[Paclitaxel plus Bevacizumab Combination Therapy for Esophageal Metastasis of Breast Cancer-A Case Report].

An 80-year-old woman with a history of left breast cancer complained of dysphagia. At the age of 67 years, she had undergone a left modified radical mastectomy, chemotherapy, and endocrine therapy for left breast cancer. Six years after adjuvant therapy completion, she developed dysphagia. Chest CT showed only midesophageal stenosis. Endoscopic examination revealed whole circumferential stenosis without mucosal abnormality located 25 cm from the incisors, and a biopsy showed histologically normal mucosa. Endoscopic balloon dilatation was performed 5 times in 1 year and 3 months. Subsequently, a biopsy specimen revealed adenocarcinoma, which suggested metastasis from the previous breast cancer. One month after the initiation of tamoxifen administration, dyspnea due to pleural effusion was encountered. We treated this via pleural adhesion therapy and changed the treatment to paclitaxel plus bevacizumab combination therapy. She continued paclitaxel plus bevacizumab therapy for 1 year and 4 months without any signs of recurrence.

[Case of Unresectable Gastric Mixed Neuroendocrine Neoplasm(MiNEN)Treated with Chemotherapy].

A 68-year-old man diagnosed with gastric mixed neuroendocrine-non-neuroendocrine neoplasia(MiNEN)concomitant with liver metastasis received chemotherapy using ramucirumab and paclitaxel. A decrease in tumor marker levels and size of the metastatic liver lesions was observed after 3 courses of treatment. However, the patient developed progressive disease after 9 courses of chemotherapy; hence, nivolumab chemotherapy was initiated. Although liver metastases were reduced after 2 courses of nivolumab, the patient developed new liver lesions after 18 courses of treatment; irinotecan, S-1 and oxaliplatin, and trifluridine/tipiracil were then administered. Liver metastases progressed despite changing the regimen, and the patient died 25 months after the initiation of chemotherapy. Gastric MiNEN usually shows poor prognosis, and there is lack of consensus regarding optimal treatment. Ramucirumab and nivolumab are relatively well-tolerated and may be effective for chemotherapy.

[Change in Therapy for Malignant Pleural Mesothelioma at Our Hospital].

When molecular target drug began to be used for chemotherapy to treat malignant pleural mesothelioma in 2014, we introduced this treatment strategy for 61 patients who were diagnosed and were being treated in our hospital. Chemotherapy was performed on 37 patients, while 12 patients underwent surgical remedy and best supportive care was provided to another 12 patients. Molecular target drug was used as the primary chemotherapy treatment in 14 cases, while it was the secondary treatment in 22 others. Pleural decortication was performed as the operative method for all the 12 cases requiring surgical remedy, and 2 of these cases were shifted to extrapleural pneumonectomy. By the chemotherapy, there were many cases of PS≥2, non‒epithelial type, advanced stage, LMR<2.74 of the biomarker. When we compared surgical remedy with the chemotherapy clinicopathologically. In the prognostic examination, in median survival time of all cases, as for 23 months, the chemotherapy, 31 months, the surgical remedy was not reached. Prognostic improvement of stage ⅢA was determined according to the stage of the chemotherapy. A multivariate variable analysis revealed that only a non‒sarcomatous type was a good prognostic factor, and surgery remedy was not.

[A Case of Intraductal Apocrine Carcinoma of the Breast].

A female in her 60s who complained of nipple discharge in her left breast for 1 year. A soft mass ill-defined margin in the border of AB area was observed. Mammography showed a focal asymmetric density. Ultrasonography disclosed an irregular heterogenous low echoic lesion in the AB area of her left breast. MRI image showed an enhanced lesion in the inner area. The pathological diagnosis by core needle biopsy was non-invasive ductal carcinoma with apocrine metaplasia. Mastectomy with sentinel lymph node biopsy of the left breast was performed. Post operative histopathological examination revealed intraductal apocrine carcinoma without lymph node metastasis. Estrogen and progesterone receptors were negative. Three years after operation without any adjuvant treatment, she has no recurrence of lesion.

[A Case of Metastatic Pancreatic Ductal Adenocarcinoma Successfully Treated with Modified FOLFIRINOX and Concurrent Radiotherapy].

A 70-year-old man with metastatic pancreatic ductal adenocarcinoma(cT4N1bM1, cStage Ⅳ)underwent chemotherapy with modified FOLFIRINOX without any severe adverse event to 20 cycles. In the middle of that, concurrent irradiation toward primary lesion(total dose, 43.2 Gy)was administered. Grade 1 adverse events include anemia, thrombocytopenia, hypoalbuminemia, hypokalemia, alkaline phosphatase increased, hypertension, peripheral sensory neuropathy, fatigue, anorexia and nausea. The relative dose intensities of oxaliplatin, irinotecan and fluorouracil at 6 months after beginning of treatment were 77.6, 84.0 and 88.3 percent, respectively. The total dose of administered oxaliplatin was 825 mg to the square meter. The primary lesion had been stable for the 20 cycles, although peritoneal dissemination had progressively increased in size. For 17 months, opioid was not necessary for the control of abdominal or back pain to the end of third-line treatment. Though safety or clinical benefits of modified FOLFIRINOX plus concurrent radiotherapy for metastatic pancreatic ductal adenocarcinoma have not been reported, in this case, such treatment might contribute to prolong prognosis or prevent developing abdominal or back pain.

[A Case of Malignant Thyroid Lymphoma That Was Difficult to Differentiate from Methotrexate-Associated Lymphoproliferative Disorders(MTX-LPD)].

A female patient in her 60s was going to get treatment for rheumatoid arthritis(RA). Considering the possibility of using biologics, CT examination was performed for screening of malignant diseases. A mass shadow in the left lobe of the thyroid gland was detected. The patient was followed up, and ultrasonography did not reveal any malignant findings. She was treated with methotrexate(MTX), and 1 year later, the thyroid mass was enlarged on CT. Ultrasonography revealed an enlarged hypoechoic region. Fine needle aspiration cytology revealed malignant lymphoma. Excisional biopsy was performed to determine the treatment plan. The pathological diagnosis was follicular lymphoma, and the possibility of methotrexate- associated lymphoproliferative disorders(MTX-LPD)persisted. It was difficult to discontinue MTX because of the high activity of RA. She was treated with rituximab for malignant lymphoma and concurrently with MTX for RA. The thyroid tumor disappeared for 3 months. Four years later, there is no sign of tumor recurrence.

Safety and efficacy of S-1 plus oxaliplatin 130 mg/m2 combination therapy in patients with previously untreated HER2-negative unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: a phase II trial (KSCC1501A).

BACKGROUND: In a randomized pivotal global phase III study, S-1 and oxaliplatin 100 mg/m2 (SOX100) combination chemotherapy was as effective as S-1 and cisplatin for advanced gastric cancer (AGC) and showed a favorable safety profile. In this phase II study, we analyzed survival outcomes to assess the efficacy and safety of the SOX regimen with oxaliplatin 130 mg/m2 (SOX130) in AGC. METHODS: Patients with HER2-negative AGC received 80 mg/m2/day S-1 orally on days 1-14 and 130 mg/m2 oxaliplatin intravenously on day 1 of each 21-day cycle until the criteria for treatment withdrawal were fulfilled. The primary endpoint was the response rate (RR), and the null hypothesis of RR in the current trial was 45%. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded according to CTCAE version 4.0. RESULTS: Seventy-one patients were enrolled from June 2015 to November 2016, but eight were excluded for ineligibility. Therefore, all final analyses were conducted with 63 patients. The confirmed RR was 46.0% (90% confidence interval [CI]: 36.1-56.3), and the disease control rate was 77.8% (90% CI: 68.1-85.1). The median PFS and OS were 4.9 (95% CI: 4.2-7.1) and 14.8 (95% CI: 11.1-18.9) months, respectively. Incidences of grade 3-4 AEs > 10% were anorexia (19.0%), peripheral neuropathy (12.7%), nausea (11.1%), and thrombocytopenia (11.1%). CONCLUSIONS: This study represents the first evaluation of SOX130 in patients with HER2-negative AGC. SOX130 showed an acceptable safety profile, but the prespecified statistical efficacy targets were not achieved.

Very delayed liver metastasis from small bowel gastrointestinal stromal tumor (32 years after resection of the small bowel GIST): Report of a case.

INTRODUCTION: Recurrent forms of gastrointestinal stromal tumor (GIST) include liver metastases and peritoneal dissemination. Recurrence often occurs within 2 years. We report a case of liver metastasis, which was detected 30 years after resection of a primary lesion in the small intestine and was resected 32 years later. PRESENTATION OF CASE: The patient was a 72-year-old woman and was being followed up for ureteral stones at the department of urology of our hospital. Computed tomography (CT) showed a small mass in segment 7 of the liver, 2 years ago. As the tumor gradually increased, a biopsy was performed, and a mesenchymal tumor was diagnosed. The tumor continued to increase in size and partial hepatectomy was performed. GIST was suspected from the sample extracted during hepatectomy. The patient had undergone a resection of the small intestine for a tumor 32 years ago. On tracing her medical records, it was confirmed that resection of the small intestine was performed for the diagnosis of leiomyosarcoma. DISCUSSION: Based on the block specimen from 32 years ago, the tumor of the intestine was confirmed to be GIST, and the liver mass was finally diagnosed as liver metastasis of the GIST that had occurred 32 years ago. CONCLUSION: We experienced a case of liver metastasis 32 years after surgery for the first small intestinal GIST. To the best of our knowledge, this case had the longest disease-free interval before metastasis to the liver.

[Two Cases of Stage â £ Occult Breast Cancer].

The first case is a 62-year-old female who complained of painful left axillary lymph node swelling. Six months later, a CT scan revealed multiple lung nodules. Biopsies of the axillary lymph node and lung showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph node and lung. ER(+), PgR(±), HER2(1+). Letrozole was administered, and effective control was achieved for 20 months. The second case is a 62-year-old female who presented with back pain. A CT scan revealed left axillary lymph node swelling and multiple osteolytic changes in the thoracolumbar spine and rib. Biopsies of the axillary lymph node and thoracic spine showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph nodule and bone. ER(+), PgR(+), HER2(1+). Fulvestrant and denosumab were administered. However, after 6 months, she discontinued the treatment. Our results suggested that effective control could be achieved through systemic therapy and local therapy was not necessary for Stage Ⅳ occult breast cancer.

[A Case of Unresectable Intrahepatic Cholangiocarcinoma Successfully Treated with Chemoradiotherapy].

A 69-year-old woman with unresectable intrahepatic cholangiocarcinoma(T3N1M1, Stage Ⅳ)underwent chemoradiotherapy with gemcitabine, cisplatin and irradiation toward primary lesion(total dose, 36 Gy). Grade 3 or 4 adverse events include leukopenia, neutropenia, and anemia. The relative dose intensities at 6 months after beginning of treatment were 58.9%(gemcitabine)and 80.2%(cisplatin), respectively. The total dose of administered cisplatin was 525 mg to the square meter. Partial response was obtained, and after that, the representative lesions have been stable with continuous administration of gemcitabine. As some studies have reported clinical benefits of chemoradiotherapy for unresectable intrahepatic cholangiocarcinoma, further clinical investigations are expected.

The relationship between peripheral neuropathy and efficacy in second-line chemotherapy for unresectable advanced gastric cancer: a prospective observational multicenter study protocol (IVY).

BACKGROUND: Paclitaxel is used in second-line conventional chemotherapies to manage patients with unresectable advanced gastric cancer (GC). Paclitaxel-induced peripheral neuropathy is a known adverse event leading to treatment discontinuation. Additionally, oxaliplatin which causes irreversible peripheral neuropathy is now commonly used in first-line chemotherapy for advanced GC in Japan. Thus, examining the incidence of peripheral neuropathy with paclitaxel after oxaliplatin is necessary to improve the quality of life and outcomes of patients with advanced GC in the second-line treatment setting. METHODS: This prospective observational multicenter study, (which we named IVY study), will evaluate the degree of chemotherapy-induced peripheral neuropathy (CIPN) and the efficacy of second-line chemotherapy for unresectable advanced GC. A patient neurotoxicity questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) will be used to assess CIPN during the second-line treatment. The key eligibility criteria are as follows: 1) unresectable or recurrent GC histologically confirmed to be primary adenocarcinoma of the stomach, 2) age over 20 years, 3) Eastern Cooperative Oncology Group performance status score of 0-2, 4) written informed consent following full study information is provided to the patient, 5) progression or intolerance for first-line chemotherapy comprising fluorinated pyrimidine and platinum anticancer drugs (cisplatin or oxaliplatin) for advanced GC. 6) presence of evaluable lesions as confirmed using a computed tomography (CT) or magnetic resonance imaging. A total of 200 patients is considered to be appropriate for inclusion in this study. DISCUSSION: The results of this study will provide some information on CIPN with the sequential usage of oxaliplatin as first-line chemotherapy to paclitaxel as second-line chemotherapy in clinical practice. TRIAL REGISTRATION: This trial is registered in the University Hospital Medical Information Network's Clinical Trials Registry with the registration number UMIN000033376 (Registered 11 July 2018).

[A Case of Breast Metastasis of Gastric Cancer after an Eight Year Latency Period].

A 66-year-old woman underwent distal gastrectomy because of gastric cancer(stage ⅠB)and received no adjuvant chemotherapy. Eight years after the operation, computed tomography showed a small nodule in the right breast. Mammography did not reveal any abnormalities. Ultrasound sonography showed a diffuse and gradual non-mass-like low echoic lesion. Core needle biopsy indicated a malignancy. Partial resection of the right breast was performed to obtain a diagnosis. On postoperative histopathological examination, signet-ring cells were found in the tumor, and immunohistochemical analysis showed that both the breast tumor and the gastric carcinoma were MUC5AC-positive and MUC1-negative. We diagnosed this breast tumor as metastasis from gastric cancer. The patient has received chemotherapy with no subsequent metastatic tumors, and good control has been achieved for 21 months after the detection of the breast metastasis.

[Incidence of Catheter-Related Thrombosis in Patients with Long-Term Indwelling Central Venous Port Who Received Chemotherapies for Unresectable Advanced Digestive Cancers].

BACKGROUND: Most patients with unresectable advanced digestive cancers require placement of a fully implantable venous access port to facilitate safe delivery of anti-cancer drugs. Anti-VEGF therapies are commonly used even though they increase the risk of thrombosis. The objective of this study was to assess the incidence of radiologically confirmed catheter-related thrombosis(CRT)in patients with advanced digestive cancers. METHODS: We retrospectively reviewed 88 patients with advanced digestive cancers who had adapted implantable ports placed in our institution for chemotherapy. RESULTS: Thirty-nine patients were diagnosed with colorectal cancer, 26 with gastric cancer, 12 with pancreatic cancer, 8 with esophageal cancer, and 3 with other cancers. During follow-up, 22 patients(25%)received anti-VEGF therapies, while 66 patients(75%)did not. Four out of 88 patients(4.5%)had asymptomatic CRT. The incidence of CRT was the same(4.5%)regardless of whether the patient received anti-VEGF therapy. CONCLUSIONS: In patients with digestive cancers who had implantable venous access ports, the incidence of the CRT was 4.5% with no association with anti-VEGF therapies.

[A Case of Long-Term Survival after Para-Aortic Lymph Node Recurrence Following the Curative Resection of Gastric Cancer Treated Using Multimodality Therapy Including Salvage Surgery].

This case was observed in a man in his 70s. Although symptomatic treatment was performed for epigastralgia, endoscopic examination revealed a type 3 tumor on the fornix of the stomach to the lesser curvature of the body just above the esophagogastric junction, and the patient was diagnosed with moderately differentiated tubular adenocarcinoma(cT4bN3aM0, cStage ⅣA). As esophageal and diaphragmatic invasion was suspected based on CT findings, S-1 plus CDDP was started as preoperative chemotherapy. Although the primary lesion and lymph node metastasis decreased in size, chemotherapy was discontinued after one course due to stenosis symptoms, and total gastrectomy and D2 dissection were performed. Postoperative adjuvant chemotherapy with S-1 was started. However, 6 months after starting the treatment, para-aortic lymph node recurrence was observed, and the treatment strategy was changed to weekly PTX. After 5 courses of weekly PTX, the lymph nodes continued to increase in size, and chemotherapy was discontinued per the patient's request. The patient was followed up with CT and PET-CT; however, no new recurrent lesions were found in other sites for approximately 1 year. Therefore, para-aortic lymph node dissection was performed as the salvage surgery. Pathological findings showed that gastric cancer metastasis was present in 1 swollen lymph node only, as confirmed by PET. At present, 6 years have passed since the first operation, and there has been no recurrence. In general, para-aortic lymph node metastasis is considered to result in poor prognosis in gastric cancer. However, in the absence of other noncurative factors, a good prognosis may be obtained with combined therapeutic modalities.

Cetuximab retreatment in patients with metastatic colorectal cancer who exhibited a clinical benefit in response to prior cetuximab: A retrospective study.

Clinical benefits of cetuximab retreatment in patients with metastatic colorectal (mCRC) have been reported. In the present study, the effect of cetuximab retreatment on predictive markers was investigated by evaluating the clinical benefit of initial cetuximab treatment prior to cetuximab retreatment. Between November 2012 and March 2017, 14 patients with KRAS proto-oncogene GTPase exon 2 wild-type mCRC who exhibited a clinical benefit (confirmed stable disease for at least 6 months or a clinical response) to an initial cetuximab-based regimen, who received multiple lines of chemotherapy following disease progression and ultimately received a second cetuximab and irinotecan regimen, were retrospectively analyzed. For retreatment, patients received bi-weekly irinotecan (120-150 mg/m2) combined with cetuximab (400 mg/m2 as an initial dose, followed by 250 mg/m2, weekly). The median age of the 14 patients (11 males, 3 females) was 68 years (32-77). The median progression-free survival (PFS) following prior cetuximab-based therapy was 6.6 months (range, 4.1-18.4). Initial cetuximab treatment was administered as a first-line treatment in 11 patients, a second-line treatment in 1 patient and a third-line treatment in 2 patients. The median interval time between the last cycle of initial cetuximab-based therapy and the first cycle of cetuximab retreatment was 13.1 months (range, 6.0-37.1). The objective response rate of cetuximab retreatment was 21.4% and the median PFS was 4.4 months (95% confidence interval, 1.4-5.6). The Spearman's correlation coefficient for the PFS following retreatment and duration of initial cetuximab-based regimens demonstrated a more marked correlation compared with that between the PFS following retreatment and the interval time between the two regimens (r=0.45, P=0.11 vs. r=0.08, P=0.79). Cetuximab retreatment may provide clinical benefit to patients with mCRC who were good responders with longer periods of initial cetuximab-based therapy.

[A Case of Primary Spinddle Cell Carcinoma of the Breast].

A 76-year-old female underwent breast-conserving surgery of the right breast and sentinel lymph node biopsy for primary breast cancer. Three years later, mammography and ultrasonography showed a small nodule in the right breast. There was nothing abnormal in the left breast. Three months later, she complained of a huge and rapid growing mass in the left breast. Malignant cells were obtained on fine needle aspiration biopsy in the right breast tumor. But it was not possible to diagnose whether the left breast tumor was benign or malignant on fine needle aspiration biopsy and needle biopsy. Bilateral mastectomy and sentinel lymph node biopsy of the right side were performed. Pathological diagnosis were squamous cell carcinoma of the right breast and spindle cell carcinoma of the left breast. Although the patient was treated with adjuvant chemotherapy, she had an early relapse with pleural, lung and bone metastases. The patient died approximately 8 months after operation. Spindle cell carcinoma presents many problems about therapy and prognosis. Further accumulation analysis is necessary.

Training system for laparoscopy-assisted distal gastrectomy.

PURPOSE: Laparoscopy-assisted distal gastrectomy (LADG) is likely to become a standard procedure for gastric cancer, which highlights the importance of establishing a training system in which even inexperienced surgeons can perform this procedure safely. This study assesses our training system for LADG based on short-term surgical outcomes. METHODS: We evaluated retrospectively the short-term outcomes of 100 consecutive LADGs with curative D1/D1+ lymph node dissection. Our training system was assessed based on the learning curve of trainees, and factors related to achieving good-quality operations were analyzed statistically. RESULTS: Overall, postoperative complications developed in 10 patients (10%), and included one case of anastomotic leakage (1%) and one case of pancreatic fistula (1%). The learning curve of the trainees plateaued after 10 operator cases in terms of operation time. The importance of the trainer's position was also confirmed by the result that the operation time was significantly longer when trainees with ≤10 operator cases performed LADG with a trainer as scopist vs. a trainer as the first assistant. Univariate and multivariate analyses revealed that >10 operator cases were the most important factor for achieving good-quality operations. CONCLUSION: These results show that our current LADG procedure and training system are appropriate and effective.

Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest.

In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer.

[A case of local recurrence of rectal carcinoma 10 years after initial surgery].

Here, we report an extremely rare case of local recurrence of rectal cancer 10 years after initial tumor resection. A 53-year-old man underwent abdominoperineal resection for advanced rectal cancer at a local hospital. The tumor was graded as pStage II (pA, pN0, pH0, pP0, pM0, curA)as per the Japanese Classification of Colorectal Carcinoma, seventh edition, and diagnosed as a moderately differentiated adenocarcinoma on histopathological examination. Subsequently, the patient received adjuvant chemotherapy for 5 years. Although the patient lived without any recurrences after adjuvant chemotherapy, unfortunately, blood examination showed a high carcinoembryonic antigen(CEA)level 10 years after the initial surgical treatment. Computed tomography(CT)and positron emission tomography(PET)/CT revealed a perineal tumor, 40mm in size, without other distant metastases. On diagnosis of local recurrence of rectal cancer, the patient underwent surgical tumor resection at Okayama University Hospital. The tumor was determined to be a well- to moderately differentiated adenocarcinoma by histopathological examination, suggesting local recurrence of the primary rectal adenocarcinoma. Moreover, the radial margin was free of cancer. The patient is now doing well without any re-recurrence 30 months after the second surgical treatment, without any adjuvant chemotherapy.

A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent cancer stem-like cells in S/G2/M phases.

PURPOSE: Because chemoradiotherapy selectively targets proliferating cancer cells, quiescent cancer stem-like cells are resistant. Mobilization of the cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of the cell cycle can eliminate quiescent cancer stem-like cells in solid cancers. Thus, we explored the use of a genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to mobilize the cell cycle and kill quiescent cancer stem-like cells. EXPERIMENTAL DESIGN: We established CD133(+) cancer stem-like cells from human gastric cancer MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent cancer stem-like cells. We visualized the treatment dynamics of OBP-301 killing of quiescent cancer stem-like cells in dormant tumor spheres and xenografts using a fluorescent ubiquitination cell-cycle indicator (FUCCI). RESULTS: CD133(+) gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133(+) cancer stem-like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle mobilization from G0-G1 to S/G2/M phases and subsequent cell death in quiescent CD133(+) cancer stem-like cells by mobilizing cell-cycle-related proteins. FUCCI enabled visualization of quiescent CD133(+) cancer stem-like cells and proliferating CD133(-) non-cancer stem-like cells. Three-dimensional visualization of the cell-cycle behavior in tumor spheres showed that CD133(+) cancer stem-like cells maintained stemness by remaining in G0-G1 phase. We showed that OBP-301 mobilized quiescent cancer stem-like cells in tumor spheres and xenografts into S/G2/M phases where they lost viability and cancer stem-like cell properties and became chemosensitive. CONCLUSION: Oncolytic adenoviral infection is an effective mechanism of cancer cell killing in solid cancer and can be a new therapeutic paradigm to eliminate quiescent cancer stem-like cells.