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New lung cancer studies feature latest treatment advances

Newswise Mar 15, 2019

New research released today provides guidance for physicians who treat patients with lung cancer. Three authors will present their findings in an online presscast today and during the plenary session on Thursday, March 14, at the 2019 Multidisciplinary Thoracic Cancers Symposium, held March 14–16 at the Hilton San Diego Bayfront. To schedule interviews with study authors and/or outside experts in lung cancer, contact ASTRO’s media relations team at press@astro.org.

Following are summaries of each study selected for the presscast:

Local consolidative therapy linked to improved overall survival for oligometastatic NSCLC (Abstract 1)

This summary includes updated data not in the abstract. A new analysis of nearly 200 patients treated with local consolidative therapy (LCT) for oligometastatic non-small cell lung cancer (NSCLC) finds that the intensive treatment approach is associated with improved overall survival. LCT, consisting of radiation therapy or surgery, extended median survival by 6 months for patients diagnosed with three or fewer metastases outside of the lungs.

“Though not all people with stage IV NSCLC are the same, there are treatment options for those with limited metastatic disease,” said Erin Corsini, MD, presenting author of the study and a clinical research fellow the University of Texas MD Anderson Cancer Center in Houston. “Specifically, in select populations of patients with oligometastatic NSCLC, local consolidative therapy to all sites of disease with surgery, radiation therapy, or a combination of the two appears to show promise in prolonging overall survival. The patients who seem to gain the most benefit are those with more favorable disease characteristics, such as adenocarcinoma, early intrathoracic stage, and absence of bone metastases.”

For the study, researchers analyzed records of 194 patients treated for stage IV NSCLC at MD Anderson between 2000 and 2017. Eligible patients included those diagnosed with one to three synchronous metastatic tumors, with intrathoracic nodal disease counted as one site; most patients (70%) had two to three distant metastases. Nearly all patients (90%) received systemic therapy in addition to LCT.

Comprehensive LCT to all disease sites (ie, the primary tumor and all distant metastases) was associated with improved overall survival. At a median follow-up of 52 months, the median overall survival was 29 months for patients who received LCT to all sites, compared to 23 months for patients who did not (P=0.03). The relationship held on multivariable analysis controlling for patient and disease characteristics (P=0.03).

LCT to the primary tumor was associated with improved control of local and regional recurrences. The rate of locoregional progression was 21% for patients who received LCT to the primary tumor, compared to 43% for patients who did not (P < 0.01). LCT to the primary tumor also trended toward an association with improved overall survival (P=0.08), although this was not the case with LCT to distant metastases (P=0.21).

“Several recent clinical trials have shown that local consolidative therapy could provide a tangible survival benefit, and our results from evaluating a relatively large group of patients are not only consistent with, but arguably bolster, the previously reported findings,” said Dr. Corsini. “Taken together, these studies make a strong case for local consolidative therapy in patients with oligometastatic NSCLC.”

“As the evidence accumulates and we learn that there are options for patients with oligometastatic disease, it is important that providers, patients, and families discuss these possibilities and how they align with their goals and priorities for treatment.”

Structured exposure to NSCLC patient guidelines fosters smoking cessation, biomarker testing (Abstract 5)

A new clinical trial finds that exposing patients to tailored versions of nationally recognized treatment guidelines for NSCLC can help drive smoking cessation, testing for potential biomarkers and, for early stage disease, more patient-centered use of chemotherapy following surgery. Findings demonstrate how evidence-based decision and communication aids can improve cancer care.

“The process of making treatment decisions can be extremely stressful for lung cancer patients, as treatment options are nuanced and may change significantly over the course of their staging workup,” said Susan Wu, MD, first author of the study and a radiation oncology resident at the University of California, San Francisco. “Educational tools can guide patients through the decision-making process and help them to synthesize the large amount of information available.”

Patients in the trial used an interactive, web-based tool that presented treatment options tailored to their clinical characteristics, such as tumor stage and margin status following surgery. Options were based on National Comprehensive Cancer Network (NCCN) guidelines and included information about treatment sequencing as well as a timeline to help patients visualize the treatment trajectory. All 76 patients were introduced to the tool by a trained coordinator, who also used the tool to facilitate discussion during their consultation with an oncologist. A separate cohort of 159 patients seen at the same institution before the tool was available was used as a comparison group.

Structured exposure to guidelines was associated with several positive outcomes, including increased smoking cessation counseling/intervention among active smokers (80% vs 4%, P < 0.001) and increased molecular testing for EGFR and ALK mutations prior to systemic therapy among patients with metastatic disease (96% vs 68%, P=0.01). Use of the tool was also correlated with decreased use of chemotherapy following surgery for stage IB-IIB NSCLC (0% vs 50%, P=0.02), particularly among patients with negative margins following resection.

“We can empower patients to make decisions that align with their priorities and goals for treatment with evidence-based tools. For example, data from patients with breast cancer suggests that those who may derive limited benefit from adjuvant therapy are more likely to forego it. We similarly found that patients with completely resected, early stage NSCLC had a tendency not to pursue additional chemotherapy,” said Dr. Wu.

Exposure to the guideline tool did not impact some outcomes, including the frequency of pathologic mediastinal staging performed prior to surgery (P=0.70) or nonsurgical treatment (P=0.55) in patients with stage III disease, nor did it influence the use of upfront chemoradiation therapy in stage III patients who were ineligible for surgery (P=0.55).

“Our goal was to help patients feel more comfortable making treatment decisions and become more active participants in the decision-making process,” said Dr. Wu. “While implementing a decision support tool does require substantial resources, such as the time and effort to develop the tool and introduce it to patients, these tools can help empower our patients, and in some cases meaningfully impact their care.”

Declining number of physicians use prophylactic cranial irradiation (PCI) for extensive-stage SCLC (Abstract 3)

This summary includes updated data not in the abstract. A new survey of radiation oncologists points to a sharp decline in the use of prophylactic cranial irradiation (PCI) for patients with extensive-stage small cell lung cancer (ES-SCLC), indicating a rapid change in standard practice for the disease following publication of a major clinical trial in 2017.

“Small cell lung cancer has a tendency to spread past the lungs to the brain, and brain metastases substantially diminish a patient’s quality of life. PCI is preventative radiation therapy given after first-line treatment to eliminate cancerous cells before they become symptomatic metastases,” said Olsi Gjyshi, MD, PhD, first author of the study and a radiation oncology resident at the University of Texas MD Anderson Cancer Center.

“Radiation oncologists largely adopted PCI for ES-SCLC following the 2007 publication of a randomized EORTC trial that linked its use to extended overall survival (Slotman et al, NEJM). However, with the recent publication of a Japanese trial showing no survival benefit from PCI compared to magnetic resonance imaging (MRI) surveillance (Takahashi et al, Lancet Oncol), it is important to come to a consensus on how best to treat these patients. Our survey indicates that most providers no longer routinely use PCI for patients with extensive-stage disease that responds to chemotherapy.”

To determine the extent of practice changes, researchers surveyed attending radiation oncologists at academic cancer centers across the United States (24% survey response rate). Anonymous email surveys were collected in September 2018, more than a year after the Takahashi et al trial was published, and the same year NCCN guidelines were updated to reflect its findings.

All 49 radiation oncologists who specialize in treating thoracic cancers were aware of the Takashashi et al trial, and two-thirds (67%) had altered their practice in response to its findings. Specifically, fewer than half of those who offered PCI for ES-SCLC prior to 2017 continued to do so after it was published (78% vs 38%, P < 0.001).

Researchers confirmed the trend of shifting away from PCI in a subsequent nationwide survey of radiation oncologists (N=431). The trend was consistent across private practices and academic centers. One-fourth of these physicians reported a decline in PCI referrals by medical oncology for patients with extensive-stage SCLC, and 12% also reported fewer referrals for limited-stage SCLC.

“With extensive-stage disease, PCI may best be reserved for patients who are likely to benefit from it, such as those with excellent performance status, younger age (<70 years) and excellent cognitive functions at baseline,” said Dr. Gjyshi. “Caution should be used in extrapolating the Takahashi et al data to patients with limited-stage disease, and further trials may be necessary to address this question.”

“Declining PCI use could impact enrollment in future clinical trials, however, so careful consideration should be given to future studies and trials that plan to investigate the role of PCI in this patient population.”

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