Misako Nagasaka

PD1/PD-L1 inhibition as a potential radiosensitizer in head and neck squamous cell carcinoma: a case report

BackgroundImmunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated.Case presentationWe report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy.ConclusionT cell activation induced by checkpoint inhibition may dramatically improve tumor response to radiation. More data are needed to identify the toxicity and efficacy of sequential or concurrent checkpoint inhibitors and radiotherapy.

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer

ABSTRACT Introduction: Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Role of Molecular Profiling in Diagnosis of Papillary Renal-cell Cancer Presenting as Cancer of Unknown Primary Site

Cancer of unknown primary site accounts for approximately 4% to 5% of all invasive cancer diagnoses. We present 2 cases of cancer of unknown primary site, both of which were successfully diagnosed as papillary renal-cell carcinoma by mRNA gene expression profiling. The use of molecular profiling should be contemplated on a case-by-case scenario. It should be strongly considered therapies are being targeted to tumor sites.

Retreatment With Osimertinib Following Pneumonitis

Drug-related pneumonitis is known to occur with epidermal growth factor receptor-targeted tyrosine kinase inhibitor (TKI) therapy. Once pneumonitis occurs, the standard of care has been to discontinue the TKI. Osimertinib is an oral epidermal growth factor receptor-TKI selective for both sensitizing mutations as well as T790M resistance mutation and is the only approved treatment for T90M-positive nonesmall-cell lung cancer. We here report 2 cases of retreatment with osimertinib in patients who had developed drug-related pneumonitis. Retreatment with osimertinib under steroid coverage could be considered after careful risk-benefit assessment.

EGFR-Mutant Non–Small Cell Lung Cancer in the Era of Precision Medicine: Importance of Germline EGFR T790M Testing

With the rapid development of precision medicine, next-generation sequencing (NGS) has provided the ability to uncode tumors at the DNA level. Identifying EGFR mutations and other molecular changes has become more crucial in the management of non-small cell lung cancer (NSCLC) than ever before. Although the histologic subtypes in patients with advanced NSCLC remain valid in determining treatment options, the detection of specific molecular signatures such as de novo T790M with sensitizing EGFR mutations could be more useful than the histologic subtype itself. Germline T790M mutation should be suspected and tested for when multiple biopsies show de novo T790M mutations or when de novo T790M is found in patients with a family history of lung cancer. This case report presents a 60-year-old woman with bilateral NSCLC with 3 different distinct histologic diagnoses. Evaluating the molecular profile using NGS completely changed the diagnosis, prognosis, and management of this rare presentation of NSCLC.

Responses in patients receiving sequential paclitaxel post progression on PD1 inhibitors

This report describes highlights the dramatic responses seen in patients who were given paclitaxel post progression on immunotherapy. There are multiple mechanisms by which synergistic effects of immunotherapy and chemotherapy occur. Further prospective studies on chemotherapy and immunotherapy are eagerly awaited.

Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic neuroinflammatory disease. While the disease usually progresses slowly without remission, there is a subgroup of patients with rapid progression and another subgroup with very slow progression. However, there have been no reports to date that have successfully determined the criteria to differentiate these subgroups. Therefore, we initially conducted a statistical modeling analysis to explore representative patterns of disease progression using data from our nationwide HAM/TSP patient registration system (“HAM-net”). The latent class mixed model analysis on the retrospective data (n = 205) of disease progression measured by the change in Osame Motor Disability Score from the onset of the disease to diagnosis demonstrated three representative progression patterns of HAM/TSP. Next, to test the effect of the progression rate at the initial phase of the disease on long-term prognosis, we divided 312 “HAM-net” registered patients into three groups (rapid, slow, and very slow progressors) based on the progression rate, then analyzed long-term functional prognosis of each group using the Kaplan–Meier method. Our data clearly demonstrated that the rapid progression at the early phase of the disease is an important poor prognostic factor. Moreover, to determine the biomarkers capable of discriminating the difference in disease activity, we compared the value of potential biomarkers of HAM/TSP among rapid (n = 15), slow (n = 74), very slow (n = 7), and controls (non-HAM/TSP patients, n = 18). The cerebrospinal fluid (CSF) levels of neopterin and C-X-C motif chemokine 10 (CXCL10) were the most valuable markers to discriminate among rapid, slow, and very slow progressors. To differentiate between rapid and slow progressors, the cut-off values of neopterin and CXCL10 were determined to be 44 pmol/mL and 4400 pg/mL, respectively. Furthermore, to differentiate between slow and very slow progressors, these values were determined to be 5.5 pmol/mL and 320 pg/mL, respectively. Notably, we found that CSF levels of these markers in very slow progressors were within the reference range. Thus, we propose a new classification criteria for disease activity of HAM/TSP that may contribute to improving the treatment algorithm for HAM/TSP.

Is this really just “fatigue”? A case series of immune-related central adrenal insufficiency secondary to immune checkpoint inhibitors

While immunotherapy with programmed cell death protein 1 (PD1) checkpoint inhibition has shown promising activity against many tumor types, adverse events are common. Hypophysitis is a rare but serious immune‐related event known to occur with anti‐PD1 inhibition. It will become more prevalent as the usage of checkpoint inhibitors increases.

Definitive chemoradiotherapy with carboplatin for squamous cell carcinoma of the head and neck: Chemoradiotherapy with Carboplatin for HNSCC

Definitive concurrent chemoradiotherapy (CRT) is considered the standard of care for organ preservation and is the only potentially curative therapy for surgically unresectable patients with stage III to IVb locally advanced squamous cell carcinoma of the head and neck. In patients with high risks for adverse events utilizing cisplatin, carboplatin has been empirically substituted. The objective of this study was to estimate the locoregional control rate, progression‐free survival, overall survival, and adverse events in locally advanced squamous cell carcinoma of the head and neck patients treated with CRT utilizing carboplatin.

Histologic Transformation in NSCLC with PD-1 therapy

Histologic Transformation in NSCLC with PD-1 therapy Misako Nagasaka, MD, Rahul S. Pansare, MD, Eman Abdulfatah, MD, Hui Guan, MD, Paul Tranchida, MD, Shirish M. Gadgeel, MD* Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, Michigan Department of Infectious Disease, Wayne State University, Detroit, Michigan Department of Pathology, Wayne State University, Detroit, Michigan Department of Surgical Pathology, Detroit Medical Center/Karmanos Cancer Institute, Detroit, Michigan