Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

Background

Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC.

Patients and methods

Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed.

Results

Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; P<0.05).

Conclusions

RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.     

Survival of Patients with Primary Brain Tumors: Comparison of Two Statistical Approaches

Purpose

We reviewed the survival time for patients with primary brain tumors undergoing treatment with stereotactic radiation methods at the Masaryk Memorial Cancer Institute Brno. We also identified risk factors and characteristics, and described their influence on survival time.

Methods

In summarizing survival data, there are two functions of principal interest, namely, the survival function and the hazard function. In practice, both of them can depend on some characteristics. We focused on nonparametric methods, propose a method based on kernel smoothing, and compared our estimates with the results of the Cox regression model. The hazard function is conditional to age and gross tumor volume and visualized as a color-coded surface. A multivariate Cox model was also designed.

Results

There were 88 patients with primary brain cancer, treated with stereotactic radiation. The median survival of our patient cohort was 47.8 months. The estimate of the hazard function has two peaks (about 10 months and about 40 months). The survival time of patients was significantly different for various diagnoses (p≪0.001), KI (p = 0.047) and stereotactic methods (p = 0.033). Patients with a greater GTV had higher risk of death. The suitable threshold for GTV is 20 cm³. Younger patients with a survival time of about 50 months had a higher risk of death. In the multivariate Cox regression model, the selected variables were age, GTV, sex, diagnosis, KI, location, and some of their interactions.

Conclusion

Kernel methods give us the possibility to evaluate continuous risk variables and based on the results offer risk-prone patients a different treatment, and can be useful for verifying assumptions of the Cox model or for finding thresholds of continuous variables.     

Streptozocin-Based Chemotherapy in Patients with Advanced Neuroendocrine Neoplasms – Predictive and Prognostic Markers for Treatment Stratification

Background and Aim

Chemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). However, predictive markers for patient selection are still missing. The aim of this study was a retrospective evaluation of the clinicopathological characteristics of pNEN patients receiving STZ-based chemotherapies and to identify predictive and prognostic markers.

Patients and Methods

We retrospectively analyzed 77 patients treated at our center between 1995 and 2013. The median overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. Uni- and multivariate analyses were performed.

Results

The median PFS (mPFS) in patients receiving STZ/5-FU/Dox was 16 months with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as independent risk factors for shorter PFS. Additionally, performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities.

Conclusions

STZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response.     

The Response,Outcome and Toxicity of Aggressive Palliative Thoracic Radiotherapy for Metastatic Non-Small Cell Lung Cancer Patients with Controlled Extrathoracic Diseases

Background and Purpose

For metastatic non-small cell lung cancer (NSCLC) patients with controlled extrathoracic disease after systemic treatment, stable or progressive primary lung lesions may cause respiratory symptoms and increase comorbidities. In the present study, we sought to investigate whether aggressive palliative thoracic radiotherapy (RT) can enhance local control and improve the survival for this subgroup of patients.

Materials and Methods

Between March 2006 and December 2014, 56 patients with metastatic NSCLC who had responsive or stable extrathoracic diseases after chemotherapy and/or molecular targets, and received thoracic RT for stable and progressive primary lung lesions were included. RT with a median dose of 55 Gy (range, 40–62 Gy) was administered in 1.8–2.5 Gy fractions to primary lung tumor and regional mediastinal lymph nodes using modern RT technique. Overall survival (OS) from diagnosis, and locoregional progression-free survival (LRPFS), and survival calculated from radiotherapy (OS-RT) were estimated using the Kaplan-Meier method.

Results

There were 37 men and 19 women with a median age of 60 years at diagnosis. The median interval from the diagnosis of metastatic disease to thoracic RT was 8 months. Following thoracic RT, 26 patients (46%) achieved complete or partial response (overall response rate, ORR). Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma (63% vs. 34%, P = 0.034). EGFR mutations was closely associated with a better ORR (45% vs. 29%, P = 0.284). At a median follow-up time of 44 months, the median OS, LRPFS after RT, and OS-RT were 50 months, 15 months, and 18 months.

Conclusion

Radical palliative throractic RT is safe and might be beneficial for primary lung lesions of metastatic NSCLC patients with controlled extrathoracic diseases.     

Perioperative Chemotherapy in Gastroesophageal Cancer. A Retrospective Monocenter Evaluation of 42 Cases

Background

Perioperative chemotherapy increases the overall and progression-free survival of patients suffering from resectable adenocarcinomas of the lower esophagus, gastroesophageal junction and stomach (GEC). Comparing different chemotherapy regimens platin-based protocols with 5-fluorouracil (5-FU)/calcium folinate (CF) or oral fluoropyrimidines were favorable in terms of efficacy and side-effects. However, there is no consensus which regimen is the most efficacious.

Methods

42 consecutive patients with resectable GEC (UICC II and III) were treated with 3 pre- and postoperative chemotherapy cycles each consisting of epirubicin, oxaliplatin and capecitabine (EOX). We analyzed the overall survival, progression-free survival and toxicity retrospectively in comparison to published data.

Results

The median overall survival in our cohort was 29 months and the progression-free survival was 17 months. The most frequent grade 3 and 4 toxicities during preoperative chemotherapy were diarrhea (16.7%), leukocytopenia (9.5%) and nausea (9.5%); overall 38.1% of our patients suffered from grade 3 or 4 toxicity. Surgery was carried out in 83% of our patients, 69% of those achieved R0 resection.

Conclusion

Comparing our data with the results of previously published randomized trials EOX is at least non-inferior with regard to overall survival, progression-free survival and toxicity. In conclusion, EOX is an appropriate perioperative therapy for patients with resectable GEC.     

An Individual Patient Data Meta-Analysis on Characteristics,Treatments and Outcomes of Glioblastoma/ Gliosarcoma Patients with Metastases Outside of the Central Nervous System

Purpose

To determine the characteristics, treatments and outcomes of patients with glioblastoma multiforme (GBM) or gliosarcoma (GS) and metastases outside of the central nervous system (CNS).

Methods

PubMed and Web of Science searches for peer-reviewed articles pertaining to GBM/ GS patients with metastatic dissemination were conducted using the keywords gliosarcoma, glioblastoma, GBM, metastasis, metastases and metastatic. Additionally, we performed hand search following the references from the selected papers. Cases with metastases to the CNS were excluded and evaluated in a separate study.

Results

109 articles published between 1928 and 2013 were eligible. They reported on 150 patients. We observed a remarkable increase in the number of cases per decade over time. Median overall survival from diagnosis of metastasis (OS_M+) was 6.0 ± 0.8 months and median overall survival from initial diagnosis (OS_ID) 13 ± 2.4 months. On univariate analyses, gender, age, the histological subtype, the time interval between initial diagnosis and diagnosis of metastasis and pulmonary involvement did not influence OS_M+. We did not observe any substantial treatment progress. A comparison of the present cohort with 84 GBM/ GS patients with exclusive CNS dissemination suggests that metastases outside the CNS are related to a slightly more favorable outcome.

Conclusions

The occurrence of extra-CNS metastasis from GBM/ GS is associated with a dismal prognosis, however it seems to compare slightly favorable to CNS dissemination. Crucial treatment progress has not been achieved over recent decades. A central registry should be considered to consecutively gain more information about the ideal therapeutic approach.     

Less Aggressive Surgical Procedure for Treatment of Solid Pseudopapillary Tumor: Limited Experience from a Single Institute

Objectives

To evaluate the clinical characteristics and radiological features of solid pseudopapillary tumor (SPT) and assess surgical therapy strategy.

Methods

A retrospective review was performed in 62 patients pathologically confirmed of SPT treated between 2003 and 2014. The clinical features, radiological examinations and surgical strategies were analyzed.

Results

56 females and 6 males were included in this study, mean age was 26 years old (range: 8–66 years old) with mean size of the tumor was 7.2 cm (range: 3–15 cm), and most tumor were commonly located in the head of pancreas (n = 29). Among all the cases, 3 patients had liver metastasis and underwent resection of SPT and liver metastasis. Furthermore, we performed 29 cases of local tumor excision; other patients underwent pancreaticoduodenectomy, middle pancreatectomy, middle pancreatectomy with splenectomy, distal pancreatectomy with spleen preservation, distal pancreatectomy with splenectomy and duodenum-preserving pancreatic head resection. No patient suffered from lymph node metastases. After median follow-up of 46 months (range: 2–135 months), no mortality or local recurrence or distant metastasis was found.

Conclusions

Solid pseudopapillary tumor is a latent malignant tumor with excellent prognosis. If feasible, less aggressive resection without regular lymphadenectomy is recommended for treatment of patients with SPT.     

Positive Lymph Node Metastasis Has a Marked Impact on the Long-Term Survival of Patients with Hepatocellular Carcinoma with Extrahepatic Metastasis

Background

The prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastasis is extremely poor. However, what is the main risk factor for survival remains unclear for these patients. We aimed to find out the relative frequency, incidence and locations of extrahepatic metastases and the risk factors of long-term survival of the patients.

Methods

132 HCC patients with extrahepatic metastasis diagnosed by ¹⁸F-FDG PET/CT and conventional workup were enrolled into this study. The incidence and locations of extrahepatic metastases were summarized, and the related risk factors of overall survival were analyzed.

Results

The most frequent extrahepatic metastatic sites were lymph nodes in 72 (54.5%), bone in 33 (25.0%) and lung in 28 (21.2%) patients. On univariate analysis, prothrombin time, Child-Pugh grade, portal/hepatic vein invasion and lymph node metastasis were independent risk factors of overall survival. On multivariate analysis, lymph node metastasis was the only independent risk factor of overall survival. The cumulative survival rates at 1- and 3-years after diagnosis of extrahepatic metastasis of HCC were 34.4% and 9.3%, respectively. The median survival time was 7 months (range 1 ∼38 months). The median survival time for patients with or without lymph node metastasis were 5 months (range 1∼38 months) and 12 months (range 1∼30 months), respectively (P = 0.036).

Conclusions

This study showed lymph nodes to be the most frequent site of extrahepatic metastases for primary HCC. Lymph node metastasis was the main risk factor of overall survival in patients with HCC with extrahepatic metastasis.     

Post-Progression Survival after EGFR-TKI for Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations

Background

Non-small cell lung cancer (NSCLC) patients that harbor epidermal growth factor receptor (EGFR) mutations benefit from receiving an EGFR-tyrosine kinase inhibitor (TKI); however, post-progression survival (PPS) after EGFR-TKI treatment has not been sufficiently studied.

Methods

We retrospectively reviewed the clinical data from stage IV or recurrent NSCLC patients who harbored EGFR mutations and who received EGFR-TKI as their first-line treatment in our institute between 2009 and 2011.

Results

In total, 36 patients received EGFR-TKI treatment as their first-line therapy. Of those 36 patients, 30 experienced recurrence and were enrolled in this study. The median progression-free survival (PFS) of these patients was 8.2 months. Twelve patients received EGFR-TKI treatment beyond the diagnosis of progressive disease (PD), and 8 received second-line therapy. The PPS after EGFR-TKI treatment was 9.1 months, and survival after the termination of EGFR-TKI treatment in those patients treated with second-line chemotherapy was 13.9 months. The site of relapse was investigated and PFS in EGFR-TKI-treated patients with relapse in the brain (11.6 months) showed a trend toward a longer PFS compared with patients with relapse at other sites (8.2 months). The median PPS after EGFR-TKI treatment also showed the same trend in each group (12.9 and 9.2 months, respectively).

Conclusions

The PPS after EGFR-TKI treatment failure was 9.1 months, while the survival of patients who underwent second-line chemotherapy after the termination of EGFR-TKI treatment was 13.9 months, comparable with the overall survival of EGFR mutation-negative patients, as previously reported. The prognosis of these NSCLC patients with EGFR mutations varied according to the sites of recurrence after first-line EGFR-TKI treatment. Of particular note was the prognosis of patients with brain metastases, which tended to be better than that of patients with metastases to other sites.     

Natural History of Malignant Bone Disease in Gastric Cancer: Final Results of a Multicenter Bone Metastasis Survey

Background

Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available.

Patients and Methods

Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed.

Results

Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005).

Conclusions

To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients.     

Characteristic and Prognostic Implication of Venous Thromboembolism in Ovarian Clear Cell Carcinoma: A 12-Year Retrospective Study

Purpose

To profile the characteristic and prognostic implications of venous thromboembolism (VTE) in Chinese ovarian clear cell carcinoma (CCC) patients.

Methods

We identified all of the cases between 2000 and 2012 by searching our institutional Ovarian CCC Database. A comprehensive review of the medical documentation was performed to collect relevant data. Kaplan-Meier models and Cox regression were employed for survival analysis.

Results

Of the 227 patients, 33 (14.5%) experienced VTE events. There was no significant difference between VTE and non-VTE group patients regarding age, serum cancer antigen 125 or tumor size. The optimal cytoreduction rate was higher in patients without VTE (70.1%) than in those with VTE (51.5%). VTE events were more likely to occur at presentation (36.4%) and recurrence (33.3%), followed by an adjuvant chemotherapy period (18.2%). VTE was more common in patients with advanced-stage disease than those with early-stage disease (P=0.003), whereas pulmonary embolism (PE) was 10-fold as common in advanced-stage disease as in early-stage disease (8.6% vs. 0.8%, P = 0.012). Patients with advanced disease tended to have thrombi in the proximal veins. Two patients died of PE, as confirmed by autopsy. Patients with VTE had reduced survival compared to those without VTE (median overall survival 54 vs. 140 months, P<0.001; median progression-free survival 17 vs. 43 months, P<0.001).

Conclusions

Overall, 14.5% of the patients with ovarian CCC experienced VTE, mainly before their cancer diagnosis or at a time of recurrence. VTE adversely impacted patient survival.     

Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer

Purpose

Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer.

Patients and Methods

This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity.

Results

Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET.

Conclusion

Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.

Trial Registration

ClinicalTrials.gov NCT00917462     

Cytoreductive Surgery of Colorectal Peritoneal Metastases: Outcomes after Complete Cytoreductive Surgery and Systemic Chemotherapy Only

Background

Cytoreductive peritoneal surgery (CRS) associated with hyperthermic peritoneal chemotherapy (HIPEC) has long been considered the standard treatment for colorectal peritoneal metastases (CPM). However, although efficacy of surgery has been demonstrated, evidence supporting HIPEC’s role is less certain.

Method

Overall survival (OS), progression-free survival (PFS) and morbidity were analysed retrospectively for fifty consecutively included patients treated for colorectal CPM with complete CRS and systemic chemotherapy only.

Results

Median peritoneal cancer index (PCI) was 8 (range 1-24). 23 patients had liver or lung metastases (LLM). 22 patients had synchronous CPM. 27 complications occurred (12 Grade 1/2, 14 Grade 3, 1 Grade 4a, 0 Grade 5). Median follow-up was 62.5 months (95 %CI 45.4-81.3), median survival 32.4 months (21.5-41.7). Three- and 5-year OS were 45.5% (0.31-0.59) and 29.64% (0.17-0.44) respectively. Presence of LLMs associated with peritoneal carcinomatosis was significantly associated with poorer prognosis, with survival at 5 years of 13.95% (95 %CI 2.9-33.6) vs. 43.87% (22.2-63.7) when no metastases were present (P= 0.018). Median PFS was 9.5 months (95 %CI 6.2-11.1).

Conclusion

With an equivalent PCI range and despite one of the highest rates of LLM in the literature, our survival data of CRS + systemic chemotherapy only compare well with results reported after additional HIPEC. Tolerance was better with acceptable morbidity without any mortality. Extra-hepatic metastasis (LLM) is a strong factor of poor prognosis. Awaiting the results of the randomized PRODIGE trial, these results indicate that CRS + systemic chemotherapy only is a robust hypothesis to treat colorectal CPM.     

Advanced Unilateral Retinoblastoma: The Impact of Ophthalmic Artery Chemosurgery on Enucleation Rate and Patient Survival at MSKCC

Purpose

To report on the influence of ophthalmic artery chemosurgery (OAC) on enucleation rates, ocular and patient survival from metastasis and impact on practice patterns at Memorial Sloan Kettering for children with advanced intraocular unilateral retinoblastoma.

Patients and Methods

Single-center retrospective review of all unilateral retinoblastoma patients with advanced intraocular retinoblastoma treated at MSKCC between our introduction of OAC (May 2006) and December 2014. End points were ocular survival, patient survival from metastases and enucleation rates.

Results

156 eyes of 156 retinoblastoma patients were included. Primary enucleation rates have progressively decreased from a rate of >95% before OAC to 66.7% in the first year of OAC use to the present rate of 7.4%. The percent of patients receiving OAC has progressively increased from 33.3% in 2006 to 92.6% in 2014. Overall, ocular survival was significantly better in eyes treated with OAC in the years 2010–2014 compared to 2006–2009 (p = 0.023, 92.7% vs 68.0% ocular survival at 48 months). There have been no metastatic deaths in the OAC group but two patients treated with primary enucleation have died of metastatic disease.

Conclusion

OAC was introduced in 2006 and its impact on patient management is profound. Enucleation rates have decreased from over 95% to less than 10%. Our ocular survival rate has also significantly and progressively improved since May 2006. Despite treating more advanced eyes rather then enucleating them patient survival has not been compromised (there have been no metastatic deaths in the OAC group). In our institution, enucleation is no longer the most common treatment for advanced unilateral retinoblastoma.     

From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC)

Backgrounds

Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications is associated with survival benefit.

Methods

Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA), selective serotonin reuptake inhibitors (SSRIs), doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1) were identified.

Results

There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002). The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively). The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828–2.525; p <0.001).

Conclusions

Results of drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic. Our data demonstrated that radiotherapy appears to be an independent survival predictor in stage 4 SCLC, therefore confirming the results of other prospective and retrospective studies.     

A20 Mutation Is Not a Prognostic Marker for Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

Background

Constitutive activation of nuclear factor κB (NF-κB) is a hallmark of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Mutations in the A20 gene activate NF-κB, but the prognostic value of A20 mutations in ABC-DLBLC is unclear.

Purpose

To investigate the prognostic value of A20 mutation in ABC-DLBCL patients.

Methods

The somatic mutation of A20 was investigated in 68 de novo ABC-DLBCLs by PCR/sequencing. The Kaplan-Meier method was used to estimate median overall survival (OS) and progression-free survival (PFS).

Results

The A20 mutation rate in ABC-DLBCL patients was 29.4%. Complete remission rates were 35% and 45.8% in patients with and without A20 mutations, respectively (P = 0.410). In patients with and without A20 mutations, the median OS was 24.0 and 30.6 months, respectively (P = 0.58), and the median PFS was 15 and 17.4 months, respectively (P = 0.52). None of the differences between the patient groups were significant.

Conclusions

Our findings suggested that the A20 mutation is a frequent event in ABC-DLBCLs. However, there was no significant difference in PFS and OS in patients with or without A20 mutations. Further study is required to completely exclude A20 somatic mutation as a prognostic marker in the ABC subtype of DLBLC.     

Marital status and survival in pancreatic cancer patients: a SEER based analysis

Background

Recent findings suggest that marital status affects survival in patients with different types of cancer. However, its role in the survival of patients with pancreatic ductal adenocarcinoma is unknown. In this study, we investigated whether there was an association between marital status and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

Adult patients diagnosed with PDAC between 1998 and 2003 with known marital statuses were identified from the Surveillance, Epidemiology, and End Results registry of the National Cancer Institute. OS for these patients was plotted using the Kaplan-Meier method. Comparative risks of mortality were evaluated by using univariate and multivariate-adjusted Cox regression models.

Results

Using Kaplan-Meier analysis, we found that the median overall survival of patients was 4 months and 3 months (p<0.001) for married and unmarried patients, respectively. Subgroup analysis on patients with cancer-directed surgery showed that the median survival was 16 months and 13 months (P<0.0005) for married and unmarried groups, respectively. Multivariate analysis adjusting for age, race, sex, stage, year of diagnosis, radiation therapy and cancer-directed surgery showed that patients who were married at the time of diagnosis had a significantly decreased risk of death at both 2 months (15% risk reduction) and 3 years (13% risk reduction) post diagnosis.

Conclusions

Marital status is an independent prognostic factor of both perioperative and long-term survival in patients with PDAC. This observation may suggest a suboptimally met psychosocial need among PDAC patients that is partially fulfilled by the support system provided by marriage.     

Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

Introduction

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor.

Methods

Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease.

Results

Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung.

Conclusion

The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00339586","term_id":"NCT00339586"}}NCT00339586     

Merkel Cell Carcinoma Analysis of Outcomes: A 30-Year Experience

Background

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with poor prognosis. Limited data exists to guide treatment decisions. Here we report on our institutional experience and outcomes treating patients with MCC.

Methods

A database search (1984-2014) of patients treated at the University of Wisconsin Hospital and Clinics was used to identify patients with histologically confirmed MCC. Patient, tumor, and treatment characteristics were examined via review of medical records. Statistical analyses were performed to assess outcomes and associated prognostic factors.

Results

A total of 87 patients with MCC were identified with a median follow-up of 17 months (mean: 38, range: 0-210 months). Two and five-year overall survival rates were 53.9% and 32.8%, respectively. Recurrence was documented in 31.0% of patients (85.2% locoregional, 48.1% distant and 33.3% both). Patients with a history of immunosuppression exhibited significantly worse survival (hazard ratio, 2.01; 95% CI, 1.1-3.7) when compared to immune-competent individuals. The head and neck region was the most common location of primary lesion (N=49) followed by the extremities (N=31). Upper extremity primaries predicted significantly better overall survival (hazard ratio, 0.48; 95% CI, 0.23-0.99) while lower extremity primaries did not have significantly better results (hazard ratio, 0.5; 95% CI, 0.21-1.2) in comparison to head and neck site of primary. Nodal involvement (hazard ratio, 2.95; 95% CI, 1.5-5.79) was also a negative prognostic factor associated with poor overall survival when compared with clinically node negative patients. Primary tumor size > 2 cm (hazard ratio, 1.76; 95% CI, 0.91-3.4) was not associated with survival.

Conclusions

This study highlights the role of various factors in determining prognosis of Merkel cell carcinoma; history of immunosuppression, nodal involvement, and head/neck primary predicted worse overall survival. These findings suggest that improvements in both distant and locoregionally directed therapies might play an important role in control of MCC and identify areas for future study.     

Concurrent Chemotherapy for T4 Classification Nasopharyngeal Carcinoma in the Era of Intensity-Modulated Radiotherapy

Objective

To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT).

Methods

From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone.

Results

The median follow-up time was 58.97 months (range, 2.79–114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group.

Conclusion

IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.