Suchita Pakkala

Lung Cancer in HIV-Positive Patients

Malignancies account for more than a third of all deaths in human immunodeficiency virus (HIV)-positive patients. Although acquired immunodeficiency syndrome-related mortality is decreasing with the introduction of effective antiretroviral therapy, the incidence of lung cancer in patients with HIV remains high. Lung cancer has now become the leading cause of mortality among the nonacquired immunodeficiency syndrome defining malignancies. Within the HIV population, the incidence of lung cancer is estimated to be approximately 2 to 4 times that of the general population. Often these patients present with advanced disease (stage III or IV) at a younger age and have an inferior overall survival, when compared with non-HIV patients. Development of lung cancer in patients with HIV has been linked to various factors including immunosuppression, CD4 count, viral load, and smoking. This article reviews the impact of HIV on the incidence, risk factors, clinical presentation, and treatment of lung cancer.

Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia

Early marrow blast clearance 14 days after induction chemotherapy is an independent prognostic indicator of outcomes in acute myeloid leukemia (AML).

Human immunodeficiency virus-associated lung cancer in the era of highly active antiretroviral therapy.

Lung cancer is the leading cause of death among non‐acquired immunodeficiency syndrome (AIDS)‐defining malignancies. Because highly active antiretroviral therapy (HAART) has improved the survival of patients with human immunodeficiency virus (HIV), the authors evaluated lung cancer outcomes in the HAART era.

Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature.

Monoclonal antibodies against programmed cell death protein 1 (PD‐1) and programmed death ligand 1 (PD‐L1) are effective therapies in patients with non‐small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD‐1 and PD‐L1 inhibitors.

Comparison of Concurrent Use of Thoracic Radiation With Either Carboplatin-Paclitaxel or Cisplatin-Etoposide for Patients With Stage III Non-Small-Cell Lung Cancer: A Systematic Review

Importance The 2 most common chemotherapy regimens used concurrently with thoracic radiation for patients with unresectable IIIA and IIIB non–small-cell lung cancer (NSCLC) are carboplatin-paclitaxel and cisplatin-etoposide. There are no prospective comparisons of these 2 regimens in this setting. Objective To conduct a systematic review of published trials to compare outcomes and toxic effects between cisplatin-etoposide and carboplatin-paclitaxel in patients with non–small-cell lung cancer receiving thoracic radiation. Evidence Review Studies that enrolled patients with stage III disease receiving radiotherapy (RT) with carboplatin-paclitaxel or cisplatin-etoposide were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase 1, enrolled less than 10 patients, or included surgical resection. A systematic analysis of extracted data was performed with software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival, progression-free survival, response rate, and toxic effects. A 2-tailed t test with a significance level of .05 was used for all comparisons. Findings Overall, 3090 patients were included from 31 studies in the cisplatin-etoposide groups (median age, 61 years; 65% male; 40% squamous histology; median radiation dose, 63.0 Gy), and 3728 patients from 48 studies in carboplatin-paclitaxel groups (median age, 63 years; 65% male; 40% squamous histology; median radiation dose, 64.6 Gy). There was no significant difference in response rates between cisplatin-etoposide and carboplatin-paclitaxel (58% vs 56%; P = .26), respectively. For cisplatin-etoposide vs carboplatin-paclitaxel, there was no significant difference in median progression free survival (12 months vs 9.3 months; P = .20), overall survival (19.6 months vs 18.4 months; P = .40), or 3-year survival rate (31% vs 25%; P = .50). Cisplatin-etoposide was associated with higher grade 3 to 4 hematological toxic effects compared with carboplatin-paclitaxel (eg, neutropenia [54% vs 23%; P < .001] and grade 3/4 nausea/vomiting [20% vs 11%; P = .03]), while rates of grade 3 to 4 pneumonitis (12% vs 9%; P = .12) and esophagitis (23% vs 21%; P = .27) were similar. Conclusions and Relevance Cisplatin-etoposide and carboplatin-paclitaxel regimens were associated with comparable efficacy when used with concurrent definitive radiotherapy for patients with stage III unresectable NSCLC. The toxic effect profiles favored the carboplatin-paclitaxel regimen.

Combined inhibition of vascular endothelial growth factor and epidermal growth factor signaling in non-small-cell lung cancer therapy.

Elucidation of molecular pathways that promote malignancies has led to the identification of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) as key components involved in regulation of tumor proliferation and angiogenesis, respectively. Biologic agents that target these individual pathways have proven effective in treating patients with advanced non-small-cell lung cancer (NSCLC), adding to previously available therapies and often with fewer side effects. However, inhibition of a single molecular pathway does not account for alternate pathways or biologic adaptations that eventually lead to resistance. Therefore, combining EGFR and VEGF inhibition is currently under investigation as a means to overcome resistance and promote synergy. Erlotinib, an anti-EGFR agent, and bevacizumab, an anti-VEGF agent, are both approved in NSCLC, demonstrating single-agent activity. The phase II trials evaluating the combination of erlotinib and bevacizumab have shown efficacy as first-line therapy or in patients with previously treated NSCLC either alone or with chemotherapy. Dual inhibition of EGFR and VEGF pathways has also been accomplished by the novel agents vandetanib and XL647, which are able to target both pathways. Vandetanib has also demonstrated activity in patients with advanced NSCLC either alone or with chemotherapy in phase I/II studies. Another novel agent, XL647, has demonstrated promising single-agent activity in patients who have been resistant to previous anti-EGFR therapy. Further evaluation of combined EGFR and VEGF inhibition is under investigation.

Concomitant Chemotherapy and Radiotherapy with SBRT Boost for Unresectable Stage III Non–Small Cell Lung Cancer: A Phase I Study

Objectives: Stereotactic body radiation therapy (SBRT) is now the standard of care in medically inoperable stage I NSCLC, yielding high rates of local control. It is unknown whether SBRT can be safely utilized in the locally advanced NSCLC setting. This multi‐institution phase I study evaluated the safety of 44 Gy of conventionally fractionated thoracic radiation with concurrent chemotherapy plus dose‐escalated SBRT boost to both the primary tumor and involved mediastinal lymph nodes. The primary end point of this study was to establish the maximum tolerated dose (MTD) of the SBRT boost. Methods: Inclusion criteria included unresectable stage IIIA or IIIB disease, primary tumor 8 cm or smaller, and N1 or N2 lymph nodes 5 cm or smaller. Tumors were staged with positron emission tomography/computed tomography (CT), and four‐dimensional CT simulation was used for radiation planning. The treatment schema was 44 Gy of thoracic radiation (2 Gy/d) with weekly carboplatin and paclitaxel chemotherapy. A second CT simulation was obtained after 40 Gy had been delivered, and a SBRT boost was planned to the remaining gross disease at the primary site and involved mediastinal lymph nodes. Consolidation chemotherapy was given at the discretion of the treating medical oncologist. Four SBRT boost dose cohorts were tested: cohort 1 (9 Gy × 2), cohort 2 (10 Gy × 5), cohort 3 (6 Gy × 5), and cohort 4 (7 Gy × 5). Patients were treated in cohorts of three patients, and the Bayesian escalation with overdose control method was used to determine the MTD of the SBRT boost. Dose‐limiting toxicities (DLTs) were defined as any grade 3 or higher toxicities within 30 days of treatment attributed to treatment, not including hematologic toxicity, or any grade 5 toxicity attributed to treatment. Results: The study enrolled 19 patients from November 2012 to December 2016. There were four screen failures, and 15 patients were treated on study. There were no DLTs in dose cohort 1 (n = 3) and 2 (n = 6). DLT developed in one patient in dose cohort 3 (n = 3) and in 2 patients in dose cohort 4 (n = 3). The calculated MTD was 6 Gy × 5. The DLT observed at this dose level was a tracheoesophageal fistula; given this substantial toxicity, there was investigator reluctance to enroll further patients at this dose level. Thus, the calculated MTD was 6 Gy × 5; however, 10 Gy × 2 is thought to be a reasonable dose as well, given that no grade 5 toxicities occurred with that dose. Conclusions: The MTD of a SBRT boost combined with 44 Gy of thoracic chemoradiation was 6 Gy × 5. A SBRT boost dose of 10 Gy × 2 could be considered safer, with no grade 3 or higher toxicities observed at this dose level during the follow‐up period in this study.

Pulmonary Sarcomatoid Carcinoma: An Analysis of the National Cancer Data Base

Micro‐Abstract Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive form of lung cancer that has been little researched. We used the National Cancer Data Base to better understand PSC. A total of 7965 patients were identified with PSC, comprising 0.5% of all non–small‐cell lung cancer (NSCLC) cases. Patients with PSC have aggressive clinical characteristics and inferior survival outcomes relative to other subtypes of NSCLC. Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a grouping of 5 rare non–small‐cell lung cancer (NSCLC) subtypes. We studied the clinical characteristics and outcomes of PSC utilizing the National Cancer Data Base (NCDB), an oncology outcomes database. Methods: The NCDB lung cancer database was queried from 1998 to 2011 for PSC using ICD‐O‐3 codes. Data were extracted for patient demographics, tumor pathology, treatment, and outcomes. Overall survival (OS) data were available for patients diagnosed from 1998 to 2006 and comorbidity data from 2003 to 2011. Univariate association with covariates between PSC and other forms of NSCLC was assessed by the chi‐square test or ANOVA, as appropriate. Results: Of the 1,547,531 NSCLC patients in the NCDB from 1998 to 2011, 7965 were identified with PSC (0.5%). PSC patients had a median age of 70 years, 59% were men, and 89% were white. At presentation, 18% had American Joint Committee on Cancer stage I disease, 10% stage II, 24% stage III, and 48% stage IV. The median OS for stage I‐II PSC was 16.9 months, 5.8 months for stage III, and 5.4 months for stage IV. There was a higher risk of death on multivariate analysis for PSC patients compared to other histologic subtypes of NSCLC in all patients (hazard ratio = 1.34 (95% confidence interval, 1.20‐1.48) P < .001) and in propensity score–matched subsets (hazard ratio = 1.34; 95% confidence interval, 1.15‐1.56; P < .001). Conclusion: PSC is a rare histologic subtype of NSCLC, accounting for 0.5% of all lung cancers. The disease of patients with PSC has aggressive clinical characteristics and an inferior survival outcome relative to other histologic subtypes of NSCLC.

Adjuvant therapy for nonsmall cell lung cancer: recent advances and future perspectives.

Purpose of review In this article, we discuss the emergence of adjuvant chemotherapy as the standard of care, the potential role of targeted and immune therapy in resected nonsmall cell lung cancer (NSCLC) patients, and the importance of ongoing clinical trials to further define the use of these agents as adjuvant therapy. Recent findings Adjuvant chemotherapy after surgical resection provides modest improvements in cure rate, though recurrence of disease still occurs in a substantial proportion of patients. The advent of targeted and immune therapies has improved outcomes for patients with advanced stage NSCLC. Recent studies have explored the role of vascular endothelial growth factor inhibitors, epidermal growth factor receptor tyrosine kinase inhibitors, vaccine therapy, and predictive biomarkers in the adjuvant setting. Summary Platinum doublet chemotherapy remains the standard adjuvant therapy for resected stage II, IIIA, and high-risk stage IB NSCLC. Ongoing clinical trials are evaluating emerging therapies to improve efficacy and reduce toxicity while aiming to improve patient selection for such therapies.

Epidermal Growth Factor Receptor Mutated Advanced Non–Small Cell Lung Cancer: A Changing Treatment Paradigm

Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved. This article reviews the current treatments, resistance mechanisms, and strategies to overcome resistance.