Goldsteinbloch3829

Intracranial disease can be challenging to accurately diagnose in a patient with MS who previously underwent radiation, as progressing lesions can be tumor growth, MS flare, or radiation necrosis.

Although patients with preexisting autoimmune diseases, including MS, might be at an increased risk of developing immune-related adverse events with ICIs, they may also experience anticancer benefit. Intracranial disease can be challenging to accurately diagnose in a patient with MS who previously underwent radiation, as progressing lesions can be tumor growth, MS flare, or radiation necrosis.

To evaluate the need for tobacco cessation services within a multidisciplinary clinic (MDC), we surveyed patients on their smoking status, interest in quitting, and willingness to participate in a clinic-based cessation program. We further evaluated the association between interest in cessation or willingness to participate in a cessation program and overall survival (OS).

From 2014 to 2019, all new patients with lungcancer in the MDC at Baptist Cancer Center (Memphis,TN) were administered a social history questionnaireto evaluate their demographic characteristics, smoking status, tobacco dependence, interest inquitting,and willingness to participate in a cessation program. We used chi-square tests and logistic regression to compare characteristics of those who would participateto those who would not or were unsure and Kaplan-Meier curves and Cox regression to evaluate theassociation between cessation interest or willingness to quit and OS.

Of 641 total respondents, the average age was 69 years (range 32-95), 47% were men, 64% white, 34% black, and 17% college graduates. A total of 90% had ever smoked 34% currently and 25% quit within the past year. Among the current smokers, 60% were very interested in quitting and 37% would participate in a cessation program. Willingness to participate in a cessation program was associated with greater interest in quitting (

< 0.0001), better OS (

= 0.02), and reduced hazard of death (hazard ratio= 0.52, 95% confidence interval 0.30-0.88), but no other characteristics.

Patients with lung cancer in an MDC expressed considerable interest in tobacco cessation services; patients willing to participate in a clinic-based cessation program had improved survival.

Patients with lung cancer in an MDC expressed considerable interest in tobacco cessation services; patients willing to participate in a clinic-based cessation program had improved survival.

amplification is a frequently observed mechanism of resistance to osimertinib, and coinhibition strategy of MET and EGFR revealed promising results in recent clinical trials. Nevertheless, acquired resistance mechanisms to combined EGFR and MET inhibition are poorly understood. In this study, we investigated the mechanisms of acquired resistance to osimertinib and savolitinib by using pretreatment and post-treatment tissue analysis.

Whole-exome sequencing was performed in

-mutant,

-amplified patients who received osimertinib and savolitinib using tissues obtained both before and after therapy. All patients achieved partial response or durable stable disease to osimertinib and savolitinib before developing acquired resistance.

After progression on osimertinib and savolitinib, whole-exome analysis revealed

-dependent mechanisms of resistance, such as acquired

p.D1246H mutation,

p.Y1230C mutation, and

copy number gain. As for

-independent mechanisms, development of

mutation and amplification and copy number gains in amplifications in

,

,

and

were observed. Patient 2 harbored an acquired

p.H1047R mutation in which resistance could be overcome with combination of PI3K inhibitor and osimertinib in the patient-derived xenograft model.

Our study reveals that acquired resistance to savolitinib plus osimertinib can occur from both MET-dependent and MET-independent mechanisms.

Our study reveals that acquired resistance to savolitinib plus osimertinib can occur from both MET-dependent and MET-independent mechanisms.Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the preferred frontline therapy for EGFR-mutant advanced NSCLC. However, despite its high initial response rates, multiple EGFR-independent mechanisms of resistance have been reported in patients receiving osimertinib. One such mechanism is the emergence of acquired, targetable oncogenic fusion events. It has been documented in other case reports that combination therapies can be efficacious in these scenarios. In our case report, we present a patient with EGFR-mutant advanced NSCLC who developed an acquired EML4-ALK rearrangement mediating resistance to osimertinib, which was overcome by using a combination of osimertinib with the ALK tyrosine kinase inhibitor alectinib.

YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study.

The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5× once-weekly infusions, followed by a 1-wk rest).

The study included 31 patients (median age= 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greaterthan or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. Thebest overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Sodium palmitate Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths.

The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.

The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.Optimal management of EGFR-mutated NSCLC with leptomeningeal (LM) disease progression through EGFR tyrosine kinase inhibitor remains unclear. We present a 39-year-old man with EGFR-mutated NSCLC and LM disease progression through osimertinib 80 mg daily, with subsequent durable radiographic and symptomatic response to systemic pemetrexed in combination with osimertinib. This builds on the limited data evaluating LM disease response to systemic pemetrexed and lends further support to consideration of this treatment strategy.

Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England.

In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information.

A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy.

We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved.

We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved.

The phase 3 RELAY global study (NCT02411448) revealed significant improvement in progression-free survival (PFS) with ramucirumab plus erlotinib (RAM+ ERL) compared with placebo plus ERL (PL+ ERL) in untreated

-mutated metastatic NSCLC (hazard ratio [HR] = 0.59 [95% confidence interval (CI) 0.46-0.76,

0.0001]). This prespecified analysis evaluates efficacy, safety, and postprogression

T790M rates of RELAY patients enrolled in Japan.

Patients were randomized (11) to oral ERL (150 mg/d) plus intravenous RAM (10 mg/kg) or PL every 2 weeks. End points included PFS (primary), safety (secondary), and biomarker analyses (exploratory). Plasma samples collected at baseline and poststudy treatment discontinuation were evaluated for

T790M mutations by next-generation sequencing.

The Japanese subset included 211 of 449 (47.0%) RELAY patients (RAM+ ERL, n= 106; PL+ ERL, n= 105). Median PFS was 19.4 versus 11.2 months for RAM+ ERL versus PL+ ERL treatment (HR= 0.610 [0.431-0.864]) in the Japanese intent-toRL-associated EGFR T790M rates at disease progression.

The role of salvage surgery for patients with locoregional (LR) recurrence or persistent SCLC after radical chemoradiotherapy (CRT) for limited-stage disease is not well established. We evaluated our experience.

We conducted a retrospective study of consecutive patients who underwent salvage pulmonary resection for LR-recurrent or persistent SCLC between 2008 and 2020 at the Amsterdam University Medical Center.

A total of 10 patients were identified. Median age at initial diagnosis of limited-stage SCLC was 58.5 years (48-71 y). All patients had radical-intent concurrent CRT. Of the 10 patients, 9 were diagnosed with LR-recurrent or persistent disease with a median of 18 months (3-78 y) after CRT. All patients underwent an anatomical radical resection and mediastinal lymph node dissection. No 90-day mortality was recorded. In addition, one patient developed a LR recurrence 7 months after resection. Distant progression was found in three patients at 6, 32, and 61 months after surgery, all of whom subsequently died of progressive SCLC. Median follow-up was 22.5 months (2-86 mos). Disease-free survival was 34 months; overall survival was not reached.

For highly selected patients with LR-recurrent or persistent SCLC after CRT, salvage surgery is feasible and can result in clinically meaningful survival. Such patients should be presented to the multidisciplinary tumor board.

For highly selected patients with LR-recurrent or persistent SCLC after CRT, salvage surgery is feasible and can result in clinically meaningful survival. Such patients should be presented to the multidisciplinary tumor board.