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Purpose: Despite marked recent advances in chemotherapy, few reports have focused on the prognosis for patients with metastatic colorectal cancer (mCRC) achieving complete response (CR) after systemic chemotherapy. This study investigated the clinical course of mCRC patients achieving CR and evaluated the role of chemotherapy in CR. Methods: This retrospective study searched a prospectively maintained database at the author's institute to identify medical records for mCRC patients achieving CR after systematic chemotherapy from January 2007 to March 2020. Results: The search yielded 23 patients with confirmed CR to systemic chemotherapy. Median time to CR from treatment initiation was 6.8 months. Maintenance chemotherapy was continued for 22 of 23 patients. Median duration of maintenance chemotherapy was 11.1 months. Disease progression occurred for 17 (73.9%) patients at a median 48.1-month follow-up. Median progression-free survival was 26.6 months. Median overall survival was 91.7 months. Conclusions: Patients with CR to chemotherapy had a high probability of disease progression, but a relatively long-term prognosis. Treatment strategies after achievement of CR should be based an understanding of the high potential that tumor cells will remain. Use of maintenance chemotherapy after achievement of CR is still unclear, and the recent data do not demonstrate a negative impact for continuing maintenance chemotherapy after CR. [ABSTRACT FROM AUTHOR]

Metastatic choroidal carcinoma is rare and generally has a poor prognosis. The present case report describes a case of choroidal metastasis from distal cholangiocarcinoma, which was successfully managed using stereotactic radiotherapy (SRT). A 67-year-old Japanese man underwent pancreaticoduodenectomy for distal cholangiocarcinoma. The pathological stage was T2N0M0 stage IIA, according to the Union for International Cancer Control 8th edition. After surgery, the patient received adjuvant chemotherapy with oral TS-1® for 1 month. A total of 2 months after surgery, the patient was readmitted to hospital due to decreased visual acuity. Fundoscopy revealed a macular hole in the right eye that accounted for the decreased visual acuity. Additionally, Goldmann three-mirror contact lens examination revealed a 4-mm choroidal mass with a yellowish color situated at a considerable distance from the optic nerve. Magnetic resonance imaging revealed an enhanced choroidal mass. Based on the findings of ophthalmologic examinations and the patient's history of cholangiocarcinoma, they were diagnosed with choroidal metastasis from distal cholangiocarcinoma. SRT was administered at a total dose of 40 Gy divided into 8 Gy fractions. A total of 1 year after SRT, the patient achieved complete remission without decreased visual acuity. The patient remains alive and in good health without recurrence, 4 years after the diagnosis of choroidal metastasis. To the best of our knowledge, this is the second reported case of intraocular metastasis from cholangiocarcinoma. In conclusion, SRT may provide an opportunity to control metastatic choroidal carcinoma without decreasing visual acuity. [ABSTRACT FROM AUTHOR]

Primary synovial sarcoma of the spermatic cord is quite rare and has not been reported in Japanese literature. We report a case of primary synovial sarcoma of the spermatic cord and localized dissemination of the tumor in a patient who experienced recurrence of intra-abdominal bleeding 7 years after curative resection of the primary lesion. A 70-year-old man was admitted with disturbance on urination and lower abdominal pain. Computed tomography (CT) of the abdomen revealed two lesions:a 10-cm intrapelvic tumor with hemorrhage and a 4-cm tumor adjacent to the bladder. Curative excision of the tumors was performed. Histological examination revealed that the larger lesion was a primary tumor of the spermatic cord with proliferation of spindle cells in cellular fascicles in a monotonous pattern, which was compatible with histologic findings of monophasic fibrous synovial sarcoma. The smaller lesion was a disseminated tumor. The diagnosis of synovial sarcoma was confirmed by the detection of a SS18 (SYT) -SSX1 fusion gene. After discharge, the patient received adjuvant chemotherapy, including ifosfamide and doxorubicin. No recurrence was evident thereafter. Seven years after the operation, the patient experienced sudden abdominal pain and swelling and was transferred to our hospital. CT showed a 17-cm tumor with massive hemorrhage in the omental bursa. Through catheterization of the superior mesenteric artery, bleeding from a branch of the dorsal pancreatic artery was identified. Because of the difficulty of catheterizing the bleeding branch, he underwent emergency resection of the tumor and partial resection of the colon. Histologic examination and genetic testing revealed that the tumor was a recurrence of the synovial sarcoma. After discharge, the patient received treatment with gemcitabine and docetaxel. However, 7 months after the second surgery, intraperitoneal manifestations recurred. The patient died 14 months after the second resection. This case suggests that curative surgical resection of the primary synovial sarcoma of the spermatic cord contributes to prolonged survival. However, because the recurrence rate of synovial sarcoma is high, multidisciplinary treatment, including chemotherapy and radiotherapy, might be necessary.

A 78-year-old man was admitted with diarrhea. Colonoscopy and computed tomography(CT)revealed rectal cancer with multiple liver metastases. Low anterior resection was performed for local control. After the operation, 5 courses of mFOLFOX6 plus bevacizumab chemotherapy were administered as first-line systemic therapy, but CT showed progressive disease with liver metastases. After the first-line systemic therapy, 2 courses of FOLFIRI plus bevacizumab chemotherapy were performed as second-line systemic therapy, but CT also revealed progressive disease with liver metastases. We retrospectively performed comprehensive genomic sequencing with a 415-gene panel and found that the patient had a hypermutation subtype. Interestingly, the panel also revealed that he had mismatch-repair(MMR)deficiency with MSH2 mutation, which is reported as a possible cause of resistance to 5-fluorouracil in colorectal cancer.

Carcinoma with elevated SRC expression is associated with distant metastasis and drug resistance. We report 2 cases of SRC amplification observed after retrospective comprehensive genomic sequencing. Case 1 was a 62-year-old man who had RAS wild-type stage IV carcinoma of the sigmoid colon with multiple liver metastases in both lobes. He underwent low anterior resection and systemic chemotherapy was initiated to treat the unresectable multiple liver metastases. Case 2 was a 73-yearold man who had RAS wild-type stage IV carcinoma of the descending colon with metastasis in the lateral segment of the liver. He underwent left hemicolectomy and lateral segmentectomy. He subsequently underwent open radiofrequency ablation and systemic chemotherapy to treat a hepatic recurrence. Several previous studies have found that molecular targeted therapy with tyrosine kinase inhibitors is effective against colorectal cancer with elevated SRC expression. This suggests that the results of comprehensive genomic sequencing may support the implementation of new treatments.

RAS mutation is an established predictive biomarker of resistance to anti-epidermal growth factor receptor(EGFR)therapy in metastatic colorectal cancer. In addition, previous studies identified mutations in ERBB2, FGFR1, PDGFRA, BRAF, MAP2K1, PTEN, and PIK3CA as potential mechanisms of resistance to anti-EGFR therapy. Testing for these mutations might be necessary to determine eligibility for anti-EGFR therapy in patients with metastatic colorectal cancer. CancerPlex®is a nextgeneration sequencer for 413 cancer genes. An analysis panel includes genes that may be associated with resistance to anti- EGFR therapy. A 65-year-old man with unresectable rectal cancer, multiple lung metastases, and a bulky liver metastasis was evaluated for expression of genes associated with resistance to anti-EGFR. The analysis found that all genes indicating resistance were wild-type genes. Cetuximab monotherapy was administered after rectal resection, with dramatic shrinkage of the metastatic tumors. A more accurate selection of patients according to tumor genetic status using CancerPlex®might improve the risk-benefit profile of anti-EGFR therapy.

Recently, targeted drugs have been developed for the treatment of colorectal cancer(CRC). Among targets, it is well known that KRAS mutations are associated with resistance to epidermal growth factor receptor(EGFR)monoclonal antibodies. However, response rates using anti-EGFR monotherapy for CRC were less than 20-30% in previous clinical studies. Thus, because the RAS/MAP2K/MAPK and PI3K/AKT pathways are associated with CRC resistance to chemotherapy, we analyzed gene mutations in Stage IV CRC patients using a genomic test(CancerPlex®). Medical records were reviewed for 112 patients who received treatment for CRC between 2007 and 2015 in Niigata University Medical and Dental Hospital or Niigata Cancer Center Hospital. There were 66 male and 46 female patients, and their median age was 62.5(range, 30-86) years. Cluster analyses were performed in 110 non-hypermutated Japanese CRC patients using Euclidean distance and Ward's clustering method, and 6 typical groups were identified. Among these, patients with all wild-type actionable genes benefited from anti-EGFR therapies. The expense of targeted drugs warrants consideration of cost-effectiveness during treatment decision-making for advanced CRC patients. To this end, based on the genetic information on CRC, it is possible to develop precision medicine using CancerPlex®.

We report a case of panitumumab-resistant rectal cancer with HER2 gene amplification detected by CancerPlex®. A 51- year-old man was diagnosed with an obstructive rectal cancer having lung and adrenal metastases. He underwent the Hartmann 's operation, and KRAS mutations were not detected. After the surgery, 3 courses of CapeOx plus bevacizumab were administered as first-line chemotherapy; however, the lung and adrenal metastases progressed. Subsequently, 24 courses of IRIS/panitumumab was administered as second-line chemotherapy, and the metastases slowly progressed. Six courses of regorafenib were administered as third-line chemotherapy followed by a course of TAS-102 as fourth-line chemotherapy. Subsequently, a left femoral head metastasis and cerebellar metastases were detected. The patient received best supportive care including palliative femoral head replacement and stereotactic irradiation for the cerebellar metastases, and he died of cancer 3 years 5 months after the primary surgery. The comprehensive genomic analysis focusing on 413 cancer-related genes with CancerPlex®revealed that EGFR, BRAF, KRAS, NRAS, and HRAS had no mutations; however, ERBB2 amplification was detected. Furthermore, immunohistochemical staining revealed overexpression of HER2 protein in both the primary and bone metastatictumor. HER2 and EGFR independently promote the RAS-RAF-MAPK pathway. In the present case, the efficacy of anti-EGFR therapy may be attenuated because of ERBB2 amplification in the metastatic tumor.