[Chemotherapy-Resistant Breast Cancer and Carcinomatous Pleuritis Successfully Treated with Abemaciclib plus Letrozole Therapy].

A 78-year-old woman was examined in the outpatient department with a chief complaint of swelling of the left breast. Examination confirmed a 10 cm mass in the left breast as along with edema and redness of the skin, following which a diagnosis of invasive micropapillary carcinoma was made after biopsy. The CT imaging showed left chest wall invasion, multiple axillary lymph node metastases, and left carcinomatous pleuritis. Since this a case of advanced breast cancer, we initiated treatment with bevacizumab plus paclitaxel. After 8 months, her medication was changed to eribulin, owing to progression of the cancer, which continued even up to 4 months. We then initiated abemaciclib plus letrozole therapy as the third treatment. We observed tumor reduction and clearing of pleural effusion with no serious adverse events, and continued her therapy for 11 months before the cancer progressed. We report a case of chemotherapy-resistant breast cancer and carcinomatous pleuritis in an older adult patient for which abemaciclib plus letrozole therapy was effective.

[A Case of Lung Metastasis of the Breast Cancer with a Remarkable Response to Stereotactic Body Radiation Therapy(SBRT)].

A 69-year-old woman admitted to our hospital with the lump in the left breast. Further examination was performed for the lesion, and it was diagnosed as invasive ductal carcinoma. Partial resection and sentinel lymph node biopsy were performed. Pathological diagnosis was metaplastic carcinoma with squamous metaplasia. As the adjuvant treatment, docetaxel and cyclophosphamide(TC)therapy and radiotherapy was performed. Following the treatment of those, tegafur-uracil was administered for 2 years. Three years after the surgery, an isolated lung metastasis was revealed by CT. Capecitabine and cyclophosphamide(XC)therapy was administered, but not effective. Stereotactic body radiation therapy(SBRT)was performed for the lesion. As a result, the metastatic lesion was obscured. Drug therapy was stopped due to adverse events, and she is observed by no medication. Thirty-six months after SBRT and 78 months after the surgery, the patient is alive without recurrence. SBRT could be an effective treatment strategy for the oligometastais of the lung.

Multicenter experience with large panel next-generation sequencing in patients with advanced solid cancers in Japan.

BACKGROUND: Application of next-generation DNA sequencing (NGS) has recently become increasingly common in the field of clinical oncology in several countries around the world. In Japan also, a system for applying NGS to routine clinical practice is gradually being established. During this process, we introduced in Japan the tumor-profiling MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) assay. METHODS: We present here our initial experience with the use of MSK-IMPACT in 68 patients selected from two institutions in Japan between June 2016 and October 2017. RESULTS: MSK-IMPACT sequencing was successful and yielded results in specimens obtained from 64 of the 68 patients, representing an overall assay success rate of 94.1%. The top three cancer types tested were endometrial cancer (17.2%), pancreatic cancer (15.6%) and colorectal cancer (12.5%). Evaluation of the clinical actionability of the genetic alterations revealed that 25.0% of patients (n = 16) harbored at least one actionable alteration. However, enrolling the patients in a genomically matched clinical trial was difficult, mainly because most clinical trials are limited to tumors arising from a specific organ/site. One patient with microsatellite instability-high status, as determined by MSK-IMPACT, was treated with pembrolizumab and showed partial response. CONCLUSIONS: Although tumor profiling by NGS and administration of genomically matched therapy is a promising strategy, because of its high cost, we need to consider how we can fit it into the Japanese medical system. Towards this end, we believe that it is important to share our initial experience for furthering precision medicine in Japan.

[An Effective Treatment of Relapsed Leiomyosarcoma with Fourth-Line Trabectedin].

A 56-year-old women underwent retroperitoneal leiomyosarcoma resection in December 2011. In July 2015, CT showed multiple liver metastases, and she received first-line chemotherapy treatment with doxorubicin. After 2 courses of doxorubicin, her performance status deteriorated; therefore, she was treated with pazopanib as second-line chemotherapy. PFS with pazopanib was 5 months and that with eribulin was 2.5 months. She was then treated with trabectedin as fourth-line chemotherapy from July 2016. The liver metastases reduced, and the disease was controlled for 1 year and 6 months following administration of trabectedin. We continue to treat this patient with trabectedin, and no serious side effects have been observed.

[A Case of Pediatric Soft Tissue Sarcoma with LMNA-NTRK1 Gene Fusion Treated with Larotrectinib under Single Patient Expanded Access System].

Tropomyosin-related kinase(TRK)fusion proteins are oncogenic drivers in multiple tumors in adults and children.Larotrectinib, an orally administered selective TRK inhibitor approved in the US, exhibits inhibitory activity against tumors harboring TRK fusions and is well tolerated.Here, we report the case of an 8-year-old female child with recurrence of an NTRK fusion low-grade sarcoma treated with larotrectinib monotherapy.The patient previously underwent resection of low-grade sarcoma in the right brachialis at 6 years of age, but local recurrence occurred after 16 months.As re-operation likely required amputation, larotrectinib was commenced at a dose of 100 mg BID.Complete radiographic remission was achieved after 3 months.There were no adverse events attributed to larotrectinib treatment.After dosing for 6 months, we performed local resection, confirming pathological complete remission.The drug was stopped, and the patient showed no evidence of relapse at 4 months after resection.In this case, larotrectinib was obtained using Single Patient Expanded Access under the FDA.In this paper, we also discuss the issues faced while accessing unapproved drugs in the precision medicine era in Japan.

[Adult T cell leukemia-lymphoma with allo-HSCT after treatment for pulmonary involvement with Mogamulizumab].

Adult T cell lymphoma-leukemia (ATL) is a highly aggressive disease and allogeneic hematopoietic transplantation (allo-HSCT) is the only therapeutic option for achieving a cure. However, some ATL patients cannot undergo HSCT. One of the important reasons for restricting HSCT in ATL is the high incidence of pulmonary complications associated with ATL including opportunistic infections, infiltration of ATL cells, and HTLV-1 associated bronchopneumonopathy. Herein, we report an ATL case with pulmonary infiltration of ATL cells successfully treated with allo-HSCT after improvement of pulmonary function with administration of the anti-CCR4 antibody mogamulizumab. To our knowledge, this is the first ATL case showing improvement of pulmonary invasion of ATL cells after treatment with mogamulizumab. In addition, this case suggests that mogamulizumab treatment might be useful as a bridge to allo-HSCT in ATL patients.

[Successful treatment with rituximab and romiplostim for thrombocytopenia associated with Waldenström's macroglobulinemia initially presenting as Evans syndrome].

A 60-year-old woman was admitted to our hospital with anemia and thrombocytopenia. Serum testing showed platelet-associated IgG elevation and she was positive on the direct and indirect Coombs tests. Together with bone marrow examination, these findings indicated a diagnosis of Evans syndrome. At diagnosis, she also had an IgM-κ type of monoclonal gammopathy of unknown significance. Initially, we administered steroids and her hemolytic anemia showed improvement. In contrast, only transient recovery of platelet counts was observed and her platelet counts rapidly decreased after steroid dose reduction. Thus, we treated her with a TPO-agonist, romiplostim. During the clinical course, she showed gradual serum IgM elevation. We thus performed another bone marrow biopsy and diagnosed her as having Waldenström's macroglobulinemia (WM). We started treatment with rituximab for WM. Together with the serum IgM reduction, she showed marked improvement of thrombocytopenia. This is a very rare case of WM initially presenting as autoimmune hemolytic anemia and immunethrombocytopenia associated with IgG class auto-antibody. Our experience suggests the usefulness of rituximab and romiplostim for the treatment of immunethrombocytopenia associated with WM.

[Development of cytomegalovirus antigenemia in 3 patients with B cell lymphoma treated with bendamustine monotherapy].

Bendamustine is one of the new key drugs for patients with indolent lymphoma. Bendamustine, together with rituximab, significantly improves the treatment outcomes of these patients. In addition, previous clinical studies have shown the complication rate of severe infection in bendamustine-containing regimens to be relatively low as compared to those of conventional chemotherapeutic regimens such as CHOP. However, some clinical case reports have raised the possibility that bendamustine may abrogate the immune responses of patients and trigger opportunistic infections including cytomegalovirus reactivation. Herein, we report three indolent lymphoma cases becoming positive on cytomegalovirus antigenemia assay during bendamustine monotherapy. All events occurred after more than three courses of treatment with bendamustine. One patient showed decreased CD4 positive T lymphocytes before the development of cytomegalovirus antigenemia. All three patients were successfully treated with valganciclovir. Although the precise risk is unknown, it should be noted that bendamustine can potentially cause reactivation of/infection with cytomegalovirus and physicians should pay attention to the possibility of this infection during treatment with bendamustine-containing regimens.

Meningeal carcinomatosis with decreased visual acuity: a case report.

Meningeal carcinomatosis is a condition in which cancer cells diffusely metastasize to the cerebral pia mater in the cerebrospinal membrane or cerebrospinal cavity. It causes a wide array of symptoms according to the site of metastasis. The prognosis is poor, especially in metastasis from solid tumors. This study reports a case of meningeal carcinomatosis caused by advanced gastric cancer, manifested by headache and vision loss. The patient was a 69-year-old man who underwent head computed tomography (CT) and magnetic resonance imaging (MRI) for persistent headaches. No abnormal findings were found; however, his vision declined, convulsions occurred, and cerebrospinal fluid (CSF) cytology showed poorly differentiated adenocarcinoma. Therefore, meningeal carcinomatosis was diagnosed. The patient died after receiving FOLFOX therapy to relieve symptoms and prolong his life. An autopsy showed no invasion of the optic nerve or surrounding tissues. As the frequency of complications of meningeal carcinomatosis in solid cancers is rare, it is crucial to actively suspect and make an early diagnosis.

[Non-traumatic splenic rupture during the chemotherapy and successful management by emergency splenectomy in a patient with blastic plasmacytoid dendritic cell neoplasm].

Spontaneous rupture of the spleen is a rare but important complication in hematological malignancies. Without splenectomy, the mortality rate of these patients is nearly 100%. We present a blastic plasmacytoid dendritic cell neoplasm case with this complication. Nine days after initiation of chemotherapy, the patient had increased epigastric pain and a drop in hemoglobin. CT scan showed an enlarged spleen surrounded by hemorrhage. Spontaneous rupture of the spleen was diagnosed. Although the patient had severe bone marrow suppression due to chemotherapy, emergency splenectomy was performed and the patient recovered.