ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data

We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients. Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT). At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of..... READ ARTICLE

The Oncologist DOI:10.1093/oncolo/oyab005

Authors: Moskovitz, Mor, Dudnik, Elizabeth, Shamai, Sivan, Rotenberg, Yakir, Popovich-Hadari, Noa, Wollner, Mira, Zer, Alona, Gottfried, Maya, Mishaeli, Moshe, Rosenberg, Shoshana Keren, Onn, Amir, Merimsky, Ofer, Urban, Damien, Peled, Nir, Maimon, Natalie, Bar, Jair

Management of Oligoprogression in Patients with Metastatic NSCLC Harboring ALK Rearrangements

Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading to substantial prognosis improvement. The exposure to TKIs triggers resistance mechanisms and the sequential administration of other TKIs and chemotherapy is, for the most part, not targeted. In this context, extending the benefit deriving from precision medicine is paramount, above all when disease progression occurs in a limited number of sites. Retrospective data indicate that, in oligoprogressive disease, targeted therapy beyond progression combined with definitive local treatment of the progressing site(s) is an effective alternative. In these cases, multidisciplinary approach becomes essential for an integrated treatment strategy, depending on the s..... READ ARTICLE

Preprints DOI:10.20944/preprints202112.0145.v1

Authors: Pisano, C.; De Filippis, M.; Jacobs, F.; Novello, S.; Reale, M.L.

Review Paper, Pre-PrintKirk SmithDecember 9, 2021oligoprogression, NSCLC, ALK rearrangement

The impact of the ALK fusion variant on clinical outcomes in EML4-ALK patients with NSCLC: a systematic review and meta-analysis

Background: Recent studies showed that ALK-fusion variants are associated with heterogeneous clinical outcomes. However, contradictory conclusions have been drawn in other studies showing no correlation between ALK variants and prognoses. Methods: A systematic review and meta-analysis was performed to evaluate the prognostic value of EML4-ALK fusion variants for patient outcomes. Results: 28 studies were included in the analysis. According to the pooled results, patients harboring variant 1 showed equivalent progression-free survival (PFS) and overall survival (OS) with non-v1 patients (hazard ratio [HR] for PFS: 0.91 [0.68–1.21]; p = 0.499; OS: 1.12 [0.73–1.72]; p = 0.610). Similarly, patients with v3 showed the same disease progress as non-v3 patients (pooled HR for PFS = 1.07 [0.72–1.58]; p = 0.741). However, pooled results for OS suggested that patients with v3 had worse survival than non-v3 patients (HR = 3.44 [1.42–8.35]; p = 0.006). Conclusion: Results suggest that patients with..... READ ARTICLE

Future Oncology DOI:10.2217/fon-2021-0945

Authors: Wang S, Luo R, Shi Y, Han X.

Review Paper, group2Kirk SmithNovember 16, 2021ALK fusion, ALK rearrangement, ALK variant, NSCLC, prognosis

Genetic and treatment profiles of patients with concurrent Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) mutations

EGFR and ALK alternations often contribute to human malignancies, including lung cancer. EGFR and ALK mutations are usually sensitive to EGFR-tyrosine kinase inhibitors (TKIs) and ALK-TKIs. Although generally mutually exclusive, these mutations do co-exist in rare cases. This study investigated the frequencies, clinical characteristics, therapeutic efficacies, and genetic profiles of lung cancer patients with EGFR and ALK co-mutations. ALK and EGFR mutations coincide at a relatively low frequency in lung cancer patients. ALK mutations developed either synchronously or heterochronously with EGFR mutations. Two ALK mutations (L1152R and STRN-ALK) may co-exist with EGFR mutations at a higher frequency than others. Most EGFR/ALK co-alteration patients (other than the EGFR/ALK L1152R type) can benefit from first line EGFR-TKIs. READ ARTICLE

BMC Cancer DOI:10.1186/s12885-021-08824-2

Authors: Xiaodan Yang, Jia Zhong, Zhuo Yu, Minglei Zhuo, Min Zhang, Rongrong Chen, Xuefeng Xia & Jun Zhao

Comparative Efficacy and Safety of Lorlatinib and Alectinib for ALK-Rearrangement Positive Advanced Non-Small Cell Lung Cancer in Asian and Non-Asian Patients

The treatment of anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) advanced non-small cell lung cancer (NSCLC) remains a challenge. We compared the safety and efficacy of lorlatinib and alectinib in patients with ALK-p ALK-inhibitor‒naïve advanced NSCLC (in overall participants and in the Asian and non-Asian subgroups). The results showed that in the overall participant group, the efficacy of lorlatinib and alectinib was not significantly different in terms of progression-free survival (PFS) and overall survival (OS). Although in the Asian subgroup, PFS was not significantly different upon treatment with lorlatinib or alectinib, in the non-Asian subgroup, PFS was significantly better in response to lorlatinib than with alectinib. Grade 3 or higher adverse events in the overall participant group were significantly more frequent with lorlatinib than with alectinib. These results will provide valuable information that would enable the improvement of treatment strategies for ALK-p ALK-inhibitor‒naïve advanced NSCLC. READ ARTICLE

Cancers DOI:10.3390/cancers13153704

Authors: Koichi Ando, Ryo Manabe,Yasunari Kishino, Sojiro Kusumoto,Toshimitsu Yamaoka, Akihiko Tanaka, Tohru Ohmori and Hironori Sagara

Real-World Outcomes, group4Kirk SmithJuly 23, 2021alectinib, ALK rearrangement, lorlatinib

Detection of acquired resistance mutation ALK G1202R after treatment with alectinib and response of lorlatinib

In the era of personalized medicine, the identification of driver mutations has paved the way towards targeted therapy. With the identification of anaplastic lymphoma kinase (ALK) as an oncogenic driver mutation, ALK rearrangements became druggable by tyrosine kinase inhibitors and, thus, have improved the prognosis for patients. Nevertheless, these approaches are limited by resistances occurring within the first or second year of administering ALK inhibitors. Among the different ALK resistant mutations, G1202R is the most common mutation, located in the kinase domain of the ALK protein resulting in resistance to treatment with the first- and second-generation kinase inhibitors (e.g., crizotinib, ceritinib, brigatenib and alectinib). Conflicting reports exist regarding the efficacy of lorlatinib, a next generation ALK inhibitor. The aim of this study is to access the potential impact of lorlatinib as a second-line treatment for a metastatic progressive NSCLC disease harboring genomic a..... READ ARTICLE

Magazine of European Medical Oncology (memo) DOI:

Authors: Louisa Hempel, Jakob Molnar, Andreas Gaumann, Sebastian Robert, Josef Scheiber, Axel Kleespies, Kristina Riedmann, Susanne Schreiber, Beate Gandorfer, Armin Piehler & Dirk Hempel

Case Study, group4Kirk SmithJuly 6, 2021alectinib, ALK rearrangement, lorlatinib

Alectinib for Miliary Lung Metastasis in ALK-Positive Lung Adenocarcinoma

We have reported a case of ALK-rearranged NSCLC with a miliary pulmonary metastasis pattern that was sensitive to alectinib and in which the serum amylase level decreased in response to treatment with alectinib. Young patients with miliary pulmonary metastasis should be checked for all driver mutations. READ ARTICLE

OncoTargets and Therapy DOI:10.2147/OTT.S300229

Authors: Satoh H, Okuma Y, Kashima J, Konnno-Yamamoto A, Yatabe Y, Ohe Y

Case StudyKirk SmithApril 30, 2021alectinib, ALK rearrangement, NSCLC, miliary pulmonary metastasis

First Case Report of Pregnancy on Alectinib in a Woman With Metastatic ALK-Rearranged Lung Cancer: A Case Report

This is the first case report of a patient with ALK-rearranged metastatic lung adenocarcinoma who became pregnant during treatment with alectinib. A multidisciplinary team of gynecologists, neonatologists, oncologists, psychologists, and pharmacologists was set up to handle the case. According to patient’s preference, the study drug was continued throughout pregnancy and the woman delivered a healthy baby girl at 35 weeks and 5 days of gestation. Fetal parameters remained normal during pregnancy. At birth, alectinib levels were 14 times higher in maternal plasma than in the fetus (259 versus 18 ng/mL). The average concentration of alectinib in the placenta was 562 ng/g. The baby was followed during her first 20 months, and no developmental anomalies were observed. After 32 months from diagnosis, the mother is well and in partial remission. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.02.005

Authors: Giovanna Scarfone, Monica Fumagalli, Martina Imbimbo, Tommaso Ceruti, Fulvia Milena Cribiù, Eugenia Di Loreto, Maurizio D’Incalci, Federica Facchin, Camilla Fontana, Marina C. Garassino, Fedro A. Peccatori, Nicola Persico, Diego Signorelli, Massimo Zucchetti

Case StudyKirk SmithMarch 30, 2021ALK rearrangement, Lung cancer, alectinib, Pregnancy

First Case Report of Pregnancy on Alectinib in a Woman With Metastatic ALK-Rearranged Lung Cancer: A Case Report

This is the first case report of a patient with ALK-rearranged metastatic lung adenocarcinoma who became pregnant during treatment with alectinib. A multidisciplinary team of gynecologists, neonatologists, oncologists, psychologists, and pharmacologists was set up to handle the case. According to patient’s preference, the study drug was continued throughout pregnancy and the woman delivered a healthy baby girl at 35 weeks and 5 days of gestation. Fetal parameters remained normal during pregnancy. At birth, alectinib levels were 14 times higher in maternal plasma than in the fetus (259 versus 18 ng/mL). The average concentration of alectinib in the placenta was 562 ng/g. The baby was followed during her first 20 months, and no developmental anomalies were observed. After 32 months from diagnosis, the mother is well and in partial remission. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.02.005

Authors: GiovannaScarfone, Monica Fumagalli, Martina Imbimbo, Tommaso Ceruti, Fulvia Milena Cribiù, Eugenia Di Loreto, Maurizio D’Incalci, Federica Facchin, Camilla Fontana, Marina C. Garassino, Fedro A. Peccatori, Nicola Persico, Diego Signorelli and Massimo Zucchetti

Case StudyKirk SmithMarch 30, 2021ALK rearrangement, Lung cancer, Alectinib, Pregnancy

Crizotinib in Patients With MET-Amplified NSCLC

Patients with high-level, MET-amplified NSCLC responded to crizotinib with the highest ORR. Use of combined diagnostics for MET and other oncogenes may potentially identify patients most likely to respond to crizotinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.02.010

Authors: D. Ross Camidge, Gregory A. Otterson, Jeffrey W. Clark, Sai-Hong Ignatius Ou, Jared Weiss, Steven Ades, Geoffrey I. Shapiro, Mark A. Socinski, Danielle A. Murphy, Umberto Conte, Yiyun Tang, Sherry C. Wang, Keith D. Wilner, Liza C. Villaruz

Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib

The spectrum of ALK-fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of ALK-rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy. READ ARTICLE

Translational Lung Cancer Research DOI:10.21037/tlcr-21-160

Authors: Jingjing Li, Bin Zhang, Yu Zhang, Feng Xu, Zhenfa Zhang, Lin Shao, Chunhe Yan, Paola Ulivi, Marc G Denis, Petros Christopoulos, Vincent Thomas de Montpréville, Eric H Bernicker, Anthonie J van der Wekken, Changli Wang, Dongsheng Yue

Concurrent EGFR mutation and ALK rearrangement in stage IV lung adenocarcinoma-a case report and a literature review

EGFR mutation and ALK rearrangement were considered mutually exclusive mutations in non-small cell lung cancer. Upfront comprehensive mutation screening, like next-generation sequencing, enabled the discovery of simultaneous mutations. We describe a case of a woman with stage IV lung adenocarcinoma with 2 synchronous mutations at diagnosis, the EGFR p.(Leu858Arg) mutation, and an ALK rearrangement. The patient is on gefitinib for 16 months, maintaining this strategy currently. Co-occurrence of 2 targetable mutations is a particular challenge when choosing first-line treatment. We discuss the treatment options and results in patients with both mutations, which were generally associated with a poor prognosis in multiple studies comparing with one single mutation. READ ARTICLE

Porto Biomedecial Journal DOI: 10.1097/j.pbj.0000000000000124

Authors: Élia Cipriano, Helena Magalhães, Catarina Tavares, João Pinto, Luís Cirnes, Fernanda Estevinho

Case StudyKirk SmithFebruary 11, 2021ALK rearrangement, EGFR mutation, concurrent EGFR and ALK mutations, NSCLC

Anaplastic lymphoma kinase (ALK) rearrangement in adult renal cell carcinoma with lung metastasis: a case report and literature review

Renal cell carcinoma (RCC) with anaplastic lymphoma kinase (ALK) rearrangement is rare, and the genetic profiles of the tumor have not been elucidated. Here, we report a case with recurrent papillary RCC and lung metastasis after nephrectomy for nearly 7 years. The patient first received sunitinib, whereas the drug toxicity was intolerable. Combined Immunohistology (IHC) and fluorescence in situ hybridization (FISH) revealed the patient has an ALK rearrangement, and the patient then was treated with crizotinib. The patient had good tolerance, and a partial response in the target lesions was achieved. In order to further understand the benefit of crizotinib in ALK-rearranged RCC, the patient was detected with whole exome sequencing (WES) to study her genetic profiles. Compared those of RCC cases without ALK rearrangement (nALK-RCC), the patient and nine RCC cases with ALK rearrangement (ALK-RCC) revealed unique genetic characteristics: 1) The common mutations that occurred in RCC were n..... READ ARTICLE

Translational Andrology and Urology DOI: 10.21037/tau-20-1343

Authors: Zhou S, Sun G, Wang J, Zhang H.

Proteasome Inhibition Overcomes ALK-TKI Resistance in ALK-Rearranged/TP53-Mutant NSCLC via Noxa Expression.

These clinical and preclinical results indicate concomitant TP53 mutations reduce the efficacy of alectinib for ALK-rearranged NSCLC and the combined use of a proteasome inhibitor with alectinib is a promising therapy for ALK-rearranged/TP53-mutated NSCLC. READ ARTICLE

Clinical Cancer Research DOI: 10.1158/1078-0432.ccr-20-2853

Authors: Azusa Tanimoto, Shingo Matsumoto, Shinji Takeuchi, Sachiko Arai, Koji Fukuda, Akihiro Nishiyama, Kiyotaka Yoh, Takaya Ikeda, Naoki Furuya, Kazumi Nishino, Yuichiro Ohe, Koichi Goto, Seiji Yano

Pre-ClinicalKirk SmithDecember 1, 2020ALK rearrangement, alectinib, p53, Noxa, Mcl-1, apoptosis

Liver and Pancreatic Injury in Response to ALK Inhibitors in a Patient with Primary Signet Ring Cell Carcinoma of the Lung: A Case Report

We report a patient with stage IV anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (primary lung signet ring cell adenocarcinoma) who received serial crizotinib, chemotherapy, and lorlatinib over more than 4 years. The patient discontinued crizotinib after approximately 4 months due to crizotinib-associated hepatotoxicity. Twenty-five days later, when transaminases had normalized, crizotinib was resumed. However, the patient’s liver enzymes rapidly increased again, and crizotinib was discontinued. After 6 cycles of platinum-based chemotherapy, lorlatinib was initiated. Hepatotoxicity did not recur with lorlatinib, a next-generation ALK inhibitor, but grade 4 hypertriglyceridemia and acute pancreatitis were induced by lorlatinib after 4 months. To our knowledge, this is the first case report of acute pancreatitis with lorlatinib. Additionally, stereotactic body radiation therapy (SBRT) was performed for residual small primary lesions in the lung without stopping lorlatinib. Given the rarity of radiation pneumonitis, especially with the relatively small fields treated by SBRT, we suspect that lorlatinib enhanced the pulmonary toxicity. Physicians should be aware that ALK inhibitors, such as lorlatinib and crizotinib, have potentially lethal side effects. READ ARTICLE

Case Reports in Oncology DOI: 10.1159/000512829

Authors: Ibrahim Yildiz

Case StudyKirk SmithOctober 27, 2020Pancreatitis, Hypertriglyceridemia, ALK rearrangement, lorlatinib

Efficacy of Incremental Next-Generation ALK Inhibitor Treatment in Oncogene-Addicted, ALK-Positive, TP53-Mutant NSCLC

Background: The anaplastic lymphoma kinase (ALK) gene fusion rearrangement is a potent oncogene, accounting for 2–7% of lung adenocarcinomas, with higher incidence (17–20%) in non-smokers. ALK-positive tumors are sensitive to ALK tyrosine kinase inhibitors (TKIs), thus ALK-positive non-small-cell lung cancer (NSCLC) is currently spearheading precision medicine in thoracic oncology, with three generations of approved ALK inhibitors in clinical practice. However, these treatments are eventually met with resistance. At the molecular level, ALK-positive NSCLC is of the lowest tumor mutational burden, which possibly accounts for the high initial response to TKIs. Nevertheless, TP53 co-mutations are relatively frequent and are associated with adverse outcome of crizotinib treatment, whereas utility of next-generation ALK inhibitors in TP53-mutant tumors is still unknown. Methods: We report the case of an ALK-positive, TP53-mutant NSCLC patient with about five years survival on ALK TKIs with ..... READ ARTICLE

Journal of Personalized Medicine DOI:10.3390/jpm10030107

Authors: László Urbán, Róbert Dóczi, Barbara Vodicska, Dóra Kormos, László Tóth, István Takács, Edit Várkondi, Dóra Tihanyi,Dóra Lakatos, Anna Dirner, István Vályi-Nagy, István Peták

Real-World OutcomesKirk SmithAugust 28, 2020NSCLC, ALK rearrangement, TP53 mutation, TKI, personalized treatment

Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors

The treatment of advanced non–small-cell lung cancer (NSCLC) has undergone a paradigm shift in the last decade. Molecular characterization of the disease has led to the rapid development of personalized medicine and swift delivery of targeted therapies to patients. The discovery of the anaplastic lymphoma kinase (ALK) gene in patients with NSCLC has resulted in rapid bench–bedside transition of several active drugs, with several others currently in clinical trials. After the first-generation ALK inhibitor crizotinib, next-generation ALK inhibitors have entered clinical applications for ALK-rearranged NSCLC. Ceritinib, alectinib, and brigatinib have all received approval for ALK-positive patients who have failed prior crizotinib, as well as first-line therapy in treatment-naïve patients based on favorable efficacy. Most recently, lorlatinib, a potent, newer-generation ALK inhibitor, has been approved as second- or third-line treatment. These advances have led to better patient outcomes,..... READ ARTICLE

Cancer Management and Research DOI:10.2147/CMAR.S260274

Authors: Abhay Singh, Hongbin Chen

Epithelioid fibrous histiocytoma of the vulva: Report of a case with next-generation sequencing analysis

Epithelioid fibrous histiocytoma (EFH), also known as epithelioid cell histiocytoma (ECH), is an uncommon benign cutaneous mesenchymal neoplasm that typically occurs in the limbs and consistently harbors ALK gene rearrangements. In this study, we report a unique case of EFH that arose in the labia majora, an unusual site which has been rarely described. The tumor occurred in a 41-year-old woman who presented with a slowly growing painless nodule in the vulva. Histological examination revealed a circumscribed lesion located within the dermis, which was composed of sheets or nests of large polygonal epithelioid cells with abundant eosinophilic cytoplasm. Nuclear atypia was minimal and mitotic figures were rare. Immunohistochemically, the neoplastic cells showed diffuse cytoplasmic staining of ALK protein. Subsequent fluorescence in situ hybridization (FISH) assessment demonstrated a balanced rearrangement of ALK gene. Further next-generation sequencing (NGS) analysis identified SQSTM1-AL..... READ ARTICLE

Human Pathology: Case Reports DOI:10.1016/j.ehpc.2020.200378

Authors: Lu Zhao, Jiahan Liu, Meng Sun, I. Weng Lao, Lin Yu, Jian Wang

Patients with NSCLCs Harboring Internal Inversions or Deletion Rearrangements of the ALK Gene Have Durable Responses to ALK Kinase Inhibitors

Background

ALK fusions are targetable drivers in non-small-cell lung cancer (NSCLC). However, patients with NSCLC harboring ALK rearrangements without a fusion partner identified in DNA have also been shown to respond to ALK inhibitors. We aimed to characterize complex ALK variants that may predict sensitivity to multiple approved ALK inhibitors.

Methods

Comprehensive genomic profiling (CGP) of DNA isolated from formalin‐fixed paraffin‐embedded (FFPE) tumor tissue or blood-based circulating tumor DNA was performed for 39,159 NSCLC patients during routine clinical care. For a subset of cases, RNA sequencing was performed, and prior ALK test results and clinical treatment information were collected from treating physicians.

Results

We queried the Foundation Medicine NSCLC database and identified ALK internal inversions, as well as internal deletions, as the sole ALK rearrangements in 6 (0.02%) and 3 (0.01%) of cases, respectively. In cases with ALK internal inversions, RNA testing i..... READ ARTICLE

Lung Cancer: Targets and Therapy DOI:10.2147/LCTT.S239675

Authors: Schrock AB, Madison R, Rosenzweig M, Allen JM, Erlich RL, Wang SY, Chidiac T, Reddy VS, Riess JW, Yassa AE, Shakir A, Miller VA, Alexander BM, Venstrom J, McGregor K, Ali SM

Case StudyKirk SmithApril 17, 2020ALK rearrangement, inversion, deletion, genomic profiling, targeted therapy

"Brigatinib and Alectinib for ALK Rearrangement-Positive Advanced Non-Small Cell Lung Cancer with or without Central Nervous System Metastasis: A Systematic Review and Network Meta-Analysis"

To date, no head-to-head trials have compared the e cacy of brigatinib and alectinib
against anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p), ALK-inhibitor-naïve,
advanced non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis.
We conducted an indirect treatment comparison (ITC) between brigatinib and alectinib, with crizotinib
as a common comparator, using a Bayesian model with non-informative prior distribution and assessed
the between-study heterogeneity of the studies. The primary e cacy endpoint was progression-free
survival (PFS), and e cacy was ranked using the surface under the cumulative ranking (SUCRA)
curve values. ITC analysis showed that there were no significant di erences in PFS between the
brigatinib and alectinib arms. However, the SUCRA values revealed that alectinib ranked the highest
by e cacy in the overall patient population, whereas brigatinib ranked the highest by e cacy in
the CNS metastasis sub-group. Although there wer..... READ ARTICLE

Cancers DOI:10.3390/cancers12040942

Authors: Koichi Ando, Kaho Akimoto, Hiroki Sato, Ryo Manabe, Yasunari Kishino,
Tetsuya Homma, Sojiro Kusumoto, Toshimitsu Yamaoka , Akihiko Tanaka,
Tohru Ohmori,Hironori Sagara