Leiomyosarcoma arising from the ovarian vein as a gynecologic malignancy: Two case reports and a review of the literature.

Leiomyosarcoma arising from the ovarian vein has rarely been reported. Herein, we report two cases from a single institute. Given their direct connections to ovarian vessels, both leiomyosarcomas were initially suspected to be gynecological malignancies. In one case, leiomyosarcoma was discovered incidentally without any clinical symptoms; it had a close connection with the ovarian vein, was removed surgically, and the patient has survived for over 12 years. In another case, bowel obstruction caused by the tumor helped to identify metastatic leiomyosarcoma. Blood flow was supplied by the ovarian artery and grew into the lumen of the ovarian vein without invading adjacent organs. After surgical resection, the patient underwent 18 months of chemotherapy prior to palliative care. We propose that leiomyosarcoma arising from the ovarian vein should be treated as a gynecologic malignancy, especially if it develops in the lower abdomen.

Phase II trial of combination treatment with S-1/cetuximab in patients with platinum-ineligible recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab. METHODS: Platinum-ineligibility was defined as: elderly (aged ≥ 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m2/day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m2, followed by 250 mg/m2 weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). RESULTS: Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49-82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22-66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0-18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1-8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%). CONCLUSIONS: Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN. Registered clinical trial number: UMIN000015123.

Early prediction of treatment outcome for lenvatinib using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma refractory to radioiodine treatment: a prospective, multicentre, non-randomised study.

BACKGROUND: Lenvatinib is widely used to treat unresectable and advanced thyroid carcinomas. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) performed 1 week after lenvatinib treatment initiation could predict treatment outcomes. RESULTS: This was a prospective, nonrandomised, multicentre study. Patients with pathologically confirmed differentiated thyroid carcinoma (DTC) and lesions refractory to radioiodine treatment were eligible for inclusion. Patients were treated with 24 mg lenvatinib as the initial dose and underwent PET/CT examination 1 week after treatment initiation. Contrast-enhanced CT was scheduled at least 4 weeks later as the gold standard for evaluation. The primary endpoint was to evaluate the discrimination power of maximum standardised uptake value (SUVmax) obtained by PET/CT compared to that obtained by contrast-enhanced CT. Evaluation was performed using the area under the receiver operating characteristic (ROC-AUC) curve. Twenty-one patients were included in this analysis. Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.714 for SUVmax after 1 week of lenvatinib treatment. The best cut-off value for the treatment response for SUVmax was 15.211. The sensitivity and specificity of this cut-off value were 0.583 and 0.857, respectively. The median progression-free survival was 26.3 months in patients with an under-cut-off value and 19.7 months in patients with an over-cut-off value (P = 0.078). CONCLUSIONS: The therapeutic effects of lenvatinib were detected earlier than those of CT because of decreased FDG uptake on PET/CT. PET/CT examination 1 week after the initiation of lenvatinib treatment may predict treatment outcomes in patients with DTC. TRIAL REGISTRATION: This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (number UMIN000022592) on 6 June, 2016.

Real-world data on the efficacy and safety of immune-checkpoint inhibitors in elderly patients with non-small cell lung cancer.

PURPOSE: Immune-checkpoint inhibitors (ICIs) are effective against advanced non-small cell lung cancer (NSCLC). However, whether the efficacy and safety of ICI treatment in elderly patients are similar to those in younger patients is unclear. This study was designed to address this question. METHODS: We enrolled patients who received ICI monotherapy in Japan between December 2015 and December 2017; those ≥75 years of age comprised the elderly group. We compared the efficacy and safety of ICI monotherapy in elderly patients with those in younger patients and explored prognostic factors in elderly patients. RESULTS: We enrolled 676 patients; 137 (20.3%) were assigned to the elderly group. The median age of the elderly and younger groups was 78 (range, 75-85) and 66 (range, 34-74) years. The median progression-free survival (4.8 months vs. 3.3 months, p = 0.1589) and median overall survival (12.3 months vs. 13.0 months, p = 0.5587) were similar between the elderly and younger groups. Multivariate analysis revealed that a significantly better OS in the elderly group was associated with better responses to first- or second-line ICI treatment (p = 0.011) and more immune-related adverse events (irAEs) (p = 0.02). IrAEs that led to ICI discontinuation occurred in 34 of 137 patients (24.8%) in the elderly group, and their survival was significantly higher than that in those who did not have irAEs. CONCLUSION: ICI is also effective in elderly NSCLC patients, and treatment discontinuation due to irAEs may be a good prognostic marker.

[Black esophagus due to acute necrotizing esophagitis: four case reports].

We describe four patients with acute esophageal necrosis who were admitted to hospital due to upper gastrointestinal bleeding. "Black esophagus" is endoscopically defined as diffuse dark pigmentation of the esophageal wall. The underlying conditions were ketoacidosis in three of the patients and diabetes mellitus in two. Three patients responded well to empirical supportive therapy and one patient died of coexisting illness rather than the esophageal status. Acute esophageal necrosis is a rare entity that should be considered in the differential diagnosis of upper gastrointestinal bleeding.

Prognostic factors in patients with advanced non-small cell lung cancer after long-term Anti-PD-1 therapy (HOT1902).

OBJECTIVES: Limited information is available on the appropriate treatment duration of immune checkpoint inhibitors (ICIs). We aimed to identify candidates who would benefit from ICI discontinuation after one year of treatment for metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective multi-institutional observational study examined medical records of all consecutive patients with advanced or recurrent NSCLC, who started ICI monotherapy at 15 institutions in Japan between December 2015 and December 2017. Patients who received initial ICI therapy for >1 year without progressive disease were defined as the long-term treatment (LT) group; others were defined as the non-long-term treatment (NLT) group. Primary outcomes included the prognostic factors in the LT group, whereas secondary outcomes included efficacy of ICI rechallenge, safety, and survival outcomes in the overall population. RESULTS: In total, 676 patients were enrolled, and 114 (16.9 %) were assigned to the LT group. The median time interval from the start of initial ICI administration to data cutoff was 34.3 months (range, 24.1-47.8); thus, all surviving patients were followed-up for at least 2 years from the start of initial ICI. Median progression-free survival (PFS) was longer in the LT than in the NLT group (33.6 months vs. 2.7 months; p < 0.001). On multivariate analysis, significantly better PFS was associated with smoking (hazard ratio [HR]=0.36, p = 0.04), and complete response (CR; HR=uncomputable, p < 0.001) in the LT group. Thirty-seven patients (5.5 %) received ICI rechallenge, including 10 in the LT group. Among patients receiving rechallenge treatment, the median PFS was 2.2 months, with no difference between the LT and NLT groups. CONCLUSIONS: In the LT group, smoking and achieving CR were significantly associated with better PFS. Since rechallenge treatment was not effective, careful consideration is required for discontinuing ICI. However, these prognostic factors are helpful in considering candidates for ICI discontinuation. TRIAL REGISTRATION: UMIN ID, UMIN000041403.

Late Onset of Non-islet Cell Tumor Hypoglycemia Managed via Multidisciplinary Treatment in a Patient with a Solitary Fibrous Tumor.

Solitary fibrous tumor (SFT) is a rare subtype of soft tissue sarcoma (STS). We herein describe a case of late onset of non-islet cell tumor hypoglycemia (NICTH) that was managed via multidisciplinary treatment in a patient with SFT. A 67-year-old man previously diagnosed with SFT 4 years prior to this presentation and treated with several rounds of surgery, presented with massive tumors. Eighteen months following his prescribed chemotherapy, the patient developed hypoglycemia. He was diagnosed with NICTH, after confirming the presence of high molecular weight insulin-like growth factor-2. This case suggests that paraneoplastic syndrome can occur even in cases of rare cancers, such as STS.