHL, PsycInfo, and ASSIA Sociological. Twenty (20) articles were selected. By analyzing critically all articles, emerges that mutuality is a key variable in the process of care giving and in mental and physical health of both caregiver and care-receiver. In the caregiver, high levels of mutuality are associated with less stress, depression and burden to a better quality of life and self perceived health; in patients high mutuality is able to speed up the recovery from the disease, to reduce anxiety and depression and to improve the quality of life. CONCLUSION: Future studies aimed at the study of this variable also in the Italian population could be of support in developing programs to improve quality of life of caregivers and care receiver.

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

The interplay between the immune system and chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is complex and multifaceted. In COPD, chronic inflammation and oxidative stress can lead to immune dysfunction that can exacerbate lung damage, further worsening the respiratory symptoms. In NSCLC, immune cells can recognise and attack the cancer cells, which, however, can evade or suppress the immune response by various mechanisms, such as expressing immune checkpoint proteins or secreting immunosuppressive cytokines, thus creating an immunosuppressive tumour microenvironment that promotes cancer progression and metastasis. The interaction between COPD and NSCLC further complicates the immune response. In patients with both diseases, COPD can impair the immune response against cancer cells by reducing or suppressing the activity of immune cells, or altering their cytokine profile. Moreover, anti-cancer treatments can also affect the immune system and worsen COPD symptoms by causing lung inflammation and fibrosis. Immunotherapy itself can also cause immune-related adverse events that could worsen the respiratory symptoms in patients with COPD-compromised lungs. In the present review, we tried to understand the interplay between the two pathologies and how the efficacy of immunotherapy in NSCLC patients with COPD is affected in these patients.

Obesity and Breast Cancer: Interaction or Interference with the Response to Therapy?

Background: Aromatase inhibitors (AI) are widely used for treating hormone-sensitive breast cancer (BC). Obesity, however, due to aromatase-mediated androgen conversion into estradiol in the peripheral adipose tissue, might impair AI inhibitory capacity. We aimed at identifying a cut-off of body mass index (BMI) with significant prognostic impact, in a cohort of stage I-II BC patients on systemic adjuvant therapy with AI. Methods: we retrospectively evaluated routinely collected baseline parameters. The optimal BMI cut-off affecting disease-free survival (DFS) in AI-treated BC patients was identified through maximally selected rank statistics; non-linear association between BMI and DFS in the AI cohort was assessed by hazard-ratio-smoothed curve analysis using BMI as continuous variable. The impact of the BMI cut-off on survival outcomes was estimated through Kaplan−Meier plots, with log-rank test and hazard ratio estimation comparing patient subgroups. Results: A total of 319 BC patients under adjuvant endocrine therapy and/or adjuvant chemotherapy were included. Curve-fitting analysis showed that for a BMI cut-off >29 in AI-treated BC patients (n = 172), DFS was increasingly deteriorating and that the impact of BMI on 2-year DFS identified a cut-off specific only for the cohort of postmenopausal BC patients under adjuvant therapy with AI. Conclusion: in radically resected hormone-sensitive BC patients undergoing neoadjuvant or adjuvant chemotherapy and treated with AI, obesity represents a risk factor for recurrence, with a significantly reduced 2-year DFS.

Antibody-Drug Conjugates for the Treatment of Renal Cancer: A Scoping Review on Current Evidence and Clinical Perspectives.

Antibody-drug conjugates (ADCs) are complex chemical structures composed of a monoclonal antibody, serving as a link to target cells, which is conjugated with a potent cytotoxic drug (i.e., payload) through a chemical linker. Inspired by Paul Ehrlich's concept of the ideal anticancer drug as a "magic bullet", ADCs are also highly specific anticancer agents, as they have been demonstrated to recognize, bind, and neutralize cancer cells, limiting injuries to normal cells. ADCs are among the newest pharmacologic breakthroughs in treating solid and hematologic malignancies. Indeed, in recent years, various ADCs have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of several cancers, resulting in a "practice-changing" approach. However, despite these successes, no ADC is approved for treating patients affected by renal cell carcinoma (RCC). In the present paper, we thoroughly reviewed the current literature and summarized preclinical studies and clinical trials that evaluated the activity and toxicity profile of ADCs in RCC patients. Moreover, we scrutinized the potential causes that, until now, hampered the therapeutical success of ADCs in those patients. Finally, we discussed novel strategies that would improve the development of ADCs and their efficacy in treating RCC patients.

Bone Metabolism Effects of Medical Therapy in Advanced Renal Cell Carcinoma.

The medical therapy of advanced renal cell carcinoma (RCC) is based on the use of targeted therapies, such as tyrosine kinase inhibitors (TKI) and immune-checkpoint inhibitors (ICI). These therapies are characterized by multiple endocrine adverse events, but the effect on the bone is still less known. Relatively few case reports or small case series have been specifically focused on TKI and ICI effects on bone metabolism. However, the importance to consider these possible side effects is easily intuitable because the bone is one of the most frequent metastatic sites of RCC. Among TKI used in RCC, sunitinib and sorafenib can cause hypophosphatemia with increased PTH levels and low-normal serum calcium levels. Considering ICI, nivolumab and ipilimumab, which can be used in association in a combination strategy, are associated with an increased risk of hypocalcemia, mediated by an autoimmune mechanism targeted on the calcium-sensing receptor. A fearsome complication, reported for TKI and rarely for ICI, is osteonecrosis of the jaw. Awareness of these possible side effects makes a clinical evaluation of RCC patients on anticancer therapy mandatory, especially if associated with antiresorptive therapy such as bisphosphonates and denosumab, which can further increase the risk of these complications.

Caregivers' contribution to self-care for patients treated with oral anticancer agents: A qualitative descriptive study.

PURPOSE: To adequately manage oral anticancer agents (OAAs) therapy, appropriate self-care behaviours must be implemented. Informal caregivers could support and contribute to patient self-care. This study aimed to explore and describe the caregiver contribution to self-care and their related experience of caring among informal caregivers of patients on OAAs. METHODS: Qualitative descriptive design. We conducted semi-structured interviews, which were transcribed, read in depth, and analysed with deductive and inductive content analysis, according to Mayring. Adult informal caregivers (>18 years) of elderly patients (>65 years) with solid malignancies undergoing OAAs therapy for at least 3 months were included. FINDINGS: Twenty-three caregivers were interviewed with mean age of 57,2 (SD ± 15,8). A total of 18 codes from the qualitative content analysis were found, of which ten were referred to caregiver contribution and classified into the three dimensions of self-care maintenance (i.e. behaviours to maintain illness stable), self-care monitoring (i.e., tracking symptoms and side effects), and self-care management (i.e., management of worsening symptoms), according to the Middle Range Theory of Self-Care of Chronic Illnesses. The eight codes on caregiver experience were aggregated into two main themes: negative aspects (i.e., burden, emotional state, self-denial, social isolation) and positive aspects of caregiving. CONCLUSION: Healthcare professionals should consider the importance of caregiver role in supporting their loved one treated with OAAs, also taking into account their needs to prevent burdensome situations. A holistic view in which a patient-centred approach is established should be encouraged through the communication and education of the dyad.

Development and Content Validity of the Self-Care of Oral Anticancer Agents Index (SCOAAI).

OBJECTIVE: To develop and test the content validity of the Self-Care of Oral Anticancer Agents Index (SCOAAI). DATA SOURCES: SCOAAI items were developed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. The Middle Range Theory of Self-Care of Chronic Illnesses informed item generation. A four-phase procedure was followed; Phase 1: items were created based on a previous systematic review and a qualitative study; Phase 2: the SCOAAI comprehensibility and comprehensiveness were established through qualitative interviews with clinical experts and with patients (Phase 3); and Phase 4: the SCOAAI was then administered through an online survey to a group of clinical experts for the Content Validity Index (CVI) calculation. CONCLUSION: The first version of the SCOAAI included 27 items. Five clinical experts and 10 patients tested the comprehensiveness and comprehensibility of instructions, items, and response options. Fifty-three experts (71.7% female, mean experience with patients on oral anticancer agents 5.8 years [standard deviation ± .2]; 66% nurses) participated in the online survey for content validity testing. The final version of the SCOAAI includes 32 items. Item CVI ranges between 0.79 and 1; the average Scale CVI is 0.95. Future studies will test the psychometric properties of the tool. IMPLICATIONS FOR NURSING PRACTICE: The SCOAAI showed excellent content validity, confirming its usefulness for assessing self-care behaviors for patients on oral anticancer agents. By implementing this instrument, nurses could define and implement targeted interventions for improving self-care and obtaining more positive outcomes (eg, better quality of life, reduced hospitalizations and emergency department visits).