Jeffrey T. Yorio

Lung Cancer Diagnostic and Treatment Intervals in the United States: A Health Care Disparity?

Introduction: Lung cancer diagnostic and treatment delays have been described for several patient populations. However, few studies have analyzed these intervals among patients treated in contemporary health care systems in the United States. We therefore studied the timing of lung cancer diagnosis and treatment at a U.S. medical center providing care to a diverse patient population within two different hospital systems. Methods: We performed a retrospective analysis of consecutive patients diagnosed with non-small cell lung cancer stage I to III from 2000 to 2005 at public and private hospitals affiliated with the University of Texas Southwestern Medical Center. We recorded patient and disease characteristics; dates of initial radiograph suspicious for lung cancer, diagnosis, and treatment; and overall survival. Associations between these factors were assessed using univariate analysis, multivariate logistic regression, and Kaplan-Meier survival analysis. Results: A total of 482 patients met criteria for analysis. In univariate analyses, the image-treatment interval was significantly associated with race, age, income, insurance type, and hospital type (76 days for public versus 45 days for private; p < 0.0001). In multivariate analysis, only hospital type remained significantly associated with the image-treatment interval; patients in the private hospital setting were more likely to receive timely treatment (hazard ratio 1.85; 95% confidence interval, 1.37–2.50; p < 0.001). In univariate analysis, the image-treatment interval was not associated with disease stage (p = 0.27) or with survival (p = 0.42). Conclusion: Intervals between suspicion, diagnosis, and treatment of lung cancer vary widely among patients. Health care system factors, such as hospital type, largely account for these discrepancies. In this study, these intervals do not appear to be associated with clinical outcomes.

Rare Though Not Mutually Exclusive: A Report of Three Cases of Concomitant KRAS and BRAF Mutation and a Review of the Literature.

KRAS mutations occur frequently in colorectal cancers (CRC) and predict lack of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. CRC BRAF mutations, most commonly at V600E, occur less than 10% of the time, and occur usually in KRAS wild-type tumors, and more frequently in microsatellite instable tumors. Concomitant KRAS and BRAF mutant CRCs are rare (occurring in 0.001%); BRAF mutations should not be routinely tested in patients with KRAS mutant tumors, unless the patients is participating in a clinical trial enriching for the presence of a KRAS or BRAF tumor. Clinical trials treating patients with either KRAS or BRAF mutant tumors should address eligibility of patients with concomitant KRAS and BRAF mutations.

Case of vemurafenib-induced Sweet's syndrome

Vemurafenib is a targeted therapy that has become standard treatment for patients with advanced melanoma with a V600E BRAF mutation. It has been associated with frequent skin toxicity, including photosensitivity, rash and squamous cell carcinomas. We present an 83‐year‐old woman with an advanced V600E BRAF‐mutant melanoma who developed a severe skin rash and fatigue after taking vemurafenib. The dose was reduced from 960 to 720 to 480 mg twice a day; however, she was subsequently admitted to the hospital with fever, chills, fatigue, confusion and a diffuse skin eruption. She then developed hypoxia and acute renal failure that required hemodialysis. A biopsy of her skin lesions revealed a neutrophilic dermatitis with papillary dermal edema, consistent with Sweets syndrome. Her symptoms resolved upon discontinuation of vemurafenib and treatment with prednisone. This constellation of symptoms and clinical course are consistent with drug‐induced Sweets syndrome caused by vemurafenib.

How Have We Diagnosed Early-Stage Lung Cancer without Radiographic Screening? A Contemporary Single-Center Experience

Background The National Lung Screening Trial (NLST), which demonstrated a reduction in lung cancer mortality, may result in widespread computed tomography (CT)-based screening of select populations. How early-stage lung cancer has been diagnosed without screening, and what proportion of these cases would be captured by a screening program modeled on the NLST, is not currently known. We therefore evaluated current patterns of early-stage lung cancer presentation. Methodology/Principal Findings We performed a single-institution retrospective analysis of patients diagnosed with stage I–II non-small cell lung cancer (NSCLC) from 2000–2009. Associations between patient and imaging characteristics were assessed using univariate and multivariate analyses. A total of 412 patients met criteria for analysis. Among those with available reason for initial imaging, the reason was symptoms in 51%, follow-up of other conditions in 43%, and screening in 6%. Reason for imaging was associated with race (P<0.001), insurance type (P = 0.005), and disease stage (P<0.001). Type of initial imaging was associated with reason for imaging (P<0.001), year (chest x-ray 67% in 2000–2004 vs. 49% in 2005–2009; P<0.001), and disease stage (P = 0.005). Among patients with available quantified smoking history, 48% were age 55–74 years and smoked 30-plus pack-years, therefore meeting NLST entry criteria. Conclusions/Significance Symptoms remain a dominant but declining reason for detection of early-stage NSCLC. The proportion of cases detected initially by CT scan without antecedent chest x-ray has increased considerably. Because as few as half of cases meet NLST eligibility criteria, clinicians should remain aware of the diverse circumstances of early-stage lung cancer presentation to expedite therapy.

Treatment decisions in a man with Hodgkin lymphoma and Guillian-Barré syndrome: a case report

IntroductionGuillain-Barre syndrome, or acute inflammatory demyelinating polyneuropathy, has been described in the presence of malignancies such as lymphoma. Guillain-Barre syndrome/acute inflammatory demyelinating polyneuropathy causes paresthesias and weakness, which can make the treatment of lymphoma with chemotherapy challenging. Given the rarity of this co-presentation it is not known if the effects of Guillain-Barre syndrome should be considered when selecting a treatment regimen for Hodgkin lymphoma. To the best of our knowledge, the impact of these treatment modifications has not been previously reported.Case presentationWe report the case of a 37-year-old Caucasian man with a diagnosis of stage IIB classical Hodgkin lymphoma with concomitant Guillain-Barre syndrome. Our patient originally presented with an enlarged cervical lymph node and quickly developed distal paresthesia and progressive weakness of all four extremities. He was diagnosed with Hodgkin’s lymphoma and initiated on treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine. Doses of bleomycin and vinblastine were held or dose-reduced throughout his initial treatment course due to underlying neuropathy and dyspnea. He continued to have persistent disease after five cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine and went on to receive salvage treatments including more chemotherapy, radiation, autologous stem cell transplant and is currently preparing for an allogeneic stem cell transplant.ConclusionsParaneoplastic syndromes such as Guillain-Barre syndrome/acute inflammatory demyelinating polyneuropathy can make the treatment of patients with Hodgkin lymphoma more challenging and can interfere with delivering full-dose chemotherapy. Further case series are needed to evaluate the effect that paraneoplastic syndromes, or adjustments made in therapy due to these syndromes, negatively affect the prognosis of patients with Hodgkin lymphoma.

A primer on the current state-of-the-science neoadjuvant and adjuvant therapy for patients with locally advanced rectal adenocarcinomas

Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in improving patient outcomes. This article serves to review the clinical studies that lay the basis for our current standard-of-care treatment of patients with locally advanced rectal cancer, as well as touch upon future ongoing experimental clinical trials of adjuvant chemoradiation therapy.

Improving the care of acute lymphocytic leukemia (ALL) at a large county hospital.

213 Background: The treatment of ALL involves complex chemotherapy regimens that are difficult to deliver to underserved populations. Lyndon B. Johnson General Hospital (LBJGH) provides care to uninsured and underinsured patients in Harris County, the third largest county in the United States. Our goal is to achieve 80% adherence to National Comprehensive Cancer Network guidelines in the care of newly diagnosed ALL patients at LBJGH. METHODS The charts of 14 patients with newly diagnosed ALL were reviewed. Demographics, initial work-up (e.g., bone marrow biopsy and aspirate), type of treatment, adherence to scheduled treatment, use of supportive medications, outpatient follow-up, stem cell transplant referral and quality of provider documentation were collected. Areas of potential improvement were then identified using provider focus groups and Ishikowa Diagram. The project was approved by the MD Anderson Quality Improvement Assessment Board. RESULTS 12/14 patients were evaluable, having received their full course of care at LBJGH. The median age was 35, 9/12 (75%) were female and 9/12 (75%) were Hispanic. 6/11 (55%) cases expressed CD20 (CD20+) and 3/11 (27%) were Philadelphia chromosome positive (Ph+). All 12 patients received induction and consolidation therapy with the HyperCVAD regimen (cyclophosphamide/vincristine/doxorubicin/dexamethasone alternating with high-dose methotrexate/cytarabine). Bone marrow biopsy at time of diagnosis, use of a tyrosine kinase inhibitor for Ph+ ALL, and use of supportive medications occurred >80% of the time. Administration of outpatient chemotherapy, use of rituximab for CD20+ ALL, outpatient lab follow-up, intrathecal chemotherapy and appropriate referral for allogeneic transplant occurred 50-80% of the time. Provider documentation was appropriate <50% of the time. CONCLUSIONS Based on these findings, we established a standard algorithm of care for ALL patients at LBJGH, enhanced provider education through the design and distribution of teaching tools, created a checklist to facilitate handoffs between providers and established expectations for documentation. In the future, we would also like to add a patient navigator to further improve coordination of care.

Presentation of early-stage non-small cell lung cancer (NSCLC) without radiographic screening: End of an era?

e17506 Background: In contrast to other common malignancies, screening for lung cancer is currently not recommended. However, recent evidence suggests that computed tomography (CT)-based screening of select populations may decrease lung cancer mortality. We determined how screening would impact current presentation patterns of early stage disease. METHODS Retrospective analysis of patients diagnosed with stage 1-2 NSCLC from 2000-2009 at the University of Texas Southwestern Medical Center. Data were obtained from tumor registries and medical records. Associations between baseline characteristics and the reason for and type of imaging were assessed using univariate analysis and multivariate logistic regression. RESULTS A total of 412 patients were included in the analysis. Mean age was 67 years, 49% were men, 70% were white, and 79% had stage I disease. Only 52% were age 55-74 years and had 30+ pack-year smoking history and would therefore have met criteria for the National Lung Screening Trial (NLST). Reason for initial imaging was symptoms in 51%, follow-up of other medical conditions in 43%, and lung cancer screening in 6%. Dominant symptoms were cough/hemoptysis (36%), dyspnea (29%), and chest pain (15%). Chest x-ray was the initial imaging modality in 57%, with CT scans accounting for almost all other cases. Reason for imaging was significantly associated with race (P<0.001), socioeconomic status (P=0.005), and stage (P<0.001), with non-white patients, indigent patients, and those diagnosed with stage 2 disease more likely to present with symptoms. Type of imaging was associated with reason for imaging (P<0.001), year of diagnosis (CXR 67% 2000-2004 vs. 49% 2005-2009; P<0.001), and disease stage (P=0.005). CONCLUSIONS Symptoms remain the dominant reason for initial detection of early stage NSCLC, particularly among underrepresented populations. The proportion of early stage NSCLC initially detected by CT scan, principally for follow-up of other medical conditions, has increased markedly in recent years. If widespread lung cancer screening is implemented, these patterns may persist, as only half of patients currently diagnosed with early stage NSCLC meet NLST eligibility criteria.