High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions.

Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT.

Methods And Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose.

Epidermal growth factor receptor signaling in adenocarcinomas with bronchioloalveolar components.

Background: Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors.

Methods: One hundred fifty tumors were classified as BAC or adeno/BAC.

Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center.

Introduction: Most studies describing the natural history and prognostic factors for malignant pleural mesothelioma antedate accurate pathologic diagnosis, staging by computed tomography, and a universal staging system. We conducted a large single-institution analysis to identify prognostic factors and assess the association of resection with outcome in a contemporary patient population.

Methods: Patients with biopsy-proven malignant pleural mesothelioma at our institution were identified and clinical data were obtained from an institutional database.

Duration of second or greater complete clinical remission in ovarian cancer: exploring potential endpoints for clinical trials.

Objective: To explore benchmarks for future consolidation strategies, we evaluated a strictly defined (normal CA-125 and normal CT) second-complete-remission (CR) ovarian cancer population for 1) the median progression-free survival (PFS), 2) the frequency with which second remission exceeds first, and 3) the proportion of patients in remission at given time points.

Methods: Retrospective sampling was carried out at Memorial Sloan-Kettering (10/1993-12/2000) and the Royal Marsden Hospital (1/1995-4/2003) for the following: histological confirmation and elevated CA-125 at diagnosis; primary surgery; first-and second-line platinum-based chemotherapy with CR; and no maintenance therapy.

Results: In 35 patients 1) the duration of first PFS was 17.

A phase II tolerability study of cisplatin plus docetaxel as adjuvant chemotherapy for resected non-small cell lung cancer.

Introduction: We undertook this phase II study to measure postoperative drug delivery and toxicity of cisplatin plus docetaxel in patients with resected stage I-III non-small cell lung cancer.

Methods: The primary endpoint was amount of cisplatin delivered over a planned four cycles of adjuvant chemotherapy. Statistical design required a cohort to close if the regimen proved unlikely to improve cisplatin delivery compared with published phase III data.

A phase 1 study of pralatrexate in combination with paclitaxel or docetaxel in patients with advanced solid tumors.

Purpose: Pralatrexate is a rationally designed antifolate with greater preclinical antitumor activity than methotrexate. Pralatrexate was synergistic with paclitaxel and with docetaxel in mouse xenograft experiments. This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer.

Induction chemotherapy, extrapleural pneumonectomy, and postoperative high-dose radiotherapy for locally advanced malignant pleural mesothelioma: a phase II trial.

Introduction: Extrapleural pneumonectomy (EPP) and adjuvant high-dose radiation therapy (RT) are associated with a median survival of 3 years in early-stage malignant pleural mesothelioma (MPM) but of less than 1 year in locally advanced disease. Although local control after EPP and RT is excellent, most patients die of distant metastases. We designed this clinical trial to test the feasibility of induction chemotherapy followed by EPP and RT in locally advanced MPM with the ultimate aim of improving survival.

Phase II trial of pralatrexate (10-propargyl-10-deazaaminopterin, PDX) in patients with unresectable malignant pleural mesothelioma.

Background: Several previous clinical trials have shown that malignant pleural mesothelioma is responsive to antifolates. The dihydrofolate reductase inhibitor, pralatrexate, has a favorable toxicity profile, primarily limited to stomatitis, and has demonstrated activity in patients with non-small cell lung cancer. In mesothelioma cell lines and xenografts, pralatrexate demonstrated significant antitumor activity.

Salvage re-irradiation for recurrent head and neck cancer.

Purpose: To present a retrospective review of treatment outcomes for recurrent head and neck (HN) cancer patients treated with re-irradiation (re-RT) at a single medical center.

Methods And Materials: From July 1996-September 2005, 105 patients with recurrent HN cancer underwent re-RT at our institution. Sites included were: the neck (n = 21), nasopharynx (n = 21), paranasal sinus (n = 18), oropharynx (n = 16), oral cavity (n = 9), larynx (n = 10), parotid (n = 6), and hypopharynx (n = 4).

A phase I trial of BMS-247550 (NSC# 710428) and gemcitabine in patients with advanced solid tumors.

The purpose of this study is to establish the maximum tolerated dose and define the dose-limiting toxicity of the investigational epothilone BMS-247550 in combination with fixed dose-rate gemcitabine. Patients with advanced, recurrent solid tumors who had received View Article and Find Full Text PDF

A phase I study evaluating the safety and pharmacokinetics of weekly paclitaxel and carboplatin in relapsed ovarian cancer.

This phase I study sought to determine the toxicity profile, pharmacokinetics, and antitumor activity of giving carboplatin every 3 weeks and paclitaxel weekly in patients with relapsed ovarian cancer. Eligible patients with relapsed epithelial ovarian cancer and prior treatment with platinum- and paclitaxel-based therapy were treated with an escalating regimen of carboplatin (day 1) at an area under the curve (AUC) of 4-6 and 1-h infusions of paclitaxel (days 1, 8, and 15) at 50-80 mg/m(2) cycled at 3-week intervals. Pharmacokinetic studies were performed on the first day of cycles 1 and 2.

American Joint Committee on Cancer staging system does not accurately predict survival in patients receiving multimodality therapy for esophageal adenocarcinoma.

Purpose: In patients with adenocarcinoma of the esophagus who receive preoperative chemoradiotherapy (CRT), American Joint Committee on Cancer (AJCC) stage, pathologic complete response (pCR), and estimated treatment response are various means used to stratify patients prognostically after surgery. However, none of these methods has been formally evaluated. The purpose of this study was to establish prognostic pathologic variables after CRT.

A faster circular binary segmentation algorithm for the analysis of array CGH data.

Motivation: Array CGH technologies enable the simultaneous measurement of DNA copy number for thousands of sites on a genome. We developed the circular binary segmentation (CBS) algorithm to divide the genome into regions of equal copy number. The algorithm tests for change-points using a maximal t-statistic with a permutation reference distribution to obtain the corresponding P-value.

A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma.

Purpose: The aim of this study was to compare toxicity/efficacy of conventional radiotherapy using delayed accelerated concomitant boost radiotherapy (CBRT) vs. intensity-modulated radiotherapy (IMRT) in the setting of concurrent chemotherapy (CT) for locally advanced oropharyngeal carcinoma.

Methods And Materials: Between September 1998 and June 2004, a total of 293 consecutive patients were treated at our institution for cancer of the oropharynx.

The prognostic importance of the number of involved lymph nodes in esophageal cancer: implications for revisions of the American Joint Committee on Cancer staging system.

Objective: The American Joint Committee on Cancer (AJCC) staging system for esophageal cancer is controversial because it relies on arbitrary definitions of the anatomic location of lymph nodes to establish N and M status. It has been proposed that the number of involved lymph nodes may better predict survival. We reviewed our experience to determine the prognostic impact of the number of involved nodes and the extent of lymphadenectomy on the current staging system.

Mortality increases for octogenarians undergoing esophagogastrectomy for esophageal cancer.

Background: As the general population ages, it becomes increasingly important to understand the potential contribution of chronologic age to mortality after esophagectomy. Because this risk is poorly defined, we sought to determine whether extreme age (>80 years) is an independent risk factor after esophagectomy.

Methods: We analyzed a prospectively maintained, single-institution database of 858 consecutive patients who underwent esophagectomy between January 1996 and May 2005.

Properties of analysis methods that account for clustering in volume-outcome studies when the primary predictor is cluster size.

In recent years health services researchers have conducted 'volume-outcome' studies to evaluate whether providers (hospitals or surgeons) who treat many patients for a specialized condition have better outcomes than those that treat few patients. These studies and the inherent clustering of events by provider present an unusual statistical problem. The volume-outcome setting is unique in that 'volume' reflects both the primary factor under study and also the cluster size.

A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers.

Background: SU5416 (semaxanib) is a synthetic small molecule inhibitor of the tyrosine kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2). This Phase II study was conducted to determine the safety and efficacy of SU5416 in patients with recurrent or metastatic head and neck cancers.

Patients And Methods: This was an open label, single arm, Phase 2 study for patients who had received no more than 2 cytotoxic regimens.

Evaluation of postradiotherapy PSA patterns and correlation with 10-year disease free survival outcomes for prostate cancer.

Purpose: To describe the prostate-specific antigen (PSA) pattern profiles observed after external beam radiotherapy with and without short-term neoadjuvant androgen deprivation therapy (ST-ADT) and to report the association of established posttreatment PSA patterns with long-term disease-free survival outcomes.

Methods And Materials: A total of 1,665 patients were treated with conformal external beam radiotherapy for clinically localized prostate cancer. Of 570 patients who had the requisite>10 consecutive PSA measurements for statistical analysis, 194 patients received a median of 3 months of ADT before radiotherapy and 376 were treated with radiotherapy alone.

A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer.

Background: Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC).

Methods: The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy.

Prevalence of COPD in women compared to men around the time of diagnosis of primary lung cancer.

Purposes: COPD is a well-known independent risk factor that is associated with primary lung cancer. There is, however, a striking paucity of women in studies demonstrating this association. The purpose of this study was to compare the prevalence of COPD as determined by pulmonary function tests (PFTs) between women and men at around the time of lung cancer diagnosis.

A method for evaluating the impact of individual haplotypes on disease incidence in molecular epidemiology studies.

Estimation of the association between haplotypes and disease from a case-control study is considered. Assuming a single "disease haplotype'' leads to the increased risk, attention focusses on the relative risks associated with a single copy, or two copies of the disease haplotype, relative to individuals with no copies. In this setting, case frequencies of the haplotype pairs are in Hardy-Weinberg Equilibrium (HWE) only if the combined influence of the two copies of the disease haplotype on risk is multiplicative.

Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma.

Background: The benefit of cytoreductive surgery for patients with recurrent epithelial ovarian cancer has not been defined clearly. The objective of this study was to identify prognostic factors for survival in patients who underwent secondary cytoreduction for recurrent, platinum-sensitive epithelial ovarian cancer and to establish generally applicable guidelines and selection criteria.

Methods: The authors reviewed all patients who underwent secondary cytoreduction for recurrent epithelial ovarian cancer from 1987 to 2001.

Topotecan and liposomal doxorubicin in recurrent ovarian cancer: is sequence important?

A variety of agents have emerged to treat patients with recurrent epithelial ovarian cancer (EOC). Most patients receive both topotecan (T) and liposomal doxorubicin (D); however, there are no data regarding the benefit of a sequence-D followed by T (DT) or T followed by D (TD). We identified 89 consecutive patients with recurrent EOC, who received both D and T from January 1994 to January 2004 at Memorial Hospital.

Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas.

Purpose: Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers.

Methods: EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis.