27-gene Immuno-Oncology (IO) Score is Associated With Efficacy of Checkpoint Immunotherapy in Advanced NSCLC: A Retrospective BC Cancer Study.

BACKGROUND: Immune checkpoint inhibitors (ICI) are standard of care in advanced non-small cell lung cancer (NSCLC). However, not all patients benefit, even among PD-L1 tumor proportional score (TPS) ≥50%, indicating an unmet need for additional biomarkers such as those assessing the tumor immune microenvironment (TIME). DetermaIO is a 27-gene assay that classifies TIME and has previously demonstrated association with ICI response. METHODS: FFPE samples were selected from BC Cancer and West Clinic Cancer Center patients with performance status (PS) ≤2 who received at least 2 cycles of ICI monotherapy in the first (1L) or second line (2L). IO scores were generated and analyzed for association with PFS and OS. RESULTS: In the entire cohort (N=147), IO score was significantly associated with OS (HR=0.68, 95%CI 0.47-0.99, P = .042) and PFS (HR=0.62, 95%CI 0.43-0.88, P = .0069). In 1L treated patients (PD-L1≥50%, N=78), IO score was significantly associated with PFS (HR=0.55, 95%CI 0.32-0.94, P = .028). In exploratory analyses, IO score was associated with benefit in 1L PS2 patients for OS (HR = 0.26, 95%CI 0.091-0.74, P = .012) and PFS (HR = 0.27, 95%CI 0.098-0.72, P = .0095) which was confirmed in PFS subgroup analysis in the independent West Cancer Center study (N=13 HR=0.14, 95%CI 0.027-0.76, P = .023). CONCLUSION: These data confirm the association of DetermaIO with ICI clinical benefit in NSCLC, and expand on previous studies by demonstrating that first line treated PD-L1≥50% patients can further be stratified by IO score to identify efficacy. Exploratory analysis suggested that the IO score identifies benefit in patients with poor PS.

Characterization of the tumor immune-microenvironment of adenocarcinoma of lung with a metastatic lesion in the pancreas treated successfully with first-line, single-agent pembrolizumab.

Single-agent immune checkpoint inhibitor therapy in advanced non-small cell lung cancer can significantly prolong progression-free and overall survival when compared with cytotoxic chemotherapy. Here, we report a case of newly diagnosed adenocarcinoma of the lung with a solitary brain metastasis and a biopsy confirmed adenocarcinoma in the tail of the pancreas. Cytomorphology and immunohistochemistry suggested the lung and pancreas tumors were distinct primaries. However, molecular analysis of the lung primary and tumor in the pancreas revealed the same mutations of functional significance in PIK3CA, NF1 and TP53, suggesting the tumors were clonal. A total of three cycles of single-agent pembrolizumab, and radiation to the lung and brain administered between cycles 1 and 2, resulted in marked responses in lung, brain and pancreatic tumors. Despite the discontinuation of the pembrolizumab after three cycles due to severe immune-mediated toxicities, the patient has had no progression 11 months after stopping all active treatment. Results of a novel 27-gene immuno-oncology (IO) expression assay revealed strong IO scores for the lung and pancreatic tumors, indicating a favorable tumor immune-microenvironment and possibly explaining the significant response.

Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for the Detection of ALK in Non-Small Cell Lung Cancer.

Patients with lung cancers harboring an activating anaplastic lymphoma kinase (ALK) rearrangement respond favorably to ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are validated and widely used screening tests for ALK rearrangements but both methods have limitations. The ALK RGQ RT-PCR Kit (RT-PCR) is a single tube quantitative real-time PCR assay for high throughput and automated interpretation of ALK expression. In this study, we performed a direct comparison of formalin-fixed paraffin-embedded (FFPE) lung cancer specimens using all three ALK detection methods. The RT-PCR test (diagnostic cut-off ΔCt of ≤8) was shown to be highly sensitive (100%) when compared to FISH and IHC. Sequencing of RNA detected full-length ALK transcripts or EML4-ALK and KIF5B-ALK fusion variants in discordant cases in which ALK expression was detected by the ALK RT-PCR test but negative by FISH and IHC. The overall specificity of the RT-PCR test for the detection of ALK in cases without full-length ALK expression was 94% in comparison to FISH and sequencing. These data support the ALK RT-PCR test as a highly efficient and reliable diagnostic screening approach to identify patients with non-small cell lung cancer whose tumors are driven by oncogenic ALK.

Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion-positive lung cancer patient.

Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene-addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present a case of an anaplastic lymphoma kinase (ALK)-positive lung cancer patient with hepatic oligometastatic progression who was successfully treated with both stereotactic ablative radiation and RFA while continuing with an ALK inhibitor.

Small lymphocytic lymphoma with florid perniosis-like features: a case report.

BACKGROUND: Small lymphocytic lymphoma is a relatively rare B-cell non-Hodgkin lymphoma that is considered to be the tissue equivalent of the much more common entity chronic lymphocytic leukemia. Cutaneous manifestations of small lymphocytic lymphoma are infrequent and the literature regarding them sparse. We describe here a case of a patient with a history of small lymphocytic lymphoma who developed perniosis-like features of the digits. CASE PRESENTATION: An 86-year old male patient with previously diagnosed small lymphocytic lymphoma developed painful erythematous swelling of the periungual area of his fingers and toes. This was associated with a dense dermal infiltration of CD5-positive B-lymphoid cells consistent with his low-grade B-cell lymphoma. Although partially refractory to local radiotherapy, the painful swelling of the fingers and toes resolved fully following systemic therapy with chlorambucil and rituximab. CONCLUSIONS: This unusual cutaneous manifestation of a lymphoma and the favourable response to systemic therapy may be instructive for the management of other patients who develop similar perniosis-like features.

Detection of a TRAF1-ALK fusion in an anaplastic large cell lymphoma patient with chemotherapy and ALK inhibitor-resistant disease.

BACKGROUND: The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, which was first identified as the fusion partner of the nucleophosmin (NPM1) gene in the recurrent t(2;5)(p23;q35) found in a subset of anaplastic large cell lymphoma (ALCL). Several distinct, non-NPM1, ALK fusions have subsequently been described in lymphomas and other tumor types. All of these fusions result in the constitutive expression and activation of ALK and ALK signaling pathways, ultimately leading to the malignant phenotype. CASE REPORT: A non-NPM1 fusion partner of ALK was identified in a 32-year-old Caucasian male ALCL patient whose disease was refractory to standard chemotherapy and autologous stem cell transplantation, and exhibited a poor response to a first-generation ALK inhibitor. Non-allele-specific ALK RT-qPCR revealed ALK overexpression and 5' RACE PCR revealed that the patient's lymphoma expressed a TRAF1-ALK fusion. CONCLUSIONS: We report the case of an ALCL patient whose tumor harbored the newly recognized TRAF1-ALK fusion and describe the clinical outcome after treatment with an ALK inhibitor. The short survival of our patient may reflect a propensity toward aggressive behavior in lymphomas that express this ALK fusion.

Awareness of risk factors among persons at risk for lung cancer, chronic obstructive pulmonary disease and sleep apnea: a Canadian population-based study.

OBJECTIVE: To assess awareness among persons at risk for lung cancer, chronic obstructive pulmonary disease (COPD) and sleep apnea regarding symptoms and risk factors of the disease, and their attitudes regarding the disease and toward those who are affected. METHODS: A quantitative hybrid telephone and Internet survey of a representative population of Canadian adults at risk for at least one of the three diseases was conducted. To measure the awareness and attitudes of First Nations, Inuit and Métis people to these diseases, a proportionate number were also surveyed.  RESULTS: A total of 3626 individuals were contacted. Of these, 3036 (84%) were eligible to participate. Of those at risk for lung cancer and COPD, 65% and 69%, respectively, were due to tobacco smoke exposure. Among those at risk, 72% believed that they were informed about lung cancer compared with 36% for COPD and 56% for sleep apnea. Most respondents were knowledgeable about the common symptoms of lung cancer, COPD and sleep apnea, but were less aware of the impact lifestyle choices could have on the development of these disorders and the availability of treatment. Most of the participants (77%) believed that smoking was an addiction rather than a habit (19%). There were no significant differences in the awareness of risk factors, symptoms and attitudes toward all three lung diseases between First Nations, Inuit and Métis people and the general population. CONCLUSIONS: Canadians are reasonably aware of risk factors and symptoms for lung cancer and sleep apnea. However, there is poor awareness of COPD as a disease entity. There is a lack of appreciation for the impact lifestyle choices and changes can have on lung diseases.

A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma.

To analyze the available literature describing the treatment of relapsed aggressive non-Hodgkin's lymphoma (NHL) with single-agent chemotherapies, several comprehensive electronic and manual inspections of the literature were performed for the period from 1966 to the present. Each paper was examined to capture the following data: study type; patient demographics and characteristics; study endpoints, including responses, and method used to evaluate response; toxicities, and the power of the study. A wide variety of single-agent protocols continue to be studied, indicating no currently accepted standard therapy in this patient population. Reported response rates varied between 0 and 67%. The majority of trials were small, uncontrolled studies that used widely varying inclusion/exclusion criteria and had limited reporting of histology, response, prior treatments, and other key parameters. We were able to find only four agents, etoposide, vincristine, vinorelbine and possibly rituximab, with sufficient reproducible evidence to suggest greater than 30% activity (CR + PR rate) when given to patients with second or greater relapse of aggressive NHL. Consequently, the usefulness of the agents in these reports remains to be established in larger trials with more detailed reporting. The advantages that would be brought by an active non-myelosuppressive agent for patients having this condition emerge clearly from this review.