Extensive-stage Disease Research Articles

Hospitalization costs of lung cancer diagnosis in Turkey: Is there a difference between histological types and stages?

To establish the direct costs of diagnosing lung cancer in hospitalized patients. Hospital data of patients who were hospitalized and diagnosed as lung cancer between September 2013 and August 2014 were retrospectively analyzed. Patients who underwent surgery for diagnosis and who were initiated with cancer treatment during the same hospital stay were excluded from study. Histological types and stages of lung cancer were determined. Expenses were grouped as laboratory costs, pathology costs, diagnostic imaging costs, overnight room charges, medication costs, blood center costs, consumable expenditures' costs and inpatient service charges (including consultants' service, electrocardiogram, follow-up, nursing services, diagnostic interventions). Of the 68 patients, 55 (81%) had non-small cell lung cancer (NSCLC), 13 (19%) had small cell lung cancer (SCLC). 47% of patients with NSCLC had stage 4 disease and 86% of patients with SCLC had extensive stage disease. Median total cost per patient was 910 (95% CI= 832-1291) Euros (€). Of all costs, 37% were due to inpatient service charges and 22% were medication costs. Median total cost per patient was 912 (95% CI= 783-1213) € in NSCLC patients and 908 (95% CI= 456-2203) € in SCLC patients (p> 0.05). In NSCLC group, total cost per patient was 873 (95% CI= 591-1143) € in stage 1-2-3 diseases and 975 (95% CI= 847-1536) € in stage 4 disease (p> 0.05). In SCLC group total cost per patient was 937 € in limited stage and 502 (95% CI= 452-2508) € in extensive stage (p> 0.05). There is no significant difference between costs related to diagnosis of different lung cancer types and stages in patients hospitalized in a university hospital.

Cell of Origin By Immunohistochemistry Is Not Prognostic of Overall Survival in HIV Associated DLBCL- Analysis of Clinical Pathological Markers in HIV DLBCL

Introduction:Diffuse large B-Cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in HIV population and the survival rate at 2 years is still only 50% (Olszewski AJ et al, Cancer 2016). Based on the cell-of-origin (COO) by immunohistochemistry (IHC), DLBCL is classified into germinal center B-cell like (GCB) and activated B-cell like (ABC or non-GCB) subtypes. While it is well accepted that the ABC subtype is associated with poor outcome in non-HIV DLBCL, the prognostic value of the COO classification in HIV DLBCL has been an issue of debate (Chadburn et al JCO 2009, Dunleavy et al 2010). Current clinical trials stratify patients based on COO in non-HIV DLBCL as the ABC subtype responds better to novel agents like Ibrutinib than GCB. Hence it is important to know whether the two subtypes retain their biological differences in HIV related DLBCL. In order to understand the effect of prognostic variables including subtype and treatment, on survival we conducted a retrospective review of HIV DLBCL in a large single center cohort.Methods:We conducted a retrospective analysis of all HIV infected patients diagnosed with DLBCL (excluding primary CNS) at Montefiore Medical Center between 2000- 2014. The variables that were utilized in the analysis are time of diagnosis of DLBCL, stage, COO subtype of DLBCL (GCB vs non-GCB based on Hans method), LDH (high = >391 u/L), extra-nodal involvement, CD4 count at diagnosis, combination anti-retroviral therapy (cART) at diagnosis, type of chemotherapy, use of rituximab and survival status. Time was divided in 5-year increments -2000 to 2005 (E1), 2005 to 2010 (E2) and 2010 to 2014 (E3).Results:A total of 128 patients with HIV-DLBCL were identified. The mean age was 47 years with a male predominance (70%). Features of high-risk disease were advanced stage III/IV (77%), presence of extra-nodal involvement (65%), and high LDH (51%) seen in 87% of patients. COO classification by IHC (n=75) showed that most were non-GCB (63%) and the rest were GCB (37%) phenotype. HIV specific factors at diagnosis were -CD4 0 to 50 cells (21%), 50-200 (53%) and >200 (25%), mean HIV viral load of 16,459 copies/ml and 61% were on cART. Overall 89% of all patients received treatment and 82% received combination chemotherapy with anthracyclines. There was no significant association between rituximab use (46%) and CD4 counts at diagnosis (p=0.24) while rituximab use was higher in E3 than E1 time period, as expected (p=0.01).The median OS was 26.6 months. On univariate analysis, high LDH (p=0.03), not receiving rituximab (p=0.01) and extensive stage disease (p= 0.034) were significantly associated with poor OS. There was no difference in survival between the 3 time periods (p=0.96). COO subtypes (non-GCB vs GCB) was not predictive of OS (P=0.90), as were HIV specific factors at diagnosis -CD4 (p=0.88) and ART (p=0.51). Cox proportional hazards model showed only rituximab use (HR=0.48 p=0.02) as an independent predictor of survival but not age (HR=1.02, p=0.09), stage (HR=1.95, p=0.09), LDH (HR=1.37, p=0.31) and extra-nodal disease (HR=1.67, p=0.1). Rituximab was the only independent predictor even when subtype was included in the model (n=58) or when restricted to the subset that received treatment (n=94).Conclusions:This is one of the largest cohorts of HIV-DLBCL analyzed. This study shows that the median age of HIV DLBCL is lower, presents with high-risk disease -higher stage, extra nodal involvement and high LDH. HIV specific risk factors like ART and CD4 counts at diagnosis were not prognostic in the era of cART. Even though stage, LDH and extranodal involvement were significant in the univariate analysis, only rituximab use was independently associated with OS in the multivariate analysis. Rituximab use was not significantly different based on CD4 counts, whilst there was an increase in use with time; OS was not significantly different between the time periods. These findings show that rituximab should be used in all HIV DLBCL independent of CD4 counts.The other important finding is that the COO sub classification was not predictive of prognosis in contrast to non HIV-DLBCL where the ABC subtype has an inferior prognosis. Higher expression of c-myc present in HIV-DLBCL may negate the better prognosis of GCB subtype (Chao C et al, CCR 2015). This needs to be explored further, new pathological prognostic markers are to be identified to risk stratify patients and therapeutic subgroups. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Serum Biomarkers Predict Outcomes in Advanced Hodgkin Lymphoma Independent of International Prognostic Score (IPS) and Treatment: Correlative Analysis from a Large North American Cooperative Group Trial

Introduction: Progress in the treatment of patients with classical Hodgkin lymphoma (cHL) depends on identifying methods to better risk-stratify patients and assess prognosis and treatment response. While prognostic scores based on clinical characteristics have utility, inflammatory markers and signaling proteins may better reflect tumor biology, the microenvironment, or host response and might serve as prognostic factors. Increased expression of tumor-associated macrophage markers in tumor tissue, such as CD68 or CD163, has been shown to be associated with inferior survival outcomes in cHL patients. Blood-based markers are more practical in that specimens are readily and serially obtainable. Such markers, if shown to track with tumor response and/or prognosticate outcomes, can be used throughout treatment and follow-up. Some soluble markers, such as TARC (chemokine (C-C motif) ligand (CCL)-17) and soluble CD163 (sCD163), have been shown to reflect tumor burden and active disease, and markers such as soluble CD30 (sCD30), interleukin (IL)-6, chemokine (C-X-C motif) ligand (CXCL)-10/IP10, and IL-2 receptor have been associated with failure-free survival (FFS).Methods: Newly diagnosed cHL patients with locally extensive or advanced stage disease were prospectively enrolled in the Intergroup E2496 randomized controlled trial, which compared ABVD with Stanford V chemotherapy. A panel of serum cytokines, chemokines, and other soluble markers including TARC, CCL22, CCL24, sCD30, sCD163, CXCL10/IP10, CXCL13, soluble CD14 (sCD14), IL-6, IL-10, IL-12, and IL-13, IL1-receptor antagonist (IL1RA)) were measured in pretreatment serum specimens from 301 cHL patients (out of 854 on study) using multiplex (Luminex) bead array immunoassay (R&D Systems). Serum marker values were log-transformed for all analyses. Epstein-Barr virus (EBV) tumor status was determined by EBER in situ hybridization. A linear regression model was used to assess the association between pre-treatment serum marker levels and baseline clinical characteristics. A stratified Cox proportional hazards regression model was used to evaluate the association between serum marker levels as continuous variables and survival outcomes, including FFS (time from registration to disease progression/relapse or death) and overall survival (OS). Patients were divided into quartile groups based on serum marker levels and Kaplan-Meier curves were constructed with comparison using the stratified log-rank test. Three stratification factors were used in all modeling/testing include: stage I-II bulky vs. stage III-IV; IPS 0-2 vs 3-7; and treatment arms (Stanford V vs. ABVD). Two-sided p-values were reported.Results: Increased pre-treatment levels of CCL24, sCD30, sCD163, IP10, sCD14, IL-6, and IL-10 were associated with the presence of B symptoms, independent of age, tumor histology, and disease stage, in multivariate analysis. Higher sCD163 and IP10 levels were associated with EBV positive tumors and higher TARC, CCL22, and CXCL13 levels were associated with EBV negative tumors, after adjusting for age and histology. Several markers were associated with factors in the International Prognostic Score (Table 1). Adjusting for IPS, stage and treatment arms, high levels of IL1RA, sCD30, sCD163, IP10, and IL-10, were significantly (p<0.05) associated with inferior FFS. While high levels of TARC (p=0.02, hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79-0.98), and CXCL13 (p=0.04, HR 0.84, 95% CI 0.72-0.99) were associated with better OS, high levels of CD14 (p=0.02, HR 2.2, 95% CI 1.11-4.38), IP10 (p<0.0001, HR 2.22, 95% CI 1.64-3.00) and sCD163 (p=0.0002, HR 2.89, 95% CI 1.65-5.06) were associated with significantly inferior OS (Figure 1). Conclusion: These findings support prior work demonstrating the prognostic significance of markers such as CD163 in cHL tumor tissue with similar findings using a more readily available (blood-based) method of assessment. The study expands upon the number of blood-based markers shown to be prognostic in cHL, and associates high pre-treatment levels of several markers with IPS factors and other baseline clinical characteristics. Further, and most importantly, IP10 and sCD163 predict inferior FFS and OS independent of IPS and treatment. [Display omitted] [Display omitted] DisclosuresCheson:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding. Winter:Pharmacyclics: Research Funding; Medivation: Other: Provision of investigational agent for clinical trial; GSK: Research Funding; Seattle Genetics: Research Funding. Friedberg:Bayer: Honoraria, Other: Data Safety Monitoring Board. Kahl:This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award number: Research Funding.

528P Incidence, risk factors, treatment outcomes and prognosis of acute kidney injury caused by chemotherapy in patients with lung cancer

Background Palliative chemotherapy is effective first-line therapy for non-small cell lung cancer (stage IIIB-stage IV) and small cell lung cancer extensive-stage disease. Acute kidney injury (AKI) may be developed by palliative chemotherapy especially including cisplatin, however its incidence, risk factors, prognosis and overall survival rate remain unclear. Methods Between Jan. 2005 and Nov. 2014, this retrospective study enrolled 207 lung cancer patients treated with first line palliative chemotherapy. The AKI was defined by serum creatinine change as described in the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline. All patients were grouped base on development of AKI and were staged for level of injury at baseline, 6- and 12-months. Results In total of the 207 patients, 79(38.1%) developed AKI in total period. The incidence of AKI during chemotherapy was 32(15.4%), and the incidence of AKI after chemotherapy was 57(27.5%). Cisplatin is most common cause in AKI during chemotherapy (n = 22). In 70 years older group, the AKI occurred in 16 patients, when compared to the younger than 70 years group, there was no difference in incidence rate. Elderly patients developed AKI earlier cycles (1st to 2nd cycles) than younger patients (81.3% vs 35%, p = 0.006). Prognosis of patients with AKI duration chemotherapy was that 16 (50%) progressed to chronic kidney disease (CKD). There were no patients of progression to end-stage renal disease (ESRD). AKI during chemotherapy group significantly prolonged median time to failure compared with normal renal function group (6.7 vs 4.5 month, P = 0.001). However median overall survival (OS) and progression free survival (PFS) were not different in the AKI during chemotherapy group compared with normal renal function group (OS, 13.7 vs 11.7 months; P = 0.086 and PFS, 5.5 vs 5.3 month; P = 0.423, respectively). Conclusions AKI is still frequent in lung cancer patients with cisplatin containing chemotherapy. AKI during chemotherapy may predispose to CKD, however does not appear to progress to ESRD. AKI during chemotherapy occurred in patients treated with many cycles of chemotherapy for long term. Legal entity responsible for the study N/A Funding Chung-Ang University (I have no funding) Disclosure All authors have declared no conflicts of interest.

Patterns of care and survival among small cell lung cancer patients: Experience from a tertiary center in India

Background/purposeLung cancer is the commonest malignancy and the most common cause of cancer related mortality in males worldwide. Non-small cell lung cancer (NSCLC) is the commonest histology while small cell lung cancer (SCLC) contributes to only 15% of all cases of lung cancer. This report intended to present the patterns of care, survival outcomes and prognostic factors of SCLC treated in a tertiary care institute. ResultsA total of 85 patients of SCLC were registered in radiotherapy unit I during the period January, 2005 to December, 2012. The median age of the cohort was 56.5years (95% CI 34–72). The majority of the patients were male with a male:female ratio of 6.7:1. Sixty eight percent of the patients were smokers. Sixty percent patients presented with extensive stage disease. Radiotherapy (RT) was used in 76% of the patients while chemotherapy was used in 75% of the patients. Platinum Etoposide was the most common regimen which was used in 70% of the patients who received chemotherapy. The median progression free survival (PFS) of the entire cohort was 11.4months (95% CI 9.11–13.58months). Stage, performance status, and use of chemotherapy were found to be significant factors affecting survival outcome in patients with SCLC. ConclusionThe pattern of care and survival outcomes in the present study parallels that of the various published retrospective reviews. Basic research and development of targeted agents may be the way forward in improving the outcome of patients with SCLC.

Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease

IntroductionThis trial assessed the safety and efficacy of LM in combination with carboplatin/etoposide therapy compared to carboplatin/etoposide treatment alone in patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). Patients and MethodsA run-in phase 1 stage was used to determine the recommended phase 2 dose and characterize the dose-limiting toxicities of LM in combination with carboplatin/etoposide followed by LM alone in patients with CD56-positive solid tumors. In phase 2, chemotherapy-naive ED-SCLC patients were randomized 2:1 to carboplatin AUC (area under the plasma concentration vs. time curve) of 5 day 1 + etoposide 100 mg/m2 days 1 to 3 plus LM (arm 1) or alone (arm 2). ResultsIn the phase 1 study (n = 33), a dose of LM at 112 mg/m2 with carboplatin/etoposide was identified as the recommended phase 2 dose. However, because of an increased incidence of peripheral neuropathy events during early phase 2, this dose was reduced to 90 mg/m2. In phase 2, a total of 94 and 47 evaluable patients were assigned to arms 1 and 2, respectively. No difference in median progression-free survival was observed between arms 1 and 2 (6.2 vs. 6.7 months). The most common treatment-emergent adverse event leading to discontinuation was peripheral neuropathy (29%). A total of 21 patients had a treatment-emergent adverse event leading to death (18 in arm 1 and 3 in arm 2); for 10 individuals, this was an infection (pneumonia or sepsis) deemed to be related to the study drug. ConclusionThe combination of LM plus carboplatin/etoposide did not improve efficacy over standard carboplatin/etoposide doublet therapy in ED-SCLC patients and showed increased toxicity, including a higher incidence of serious infections with fatal outcomes.

Overexpression of pro-gastrin releasing peptide promotes the cell proliferation and progression in small cell lung cancer

Pro-gastrin releasing peptide (ProGRP) plays the role of oncogene in small cell lung cancer (SCLC). In this study, we aim to explore the biological function of ProGRP in SCLC cells and its potential mechanism. Expression of ProGRP in SCLC tissues and cell lines were detected by immunohistochemistry and western blot analysis, respectively. The transduced cell lines with ProGRP down-regulation were established using RNA interference technology. Cell viability, cologenic, apoptosis-associated assay and the biomarker levels determination for cell supernatant were performed in the transduced cells to elucidate the biological functions and mechanisms of ProGRP in SCLC cells. Our data showed that ProGRP protein was demonstrated a higher level in SCLC tissues and cells compared with the control, and its diagnostic efficiency was better than NSE, further, the higher levels of ProGRP were detected in the patients with extensive disease stage (P < 0.05), were also the unfavorable factor to the prognosis of SCLC patients.Additionally, the concentration of serum ProGRP is a useful biomarker in disease-monitoring of the patients with SCLC. Down-regulation of ProGRP significantly reduced SCLC cell growth, repressed colony formation, but increased cancer cell apoptosis. Additionally, repression of ProGRP also induced change in the cell cycle and output of NSE. Our data indicated that ProGRP serve as the useful biomarker in the management of SCLC and might be a potential therapeutic target.

Targeting angiogenesis in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive and lethal malignancy. Despite high initial response rates to systemic chemotherapy, the disease eventually relapses; further treatment only modestly improves outcomes and overall survival (OS) for patients with extensive stage disease is less than one year. Little progress has been made during the past decades, with no new drugs approved. Consequently, the development of novel strategies is an unmet need. The inhibition of angiogenesis, a defining characteristic of cancer, has demonstrated modest efficacy in several human malignancies, including non-small cell lung cancer (NSCLC). However, results from clinical trials in SCLC have been disappointing, and no anti-angiogenic agent has received regulatory approval due to lack of clinical efficacy. The elucidation of underlying mechanisms responsible for tumor resistance to angiogenic therapy and the simultaneous blockade of multiple elements that play a role in angiogenesis need to be further explored.

An orthotopic mouse model of small cell lung cancer reflects the clinical course in patients.

Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with very poor prognosis due to early metastatic spread and development of chemoresistance. In the last 30years the study of SCLC has been constrained by a lack of primary human tumor specimen thus highlighting the need of a suitable mouse model. In this article we present the establishment of an orthotopic xenograft mouse model which accurately reproduced the clinical course of SCLC. Orthotopic implantation enabled engraftment of primary lung tumors in all injected mice. Furthermore, immunodeficiency of mice allowed formation of spontaneous metastases in characteristic organs. Bioluminescence Imaging, Magnetic Resonance Imaging and Positron emission tomography were applied to monitor engraftment, metabolism and the exact growth of tumors over time. In order to mimic the extensive disease stage, mice were injected with aggressive human chemoresistant cells leading to development of chemoresistant tumors and early metastatic spread. As a proof of concept treatment of tumor-bearing mice with conventional chemotherapeutics reduced tumor volumes, but a complete regression of tumors was not achieved. By mimicking the extensive disease stage our mouse model can facilitate the study of mechanisms contributing to chemoresistance and metastasis formation, as well as drug screening and evaluation of new treatment strategies for SCLC patients.

Pilot study of first-in-class antimitochondrial metabolism agent, CPI-613, as salvage monotherapy for small cell lung cancer.

e20100Background: Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease...

CheckMate 451: A randomized, double-blind, phase III trial of nivolumab (nivo), nivo plus ipilimumab (ipi), or placebo as maintenance therapy in patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC) after first-line platinum-based doublet chemotherapy (PT-DC).

TPS8579Background: Most SCLC pts present with ED-SCLC. Initial response rates are high, but disease often rapidly recurs or progresses. Outcomes with second-line treatment are poor. No maintenance therapy has been approved for pts who respond to first-line PT-DC. Nivo, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor, is approved for previously treated metastatic NSCLC in the US and for previously treated squamous NSCLC in the EU based on 2 phase III trials demonstrating superior survival over docetaxel. Nivo monotherapy and nivo + ipi, a fully human IgG1 cytotoxic T lymphocyte antigen-4 immune checkpoint inhibitor, are being evaluated in previously treated pts with advanced or metastatic SCLC in a phase I/II trial (CheckMate 032, SCLC cohort). Nivo (vs chemotherapy) is also being evaluated in relapsed SCLC in a phase III trial (CheckMate 331). From CheckMate 032, preliminary data of nivo and nivo + ipi has shown antitumor activity with durable tumor responses and manageable safety...

Seeking New Approaches to Patients With Small Cell Lung Cancer.

The fundamental approach to the treatment of small cell lung cancer (SCLC) has not changed in the last several decades, with most advances being restricted to improved radiation approaches. The standard first-line chemotherapy regimen in the United States and Europe remains cisplatin or carboplatin plus etoposide in the treatment of limited stage (LS-SCLC) and extensive stage (ES-SCLC) disease. Radiation therapy is administered to those patients with LS-SCLC, whose cancer is confined to the chest in a single tolerable radiation field. This article will summarize a number of exciting observations regarding the biology of SCLC and how a deeper understanding of newly integrated targets and target pathways may lead to new and better therapeutic approaches in the near future.

Clinical correlation of extensive-stage small-cell lung cancer genomics

Genomic studies in small-cell lung cancer (SCLC) lag far behind those carried out in nonsmall-cell lung cancer (NSCLC). To date, most SCLC studies have evaluated patients with surgically resectable disease. Here we sought to evaluate the genomic mutation spectrum of 'every-day' SCLC patient tumors with extensive stage disease (ES-SCLC) and to correlate mutations with the main clinical outcomes of response to chemotherapy, progression-free (PFS) and overall (OS) survival. A total of 50 SCLC patient tumors were examined in this study; targeted exome sequencing was obtained on 42 patients and whole-exome sequencing on 8 patients. Mutated genes were correlated with clinical outcomes using Kaplan-Meier methods (PFS, OS) and logistic regression (chemo-response). RB1 protein expression was detected by either western blotting of cultured cell lysates or immunohistochemistry of tumor specimens. In all, 39 patients had ES-SCLC; 15 patients had either primary refractory/resistant disease and 21 patients had sensitive disease. The two most frequently mutated genes were TP53 (86%) and RB1 (58%); other frequently mutated genes (>10% patients) were involved in epigenetic regulation as well as the mTOR pathway. We identified a number of low-frequency, targetable mutations, including RICTOR, FGFR1, KIT, PTCH1 and RET. Using multivariate analysis, RB1 was the only significant factor (P = 0.038) in predicting response to first-line chemotherapy, with an odds ratio of 5.58 comparing mutant RB1 with wild-type. Patients with mutant RB1 had both better OS (11.7 versus 9.1 months P = 0.04) and PFS (11.2 versus 8.6 months, P = 0.06) compared with patients with wild-type RB1. Interestingly, ∼25% of SCLC cell lines and tumor specimens expressed RB1 protein, possibly representing the subgroup with wild-type RB1. We found that SCLC tumors harboring no mutation in RB1 had a poor response to chemotherapy.

Reirradiation of locally recurrent nasopharyngeal cancer: history, advances, and promises for the future.

Local or locoregional recurrence of nasopharyngeal carcinoma (NPC) after high-dose radiotherapy remains a significant clinical problem. This is especially important in regions of the world in which NPC is endemic, such as Southern China. In this review, we briefly present the evolution in the definitive treatment of NPC, but focus more so on the historical and contemporary treatment approaches and outcomes utilized in the recurrent setting. Specifically, we highlight the various treatment strategies (repeat surgery, brachytherapy, conventional re-irradiation, SRS/SBRT, and salvage IMRT), and their technical, physical and biological limitations. Special attention is given towards salvage IMRT, as this is becoming the standard of care for locally recurrent NPC. Further, it is the most commonly indicated modality, since it can be used to treat larger tumors and more extensive disease stages, which represent the majority of recurrent cases. Predictive and prognostic factors for the efficacy of repeat treatment are discussed as well. The toxicities brought about by repeat radiotherapy courses are also highlighted, with an emphasis on their impact on mortality and quality of life, which underscore the difficulty that this clinical entity presents. Lastly, the rationale for particle radiation therapy, which is potentially safer and more efficacious, for the treatment of locally recurrent NPC is presented.

Targeted drugs in small-cell lung cancer.

In contrast to non-small-cell lung cancer (NSCLC), few advances have been made in systemic treatment of small-cell lung cancer (SCLC) in recent years. Most patients are diagnosed with extensive stage disease and are commonly treated with platinum-based chemotherapy which, although attaining high initial objective responses, has a limited impact on survival. Due to the dismal prognosis of SCLC, novel and more effective treatment strategies are urgently needed. A deeper characterization of the genomic landscape of SCLC has led to the development of rational and promising targeted agents. However, despite a large number of clinical trials, results have been disappointing and there are still no approved targeted drugs for SCLC. Recent comprehensive genomic studies suggest SCLC is a heterogeneous disease, characterized by genomic alterations targeting a broad variety of genes, including those involved in transcription regulation and chromatin modification which seem to be a hallmark of this specific lung cancer subtype. Current research efforts are focusing on further understanding of the cellular and molecular abnormalities underlying SCLC development, progression and resistance to chemotherapy. Unraveling the genomic complexity of SCLC could be the key to optimize existing treatments, including chemotherapy and radiotherapy, and for identifying those patients most likely to benefit from selected targeted therapeutic approaches.

Seeking New Approaches to Patients With Small Cell Lung Cancer

The fundamental approach to the treatment of small cell lung cancer (SCLC) has not changed in the last several decades, with most advances being restricted to improved radiation approaches. The standard first-line chemotherapy regimen in the United States and Europe remains cisplatin or carboplatin plus etoposide in the treatment of limited stage (LS-SCLC) and extensive stage (ES-SCLC) disease. Radiation therapy is administered to those patients with LS-SCLC, whose cancer is confined to the chest in a single tolerable radiation field. This article will summarize a number of exciting observations regarding the biology of SCLC and how a deeper understanding of newly integrated targets and target pathways may lead to new and better therapeutic approaches in the near future.

464P Comparision of irinotecan/cisplatin with etoposide/cisplatin in North-West Indian population with extensive-stage disease small-cell lung cancer

464P Comparision of irinotecan/cisplatin with etoposide/cisplatin in North-West Indian population with extensive-stage disease small-cell lung cancer

Pattern of treatment and clinico-epidemiological analysis of 804 lung and pleura cancer patients treated in radiation oncology department, NCI-Egypt

BackgroundEpidemiological profile and treatment outcomes of Lung and pleural malignancies vary among different geographical regions. The aim of the study is to analyze the clinico-pathological profile and pattern of treatment of lung and pleural cancers at the Radiation Oncology department, NCI, Cairo University. Materials and methodsA review of 804 clinical patient records with 770 pathologically/cytologically confirmed patients from Jan 2008-December 2012 was performed. Patients were evaluated (clinical, demographic and pathological profiles) in addition to the treatment adopted. ResultsMedian age was 56years with a male: female ratio of 4:1. Smoking was reported in 63% of patients. Dyspnea and chest pain were the most presenting symptoms (53%). Among lung cancer patients; 78% were NSCLC and 12% SCLC with mesothelioma comprising 10%. Among NSCLCs, adenocarcinoma and large cell undifferentiated carcinoma were the commonest histological subtype (72%). Among NSCLC, 58% cases were of stage IV while among SCLC 73% cases had extensive stage disease. Chemotherapy was administered to 47% (55% vs. 67%, and 35% vs. 31% among non-metastatic lung cancer, mesothelioma patients and metastatic lung cancer and mesothelioma patients respectively). Distant metastases (brain 48%, bone 36%) were reported in 45% of patients. The pattern of treatment intent was palliative (88%) vs. 12% treated with radical intent. ConclusionsAdvanced stages at presentation reflect the palliative pattern of treatment. Hypo-fractionated radiotherapy for lung and pleura malignancies as a palliative measure is the current practice. Implementation of early palliative care should be considered for metastatic patients.

When is surgery indicated for small-cell lung cancer?

Small-cell lung cancer (SCLC) comprises 13-20% of all lung cancers but is the fifth leading cause of cancer death worldwide. SCLC prognosis remains poor despite improvements in diagnosis and therapy over the last 30 years. Current treatment is systemic chemotherapy, flanked by thoracic irradiation for limited stage disease; however, about two-thirds of patients are diagnosed with extensive stage disease when thoracic irradiation is not worthwhile. Randomized trials on surgical resection in patients with limited stage disease conducted in the pre-PET era, when both staging and treatment were inadequate, did not support a role for surgery in disease management. However recent retrospective and population-based studies indicate that outcomes after surgery in patients with very early SCLC are comparable to those in patients with non-SCLC, and that survival is better than in SCLC patients not given surgery. CT screening identifies SCLC at an earlier stage - with better survival - than usual care, and offers the hope that more SCLC patients may become long-term survivors. However, cases must be exhaustively staged to identify those likely to benefit from surgery. Finding a specific SCLC marker to facilitate early diagnosis remains a priority.

Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline.

The American College of Chest Physicians (ACCP) produced an evidence-based guideline on treatment of patients with small-cell lung cancer (SCLC). Because of the relevance of this guideline to American Society of Clinical Oncology (ASCO) membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel updated the literature search, reviewed the content, and considered additional recommendations. The ASCO Endorsement Panel determined that the recommendations from the ACCP guideline, published in 2013, are clear, thorough, and based on current scientific evidence. ASCO endorses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements. Surgery is indicated for selected stage I SCLC. Limited-stage disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle one or two of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. Extensive-stage disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in patients with limited-stage disease who achieve a complete or partial response to initial therapy and may do so in similarly responding patients with extensive-stage disease as well. Additional information is available at http://www.asco.org/endorsements/sclc and http://www.asco.org/guidelineswiki.