Mohammed Almubarak

Can Positron Emission Tomography Be Used as a Staging Tool for Small-Cell Lung Cancer?

PURPOSE Positron emission tomography (PET) is widely used for the staging evaluation of non-small-cell lung cancer; however, its use in small-cell lung cancer (SCLC) remains investigational. PATIENTS AND METHODS We did a retrospective study of 137 patients to evaluate the role of PET in SCLC. Fifty-one of 137 patients had computed tomography (CT) and PET scans during initial evaluation of a lung mass. RESULTS All 51 patients had PET-positive results for malignancy (100% sensitivity). In 40 of 51 cases (78%), the PET staging correlated with that on CT. Two of 51 patients (4%) had disease that was accurately upstaged by PET. Positron emission tomography accurately downstaged disease in 6 of 51 patients (12%). Positron emission tomography detected additional sites of disease in 13 of 42 patients (32%). Of the 13 additional sites of disease, PET detected supraclavicular nodes in 4 of 13 patients (30%) and bone lesions in 4 of 13 patients (30%). The sensitivity to detect brain lesions was 5 of 11 patients (45%) in this series. In this series, the PET results from 8 of 51 patients (16%) resulted in a change in disease management. Because of PET results, 6 of 51 patients (12%) who otherwise would not have been treated, were treated with radiation. CONCLUSION Positron emission tomography is potentially useful for accurate initial staging of SCLC and can ensure that a patients disease is not overstaged by CT scan, which might result in denied potentially curative treatment for limited-stage SCLC. It can identify the occult adrenal metastasis and metastasis to supraclavicular lymph nodes that are missed by CT; however, brain lesions are difficult to assess by PET.

Guideline-concordant lung cancer care and associated health outcomes among elderly patients in the United States

OBJECTIVES In the United States (US), the elderly carry a disproportionate burden of lung cancer. Although evidence-based guidelines for lung cancer care have been published, lack of high quality care still remains a concern among the elderly. This study comprehensively evaluates the variations in guideline-concordant lung cancer care among elderly in the US. MATERIALS AND METHODS Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2002-2007), we identified elderly patients (aged ≥65 years) with lung cancer (n = 42,323) and categorized them by receipt of guideline-concordant care, using evidence-based guidelines from the American College of Chest Physicians. A hierarchical generalized logistic model was constructed to identify variables associated with receipt of guideline-concordant care. Kaplan-Meier analysis and Log Rank test were used for estimation and comparison of the three-year survival. Multivariate Cox proportional hazards model was constructed to estimate lung cancer mortality risk associated with receipt of guideline-discordant care. RESULTS Only less than half of all patients (44.7%) received guideline-concordant care in the study population. The likelihood of receiving guideline-concordant care significantly decreased with increasing age, non-white race, higher comorbidity score, and lower income. Three-year median survival time significantly increased (exceeded 487 days) in patients receiving guideline-concordant care. Adjusted lung cancer mortality risk significantly increased by 91% (HR = 1.91, 95% CI: 1.82-2.00) among patients receiving guideline-discordant care. CONCLUSION This study highlights the critical need to address disparities in receipt of guideline-concordant lung cancer care among elderly. Although lung cancer diagnostic and management services are covered under the Medicare program, underutilization of these services is a concern.

Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond

Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

Reinduction of Bevacizumab in Combination with Pegylated Liposomal Doxorubicin in a Patient with Recurrent Glioblastoma Multiforme Who Progressed on Bevacizumab/Irinotecan

Glioblastoma multiforme (GBM) carries a dismal prognosis despite the current standard of multimodality treatments. Recent studies showed promising results to a regimen consisting of a VEGF inhibitor, (bevacizumab) and a topoisomerase I inhibitor (irinotecan) [BI] in recurrent GBM. However, those patients with GBM who progress on BI will succumb to their disease generally in a very short period of time. We report a case of a 56-year-old male patient with GBM who declined surgical resection and received chemoradiation with temozolomide. This treatment was withheld secondary to significant thrombocytopenia. Subsequently, he achieved stable disease for 10 months with a regimen consisting of thalidomide and tamoxifen before progressing. This was followed by bevacizumab with irinotecan [BI], for which he had a significant partial response for 8 months with subsequent progression. Reinducing the patient with bevacizumab in combination with a pegylated liposomal doxorubicin [PLD] (a topoisomerase II inhibitor) demonstrated antitumor activity with significant shrinkage of contrast enhancing mass and peritumoral edema.

Cerebrospinal Fluid Leak During Treatment With Bevacizumab and Irinotecan After Carmustine-Impregnated Wafers Placement in Patients With Grade 2 Oligodendroglioma and Glioblastoma Multiforme: Report of Two Cases and Review of Literature

ABSTRACT Placement of carmustine-impregnated wafers has become a common practice after surgical resection of malignant gliomas. Bevacizumab is used as a second-line agent for the treatment of malignant gliomas and is sometimes used in patients who have had recent wafer implantation. We describe two cases of fatal cerebrospinal fluid (CSF) leak in patients treated with bevacizumab and irinotecan after 4 weeks of carmustine wafer implantation. Possible mechanisms for the CSF leak in these patients are discussed. We recommend waiting for a longer period of time before starting bevacizumab in patients who had implantation of carmustine wafers.

Definitive Upfront Stereotactic Ablative Radiotherapy Combined with Image-Guided, Intensity Modulated Radiotherapy (IG-IMRT) or IG-IMRT Alone for Locally Advanced Non-Small Cell Lung Cancer.

Background Image-guided (IG) intensity-modulated radiotherapy (IMRT) enables maximal tumor margin reduction for the sparing of organs at risk (OARs) when used to treat locally advanced non-small cell lung cancer (NSCLC) with definitive chemo-radiation. It also allows for the incorporation of stereotactic ablative radiotherapy (SABR) into the treatment regimen. Here, we describe our initial experience in combining definitive upfront SABR to the primary lesion with chemo-radiation delivered with conventionally fractionated IG-IMRT to the remaining regional disease; along with clinical outcome following chemo-radiation with conventionally fractionated IG-IMRT alone in the treatment of locally advanced NSCLC. Methods The clinical outcome of 29 patients with locally advanced NSCLC who underwent conventionally fractionated IG-IMRT, or definitive upfront SABR followed by IG-IMRT combined with chemotherapy (induction, concurrent, or both) was retrospectively reviewed. Results After a median follow up of 23.7 months, the median overall survival (OS) and progression-free survival (PFS) were 19.8 and 11.3 months, respectively. The 2 year local, regional, and distant control was 60%, 62%, and 38%, respectively. No local failure was observed in 3 patients following SABR + IG-IMRT while 6/26 patients failed locally following IG-IMRT alone. SABR + IG-IMRT was well tolerated. No ≥ grade 3 radiation-related toxicity was observed. Conclusion Definitive upfront SABR followed by IG-IMRT in selected patients with locally advanced NSCLC warrants further investigation in future clinical trials, while chemo-radiation with IG-IMRT alone was well tolerated.

Patient Understanding and Impression of Hematology/Oncology Fellows

Background:Hematologists/Oncologists spend years of training in a fellowship program. At academic centers, patients receiving treatment are often seen by fellows. It has not been established what patients understand about fellowship training, therefore the purpose of this study was to explore their understanding and whether they are content with fellows taking part in their care. Methods:At West Virginia University/Mary Babb Randolph Cancer Center, the authors drafted a survey. This anonymous and voluntary survey abstracted basic patient demographic data and experience being cared for by fellows and basic knowledge of a Hematology/Oncology fellowship. Multiple-choice questions were drafted with 4 to 6 answer choices with no option for unknown. Surveys were collected over a 3-week period in July 2012. Patients were surveyed at outpatient appointments, infusion center visits, and laboratory draws. Results:Two hundred twenty-six surveys were collected. Statistical analysis was performed and a binomial regression was fit to the data. There is evidence that higher levels of education are more likely to give correct answers (P = 0.035). Patients who stated that they had not seen a fellow or were unsure whether they had seen a fellow were more likely to select incorrect answers (P = 0.001). There is no statistical significance differentiating between cancer types in likelihood of getting answers correct. Of those surveyed, 1.77% felt that they completely understand the role of a fellow in their care, whereas 80.45% desired further information about fellows. Only 2.2% disliked having a fellow involved in their care. Conclusions:Patients at academic centers being seen by Hematology/Oncology fellows appear to have a lack of knowledge of a fellows role and background but have a desire to be educated. Educational initiatives can be introduced to teaching institutions to help patients better understand the role of a fellow.

Patient understanding and impression of hematology/oncology fellows.

9 Background: Hematologists/oncologists spend years training in a fellowship program. At academic centers, patients receiving treatment are often seen by fellows. It has not been established what patients understand about fellowship training, therefore our purpose was to explore their understanding and if they are content with fellows taking part in their care. METHODS At West Virginia University/Mary Babb Randolph Cancer Center we drafted a survey. This anonymous and voluntary survey abstracted patient data that included: age, sex, race, level of education, type of cancer diagnosis, amount of time being treated for cancer, experience being cared for by fellows and basic knowledge of a hematology/oncology fellowship. Multiple-choice questions were drafted with 4 to 6 answer choices with no option for unknown. Surveys were collected over a three-week period from July 3, 2012 through July 24, 2012. Patients were surveyed at outpatient appointments, infusion center visits, and laboratory draws. RESULTS 226 surveys were collected. Statistical analysis was performed and a binomial regression was fit to the data. There is evidence that higher levels of education are more likely to give correct answers (p value 0.035). Patients who stated they had not seen a fellow or were unsure they had seen a fellow were more likely to select incorrect answers (p value 0.001). There is no statistical significance differentiating between cancer types in likelihood of getting answers correct (Table). 1.77% of those surveyed felt they completely understand the role of a fellow in their care, while 84.51% desired further information about fellows. Only 2.21% disliked having a fellow involved in their care. CONCLUSIONS Patients at academic centers being seen by hematology/oncology fellows appear to have a lack of knowledge of a fellows role and background but have a desire to be educated. Educational initiatives can be introduced to teaching institutions to help patients better understand the role of a fellow. [Table: see text].

Histologic review of second-line permetrexed treatment in patients with non-small cell lung cancer (NSCLC).

e18071 Background: NSCLC accounts for approximately 85% of lung cancers. It is subdivided into adenocarcinoma (including bronchoalveolar), squamous cell carcinoma (SCC), and large cell histologies. Chemotherapy is indicated for advanced disease based on histology. Upfront combination chemotherapy with platinum plus microtubule agent or gemcitabine is recommended for SCC. For non-squamous cell, carboplatin-paclitaxel-bevacizumab or cisplatin-permetrexed combinations are recommended based on superior efficacy in Phase II/III trials. Analyses of Phase III studies also suggest that permetrexed is effective when used in non-squamous NSCLC as maintenance therapy and as a second-line agent. However, the data is scant. We present histology based review of previously treated NSCLC patients who received permetrexed upon progression. METHODS Charts were reviewed for 49 consecutive previously treated NSCLC patients who upon progression had received permetrexed at West Virginia University between Sept. 2004 and Dec. 2010. Tumor histology, stage, performance status, prior therapies, permetrexed details (number of cycles, clinical and radiologic response) and survival data were reviewed. RESULTS The median age was 64 (47 % males, 53% females). Most patients (96%) had good performance status (ECOG 0-1). 63% had received at least 2 prior therapies including a tyrosine kinase inhibitor. Histological distribution was as follows: adenocarcinoma (AD) 47%, squamous cell (SCC) 20%, large cell (LG) 2%, not specified (NOS) 31%. Initial RECIST response (after 2 cycles) showed differential efficacy based on histology; AD - response rate (RR) 18%, stable disease (SD) 55%, progressive disease (PD) 27%, SCC - SD 22%, PD 78%, LG - PD 100% (1 patient), NOS - RR 9%, SD 55%, PD36%. Mean time-to-progression were as follows: AD 5.7 months (Range 1.1 to 28.7), SCC 1.4 months (Range 1.3 to 1.9) and NOS 7.6 months (Range 1.1 to 20.2). Data was insufficient to perform survival analysis. CONCLUSIONS Permetrexed has superior efficacy when used in patients with non-squamous NSCLC who have previously been treated with chemotherapy. It was not effective in squamous cell histology, therefore alternative therapies should be considered.