NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2020.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."

Adjuvant chemotherapy is associated with improved survival in patients with nodal metastases after neoadjuvant therapy and esophagectomy.

BACKGROUND: Studies supporting adjuvant chemotherapy after complete resection of esophageal cancer are scarce, and current clinical guidelines recommend either adjuvant chemotherapy or observation. We aimed to clarify the role of adjuvant chemotherapy in patients found to have persistent nodal metastases after neoadjuvant chemoradiation and complete resection of esophageal adenocarcinoma. METHODS: We queried the National Cancer Database (NCDB) for all patients from 2006 to 2012 with esophageal adenocarcinoma who received neoadjuvant chemoradiotherapy, underwent esophagectomy with complete resection, and were found to have lymph node metastases on final pathology. We compared patients who received adjuvant chemotherapy with patients followed by observation only. After performing propensity-score matching to create a well-balanced cohort, we compared survival using the Kaplan-Meier method. RESULTS: We identified 2,046 patients with lymph node metastases after neoadjuvant chemoradiotherapy and esophagectomy; 295 received adjuvant chemotherapy, and 1,751 did not. The median survival in the unmatched cohort was 2.6 years with adjuvant chemotherapy and 2.1 years with observation only (P=0.0185). Five-year survival was 27.9% with adjuvant chemotherapy and 21.5% with observation only. When we examined survival in a balanced cohort of 295 propensity-matched pairs, median survival was 2.6 years with adjuvant chemotherapy and 2.0 years with observation only (P=0.031). Five-year survival was 27.9% with adjuvant chemotherapy and 20.2% with observation only. CONCLUSIONS: In a large, propensity-matched cohort, adjuvant chemotherapy was associated with significantly improved survival for patients with node-positive esophageal adenocarcinoma after neoadjuvant therapy and complete resection. This finding supports the use of adjuvant therapy for patients with node-positive adenocarcinoma after neoadjuvant therapy and surgery.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

Adding Radiotherapy to Adjuvant Chemotherapy Does Not Improve Survival of Patients With N2 Lung Cancer.

BACKGROUND: The management of N2 non-small cell lung cancer (NSCLC) found at operation is controversial. Current guidelines recommend adjuvant chemotherapy or adjuvant chemoradiotherapy. We evaluated whether adjuvant chemoradiotherapy was associated with improved survival compared with adjuvant chemotherapy in patients with N2 NSCLC after complete resection. METHODS: We queried the National Cancer Database for all patients with clinical N0, pathologic N2 NSCLC who did not receive preoperative therapy and underwent complete (R0) surgical resection, followed by adjuvant chemotherapy or chemoradiotherapy. We performed propensity matching to create a well-balanced cohort of patients with respect to age, sex, race, comorbidities, treating facility, tumor size, year of diagnosis, and number of positive nodes. Survival was examined using the Kaplan-Meier method with log-rank analysis. RESULTS: We identified 2,031 eligible patients; 1,149 (56.6%) received adjuvant chemotherapy and 882 (43.4%) received chemoradiotherapy. Patients in the unmatched cohort who received chemoradiotherapy tended to be younger (64.2 vs 65.4 years) and to have a comorbidity score of 0 (57.5% vs 52.1%). Median survival was similar (3.9 years with chemoradiotherapy vs 3.8 years with adjuvant chemotherapy, p = 0.518). We then identified 848 well-matched pairs and again did not detect differences in median survival (3.9 years with chemoradiotherapy vs 3.8 years with adjuvant chemotherapy, p = 0.705). CONCLUSIONS: In a large database study, the addition of radiotherapy to adjuvant chemotherapy after resection of N2 NSCLC was not associated with improved survival. Until more definitive data are available, consideration should be given to treating patients with N2 disease detected at resection with adjuvant chemotherapy only.

Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016.

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016.

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

Non-Small Cell Lung Cancer, Version 6.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.

Non-small cell lung cancer, version 1.2015.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

Phase I dosage finding and pharmacokinetic study of intravenous topotecan and oral erlotinib in adults with refractory solid tumors.

PURPOSE: Topotecan is widely used for refractory solid tumors but multi-drug resistance may occur due to tumor expression of ATP-binding cassette (ABC) transporters. Since erlotinib, an inhibitor of the epidermal growth factor receptor, also inhibits several ABC transporters, we performed a phase I study to evaluate the safety, efficacy, and pharmacokinetics of intravenous topotecan given in combination with erlotinib. METHODS: Patients received 150 mg of oral erlotinib daily and a 30 min intravenous infusion of topotecan on days 1-5 of a 21-day cycle. Dosage escalation of topotecan occurred with a starting dosage of 0.75 mg/m(2). The pharmacokinetics of topotecan was evaluated on day 1 of cycle 1 without erlotinib and on day 1 of cycle 2 or 3 with erlotinib. RESULTS: Twenty-nine patients were enrolled. The maximum tolerated dosage was determined to be 1.0 mg/m(2). Dose-limiting toxicities included neutropenia and thrombocytopenia. The average duration of treatment was 97 days. Two partial responses were observed. Topotecan clearance and exposure were similar with and without erlotinib. CONCLUSIONS: The combination of topotecan and erlotinib is tolerable at clinically effective doses. Erlotinib does not affect the disposition of topotecan to a clinically significant extent.

Non-small cell lung cancer, version 2.2013.

These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

Thymomas and thymic carcinomas: Clinical Practice Guidelines in Oncology.

Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab.

PURPOSE: We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab. EXPERIMENTAL DESIGN: This double-blind, randomized, placebo-controlled phase IIb study (ClinicalTrials.gov NCT00493636) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer and prior bevacizumab treatment. Patients were randomized to chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1,000 mg/m(2) i.v., days 1, 8/21), but later, capecitabine (1,000 mg/m(2) orally twice daily, days 1-14/21) was allowed as an alternative. The primary endpoint was progression-free survival (PFS). RESULTS: One hundred and sixty patients were randomized. More patients received gemcitabine (82.5%) than capecitabine (17.5%). Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [3.4 vs. 2.7 months; HR = 0.65; 95% confidence interval (CI): 0.45-0.95; P = 0.02], time to progression was increased (median, 3.6 vs. 2.7 months; HR = 0.64; 95% CI: 0.44-0.93; P = 0.02), and overall response rate was 19.8% versus 12.7% (P = 0.23). Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71-1.44; P = 0.95). Addition of sorafenib versus placebo increased grade 3/4 hand-foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%). CONCLUSION: The addition of sorafenib to gemcitabine/capecitabine provided a clinically small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions.

Experiencing neutropenia: quality of life interviews with adult cancer patients.

BACKGROUND: Neutropenia is a common toxicity in chemotherapy but detailed information about how neutropenia is associated with changes in patients' quality of life is not readily available. This prospective study interviewed patients with grade 4 neutropenia to provide qualitative information on patients' experience of developing and coping with grade 4 neutropenia during a cycle of chemotherapy. METHODS: A sample of 34 patients who developed grade 4 neutropenia during the first cycle of chemotherapy completed a total of 100 structured clinical interviews. Interviews were transcribed, and 2 raters inductively developed 5 broad categories comprising 80 specific complaint domains nominated by patients. Thirty-five patient-nominated problems were mentioned in 5% or more of the interviews. RESULTS: Fatigue was the most common physical symptom. Interference in daily routine, negative self-evaluation, negative emotion, and social isolation were other common complaints associated with neutropenia. CONCLUSION: Neutropenia is associated with a number of negative experiences among cancer patients undergoing chemotherapy, and these negative experiences have an adverse effect on the patient's quality of life. Oncology nurses can play a key role in helping patients manage adverse effects to maintain their quality of life.

Impact of chemotherapy-induced neutropenia on quality of life: a prospective pilot investigation.

PURPOSE: In this exploratory, prospective study evaluated quality of life (QoL) changes in patients with diverse cancers during the first cycle of myelosuppressive chemotherapy. PATIENTS AND METHODS: Of 80 patients enrolled, 71 were observed during one of five chemotherapy regimens: docetaxel; CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone); carboplatin-paclitaxel; carboplatin-docetaxel; and carboplatin-gemcitabine. Complete blood counts were taken weekly. QoL and symptom burden measures were administered at baseline and throughout the cycle, and included SF-36, Cancer Care Monitor (CCM), Hospital Anxiety and Depression Scale (HADS), and Psychosocial Adjustment to Illness Scale (PAIS). Using generalized estimating equations, we modeled the change in each measure from baseline to the end of each week using the following covariates: baseline QoL measure, baseline SF-36 Physical and Mental Health Summary scores, sex, age, cycle week, grade 4 neutropenia any time in the past 7 days (yes/no), and the interaction of the latter two covariates. RESULTS: Of the 71 patients observed, 33 developed grade 4 neutropenia during the first 2 weeks. Changes from baseline in SF-36 Bodily Pain, HADS Anxiety, and PAIS Social Environment scores were significantly less favorable (P<0.05) when patients experienced grade 4 neutropenia any time in the past 7 days compared to when they did not (grade 0-3). A similar, but non-significant, trend was also observed for 12 other QoL measures. CONCLUSION: QoL may be adversely affected up to 7 days after patients experience grade 4 (versus grade 0-3) neutropenia. Such findings need to be examined further in studies with adequate statistical power to test a priori hypotheses regarding specific QoL measures.

Medical visits for chemotherapy and chemotherapy-induced neutropenia: a survey of the impact on patient time and activities.

BACKGROUND: Patients with cancer must make frequent visits to the clinic not only for chemotherapy but also for the management of treatment-related adverse effects. Neutropenia, the most common dose-limiting toxicity of myelosuppressive chemotherapy, has substantial clinical and economic consequences. Colony-stimulating factors such as filgrastim and pegfilgrastim can reduce the incidence of neutropenia, but the clinic visits for these treatments can disrupt patients' routines and activities. METHODS: We surveyed patients to assess how clinic visits for treatment with chemotherapy and the management of neutropenia affect their time and activities. RESULTS: The mean amounts of time affected by these visits ranged from approximately 109 hours (hospitalization for neutropenia) and 8 hours (physician and chemotherapy) to less than 3 hours (laboratory and treatment with filgrastim or pegfilgrastim). The visits for filgrastim or pegfilgrastim were comparable in length, but treatment with filgrastim requires several visits per chemotherapy cycle and treatment with pegfilgrastim requires only 1 visit. CONCLUSIONS: This study provides useful information for future modelling of additional factors such as disease status and chemotherapy schedule and provides information that should be considered in managing chemotherapy-induced neutropenia.

The Cancer Care Monitor: psychometric content evaluation and pilot testing of a computer administered system for symptom screening and quality of life in adult cancer patients.

Technology is making the routine screening of symptoms and the measurement of quality of life (QoL) more feasible at the point of care. However, most existing symptom screening scales and QoL measures were not developed for clinical use and were not formatted and validated for administration through computerized mediums. The Cancer Care Monitor (CCM) is a symptom-based scale developed for administration on pen-based computers. This study is an initial evaluation of the reliability and validity of the CCM. Three samples of adult outpatients provided ratings on 38 physical, psychological, and functional oriented items of the CCM that comprise six symptom scales and one global QoL index. All additive scales are converted to normalized T scores. Reliability was examined through internal consistency and confirmatory factor analysis. Convergent and divergent validity were examined by comparing CMM scores to established measures of corresponding constructs and physician judgments. Alternative forms reliability was established by comparing paper and pencil administration with computer administration. Internal consistency reliability and factor analyses confirmed the structure of the CCM as comprising six primary symptom scales and one global QoL index. Internal consistency reliabilities ranged from 0.80 to 0.89. The pattern of correlations between CCM scales and established measures supported the convergent and divergent validity of the CCM scales. Alternate forms reliability based on paper and computer forms of the CCM scales was high. Patients indicated a preference for the computer-administered version. Results suggest that CCM items can be scored as a reliable and valid measure of constructs related to physical, psychological, and functional status, and global health-related QoL in adult cancer patients. Future studies should replicate and further evaluate the properties of the CCM, especially in relation to clinical utility.

The Zero Acceptance of Pain (ZAP) Quality Improvement Project: evaluation of pain severity, pain interference, global quality of life, and pain-related costs.

The Zero Acceptance of Pain (ZAP) Quality Improvement Project was a multi-site effort to improve the lives of outpatients with cancer pain by enhancing the clinical practice of pain assessment and management. Independent samples of patients completed self-report measures of severity of pain, pain interference, global quality of life, pain treatment satisfaction, general medical treatment satisfaction, pain attitudes, and pain-related medical costs before and after the implementation of ZAP. Results suggested that ZAP decreased the severity of recent pain, decreased interference of pain on daily functioning, and improved satisfaction with pain treatment and attitudes about addiction to opioid medication. Direct medical costs consisting of pain-related hospitalizations, emergency department visits, and physician office visits were greatly reduced. In summary, the findings of this study support the idea that clinic-based efforts to improve the practice of pain management are effective in improving the lives of cancer patients who are experiencing pain.