Multi-omics and clustering analyses reveal the mechanisms underlying unmet needs for patients with lung adenocarcinoma and identify potential therapeutic targets.

BACKGROUND: The cancer genome contains several driver mutations. However, in some cases, no known drivers have been identified; these remaining areas of unmet needs, leading to limited progress in cancer therapy. Whole-genome sequencing (WGS) can identify non-coding alterations associated with the disease. Consequently, exploration of non-coding regions using WGS and other omics data such as ChIP-sequencing (ChIP-seq) to discern novel alterations and mechanisms related to tumorigenesis have been attractive these days. METHODS: Integrated multi-omics analyses, including WGS, ChIP-seq, DNA methylation, and RNA-sequencing (RNA-seq), were conducted on samples from patients with non-clinically actionable genetic alterations (non-CAGAs) in lung adenocarcinoma (LUAD). Second-level cluster analysis was performed to reinforce the correlations associated with patient survival, as identified by RNA-seq. Subsequent differential gene expression analysis was performed to identify potential druggable targets. RESULTS: Differences in H3K27ac marks in non-CAGAs LUAD were found and confirmed by analyzing RNA-seq data, in which mastermind-like transcriptional coactivator 2 (MAML2) was suppressed. The down-regulated genes whose expression was correlated to MAML2 expression were associated with patient prognosis. WGS analysis revealed somatic mutations associated with the H3K27ac marks in the MAML2 region and high levels of DNA methylation in MAML2 were observed in tumor samples. The second-level cluster analysis enabled patient stratification and subsequent analyses identified potential therapeutic target genes and treatment options. CONCLUSIONS: We overcome the persistent challenges of identifying alterations or driver mutations in coding regions related to tumorigenesis through a novel approach combining multi-omics data with clinical information to reveal the molecular mechanisms underlying non-CAGAs LUAD, stratify patients to improve patient prognosis, and identify potential therapeutic targets. This approach may be applicable to studies of other cancers with unmet needs.

Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

BACKGROUND: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case. Despite this, most cancer research has approached the analysis of these data sets separately, without merging and comparing the data, and there are no examples of integrated analysis in LUAD. METHODS: We performed an integrated analysis of super-enhancers and structural variants in a cohort of 174 LUAD cases that lacked clinically actionable genetic alterations. To achieve this, we conducted both WGS and H3K27Ac ChIP-seq analyses using samples with driver gene mutations and those without, allowing for a comprehensive investigation of the potential roles of super-enhancer in LUAD cases. RESULTS: We demonstrate that most genes situated in these overlapped regions were associated with known and previously unknown driver genes and aberrant expression resulting from the formation of super-enhancers accompanied by genomic structural abnormalities. Hi-C and long-read sequencing data further corroborated this insight. When we employed CRISPR-Cas9 to induce structural abnormalities that mimicked cases with outlier ERBB2 gene expression, we observed an elevation in ERBB2 expression. These abnormalities are associated with a higher risk of recurrence after surgery, irrespective of the presence or absence of driver mutations. CONCLUSIONS: Our findings suggest that aberrant gene expression linked to structural polymorphisms can significantly impact personalized cancer treatment by facilitating the identification of driver mutations and prognostic factors, contributing to a more comprehensive understanding of LUAD pathogenesis.

Application of non-negative matrix factorization in oncology: one approach for establishing precision medicine.

The increase in the expectations of artificial intelligence (AI) technology has led to machine learning technology being actively used in the medical field. Non-negative matrix factorization (NMF) is a machine learning technique used for image analysis, speech recognition, and language processing; recently, it is being applied to medical research. Precision medicine, wherein important information is extracted from large-scale medical data to provide optimal medical care for every individual, is considered important in medical policies globally, and the application of machine learning techniques to this end is being handled in several ways. NMF is also introduced differently because of the characteristics of its algorithms. In this review, the importance of NMF in the field of medicine, with a focus on the field of oncology, is described by explaining the mathematical science of NMF and the characteristics of the algorithm, providing examples of how NMF can be used to establish precision medicine, and presenting the challenges of NMF. Finally, the direction regarding the effective use of NMF in the field of oncology is also discussed.

Comparison of Vision Transformers and Convolutional Neural Networks in Medical Image Analysis: A Systematic Review.

In the rapidly evolving field of medical image analysis utilizing artificial intelligence (AI), the selection of appropriate computational models is critical for accurate diagnosis and patient care. This literature review provides a comprehensive comparison of vision transformers (ViTs) and convolutional neural networks (CNNs), the two leading techniques in the field of deep learning in medical imaging. We conducted a survey systematically. Particular attention was given to the robustness, computational efficiency, scalability, and accuracy of these models in handling complex medical datasets. The review incorporates findings from 36 studies and indicates a collective trend that transformer-based models, particularly ViTs, exhibit significant potential in diverse medical imaging tasks, showcasing superior performance when contrasted with conventional CNN models. Additionally, it is evident that pre-training is important for transformer applications. We expect this work to help researchers and practitioners select the most appropriate model for specific medical image analysis tasks, accounting for the current state of the art and future trends in the field.

Endoscopic mucosal ischemic index for predicting anastomotic complications after esophagectomy: a prospective cohort study.

BACKGROUND: Postoperative complications related to gastric conduit reconstruction are still common issues after McKeown esophagectomy. A novel endoscopic mucosal ischemic index is desired to predict anastomotic complications after McKeown esophagectomy. AIMS AND METHODS: The purpose of this study was to prospectively evaluate the safety and efficacy of endoscopic examinations of the anastomotic region in the acute period after esophagectomy. Endoscopic examinations were performed on postoperative days (PODs) 1 and 8. The severity of ischemia was prospectively validated according to the endoscopic mucosal ischemic index (EMII). RESULTS: A total of 58 patients were included after evaluating the safety and feasibility of the endoscopic examination on POD 1 in 10 patients. Anastomotic leakage occurred in 6 patients. Stricture occurred in 13 patients. A greater than 67% circumference and lesion length greater than 20 mm of anastomotic ischemic area (AIA) on POD 1 were associated with developing anastomotic leakage after esophagectomy (OR: 14.5; 95% CI: 1.8-306.5; P = 0.03, OR: 19.4; 95% CI: 1.7-536.8; P = 0.03). More than 67% circumferential ischemic mucosa and ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were associated with developing anastomotic strictures after esophagectomy (OR: 6.4; 95% CI: 1.4-31.7; P = 0.02, OR: 5.9; 95% CI: 1.2-33.1; P = 0.03). Patients with either more than 67% circumferential ischemic mucosa or ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were defined as EMII-positive patients. The sensitivity, specificity, and positive and negative predictive values of EMII positivity on POD 1 for leakage were 100%, 78.8%, 35.3%, and 100%, respectively. The sensitivity, specificity, and positive and negative predictive values of the EMII positivity on POD 1 for strictures were 69.2%, 82.2%, 52.9%, and 90.2%, respectively. CONCLUSIONS: The application of an endoscopic classification system to mucosal ischemia after McKeown esophagectomy is both appropriate and satisfactory in predicting anastomotic complications. TRIAL REGISTRATION: Clinical Trial.gov Registry, ID: NCT02937389, Registration date: Oct 17, 2015.

Phase II study of S-1 and oxaliplatin as neoadjuvant chemotherapy for locally advanced adenocarcinoma of the gastric or esophagogastric junction: KSCC1601.

BACKGROUND: Perioperative chemotherapy is the standard of care for locally advanced gastric cancer (LAGC). This phase II study investigated the efficacy and safety of S-1 and oxaliplatin (SOX) as neoadjuvant chemotherapy (NAC) for LAGC and esophagogastric junction cancer (EGJC). METHODS: Patients completed up to three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for 2 weeks every 3 weeks), followed by gastrectomy and D2 lymphadenectomy. The primary endpoint was the pathological response rate (pRR). The anastomosis leakage rate was the secondary endpoint in patients with EGJC, and other secondary endpoints were the R0 resection, overall survival (OS), and relapse-free survival (RFS) rates. RESULTS: Between April 2016 and July 2017, 47 patients (24 EGJC, 23 LAGC) were enrolled in this study. Forty-two patients (89.4%, 95% confidence interval [CI] = 76.9-96.5) underwent surgery, and R0 resection was achieved in 41 patients. The pRR was 59.5% (90% CI = 45.7-72.3). The major grade 3 or 4 toxicities were appetite loss in six patients (12.8%), thrombocytopenia in five patients (10.6%), and neutropenia and diarrhea in three patients (6.4%) each. The rate of severe anastomotic leakage (Clavien-Dindo classification grade III or higher) in 20 EGJC was 25.0% (90% CI = 10.4-45.6). The 3-year OS and RFS rate were 62.9% (95% CI = 47.2-75.1) and 53.2% (95% CI = 38.1-66.2), respectively. CONCLUSION: SOX130 demonstrated substantial benefit for LAGC and EGJC. However, special attention should be paid to anastomotic leakage during surgery for EGJC.

Impact of chronological age on efficacy and safety of fluoropyrimidine plus bevacizumab in older non-frail patients with metastatic colorectal cancer: a combined analysis of individual data from two phase II studies of patients aged >75 years.

OBJECTIVE: Many clinical trials for older patients with metastatic colorectal cancer have been conducted, and fluoropyrimidine and bevacizumab are standard treatments. However, the relationship between age and the efficacy and safety of this treatment is unclear in older metastatic colorectal cancer patients. METHODS: Individual data from two phase II studies on older (≥75 years), non-frail patients with metastatic colorectal cancer treated with uracil-tegafur/leucovorin or S-1 combined with bevacizumab were collected. Patient characteristics were evaluated with multiple regression analyses for survival outcomes, using the Cox proportional hazard model and linear regression analyses for the worst grade of adverse events. RESULTS: We enrolled 102 patients with a median age of 80 years (range, 75-88 years). Of the 70 patients who died, seven (10%) died of causes unrelated to disease or treatment. The study treatment was discontinued due to adverse events in 19 patients (18.6%), with 63% aged ≥85 years. The adverse event that most commonly resulted in treatment discontinuation was grade 2 fatigue (21%). Chronological age was not associated with progression-free survival (Hazard ratio, 1.03; P = 0.40) or overall survival (Hazard ratio, 1.02; P = 0.65). Age was weakly associated with non-hematologic adverse events (regression coefficient [R], 0.27; P = 0.007), especially fatigue (R, 0.23; P = 0.02) and nausea (R, 0.19; P = 0.06), but not with hematologic (R, 0.05; P = 0.43) or bevacizumab-related (R, -0.06; P = 0.56) adverse events. CONCLUSIONS: The efficacy of fluoropyrimidine plus bevacizumab was age-independent in patients with metastatic colorectal cancer aged ≥75 years, and attention should be paid to non-hematologic adverse events as age increases.

[Surgical Treatment for Lung Cancer Associated with Hypertrophic Pulmonary Osteoarthropathy].

Hypertrophic pulmonary osteoarthropathy( HPO) is a rare paraneoplastic manifestation of lung cancer that causes joint pain, joint swelling, and limited range of motion. Two surgical cases of lung cancer with HPO are presented. Case1:A 43-year-old female was referred to our department with a diagnosis of cStage ⅡB left hilar lung cancer. She had difficulty in walking due to arthralgia caused by HPO. Left pneumonectomy was performed and the arthralgia disappeared on the first postoperative day. The patient is being well after surgery without relapse of joint symptoms. Case2:The patient was a 65-year-old male with cStage ⅡA right lung cancer. The symptoms of HPO appeared after he was found to have lung cancer. After right upper lobectomy, the arthralgia disappeared on the first postoperative day. Currently, he is receiving adjuvant chemotherapy, without relapse of joint symptoms.

[Congenital Pulmonary Airway Malformation Diagnosed in Adulthood].

Congenital pulmonary airway malformation diagnosed in adulthood is very rare. A 54-year-old woman was admitted to our hospital with complaints of abnormal chest shadow. Computed tomography( CT) demonstrated multiple cysts, mass lesions, and consolidation in left lower lobe. Bronchofiber scopy could not establish the diagnose. Left lower lobectomy was performed for diagnosis and treatment. Pathologically the lesion was diagnosed as congenital pulmonary airway malformation.

The sphingosine-1-phosphate receptor modulator, FTY720, prevents the incidence of diabetes in Spontaneously Diabetic Torii rats.

The sphingosine-1-phosphate (S1P) receptor modulator regulates lymphocyte trafficking, resulting in its depletion from circulation, which ultimately causes immunosuppression. In this study, we investigated the preventive effect of fingolimod (FTY720) in the non-obese type 2 diabetic model, Spontaneously Diabetic Torii (SDT) rats. The S1P receptor modulator, FTY720 (0.3 mg/kg p.o.), was administered for 12 weeks to SDT rats from 5 to 17 weeks of age. Based on our findings, FTY720 could suppress the incidence of diabetes in SDT rats. Further, glucose intolerance was improved in FTY720-treated SDT rats at 14 weeks of age. Based on the haematological and histological analyses performed at 17 to 18 weeks of age, a decrease in lymphocytes and monocytes in the peripheral blood and a decrease in lymphocyte and atrophy in spleen occurred in the FTY720-treated SDT rats. Furthermore, the pancreatic changes, such as inflammation, atrophy, and fibrosis in islets observed in SDT rats were improved by FTY720 treatment. These findings suggest that the immunomodulatory effects of FTY720 reduced the pancreatic lesion in SDT rats, thereby demonstrating its preventive effect against diabetes. The development of diabetes in SDT rats is related to disorders of the immune system. However, the S1P receptor modulator may be useful for treating type 2 diabetes.

[Long-term Relapse-free Survival after Gefitinib Treatment Followed by Salvage Surgery for Postoperative Recurrence of Non-small Cell Lung Cancer:Report of a Case].

We present a case of a 54-year-old woman who had been performed video-assisted thoracic surgery (VATS) right upper lobectomy for stageⅡB adenocarcinoma. The patient had the recurrence of multiple lung metastases at 12 months after the surgery and was administrated gefitinib. The lung metastases disappeared at 3 months after the administration of gefitinib. A single metastasis in the left lower lung appearance again and VATS wedge left lung resection as salvage surgery was performed in postoperative 82 months. After salvage surgery, the patient has been followed up without additional treatment and is alive recurrence-free at 19 months.

[A Case of Unresectable Gastric Cancer with Paraaortic Lymph Node Metastasis Treated with Conversion Therapy].

We present a case of advanced gastric cancer with paraaortic lymph node metastasis successfully treated by conversion therapy. The patient was a 71‒year‒old male. Because of paraaortic lymph node metastasis, we initiated intensive chemotherapy with S‒1, oxaliplatin, and trastuzumab. After 6 courses, CT examination revealed that the size of the primary tumor decreased, suggesting a complete response(CR). Furthermore, the metastatic lymph nodes decreased in both number and size, suggesting a partial response(PR). We continued chemotherapy, changing to S‒1 and trastuzumab only because of Grade 3 neutropenia, and conducted continuous infusion chemotherapy. After 5 courses, we performed an upper gastrointestinal endoscopy. The primary tumor recurred, suggesting a progressive disease(PD), while metastasis to the paraaortic lymph nodes disappeared. We decided that a curative resection was possible and performed distal gastrectomy with D2 and paraaortic lymph node dissection. The postoperative courses were uneventful, and the patient was discharged from the hospital 12 days postoperation. The patient is well without any recurrence of cancer at 1 year 3 months postoperation. Conversion therapy may offer the possibility of prolonged survival for patients with gastric cancer previously considered unresectable.

Improvement of native pulmonary alveolar proteinosis after contralateral single living-donor lobar lung transplantation: A case report.

PAP is a rare disease characterized by the accumulation of surfactant materials in the alveolar spaces due to the imbalance of surfactant homeostasis (production and clearance). We herein report a case of an 8-year-old girl who developed PAP after BMT from her mother for the treatment of DBA. The anemia was improved by BMT; however, respiratory dysfunction due to graft-versus-host disease gradually progressed. She eventually underwent right single LDLLT from her mother when she was 14 years old. A pathological examination of the excised lung confirmed the finding of diffuse bronchiolitis obliterans and unexpectedly revealed widespread alveolar proteinosis. Interestingly, the GGO of her native left lung on chest X-ray was improved after LDLLT. We present the very unique clinical course of this patient and discuss the mechanisms underlying the development of PAP after BMT and its improvement after LDLLT from the same donor.

[Iatrogenic Injury of the Bronchus Suspiciously Caused by Sengstaken-Blakemore Tube into the Airway].

BACKGROUND: Tracheobronchial injury is often operated urgently because of the risk of high mortality. However, small injuries can recover by conservative management. CASE: A 65-year-old man was treated for esophageal varix with transcatheter arterial embolization therapy. He vomited blood and endoscopic sclerotherapy was performed because a Sengstaken-Blake-more tube could not be inserted. Thereafter, computed tomography( CT) detected mediastinal emphysema and an injury to his left main bronchus. The patient consulted our department and bronchoscopy detected a laceration of the left main bronchus. Conservative management was chosen because the laceration was limited to the membranous portion, with the improvement of inflammatory reaction. Several weeks later, CT and bronchoscopy confirmed recovery from the injury of the left main bronchus without stricture. CONCLUSION: An operation is indicated for many tracheobronchial injuries. However, some injuries can recover with conservative management. It is important that indication for surgery should be considered based on bronchoscopic findings and the progress of inflammatory reaction.

[Locally Advanced Rectal Cancer Curatively Resected after Modified FOLFOXIRI plus Bevacizumab Chemotherapy-A Case Report].

A 69-year-old man with dyschezia was diagnosed with locally advanced colorectal cancer invading the urinary bladder and pelvis. We performed ileostomy to avoid passage disturbance because curative resection was difficult. The patient received 2 courses of modified FOLFOXIRI plus bevacizumab. The size of the primary tumor and lymph nodes decreased after chemotherapy. High anterior resection with D3 lymph node dissection was performed. Histopathological analysis revealed that the tumor stage was pT3, N0, M0, StageⅡ. The patient has been receiving adjuvant chemotherapy with oral UFT/UZEL for 6months. No recurrence has been observed for the past 4 months.

[Trends in Outpatient Chemotherapy for Thoracic Oncology].

We conducted a survey of the outpatient pharmacotherapy we administered from April 2016 to March 2019 to understand trends in chemotherapy for respiratory thoracic malignancies, such as lung cancer. Over the 3-year period, 19,408 were treated in the outpatient chemotherapy department. Of these, 1,270(6.5%)had respiratory thoracic malignancies. The total number of patients and the number of patients with thoracic malignancies(%) were 5,815 and 320(5.5%); 6,344 and 434(6.8%); and 7,247 and 516(7.1%)in FY2016, FY2017 and FY2018, respectively. This shows that both increased during the study period. Each patient was treated in the chemotherapy department multiple times, and treatment for thoracic malignancies was initiated in 161 patients. The female:male ratio was 27%:73%, and the patients' median age(range)was 68 years(range: 36-84 years). Lung cancer was the most common disease(91%), followed by malignant pleural mesothelioma(5%), thymoma(2%), thymic carcinoma(1%), and synovial sarcoma(1%). The most common histological type of lung cancer was adenocarcinoma(67%), followed by squamous cell carcinoma(17%), small cell carcinoma( 7%), and others(9%). Outpatient chemotherapy was introduced as a first-line, second-line, and third-line or later treatment in 46%, 28%, and 22% of cases, respectively. While the number of patients increased, the number of new patients with thoracic malignancies decreased from 58 in FY2016 to 52 in FY2017 and 51 in FY2018. Conversely, the number of visits to the chemotherapy department by each new patient almost doubled from 5.5 in FY2016 to 8.5 in FY2017 and 10.1 in FY2018. The proportion of patients for which immunotherapy was included in the induction treatment regimen increased from 28% and 24% in FY2016 and FY2017, respectively, to 39% in FY2018. The increase in the use of outpatient chemotherapy for respiratory thoracic malignancies was due to the increase in the proportion of patients undergoing immunotherapy and the number of visits to the chemotherapy department per patient. It is important to implement measures to help prolong and increase the use of outpatient pharmacotherapy for respiratory thoracic malignancies by cooperating with surrounding medical institutions and increasing the number of beds available.

A hybrid technique of intracavitary and interstitial brachytherapy for locally advanced cervical cancer: initial outcomes of a single-institute experience.

BACKGROUND: Locally advanced uterine cervical cancer (LAUCC) with lateral tumor extension may not always be covered adequately by conventional intracavitary brachytherapy (ICBT). Hybrid intracavitary and interstitial brachytherapy (HBT) seems to be an effective alternative by improving anatomy-oriented dose optimisation. The purpose of this study was to report initial clinical result for LAUCC treated by HBT. METHODS: Between January 2012 and November 2015, 42 patients with LAUCC (T1b2-4a) were treated with primary radiation therapy including HBT. Patients with distant metastasis other than para-aortic lymph node spread were excluded from this study. A retrospective analysis was performed for toxicity evaluation and oncological outcome calculation. RESULTS: Median follow-up was 23.2 months (range 13.2-71.4). Two-year overall survival, progression free survival, and local control rate were 81.6, 54.4, and 80.2%, respectively. Seven patients experienced local recurrence (16.6%). Of those, five were confined to the uterus and two at the parametria. Late adverse events ≥ grade 3 were seen in 3 patients. CONCLUSIONS: HBT can generate favorable local control in tumors which cannot be adequately covered by ICBT.

Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER).

BACKGROUND: Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer. PATIENTS AND METHODS: Eligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival. RESULTS: Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75-88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7-9.5 months). The median overall survival was 23.1 months (95% CI 17.4-28.8 months). The response rate was 44% (95% CI 30.2-57.8%), and the disease control rate was 88% (95% CI 79.0-97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events. CONCLUSION: S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.

Efficacy and safety of ramucirumab plus modified FOLFIRI for metastatic colorectal cancer.

BACKGROUND: Dose modification of chemotherapy for metastatic colorectal cancer (MCRC) is often needed, especially in second-line and later-line treatments due to adverse events of previous treatment and poor patient condition. No study has focused on ramucirumab plus modified dose of FOLFIRI for MCRC, and whether low relative dose intensity (RDI) affects treatment efficacy has not been clarified. METHODS: MCRC patients who received ramucirumab plus FOLFIRI, which consisted of 150 mg/m2 of irinotecan, at six institutions were retrospectively analyzed. RESULTS: A total of 43 patients were assessed. Median age was 63 years, and 22 patients (51%) were women. Twenty-six patients (60%) were given ramucirumab plus FOLFIRI as second-line therapy, and 17 (40%) as third or later-line. The median relative dose intensity (RDI) of irinotecan was 60.6%, which is lower than that in the pivotal phase 3 study (RAISE), and other agents showed the same trend. Median progression-free survival was 4.8 [95% confidence interval (CI) 3.2-5.7] months for all patients, 5.4 (95% CI 3.5-7.2) months for second-line patients, and 2.8 (95% CI 1.6-5.8) months for third or later-line patients. Median overall survival was 17.3 (95% CI 11.5-22.4) months for all patients. Patients with irinotecan RDI less than 60% showed similar treatment efficacy. Hematological toxicities of grade 3 or worse were observed in 21 patients, but all were manageable. CONCLUSION: Low RDI did not compromise the treatment efficacy of ramucirumab plus modified FOLFIRI for MCRC patients.

[A Pulmonary Mucoepidermoid Carcinoma with Anaplastic Lymphoma Kinase Fusion Responding to Alectinib Hydrochloride].

Few cases of lung mucoepidermoid carcinomas with anaplastic lymphoma kinase (ALK) fusion have been reported. A 35-year-old woman was found to have an abnormal chest X-ray. A tumor and obstructive pneumonitis in her left upper lobe was detected using computed tomography (CT). She was admitted to our hospital, and was diagnosed with mucoepidermoid carcinoma by transbronchial biopsy. Left pneumonectomy and lymphadenectomy were performed for lung mucoepidermoid carcinoma and a mediastinal lymph node metastasis (pT2aN2M0, stage ⅢA). Postoperative radiotherapy (50 Gy) to the mediastinum and chemotherapy were performed followed by several radiotherapies for cervical and mediastinal lymph node and right ischium metastases. Since then, further radiotherapy was impossible. However, we detected ALK fusion in the resected specimen and the cancer responded to alectinib hydrochloride.