Median Survival Of Untreated Patients Research Articles

Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy.

Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4-8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM; however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy for different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20-40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.

Outcomes and Characteristics of Untreated Diffuse Large B-Cell Lymphoma (DLBCL) Patients: A SEER-Medicare Database Analysis

INTRODUCTION Diffuse Large B-cell Lymphoma (DLBCL) is most frequently diagnosed in the elderly, with a median age of presentation of 66 years. While approximately 60% of patients can achieve a cure with intensive anthracycline - based chemoimmunotherapy, treatment is associated with toxicity and may not always be safe in frail or elderly patients. Little is known about characteristics and outcomes in patients who are too frail for treatment or opt to not receive systemic therapy. METHODS: We used the Surveillance, Epidemiology, and End Results Program (SEER) linked with Medicare claims to identify 6,214 DLBCL patients (pts) diagnosed between 2007 and 2017. Data collected included demographic variables; comorbidity burden calculated using the Elixhauser comorbidity index with conditions present 30 to 365 days prior to DLBCL diagnosis. Initial therapy was defined as prescribed -30 to 100 days post-diagnosis. Patients who did not receive outpatient treatment but had current procedural terminology (CPT) codes reflecting inpatient chemotherapy were excluded from analysis. RESULTS: Of the 6,214 patients, 1,644 (26.5%) were untreated. Untreated patients were older with a median age of 81 years (interquartile range (IQR) 74-87) compared to 78 years old (IQR: 72-84) in the total cohort. Patients 85 years and older (≥85 y) represented 22.0% of the total cohort, 36.2% of untreated patients and 13.8% of patients receiving treatment for DLBCL. Overall, 43.6% of patients ≥85 y did not receive treatment. This percentage also varied by race: Of 194 black patients, 33% were not treated, compared to 26.4% of white patients. During the study period, 60.7% of the total cohort died. The proportion of deaths was higher in the untreated cohort (83.7%) and lower (45.4%) in the chemotherapy-treated cohort. Median survival of untreated patients was 3 months (IQR 2-27) . The median survival of the total cohort was 18 months (IQR 4-47). The comorbidity burden was higher in the untreated patients compared to both the total cohort and chemotherapy treated patients: 15% had congestive heart failure (CHF), 16.4% had peripheral vascular disease, and 10.8% had diabetes with complications. Table 1 lists selected Elixhauser comorbidities at time of diagnosis. Of 562 DLBCL patents with a diagnosis of CHF, 44.0% did not receive any treatment. CONCLUSIONS: Approximately one quarter of DLBCL patients in the SEER - Medicare database are listed as not receiving treatment. Untreated patients were older and had a higher burden of baseline comorbidities. Black patients were more likely to receive no treatment than white patients. Expectedly, untreated patients had short overall survival, highlighting the continued need for new tolerable therapies for DLBCL. Future analysis will focus on lymphoma specific mortality, time to event analyses and identification of populations at highest risk of not receiving therapy. These populations should be the target of research of novel therapeutic strategies in order to improve outcomes with minimized toxicity. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Positive impact of academic center care on overall survival in malignant pleural mesothelioma (MPM): A National Cancer Database (NCDB) socioeconomic factor analysis.

8558 Background: MPM is a rare cancer with a poor prognosis. Median survival for untreated patients is 4-13 months, and for treated patients is 6-18 months. Despite asbestos regulations in the United States, annual deaths from MPM rose from 2,479 in 1999 to 2,597 in 2015. Given recent treatment advances, including improvements in multimodality therapy and the introduction of immunotherapy as a treatment option in the frontline setting, the impact that patient demographics and treatment factors have on survival outcomes for MPM requires further evaluation. Methods: We identified all patients with MPM in the NCDB from 2004 to 2017. Differences in demographic, disease, and treatment characteristics were assessed by year of diagnosis using Chi-square test. The effect of age, race, insurance status, income, distance to treatment center, and education level on overall survival (OS) was assessed by log-rank test. Results: There were 15,287 MPM diagnoses in the NCDB between 2004-2010 and 17,059 diagnoses between 2011-2017. OS improved between the two time periods, with median OS of 9.46 months (95% CI: 9.23-9.63) and 5-year OS rate of 8.3% (95% CI: 7.9-8.7%) in patients from 2004-2011 and median OS of 11.33 months (95% CI: 11.01-11.7) and 5-year OS rate of 12.4% (95% CI: 11.8-13.1%) in patients after 2011, despite an increase in stage IV disease in the latter group. Older patients (≥65 years-old), males, patients with stage IV disease, patients with government primary payer insurance, and patients from urban areas all had significantly worse OS. Patients without comorbidities and those treated at an academic center had significantly better OS. OS was found to significantly increase as both income and education level increase. Patients diagnosed after 2011 were significantly older, were more frequently female, had more stage IV disease, were more frequently treated at academic centers, more commonly had government primary payer insurance, and lived significantly further away from their treatment center. Patients’ time to treatment was significantly increased after 2011 (from 28 to 31 days). Conclusions: Socioeconomic factors play an important role in survival outcomes for patients with MPM. Many of these are linked with access to healthcare resources, which may increase the likelihood of evaluation at academic centers. For a rare malignancy such as mesothelioma, subspecialty care consisting of a comprehensive thoracic surgical evaluation and appropriate multimodality treatment are of great importance. Time to treatment increased during the study period yet OS improved, which our findings suggest are a result of an increase in evaluation and treatment at academic centers by providers skilled in delivering care to MPM patients.

S2923 Leptomeningeal Carcinomatosis as Initial Presentation of Gastric Cancer in a Patient With Rapid Deterioration of Neurological Function

INTRODUCTION: Leptomeningeal carcinomatosis (LMC) is a rare, late-stage complication typically seen in advanced solid tumors. It is found in 2–4% of all solid cancers and although the incidence is increasing, GI tract involvement is rarely reported. We report a case of LMC in a previously healthy man who presented with ataxia and slurred speech followed by rapid deterioration of neurological function as an initial presentation of signet cell gastric adenocarcinoma. CASE DESCRIPTION/METHODS: A 59-year old Caucasian man presented with progressive ataxia, slurred speech and nausea. His medical history was remarkable for flu-like symptoms two weeks prior and gastroesophageal reflux disease. Shortly after presentation, his neurologic and respiratory function suddenly deteriorated, becoming non-verbal and requiring intubation for respiratory failure. His CT head was negative for stroke, but a CTA revealed multiple enlarged cervical lymph nodes. A lumbar puncture revealed malignant cells. An MRI head was suggestive of leptomeningeal carcinomatosis and a CT chest revealed thickening of the distal esophagus. Esophagogastroduodenoscopy (EGD) revealed a 6 cm ulcerated, friable gastroesophageal junction mass encompassing 50% of the lumen. Biopsies from both EGD and cervical lymph nodes revealed poorly differentiated adenocarcinoma of the stomach with signet ring cell features. A paraneoplastic component was thought to have contributed to his worsening mental status and a trial of plasmapheresis was done without improvement. Given his worsening neurological function, spread to the leptomeninges and overall poor status, systemic and intrathecal chemotherapy was not offered. The family opted for a palliative approach and the patient died in the ensuing days. DISCUSSION: LMC is a rare complication of advanced cancer with a dismal prognosis. The incidence of LMC secondary to gastric cancer is reported to be approximately 0.14–0.24%, with signet cell morphology being particularly aggressive. Median survival of untreated patients is around 4–6 weeks. Tumor spread to the meninges can occur through arteries and lymphatics, perineural and perivascular spaces, retrograde flow of Batson's plexus and direct infiltration. Therapeutic options can include systemic and intrathecal chemotherapy, but most patients trend towards palliative care. Our case displays the latent nature of gastric cancer and highlights the need to have a comprehensive evaluation for malignancy in these patients centered around imaging, CSF studies, and endoscopy.Figure 1.: Ulcerated gastroesophageal junction mass.Figure 2.: Leptomeningeal enhancement, MRI T1 post-contrast.Figure 3.: Poorly differentiated adenocarcinoma with signet ring cell features (400x).

Therapy and Prophylaxis of Peritoneal Metastases from Colorectal Cancer.

Stage IV colorectal cancer is associated with high mortality, and the prognosis is significantly worse for patients have peritoneal metastases. Peritoneal carcinomatosis from colorectal cancer was considered incurable with an infaust prognosis. Median survival of untreated patients is about 6 months and palliative systemic chemotherapy can prolonge this time up to 20 months. Patients with this disease were previously only surgically treated if they had severe clinical symptoms or complications. This view has changed dramatically over the past 15 years. Aggressive cytoreductive surgery in combination with intraperitoneal chemotherapy may prolong median survival for more than 40 months in selected patients. The Peritoneal Surface Oncology Group International (PSOGI), the international authority on the treatment of peritoneal tumors, recommends cytoreduction with intraperitoneal chemotherapy as the standard of care for selected patients with moderate-to-small volume peritoneal metastases secondary to colorectal cancer. Macroscopic cytoreduction appears to be essential; however, the role of hyperthermic intraperitoneal chemotherapy and the optimal chemotherapeutic agent for intraperitoneal lavage to treat peritoneal metastases from colorectal cancer remain unclear. The results of ongoing and future clinical trials are eagerly awaited.

Unknown primary carcinoma in the Netherlands: decrease in incidence and survival times remain poor between 2000 and 2012

Background/aimUnknown primary tumour (UPT) is the term applied to metastatic cancer, the origin of which remains unidentified. Since cancer treatment is primarily based on the tumour site of origin, treatment of UPT patients is challenging. The number of reports on incidence, treatment and survival of UPT is limited. We hereby report data on patients (2000–2012) with UPT in the Netherlands. MethodsThe age-standardised rate (ASR) of ‘other and unspecified’ malignancies in the Netherlands was compared with other European countries. Patients diagnosed with UPT between 2000 and 2012 were selected from the Netherlands Cancer Registry (NCR) to calculate incidence rates. Patient characteristics, treatment and survival rates were assessed. ResultsThe ASR of ‘other and unspecified’ malignancies in the Netherlands did not differ from the European average ASRs (2008–2012). A total of 29,784 patients with an unknown primary tumour were selected from the NCR (2000–2012). The incidence decreased from 14 per 100,000 person years (European standardised rate) in 2000 to 7.0 in 2012. The most common metastatic sites were liver, lymph nodes, bone and lung (42%, 22%, 16% and 14%, respectively), and approximately two-thirds of patients were diagnosed with metastases at a single site. One-third of the patients were treated; these were mainly younger patients. The overall median survival for all patients was 1.7 months. The median survival of untreated patients was 1.0 month and of treated patients 6.3 months. ConclusionThe incidence of UPT between 2000 and 2012 is decreasing in the Netherlands, and one-third of these patients received treatment. Survival after diagnosis is limited to months rather than years.

Abstract 2171: Efficacy of chemotherapeutic agents in brain metastases of lung cancer model

Abstract Background: Lung cancer is not only the second most common cancer in the United States, but it is also the highest cause of cancer-related death worldwide. In 2017, it is estimated that there will be over 200,000 new cases and 150,000 deaths as a result of lung cancer. The associated high mortality can in part be attributed to the high rate of primary lung cancer metastasis to the brain. Median survival for untreated patients with metastatic brain lesions is approximately 4 to 9 months, while treated patients still typically die within two years. Treatment options are limited for patients with brain metastases due in part to chemotherapeutic ineffectiveness, as many agents used to treat the primary tumor are not able to penetrate the blood-brain barrier (BBB). This study aims to investigate the efficacy of various chemotherapies on brain metastases of lung cancer via bioluminescence imaging data as a surrogate for tumor burden and overall survival data. Methods: Female athymic nude mice underwent intracardiac injection with brain-seeking PC-9 lung cancer cells transfected with Luc-2 and TdTomato. Tumor burden was monitored using bioluminescent imaging biweekly. Upon tumor burden establishment, mice were administered either Doxil (peglylated liposomal doxorubicin) (6 mg/kg), irinotecan (50 mg/kg), gemcitabine (60 mg/kg), docetaxel (10 mg/kg), eribulin (1.5 mg/kg), vinorelbine (10 mg/kg), cisplatin (5 mg/kg) + etoposide (10 mg/kg), cisplatin (5 mg/kg) + pemetrexed (100 mg/kg), osimertinib (25 mg/kg), or gefitinib (6.25 mg/kg). Upon sacrifice, brains were perfused to visualize tumors and permeability using fluorescent microscopy. Survival data were collected and plotted on a Kaplan-Meier curve for statistical analyses. Results: Bioluminescence for nontargeted chemotherapy was nearly equal to that of vehicle. Osimertinib (25 mg/kg) demonstrated immediate decreased tumor burden and increased survival. Vehicle and all nontargeted agents had a survival of 42 +/- 3 days. Images taken of metastatic lesions indicate permeability has increased compared to normal brain, but is not as drastic as expected (1.5 to 1.8 fold increase) and displays heterogeneity between tumors. Conclusion: The efficacy of chemotherapies in brain metastases of lung cancer is not necessarily associated with increased permeability. No smaller nontargeted agent showed improved survival or superior tumor control compared to vehicle, while the third-generation EGFR inhibitor osimertinib showed superior tumor burden control and survival in vivo. Future directions aim to investigate methods to increase drug permeation into tumors so that they may overcome the BBB and accumulate to cytotoxic levels in tumors. Citation Format: Rachel M. Tallman, Neal Shah, Sam Sprowls, Mark Pinti, Afroz Mohammad, Paul Lockman, Pushkar Saralkar. Efficacy of chemotherapeutic agents in brain metastases of lung cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2171.

Patients of all ages with advanced non-small cell lung cancer are not receiving chemotherapy.

Patients of all ages with advanced non-small cell lung cancer are not receiving chemotherapy.

The Biology of Brain Metastasis: Challenges for Therapy.

Many patients with lung cancer, breast cancer, and melanoma develop brain metastases that are resistant to conventional therapy. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with surgery, radiotherapy, and chemotherapy. The outcome of metastasis depends on multiple interactions of unique metastatic cells with host homeostatic mechanisms which the tumor cells exploit for their survival and proliferation. The blood-brain barrier is leaky in metastases that are larger than 0.5-mm diameter because of production of vascular endothelial growth factor by metastatic cells. Brain metastases are surrounded and infiltrated by microglia and activated astrocytes. The interaction with astrocytes leads to up-regulation of multiple genes in the metastatic cells, including several survival genes that are responsible for the increased resistance of tumor cells to cytotoxic drugs. These findings substantiate the importance of the "seed and soil" hypothesis and that successful treatment of brain metastases must include targeting of the organ microenvironment.

Prise en charge des atteintes métastatiques leptoméningées des tumeurs solides

The incidence of metastases of the central nervous system (CNS) is increasing, due to the improvement of the overall survival of cancer patients. Leptomeningeal metastases (LM) are now more often identified, although the criteria used for the diagnosis and monitoring remains inadequate. LM should be diagnosed at an early stage of the disease before the setting of neurological deficits, in order to improve the quality of life of patients. Therapeutic indications remain difficult, though some criteria have been proposed. Prolonged survivals have been reported even in the presence of identified poor prognostic factors at the time of the diagnosis of LM. The median survival of untreated patients is 4 to 6 weeks. Specific treatment may prolong survival by several months. Only six randomized studies are available. All theses studies have limitations due to the difficulty of including these patients in homogeneous trials, with a good methodology and for a time acceptable to the patient enrolment. The treatment requires a combination of chemotherapy and targeted therapies administrated systemically or via intra-cerebrospinal fluid (CSF) route, surgery and radiotherapy. Patient management is specific but requires a multidisciplinary approach, which may vary according to the characteristics of meningeal disease, the characteristics of primary tumors, the general condition of patients and previous lines of treatments. Our objective was to describe the current management of LM of solid tumors.

A reclassification of Myelodysplastic Syndrome (MDS) patients of RAEB-1 subgroup according to IPSS-R improves discrimination of high risk patients and better predicts overall Survival. A retrospective analysis of 49 Patients

Abstract 4957Refractory anemia with excess of bone marrow (BM) blasts up to 10% (RAEB-1) has been generally considered a MDS subgroup with moderate prognosis and most of the patients are not indicated for immediate intensive treatment. In our retrospective study, 27 out of 49 patients with RAEB-1 had intermediate-1 (IM-1) risk and 22 patients were classified as intermediate-2 (IM-2) risk group according to the IPSS. Nevertheless, median survival of untreated patients with RAEB-1. was only 5. 0 months compared to 36. 3 months in untreated patients with ≤ 5% BM blasts at the time of diagnosis (P<0. 0001). After reclassification of patients according to revised IPSS (IPSS-R) only 14 patients remained in the intermediate (IM) risk group and 3 patients were even shifted to the low (L) risk group. On the other hand, 14 patients have fulfilled criteria for high (H) risk group and 18 out of 49 patients (37%) had very high (VH) risk score. Median survival of patients treated with low dose chemotherapy (9. 0 months) or hydroxyurea (8. 8 months) was not significantly different from that in patients who received supportive care only. A significant benefit in median survival was observed after combination chemotherapy (14. 0 months) or after stem cell transplantation (SCT) (17. 0 months). SCT was the only treatment connected with prolonged survival, nevertheless, estimated 5 years overall survival of 31. 2 months was significantly inferior (P=0. 02) to that of transplanted patients not only with ≤ 5% BM blasts (62. 2 months) but also with > 10% BM blasts (55. 6 months). Univariate analysis using Kaplan-Meier curves and log-rank2 test revealed as significant variables affecting overall survival: poor cytogenetics IPSS subgroup (P=0. 001), ECOG > 2 (P=0. 001), IM-2 IPSS risk group (P=0. 001), treatment with SCT (P=0. 003), platelet (PLT) count < 20×109/l (P=0. 004), high or very high IPSS-R risk group (P=0. 01) and age > 60 years (P=0. 03). The most important independent variable for determining overall survival (studied by Cox regression multivariate analysis) was poor cytogenetics according IPSS (P=0. 0001, χ2=52. 623), followed by PLT count < 20×109/l (P=0. 001, χ2= 10. 382), and ECOG > 2 (P=0. 002, χ2= 9. 794). Our data suggest that RAEB-1 represent a poor prognostic MDS subgroup with similar outcome as advanced MDS with > 10% BM blasts. The analysis confirms the usefulness of IPSS-R for prediction of survival and for better discrimination of high risk patients in subgroups of patients with less advanced disease. Moreover, the results of regression analysis justify the high scoring value of cytogenetic abnormalities used in IPSS-R. SCT represents the only treatment enabling a long-term survival of RAEB-1 patients, nevertheless, our results of SCT were inferior to that achieved in patients with advanced MDS. Thus, more extensive clinical trials validating efficiency of hypomethylating agents and other new drugs in the treatment of RAEB-1 patients are needed. Disclosures:No relevant conflicts of interest to declare.

Astrocytes Upregulate Survival Genes in Tumor Cells and Induce Protection from Chemotherapy

In the United States, more than 40% of cancer patients develop brain metastasis. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with conventional radiotherapy and chemotherapy. The growth and survival of metastasis depend on the interaction of tumor cells with host factors in the organ microenvironment. Brain metastases are surrounded and infiltrated by activated astrocytes and are highly resistant to chemotherapy. We report here that coculture of human breast cancer cells or lung cancer cells with murine astrocytes (but not murine fibroblasts) led to the up-regulation of survival genes, including GSTA5, BCL2L1, and TWIST1, in the tumor cells. The degree of up-regulation directly correlated with increased resistance to all tested chemotherapeutic agents. We further show that the up-regulation of the survival genes and consequent resistance are dependent on the direct contact between the astrocytes and tumor cells through gap junctions and are therefore transient. Knocking down these genes with specific small interfering RNA rendered the tumor cells sensitive to chemotherapeutic agents. These data clearly demonstrate that host cells in the microenvironment influence the biologic behavior of tumor cells and reinforce the contention that the organ microenvironment must be taken into consideration during the design of therapy.

Abstract 3428: Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy

Abstract Background. In the USA, more than 40% of cancer patients develop brain metastasis. The median survival of untreated patients is 1-2 months which may be extended to 6 months with conventional therapy. The resistance of tumor cells growing in the brain to chemotherapy has been attributed to the blood-brain barrier (BBB). Recent data, however, reveal that tumor cells growing in the brain release VEGF that leads to vascular permeability, ruling out that the BBB is a sole mechanism of drug resistance. Brain metastases are surrounded and infiltrated by activated astrocytes whose role in physiology is to protect neurons from toxicity. We became intrigued by the possibility that tumor cells exploit astrocytes for protection from apoptosis induced by chemotherapeutic drugs. Material and Methods. Human breast cancer cells (MDA231) and human lung cancer cells (PC14Br4) were co-cultured with GFP-labeled murine astrocytes or NIH3T3 fibroblasts. Chemosensitivity assays against P-glycoprotein (P-gp)-1-associated chemotherapeutic agents, such as paclitaxel, adriamycin, vinblastine, and vincristine, or P-gp-1-dissociated agents such as 5-FU and cisplatinum, were performed by propidium iodide staining and FACS analysis. The development of tumor cell resistance from chemotherapeutic agents was correlated with gap junction communication and expression of survival genes. Identified genes were knocked-down by SiRNA and chemosensitivity was repeated for functional validation. Lastly, to confirm the influence of the microenvironment, tumor cells were first co-cultured with murine astrocytes or fibroblasts and then cultured with either murine astrocytes or fibroblasts. Chemosensitivity assays and gene arrays were performed. Results. Direct cultures of murine astrocytes (but not fibroblasts) with human breast cancer cells or lung cancer cells protected the tumor cells against all tested chemotherapeutic agents, correlating with upregulation of survival genes including GSTA5, BCL2L1, and TWIST1, and activation of Akt and MAPK pathways in the tumor cells. The upregulation of the survival genes and consequent drug resistance were dependent on direct contact between the astrocytes and tumor cells through gap junctions. Knocking down the genes in the tumor cells using specific SiRNA rendered the tumor cells sensitive to the chemotherapeutic agents. The gene expression profiles and chemoresistance were transient, i.e., loss of direct contact of tumor cells with murine astrocytes resulted in loss of resistance and downregulation of the survival genes. Conclusion. Our data clearly demonstrate that host cells, e.g., astrocytes, influence the biological behavior of tumor cells and reinforces the contention that successful therapy of brain metastasis requires targeting both tumor cells and the organ microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3428.

Diagnóstico y tratamiento de las metástasis encefálicas

Cerebral metastasis occur in 20 to 30 percent of patients with systemic cancer and are the most common type of intracranial tumor. The median survival of untreated patients is one month with a slightly longer survival in those treated with steroids. Patients treated with whole brain radiation therapy survive between 3 to 6 months. In selected cases survival can increase to 10 to 12 months with combination of surgery and radiotherapy or stereotactic radiosurgery alone or associated to radiotherapy. Most brain metastasis arise from lung, breast and melanomas. The most important criteria for selecting patients who will benefit from surgery or stereotactic radiosurgery are a Karnofsky score of 70 or more, systemic control of the cancer and absence of leptomeningeal involvement. Surgery is indicated in patients with a single lesion located in an accessible zone and stereotactic radiosurgery is indicated for lesions up to 3 cm of diameter, and in patients with up to 3 or 4 metastasis, no matter their location. The survival benefit of chemotherapy in brain metastasis has not been demonstrated.

Diagnosis and treatment of brain metastasis

Cerebral metastasis occur in 20 to 30 percent of patients with systemic cancer and are the most common type of intracranial tumor. The median survival of untreated patients is one month with a slightly longer survival in those treated with steroids. Patients treated with whole brain radiation therapy survive between 3 to 6 months. In selected cases survival can increase to 10 to 12 months with combination of surgery and radiotherapy or stereotactic radiosurgery alone or associated to radiotherapy. Most brain metastasis arise from lung, breast and melanomas. The most important criteria for selecting patients who will benefit from surgery or stereotactic radiosurgery are a Karnofsky score of 70 or more, systemic control of the cancer and absence of leptomeningeal involvement. Surgery is indicated in patients with a single lesion located in an accessible zone and stereotactic radiosurgery is indicated for lesions up to 3 cm of diameter, and in patients with up to 3 or 4 metastasis, no matter their location. The survival benefit of chemotherapy in brain metastasis has not been demonstrated.

The effect of noninvasive ventilation on ALS patients and their caregivers

Noninvasive ventilation (NIV) reduces mortality and improves some aspects of quality of life (QoL) in ALS. However, concerns remain that progressive disability may negate these benefits and unnecessarily burden caregivers. Thirty-nine patients requiring NIV were offered treatment. Twenty-six were established on NIV, but 13 declined or could not tolerate NIV. Fifteen patients without respiratory muscle weakness (RMW) but with similar ALS severity and age were studied in parallel. Caregivers of 21 NIV, 7 untreated, and 10 patients without RMW participated. Patients and caregivers had detailed QoL measurements for 12 months. NIV patients underwent cognitive testing before and after treatment. RMW correlated with lower QoL. The median survival of untreated patients (18 days; 95% CI 11 to 25 days) was shorter than for NIV patients (298 days; 95% CI 192 to 404 days) and non-RMW patients (370 days; 95% CI 278 to 462 days; log rank test [2 df] = 81, p = 0.00001). A wide range of QoL measures improved within 1 month of starting NIV, and improvements were maintained for 12 months. QoL of non-RMW patients declined as RMW progressed. Caregivers of NIV and non-RMW patients showed similar increases in burden, but NIV patient caregivers developed a deterioration in the Short Form-36 Vitality score. No improvements were found on measures of learning and recall in the NIV patients. Respiratory muscle weakness has a greater impact on quality of life (QoL) than overall ALS severity. Noninvasive ventilation (NIV) improves QoL despite ALS progression. NIV has no impact on most aspects of caregiver QoL and does not significantly increase caregiver burden or stress.

Leptomeningeal Metastases: Current Concepts and Management Guidelines

Neoplastic infiltration of the meninges occurs when malignant cells gain entry into the cerebrospinal fluid (CSF). This is clinically recognized in 4% to 7% of all cancer patients. Leptomeningeal metastases may involve any part of the neural axis via tumor seeding; thus, a multitude of clinical presentations involving one or more domains exist, including the cerebral hemisphere, cranial nerves, and spinal cord and roots. The diagnosis of CSF metastases is often delayed and not appreciated until fixed neurologic deficits become evident. Adequate cytologic analysis of CSF fluid, neuroradiography of brain and spine, and an appropriate clinical context are the key element in diagnosing leptomeningeal metastases. A major challenge of treating neoplastic meningitis is the importance of treating the entire neural axis and stratifying patients in poor risk or good risk categories. Treatment is palliative and involves stabilizing neurologic status and prolonging survival. Median survival for untreated patients is 4 to 6 weeks. Treatment in a broad perspective entails radiotherapy and chemotherapy (systemic and intra-CSF). Commonly used intra-CSF chemotherapy regimens use drugs such as methotrexate, cytarabine, thiotepa, and a sustained-release liposome-encapsulated form of cytarabine (Depocyt, SkyePharma, London, UK). Patients with neoplastic meningitis usually experience a limited survival, even when treated using close adherence to evaluation algorithms and treatment protocols. In randomized controlled clinical trials using currently available intra-CSF chemotherapeutic agents, median survival in carefully selected, study-eligible groups of patients was 2 to 6 months.

The treatment of early squamous cell carcinoma of the piriform fossa

The treatment of early piriform fossa cancer can be either primary radiotherapy with salvage surgery, if necessary, or with primary surgery. The present study investigates 65 patients with T1, > or = 2 or T3 stage disease with no cervical lymph node metastases at presentation. Of this group, 17 were treated by primary irradiation, 34 underwent primary surgery and 14 were unsuitable for any curative treatment. The adjusted actuarial 5-year survival rate for those patients receiving primary radiotherapy was 55% (95% CI 16-78%) and for the surgery group it was 44% (95% CI 18-67%). This difference was not significant (chi 2(1) = 1.29). The median survival for untreated patients was 7 months (4-12 months). There was no significant differences in the time to recurrence at the primary site or in the neck, or in survival after recurrence at these sites. Thirty-five per cent of patients treated by primary irradiation were controlled at the primary site compared with 68% in the surgical group. Failure in the neck was similar for the two groups at 12% and 15% respectively. Salvage surgery was effective for the radiotherapy group with eight out of 11 patients being suitable for treatment. In the final analysis in the radiotherapy group two patients were alive and with their larynx and two alive without their larynx, the remainder of patients having died from the original tumour, intercurrent disease or second primary tumours. The survival figures for the surgery group were proportionately similar except of course, that all patients had lost their larynx.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha‐2a‐interferon/melphalan/prednisone versus melphalan/prednisone in previously untreated patients with multiple myeloma

Alpha-2a-interferon (IFN) has demonstrable activity in advance and refractory multiple myeloma (MM), because of the in vitro synergism between IFNs and cytotoxic agents we report the preliminary results of a therapeutic trial of 50 patients with MM. Twenty-eight patients were randomized to receive melphalan plus prednisone (MP) and 22 were randomized to receive IFN plus MP (IFN-MP). Criteria for response, progression and relapse were those of the Southwestern Oncology Group. 95% of the patients receiving IFN-MP responded to therapy as opposed to 68% of the patients receiving MP (P less than 0.05). Response was independent of M-component immunoglobulin class but in stage III it was higher in the IFN-MP group than in the MP group (P less than 0.05). The combination IFN-MP was well tolerated without unusual or unexpected toxic effects. The response duration time was longer in the IFN-MP group than in the MP group (P less than 0.025). The median survival was 80 weeks in the MP group and in the IFN-MP group the 93% of patients were still alive after 90 weeks (P less than 0.025). Our results show that the use of the IFN as an adjuvant to MP improves the percentage of responders, the response duration time and the median survival of untreated patients with MM.

Ploidy as a prognostic indicator in end stage squamous cell carcinoma of the head and neck region treated with cisplatinum

We measured tumour cellular DNA in 102 patients entered into two phase III trials of chemotherapy for end stage squamous carcinoma of the head and neck. The median survival of untreated patients with aneuploid tumours was 55 days compared with 224 days for patients treated with cisplatinum. This difference was highly significant. In contrast the median survival of untreated patients with diploid tumours was 74 days compared with 118 days for treated patients. Although this difference is statistically significant, the increased survival of 6 weeks is of no clinical benefit compared with the prolongation of survival of 6 months in patients with aneuploid tumours. Multivariate analysis showed that the significant predictors of survival were Karnofsky status, response to chemotherapy and ploidy.