Advanced Non–Small-Cell Lung Cancer in the Elderly

Systemic chemotherapy provides improvement in both survival and quality of life for patients with advanced non–small-cell lung cancer (NSCLC). Elderly patients have more comorbidities and tend to tolerate more poorly aggressive chemotherapy and radiation therapy than younger individuals. Our purpose in this article is to summarize recent studies of single-agent chemotherapy and combination regimens with cytotoxic or targeted therapies in the management of elderly patients with advanced NSCLC. We have reviewed the available evidence in the literature to gauge the results of therapy for elderly patients with lung cancer. We found that single-agent chemotherapy remains the standard of care for nonselected elderly patients. Retrospective analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with increased but acceptable toxicity for elderly patients. Therefore, the outcomes in the fit elderly mirror results observed in younger patients, although toxicity is generally greater.     

Platinum-Based Chemotherapy ‘Rechallenge’ in Advanced Non-ovarian Solid Malignancies

Platinum-based chemotherapy forms the backbone of treatment for many solid cancers. However, resistance inevitably develops in those with advanced disease. Platinum rechallenge is a well-established concept in the management of ovarian cancer, small cell lung cancer and germ cell tumours. In other solid malignancies there is a lack of quality evidence to support platinum rechallenge, yet it is a widely adopted strategy. Often, patients are within the last year of life, making questions of efficacy, treatment-related toxicity and quality of life critical factors for treatment recommendations. In this overview we appraise the available evidence for platinum rechallenge and strategies being developed to attempt resensitisation of tumours to platinum-based chemotherapy.     

Treatment of Unresectable Advanced Gastric Cancer Using Iodine-125 Brachytherapy

OBJECTIVE The purpose of the study was to examine the efficacy of treating patients with advanced gastric cancer using iodine-125 （^125Ⅰ） brachytherapy. METHODS Ten patients with unresectable advanced gastric cancer were selected based on their pattern of CT scans. We utilized a brachytherapy planning system to determine the distribution of the ^125Ⅰ seeds, their activity and quantity. The matched peripheral dose （MPD） was 110-135 Gy.^125Ⅰ seeds were implanted in a single plane or biplane by an intraoperative small incision or percutaneous puncture. The postoperative hemogram, CT, KPS, pain-relieving period and survival period were recorded. RESULTS One patient developed a complete response （CR）, 4 patients a partial response （PR）, 3 patients showed no change （NC） and 2 patients developed progressive disease （PD）. The overall response rate （CR＋PR） was 50% （5/10）. The pain-relieving rate was 89% （8/9）. The patients＇ appetite and KPS were improved. The longest survival period was 10 months and median life span was 4 months. There were 8 patients whose seeds fell off resulting in an expulsion rate of 3.8% （26/692）. The patients showed 0-1 degree acute radio-therapeutic side-effects without other symptoms such as abdominal pain, vomitus cruentes or intestinal obstruction etc. CONCLUSION Applying ^125Ⅰ implantation to treat advanced gastric cancer with a reasonable seed distribution can significantly improve clinical symptoms and their quality of life. The radioactive damage is mild. This method can be used as an important supplementary treatment for unresectable advanced gastric cancer.     

Treatment of Unresectable Advanced Gastric Cancer Using lodine-125 Brachytherapy

At present, gastric cancer ranks high in frequency of all malignant tumors, although its incidence and morbidity are slowly decreas- ing. When found, most patients are in an advanced stage and even in developed countries only 10% of gastric cancers are in…     

Palliative Care in Advanced Cancer Patients: How and When?

Cancer patients develop severe physical and psychological symptoms as a result of their disease and treatment. Their families commonly suffer great emotional distress as a result of caregiving. Early palliative care access can improve symptom control and quality of life and reduce the cost of care. Preliminary results show that early palliative care access can also extend survival. Unfortunately, only a minority of cancer centers in the U.S. have the two most important resources for palliative care delivery: outpatient palliative care centers and inpatient palliative care units. In this article, we use a case presentation to discuss the impact of early palliative care access in light of the currently available evidence, and we recommend ways to improve early access to palliative care through education and research.     

Oxaliplatin in First-line Therapy for Advanced Non–Small-Cell Lung Cancer

Platinum doublets are the recommended standard first-line chemotherapy for stage IIIB/IV non–small-cell lung cancer (NSCLC). As efficacy outcomes associated with currently approved agents (cisplatin and carboplatin) are broadly similar, the decision about which platinum-based doublet to use is based on other factors such as toxicity. The goals for new platinum agents are to maintain and perhaps improve current efficacy and to improve toxicity. The aim of this article is to review the available clinical data from studies investigating the third-generation platinum analogue oxaliplatin in patients with advanced NSCLC. Information was obtained from the PubMed database and from recent presentations at national and international meetings. Oxaliplatin has been studied as monotherapy and in combination with a wide range of other chemotherapies (vinca alkaloids, taxanes, gemcitabine, and pemetrexed), mainly in phase II trials. Preliminary results from studies in which oxaliplatin-based doublets have been combined with targeted agents (eg, bevacizumab) are now available. In general, the clinical activity observed with oxaliplatin-based therapy is similar to that seen with other currently used platinum regimens, although outcomes vary between individual trials (response rates, 23%-48%; median progression-free survival, 2.7-7.3 months; median overall survival, 7.3-13.7 months). The toxicity profile of oxaliplatin, particularly when compared with cisplatin, makes it an alternative treatment, especially in patients unable to tolerate cisplatin. However, well-conducted randomized phase III trials will be needed to clarify which particular groups of patients with NSCLC may benefit from oxaliplatin-based therapy.     

Molecularly Targeted Therapies in Locally Advanced Non–Small-Cell Lung Cancer

Approximately a third of the patients with non-small cell lung cancer (NSCLC) present with locally advanced disease not amenable to curative resection. Concurrent chemoradiation is currently the treatment of choice for these patients. Outcomes in patients with locally advanced NSCLC treated with concurrent chemoradiation are modest at best. No significant progress has been made over the past decade in this subset of patients with NSCLC. Several trials have examined the role of molecular targeted therapies in this setting. We review the results of these trials and present the outline of a proposed prospective clinical trial to evaluate targeted drugs in molecularly selected group of patients with locally advanced NSCLC.     

Advanced Breast MRI Techniques: Helpful for Screening Breast Cancer?

Breast magnetic resonance imaging (MRI) is increasingly used in conjunction with mammography as a screening tool to detect breast cancers in asymptomatic high-risk women. Conventional dynamic contrast-enhanced (DCE) breast MRI has a high sensitivity but only moderate specificity for the detection of breast cancer. The primary goal of developing and applying advanced breast MRI techniques that can assess tissue biology is to improve lesion specificity. This review provides a summary of the advances in DCE-MRI techniques and the use of diffusion-weighted imaging and magnetic resonance spectroscopy for breast cancer detection. Publications on the use of these advanced MRI techniques are largely single-institution studies with small numbers of patients, which limits the generalization of this data to a wider screening population. In their current forms, these adjunctive techniques require further research, incorporating an expanded patient population, to validate their utility for breast cancer screening.     

Advanced pancreatic cancer: is there a role for combination therapy?

Once thought to be a relatively untreatable disease, pancreatic cancer has recently become a focus of intense clinical research. The systemic administration of gemcitabine (Gemzar) is currently considered the standard first-line treatment for patients with advanced disease. While treatment with gemcitabine has been shown to result in both clinical benefit and prolongation of survival, objective tumor responses are relatively uncommon and median survival times remain short. Several recent efforts have therefore focused on evaluating chemotherapy regimens in which gemcitabine is combined with other cytotoxic drugs. While randomized trials have now confirmed that such combinations are associated with higher response rates, they have not yet clearly demonstrated that combination therapy results in a survival advantage. Increasingly, attention has turned to a number of novel chemotherapeutic and biologic agents that appear promising and are likely to play an important future role in the treatment of patients with this disease.     

Can Megestrol Acetate Induce Thrombosis in Advanced Oncology Patients Receiving Chemotherapy?

Background: Megestrol acetate (MA) is a steroid origin medicine often used for control of cachexia in oncologicpalliative care. Thrombosis is a common problem in oncology patients. One question is whether MA can causethrombosis. This retrospective, registry-based analysis was therefore conducted to assess thrombotic processes inoncology patients using MA concurrent with chemotherapy. Materials and Methods: Data on oncology patientsat the metastatic stage using MA were obtained from the archives of our center. Outcomes of patients wereevaluated for thromboembolic events (VTEs) during treatment. Results: Ninety-seven oncology patients witha median age of 62 (33-84) years were included. During the median follow-up of 17 months, 58 (59.8%) diedleaving 39 (31.2%) still alive. Median overall survival (OS) was 19 months (6-180). Mean time of MA use was 8.69months(±3.53), with a median dose of 160mg (range 160-480mg). Eleven VTEs were detected after MA use, 4 ofthese in pancreatic cancer cases. The patients with thrombosis non-significantly had worse OS, than those withoutthrombosis (p=0.106). Conclusions: This trial revealed that the 11.3% of all patients developed thrombosis,whohad been treated with MA and chemotherapy concomittantly. There was no statistically significant differenceregarding to occurrence of thrombotic process, among the patients receiving different chemotherapy regimenswith MA concomittantly. Pancreatic cancer seemed to be related to thrombosis rather than MA use.     

Advanced Vulvar Cancers: What are the Best Options for Treatment?

The treatment of patients with vulvar cancer remains challenging for gynecologic oncologists. Up to 30 % of the cases are diagnosed in a clinical condition of irresectability, and some kind of strategy has to be taken into account beyond surgery. In this regard, a common and standard definition is critical to maximize oncological results and minimize complications after treatments. Each patient treatment must be tailored individually according to their clinical and biological features and to the setting in which they are dealing with.     

New Generation Aromatase Inhibitors – from the Advanced to the Adjuvant Setting

A wide variety of routes of administration and formulations are employed in estrogen replacement therapy. These exhibit differences in the pharmacokinetics and metabolism of estradiol and in the resulting biological effects. This study set out to investigate the effects of pulsed estrogen administration (via the nasal route) compared to oral therapy, as a reference, with regard to breast cancer risk. This was assessed in an experimental model whereby mammary tumours were induced by 7,12-dimetbylbenz(a)anthracene in ovariectomised rats. To mimic a pulsed treatment given via the nasal route doses of estrogen were administered by I.V. route (0.4, 10 and 250g/kg). These dosages were predicted to have similar estrogenic activity to doses administered by the oral route (100, 300 and 900g/kg). Controls were groups of ovariectomised and SHAM-operated rats and ovarectomised rats administered with either vehicle alone. Two studies were carried out on separate populations of rats and ran in parallel. Tumour appearance (study 1) and tumour growth (study 2) were evaluated. In study 1 (n=20/group), treatments with estradiol were conducted for 20 weeks after carcinogen administration; in study 2 (n=10/group), an 8-week treatment with estradiol was initiated once 7,12-dimethylbenz(a)anthracene-induced tumours appeared. Intravenous dose levels achieved equivalent estrogenicity to corresponding oral dose levels, as assessed by measuring uterus weight. Estrogen deficit was made up by both routes but only the higher doses restored physiological uterus weight. Nevertheless administration via the I.V. route resulted in a lower rate of tumour incidence (p0.05) than the rate recorded for the oral route. In addition, tumour development was lower with the I.V. route. In conclusion, in this experimental model, pulsed estrogen therapy with 17 -estradiol administered via the I.V. route resulted in a reduced effect on mammary carcinogenesis when compared to oral administration.     

The Efficacy of High-Intensity Focused Ultrasound （HIFU） in Advanced Pancreatic Cancer

OBJECTIVE To observe the efficacy of high-intensity focused ultrasound (HIFU) in the treatment of late-stage pancreatic cancer. METHODS Sixteen patients with advanced pancreatic cancer received HIFU therapy.Evaluation of efficacy was made on the basis of changes in clinical symptoms and variations in the tumor echo and size. RESULTS Clinical symptoms such as pain were significantly alleviated,echo of the tumor was enhanced with B-US and the quality of life such as eating,sleeping and mental status was markedly improved;no serious complications were observed. CONCLUSION The use of HIFU in the treatment of advanced pancreatic cancer is feasible and safe.It is effective in killing the carcinoma cells and alleviating pain.This technique may offer non-invasive therapy for the treatment of patients with late-stage pancreatic cancer.     

Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC

Introduction

Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non–small-cell lung cancer who have been pre-treated with EGFR–tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine.