Application of the NSE score (Neurology-Stability-Epidural compression assessment) to establish the need for surgery in spinal metastases of elderly patients: a multicenter investigation.

PURPOSE: This retropective multicentric study aims to investigate the clinical applicability of the NSE score in the elderly, to verify the role of this tool as an easy help for decision making also for this class of patients. METHODS: All elderly patients (> 65 years) suffering from spinal metastases undergoing surgical or non-surgical treatment at the authors' Institutions between 2015 and 2022 were recruited. An agreement group (AG) and non-agreement group (NAG) were identified accordingly to the agreement between the NSE score indication and the performed treatment. Neurological status and axial pain were evaluated for both groups at follow-up (3 and 6 months). The same analysis was conducted specifically grouping patients older than 75 years. RESULTS: A strong association with improvement or preservation of clinical status (p < 0.001) at follow-up was obtained in AG. The association was not statistically significant in NAG at the 3-month follow-up (p 1.00 and 0.07 respectively) and at 6 months (p 0.293 and 0.09 respectively). The group of patients over 75 years old showed similar results in terms of statistical association between the agreement group and better outcomes. CONCLUSION: Far from the need or the aim to build dogmatic algorithms, the goal of preserving a proper performance status plays a key role in a modern oncological management: functional outcomes of the multicentric study group showed that the NSE score represents a reliable tool to establish the need for surgery also for elderly patients.

Do Sleep Disorders Influence the Prognosis and the Response to the Therapy in Enuretic Children?

OBJECTIVE: The current study describes the prevalence of sleep disorders in enuretic children, playing as influencing factors in the response to treatment and risk of relapse. MATERIALS AND METHODS: Data were collected from September 2020 to February 2021 in 114 children aged between 5 and 14 years, with a diagnosis of nocturnal enuresis and concomitant sleep disorders, referred to the Pediatric Unit, Campus BioMedico University, Rome. Enuretic children were subjected to an anamnestic and clinical assessment. Sleep disorders investigated were sleep apnea, sleep talking, snoring, bruxism, restless sleep, and somnambulism. Each patient was subjected both to pharmacological and to non-pharmacological treatments and monitored for 3 months to identify the presence of relapse. Patients were divided into 2 groups according to therapy response, and statistical analysis was performed to evaluate possible variables involved in enuresis relapse. RESULTS: A high prevalence of sleep disorders was documented: 8/114 children (7%) had sleep apnea, 47/114 (41.2%) had bruxism, 66/114 (57.8%) had snoring, 54/114 (47.3%) had sleep talking, 18/114 (15.7%) had restless sleep. Forty-three of 114 children (37.7%) had relapses: 21/43 (49%) relapses occurred in children with only 1 sleep disorder, while 22/43 (51%) relapses occurred in children with 2 or more sleep disorders. Lower risk of relapses was reported in children subjected to dual therapy. CONCLUSION: Sleep disorders were widely associated with nocturnal enuresis, acting as comorbidities in the clinical course of nocturnal enuresis. Combined therapy seems to be associated with a lower rate of relapse of enuresis in a 3-month follow-up. A multidisciplinary approach is required to improve patients' management.

Natural History of Non-Small-Cell Lung Cancer with Bone Metastases.

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.

Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis?

PURPOSE: Aim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC). MATERIALS AND METHODS: Data of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: <1 year, between 1 and 5 years and >5 years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance. RESULTS: 470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16 months (range 0 - 44y) with Median OS of 17 months. Number of metastatic sites (including bone, p = 0.01), concomitant metastases, high Fuhrman grade (p < 0.001) and non-clear cell histology (p = 0.013) were significantly associated with poor prognosis. Patients with TTBM >5 years had longer OS (22 months) compared to patients with TTBM <1 year (13 months) or between 1 and 5 years (19 months) from nephrectomy (p < 0.001), no difference was found between these two last groups (p = 0.18). At multivariate analysis, ECOG-PS, MSKCC group and concomitant lung or lymph node metastases were independent predictors of OS in patients with BMs. CONCLUSIONS: Our study suggest that age, ECOG-PS, histology, MSKCC score, TTBM and the presence of concomitant metastases should be considered in order to optimize the management of RCC patients with BMs.

Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey.

BACKGROUND: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. RESULTS: Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; P<0.05). CONCLUSIONS: RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.

Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting.

New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

Added value of combined gene and protein expression of CK20 and CEA in non-macroscopically involved lymph nodes of colorectal cancer.

A methacarn fixation permits an approach that comprises multiple techniques. In this study the procedure is used to examine 100 mesenteric lymph nodes from patients with colon cancer by means of histology, immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR). The evaluated nodes are found to be grossly free of metastases. The combined expression of both messenger RNA (mRNA) and protein is investigated to validate the presence of structural (cytokeratin 20, or CK20) and tumor-specific (carcinoembryonic antigen, or CEA) markers. Histological analysis shows micrometastases on 4 nodes. IHC analysis identifies isolated (CK20 and CEA positive) tumor cells on 14 other nodes. In this group, none of the nodes that are positive for CK20 IHC express the related mRNA. RT-PCR confirms the CEA IHC positivity in 50% of the cases. The double CEA IHC/RT-PCR positivity would have up-staged 33% of the pN0 cases to pN1. This approach offers a technological framework for further studies that aim to validate the clinical significance of protein/mRNA expression of tumor markers in colorectal cancer sentinel lymph nodes.

Pain treatment with high-dose, controlled-release oxycodone: an Italian perspective.

OBJECTIVE: To investigate the possible role and tolerability of high-dose (>160 mg/day) oxycodone controlled release (CR) for the treatment of cancer and non-cancer pain. DESIGN: 227 patients with cancer or non-cancer pain were enrolled in an open-label, multi-center, Italian study in order to assess the adequacy of their existing pain management (using a numerical rating scale [NRS]) and the possible benefit high-dose oxycodone CR may offer patients experiencing uncontrolled pain. RESULTS: Pain was poorly controlled at baseline, with only 18.1% of patients reporting adequate pain relief (NRS <3.5). All other patients reported uncontrolled pain, with an average NRS of 7.81. At baseline assessment, 47.89% of patients had been in pain for up to 3 months, 32.82% for 3-6 months, and 19.19% for more than 6 months. After baseline assessment, patients were switched to oxycodone CR monotherapy. The starting dose was individualized to each patient and titrated up over a 3- to 4-day period until effective pain management was achieved. Treatment was continued for an average of 37.24 days during the study. Pain control (final mean NRS of 2.85) was attained with an average dose of oxycodone CR 221.84 mg/day. Standard adverse events (including constipations, nausea, and vomiting) were recorded in 39.64% of patients receiving high-dose oxycodone CR monotherapy. Side-effects tended to subside after the initial week of treatment and did not result in any participants leaving the study. CONCLUSION: High-dose oxycodone CR can achieve rapid and effective management of moderate to severe cancer and non-cancer pain with minimum side-effects.

Fractionated dose of cisplatin (CDDP) and vinorelbine (VNB) chemotherapy for elderly patients with advanced non-small cell lung cancer: phase II trial.

BACKGROUND: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly representing about 30% of NSCLC patients over 70 years old. The aim of this study was to evaluate the response, survival and tolerability of a modified schedule with cisplatin-vinorelbine in elderly patients with advanced NSCLC. METHODS: Between November 2001 and March 2003, 30 patients were included into the study. Median age was 73 (range 70-77). Male/female 27/3 (90%/10%); 60% of patients were stage IV at diagnosis and only one patient presented with brain metastasis. Treatment consisted of cisplatin 30 mg/m(2) on days 1 and 8, and vinorelbine 25 mg/m(2) on days 1 and 8 every 21 days. RESULTS: A total of 120 cycles were administered with a median of four cycles per patient. The most relevant WHO toxicities were: neutropenia grade 3 in 6 (20%) patients and grade 4 in 13 (43%) patients. There were three (10%) treatment-related deaths: two caused by neutropenic fever and one due to acute pulmonary oedema. No other relevant hematological and non-hematological toxicities occurred. By intention-to-treat analysis, 10 patients (33%) showed stable disease and 10 patients (33%) showed a partial response while 10 patients (33%) showed treatment failure. Median survival time was 7.4 months; 1-year survival was 36.6% and median time to progression was 5.14 months. CONCLUSION: At this dose and schedule, the combination of vinorelbine and cisplatin obtained a response rate and survival comparable to the most active regimens. Non-hematologic toxicity was mild while neutropenia was the most relevant toxicity.

IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor.

BACKGROUND: Interleukin-7 (IL-7) is a potent regulator of lymphocyte development, which has also significant effects on bone; in fact it is a potent osteoclastogenic factor. Some human solid tumors produce high IL-7 levels, suggesting a potential IL-7 role on tumor development and progression. METHODOLOGY: We studied 50 male patients affected by solid tumors, and their blood samples were collected at tumor diagnosis. PBMCs were isolated and cultured with/without IL-7 to study its influence on osteoclastogenesis. Serum and cell culture supernatant IL-7 levels were measured by ELISA. The quantitative analysis of IL-7 expression on T and B cells was performed by Real-Time PCR. PRINCIPAL FINDINGS: Serum IL-7 levels were highest in osteolytic cancer patients, followed by cancer patients without bone lesions, and then healthy controls. We showed the IL-7 production in PBMC cultures and particularly in monocyte and B cell co-cultures. A quantitative analysis of IL-7 expression in T and B cells confirmed that B cells had a high IL-7 expression. In all cell culture conditions, IL-7 significantly increased osteoclastogenesis and an anti-IL-7 antibody inhibited it. We demonstrated that IL-7 supports OC formation by inducing the TNF-alpha production and low RANKL levels, which synergize in promoting osteoclastogenesis. CONCLUSIONS: We demonstrated the presence of high serum IL-7 levels in patients with bone metastasis, suggesting the use of serum IL-7 level as a clinical marker of disease progression and of bone involvement. Moreover, we showed the capability of IL-7 to stimulate spontaneous osteoclastogenesis of bone metastatic patients and to induce osteoclastogenesis in cancer patients without bone involvement. These findings add further details to the disclosure of the mechanisms controlling bone metastasis in solid tumors.

Sequential chemotherapy of cisplatin and vinorelbine followed by paclitaxel and gemcitabine in advanced non-small-cell lung cancer. A single institution phase II study.

BACKGROUND: To determine the activity and safety of a sequential regimen of cisplatin and vinorelbine followed by paclitaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment was two cycles of cisplatin 80 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 3 weeks followed by two cycles of paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 every 3 weeks. RESULTS: Fifty-five patients with inoperable NSCLC, performance status 2 or less were enrolled, including 19 patients with brain lesions. There were 23 partial responses (42%; 95% confidence interval 29-55). The median time to progression and overall survival were 5.8 and 10.3 months, respectively (6.5 and 12.8 in the patient subset without brain metastases). One-year survival rate was 47.5%. Grade III/IV neutropenia was the major side effect; it occurred in 56% of patients and was mainly limited to the first two chemotherapy cycles with cisplatin and vinorelbine. CONCLUSIONS: Sequential combination of cisplatin and vinorelbine followed by paclitaxel and gemcitabine is a manageable and active regimen for patients with NSCLC. It deserves to be tested against a standard two-drug scheme in a phase III trial.