ABSTRACT
BACKGROUND: Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal. METHODS: TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS). RESULTS: From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) (P = .001), opioid use (P = .004), bone metastases number (P < .001), baseline PSA (P = .006), Hb (P < .001), ALP (P < .001) and LDH (P = .002), time between ADT and docetaxel start (P = .018), 3-month PSA (P < .001) and ALP (P < .001), and number of docetaxel cycles (P < .001). OS-related variables were PSA at diagnosis (P = .024), primary tumor treatment (P = .022), baseline pain (P = .015), opioid use (P < .001), bone metastases number (P < . 001), baseline Hb (P < .001), ALP (P < .001) and LDH (P = .001), NLR ratio (P = .039), 3-month PSA (P < .001) and ALP (P < .001) and docetaxel cycles number (P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS. CONCLUSION: Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy.
Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Male , Humans , Docetaxel , Retrospective Studies , Analgesics, Opioid/therapeutic use , Androgen Antagonists/therapeutic use , Treatment Outcome , Prostatic Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols , Pain/etiology , HormonesABSTRACT
OBJECTIVE: Sarcoma diagnosis and its treatment trajectory may deeply affect the somatopsychic balance of patients and their caregivers. This systematic review aimed at deepening the understanding of sarcoma's impact on the entire family unit involved in the illness experience on a physical (e.g. fatigue), psychological (e.g. mental health, affective regulation, defense mechanisms), and interpersonal (e.g. social isolation, loneliness) level. METHODS: The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The literature search led to the identification and subsequent inclusion of 44 articles focused on sarcoma patients. Results were classified into seven categories: Quality of Life, worries and distress, anxiety and depression, suicide ideation, financial and occupational consequences, unmet needs, and coping strategies. Our search identified only one study focusing on informal caregivers, thus we could not perform a systematic review on these results. RESULTS: Our findings underlined the traumatic impact of the sarcoma diagnosis. Patients can experience an impoverished emotional life, somatization, social withdrawal, difficulty in decision-making, increased feelings of discouragement and demoralization, and profound experiences of helplessness and vulnerability. Moreover, they seemed to display anxiety and depression and might present a higher suicide incidence than the general population. CONCLUSION: Our review highlighted that the psychosocial aftermath of sarcoma patients should guide institutions and healthcare professionals toward the design of assessment and intervention models that could contemplate the different dimensions of their suffering. Furthermore, it points out that there is still a lack of evidence regarding the psychosocial impact affecting sarcoma patients' caregivers.
Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Quality of Life/psychology , Depression/psychology , Sarcoma/therapy , Mental HealthABSTRACT
Angiogenesis has a direct stimulatory effect on tumor growth, duplication, invasion and metastatic development. A significant portion of conventional renal cell carcinomas are angiogenesis-dependent tumors and the pathways supporting this process have been thoroughly investigated over the last 20 years. As a consequence, many tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, pazopanib, axitinib, and cabozantinib), one monoclonal antibody (bevacizumab), and two mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus) have been investigated and approved for the treatment of advanced or metastatic clear cell renal carcinoma (metastatic CCRC) in first-line, as well as second-line, therapy, with impressive results in progression-free survival and in the objective response rate compared with previously available therapies or placebo. Recently, a new type of drug has been approved for metastatic CCRC: immunomodulatory checkpoint inhibitors (ICIs), alone or in combination with TKIs. However, many questions and areas to be explored still remain with regard to clear cell renal carcinoma (CCRC) treatment: research on predictive biomarkers, the best patient selection, how to overcome the mechanisms of resistance, and the best sequence of therapies in daily clinical practice. This review focuses on the pharmacological properties and anticancer activities of these drugs. The toxicity profile and clinical limitations of these therapies are also discussed.
ABSTRACT
Patients with advanced and incurable colorectal cancer have a very poor prognosis. Curative-intent resection was performed in 70%-90% of cases in reported series of colorectal cancer, sometimes after neoadjuvant chemotherapy and radiotherapy. The remaining 10%-30% of patients are treated with palliative intent, where treatment is aimed at relieving disease-related symptoms and improving quality of life. The provision of palliative care for these patients is complicated and outcomes are often disappointing. Although there are many available options including a variety of surgical and nonsurgical interventions, the best management remains controversial. Transarterial chemoembolization with irinotecan-loaded drug-eluting beads (DEBIRI) is an effective, minimally invasive procedure performed by interventional radiologists that allows intra-arterial drug delivery to stop vascular feeding and exert local cytotoxic effects. We here report on a patient treated with DEBIRI followed by systemic chemotherapy with the FOLFOX regimen for locally advanced, inoperable colorectal cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Chemoembolization, Therapeutic , Mesenteric Artery, Inferior , Rectal Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Chemoembolization, Therapeutic/methods , Female , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Microspheres , Middle Aged , Organoplatinum Compounds/administration & dosage , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Treatment Outcome , Tumor BurdenABSTRACT
Androgen deprivation therapy (ADT) leads to important changes in body composition. No data are currently available about the relationship between these treatment-related changes and patient outcome. Using dual-energy X-ray absorptiometry, bone mineral density (BMD), fat body mass (FBM), and lean body mass (LBM) were determined at baseline, and after 1 and 2 years in 53 non-metastatic prostate cancer (PC) patients with high-risk disease treated with adjuvant ADT. Changes in these parameters were correlated with patient outcome in terms of adverse skeletal events, disease recurrence, and overall survival. ADT led to a significant decrease in BMD (p < 0.03) and LBM (p < 0.03), and an increase in FBM, (p < 0.0001). Changes in BMD failed to show any relationship with time to skeletal-related events (SRE), disease recurrence, and death. FBM increase was a significant predictor of higher risk of SRE [hazard ratio (HR) 3.024, 95 % CI 1.004-10.353, p < 0.02], higher risk of death (HR 2.373, 95 % CI 1.012-5.567, p = 0.04), and a non-significant higher risk of disease recurrence (HR 2.219, 95 % CI 0.956-5.150, p = 0.13). LBM decrease did not correlate with either time to SRE or survival, while a non-significant association with disease recurrence (HR 1.550, 95 % CI 0.670-3.605, p = 0.06) was observed. The early increase in FBM may provide predictive information of poor outcome in PC patients given ADT. These data suggest that the adoption of early preventive measures aiming to reduce fat increase can potentially reduce the morbidity and mortality risk.
Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/adverse effects , Bone Density/drug effects , Outcome Assessment, Health Care , Prostatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Androgen Antagonists/administration & dosage , Humans , Male , Middle Aged , Prognosis , RiskSubject(s)
Bone Density Conservation Agents/administration & dosage , Calcitriol/administration & dosage , Prostatic Neoplasms/drug therapy , Taxoids/administration & dosage , Antineoplastic Agents/administration & dosage , Bone Neoplasms/complications , Bone Neoplasms/secondary , Clinical Trials as Topic , Docetaxel , Drug Synergism , Humans , Hypocalcemia/etiology , Hypocalcemia/prevention & control , MaleABSTRACT
PURPOSE: We assessed chromogranin A as a tissue biomarker in prostate needle biopsies or as a plasma biomarker, a risk factor for hormone refractory prostate cancer. MATERIALS AND METHODS: A total of 211 patients with newly diagnosed prostate cancer treated with luteinizing hormone releasing hormone analogues constituted the study cohort. Univariate and multivariate Cox regression analyses were used to assess the predictive role of tissue and plasma chromogranin A expression. RESULTS: Chromogranin A expression in less than 30% or in 30% or more tumor cells was significantly associated with a shorter time to hormone refractory disease on univariate analysis (HR 2.0, 95% CI 1.3-3.1 and HR 6.0, 95% CI 2.7-12.9), or on multivariate analysis after adjusting for Gleason score, serum prostate specific antigen and disease stage (HR 1.7, 95% CI 1.0-2.8 and HR 3.9, 95% CI 1.7-9.0), respectively. Plasma chromogranin A measured at baseline (HR 3.0, 95% CI 1.8-5.2), and after 1 year (HR 5.8, 95% CI 3.1-10.1) and 2 years (HR 3.5, 95% CI 1.6-7.6), was predictive of hormone refractory risk confirming the tissue results. Plasma as well as tissue chromogranin A expression negatively correlated with overall survival. CONCLUSIONS: Chromogranin A expression in prostate cancer biopsies is an independent predictive factor of hormone refractory disease in patients with newly diagnosed prostate cancer on early androgen deprivation therapy. Plasma chromogranin A is also a reliable predictive marker and the predictive significance is maintained over time. These results deserve validation in another data set.