The benefit of palliative chemotherapy (PC) in patients with advanced solid tumors and poor performance status (ECOG-PS) has not been prospectively validated, which makes treatment decision ...challenging. We aimed to evaluate the overall survival, factors associated with early mortality, and adoption of additional procedures in hospitalized patients with advanced cancer and poor ECOG-PS treated with PC.
We analyzed a retrospective cohort of patients with advanced cancer treated with PC during hospitalization at an academic cancer center in Brazil from 2014 to 2016. Eligibility criteria included: ECOG-PS 3-4 and start of first-line PC; or ECOG-PS ≥ 2 and start of second or subsequent lines. Primary endpoint was 30-day survival from start of PC. Kaplan-Meier method was used for survival estimates and Cox regression for factors associated with 30-day mortality.
Two hundred twenty-eight patients were eligible. 21.9, 66.7 and 11.4% of patients had ECOG-PS 2, 3 and 4, respectively. 49.6% had gastrointestinal tumors. Median follow-up was 49 days (range 1-507). 98.2% of patients had died, 32% during the index hospitalization. The 30-day and 60-day survival rates were 55.7 and 38.5%, respectively. 30% of patients were admitted to the intensive care unit. In a multivariable analysis, ECOG-PS 3/4 (HR 2.01; P = 0.016), hypercalcemia (HR 2.19; P = 0.005), and elevated bilirubin (HR 3.17; P < 0.001) were significantly associated with 30-day mortality.
Patients with advanced cancer and poor ECOG-PS had short survival after treatment with inpatient PC. Inpatient PC was associated with aggressive end-of-life care. Prognostic markers such as ECOG-PS, hypercalcemia and elevated bilirubin can contribute to the decision-making process for these patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in ...women with breast cancer. Sixteen women (age: 47.0 ± 2.0 yr; body mass index: 24.2 ± 1.5 kg/m) with stage II-III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m
) and CY (600 mg/m
) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (microneurography), calf blood flow (CBF; plethysmography) and calf vascular conductance (CVC), heart rate (HR; electrocardiography), and beat-to-beat blood pressure (BP; finger plethysmography) were measured at rest before, during, and after each session. Venous blood samples (5 ml) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs; flow cytometry), a surrogate marker for endothelial damage. MSNA and BP responses were increased (
< 0.001), whereas CBF and CVC responses were decreased (
< 0.001), during and after CHT session when compared with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT (
= 0.03, CHT vs. SL session). No difference in HR response was observed (
> 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions.
It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure.
Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more ...than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC.
This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib.
The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity.
Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.
Treatment of adult osteosarcoma (AOS) includes perioperative chemotherapy and surgery. Standard chemotherapy consists of cisplatin (CP) and doxorubicin (DOX). Although considered the standard of care ...for pediatric patients, high-dose methotrexate (HDM) remains controversial in adults. We aimed to evaluate the role of HDM in AOS treated with curative intent. This study included patients with AOS who received perioperative chemotherapy with DOX and CP (group 1; N=16) and DOX, CP, and HDM (group 2; N=10). The primary endpoint was grade 3 or superior toxicities. The secondary endpoints included overall survival (OS) and disease-free survival. Despite lower average age (35.0±12.1 vs. 18.9±2.1 years), group 2 presented more grade 3–4 thrombocytopenia (0 vs 50%) and mucositis (0 vs 40%), whereas group 1 presented more grade 3–4 neutropenia (43.75 vs 40%). No grade 3–4 renal toxicities occurred. Two grade 5 toxicities occurred in group 2, both after the first HDM cycle. Disease-free survival (4.38±0.61 vs. 2.3±0.54 years, P=0.228) and OS (4.70±0.56 vs 2.52±0.57 years, P=0.107) were not statistically different, but presented a trend toward better outcomes in group 1. The 4-year OS was 65.6 and 32.8% for groups 1 and 2, respectively. In conclusion, HDM was associated with greater severe and lethal toxicity when added to CP and DOX in AOS. Also, it does not seem to impact on treatment efficacy. These data do not support the use of HDM for the perioperative treatment of AOS.
Cervical cancer remains a prevalent and deadly disease in low-income countries, especially among young and otherwise healthy women. Multimodality treatment has led to a significant improvement in ...outcomes for patients with locally advanced disease, and this is mainly because of the incorporation of platinum-based chemoradiotherapy in current treatment protocols. However, locally advanced tumors are associated with a greater risk for para-aortic lymph node (PALN) involvement, which is an important adverse prognostic factor. Most staging techniques have low accuracy for detection of disease in this area, which could lead to understaging and undertreatment. Meanwhile, patients with PALN disease are underrepresented in trials addressing the treatment of advanced cervical cancer and a few studies have been directed at this population. The aim of this review is to analyze the current data regarding staging and treatment of cervical cancer with PALN disease to determine which strategy is best when managing these patients.
•Surgical stress can lead to immune system changes.•Peripheral Mononuclear Cells were studied post-operatively following lung resection.•Lung resection can be performed with thoracotomy or ...thoracoscopic surgery.•Surgical approach does not affect peripheral mononuclear cells levels.
The multimodal management of operable non-small cell lung cancer (NSCLC) continues to evolve rapidly. The immune milieu allowing for immunotherapeutic benefit can be affected by multiple parameters including clinicopathologic and genetic. Surgery induced physiological changes has received attention for modulating and affecting post-operative oncotaxis and immunosuppression. Here, we sought to investigate how surgical stress influences phenotype of peripheral blood mononuclear cells (PBMCs) in patients with NSCLC who underwent lobectomy.
Blood was prospectively collected from patients with Stage IA-IIIA NSCLC undergoing lung resection between 2016 and 2018. Samples were obtained pre-operatively, 24 h and 4 weeks after surgery. PBMCs were isolated and subject to high-dimensional flow cytometry, analyzing a total of 115 cell populations with a focus on myeloid cells, T cell activation, and T cell trafficking. We further evaluated how surgical approach influenced post-operative PBMC changes, whether the operation was conducted in an open fashion with thoracotomy, or with minimally invasive Video Assisted Thoracoscopic Surgery (VATS).
A total of 76 patients met the inclusion criteria (Open n = 55, VATS n = 21). Surgical resection coincided with a decrease in T lymphocyte populations, including total CD3+ T cells, CD8+ T cells, and T effector memory cells, as well as an increase in monocytic myeloid-derived suppressor cells (mMDSC). Post-operative changes in PBMC populations were resolved after 4 weeks. Surgical-induced changes in immune populations were equivalent in patients undergoing open thoracotomy and VATS.
Surgical stress resulted in transient reduction in T cells and T effector memory cells, and increase of mMDSC following resection in NSCLC patients. The immune profile modulation was similar regardless of surgical approach. These findings suggest that surgical approach does not seem to affect mononuclear cell lines obtained from peripheral blood. Thus, the decision regarding surgical approach should be patient centered, rather than based on post-operative treatment response optimization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Cervical cancer (CC) is the second most common cancer in Brazilian women, and approximately 10% of cases occur in elderly patients (pts). In this age group, disease is usually ...diagnosed in more advanced stages and oncological therapies are usually less intensive, due to comorbidities and impaired performance status. Methods Retrospective analysis of pts ≥65 years old with CC admitted at a Brazilian University Cancer Center from August 2008 to February 2012. We performed a descriptive analysis of baseline performance status (PS), disease stage (FIGO), histology, body mass index (BMI), treatment received and overall survival, using the Kaplan–Meier method. Results 900 medical records were analyzed and 75 pts (8%) fulfilled the inclusion criteria. Median age was 73.4 years old (±5.5 years). Squamous cell carcinoma (SCC) was the most common histology (71 pts, 94.7%). 67 (89.3%) had PS 0 or 1 and 52 pts (69.3%) were eutrophic (BMI 18.5–25 kg/m2 ). At presentation, disease staging consisted of 18 pts (24%) stage I, 35 pts (46.7%) stage II, 8 pts (10.7%) stage III, 12 pts (16%) stage IVa and 2 pts (2.7%) stage IVb. 24 pts (32%) underwent surgery (hysterectomy, adnexectomy, pelvic and paraaortic lymphadenectomy). Adjuvant treatment with radiotherapy (RT) was performed in 13 pts (total dose of external RT in pelvis ranged from 39.6 to 45 Gy, parametrial boost ranged from 14 to 20 Gy and 4 inserts from 7 to 7.5 Gy of brachytherapy); 8 of them received concomitant platinum-based chemotherapy (CT). 30 pts underwent definitive CRT, 17 definitive RT, 1 palliative CT and 3 best supportive care. In the CRT group, 18 pts received cisplatin (CDDP 40 mg/m2 /w/6w) and 12 carboplatin (AUC 2/w/6w). During definitive CRT, treatment was discontinued in 39% of pts who received CDDP and 25% of pts who received carboplatin, all due to treatment toxicities. CDDP was associated with more nefrotoxicity (5 pts, 28%) than carboplatin (1 pt, 8.3%). The CDDP group also presented more radiodermatitis and stroke. However, myelosuppression and diarrhea were similar in both groups. After a 26.1-month follow-up, median OS was not reached. Conclusions Despite advanced age, more than 60% of pts underwent complete CRT treatment. Thus, age should not be the only factor to guide therapeutic decisions in CC. Carboplatin was better tolerated than CDDP in CRT group, but prospective trials are necessary to evaluate the best treatment option in this population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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TRACERx: Tracking tumor evolution to impact the course of lung cancer Negrao, Marcelo Vailati; Quek, Kelly; Zhang, Jianjun ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
March 2018, 2018-03-00, 20180301, Volume:
155, Issue:
3
Journal Article
Peer reviewed
Open access
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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