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Introduction: Although systemic therapy, including multi-kinase inhibitors and cytotoxic chemotherapy, is an option for recurrent or metastatic adenoid cystic carcinoma of the head and neck (HNACC), it is not proven whether these therapies can prolong overall survival (OS). The present study investigated the impact of cytotoxic chemotherapy on survival outcomes compared with observation without chemotherapy. Methods: We retrospectively reviewed the medical records of the patients diagnosed with recurrent or metastatic HNACC. We compared the survival outcomes, including survival time from recurrence/metastasis (OS) patients who received systemic chemotherapy with paclitaxel (200 mg/m2) and carboplatin (area under the curve 6) (TC) on day 1 of a 3-week cycle and observation alone. Subgroup analysis was conducted to identify patients who can get benefit from TC. Results: Seventy-five patients (32 in TC and 43 in observation) were analyzed. There was no difference in median OS between TC and observation (52.2 months vs. 44.0 months, hazard ratio 0.76, 95% confidence interval 0.32–1.30, p = 0.21). Landmark analysis to reduce immortal bias also showed no difference between TC and observation in terms of OS. Subgroup analysis showed nonsignificant trends toward longer OS in asymptomatic patients with pulmonary metastasis and without bone metastasis. Conclusions: In our non-randomized comparison, patients who underwent TC did not show prolonged survival time from recurrence and/or metastasis diagnosis compared with observation alone in patients with recurrent or metastatic HNACC. Although systemic chemotherapy is a possible option for metastatic/recurrent HNACC, initial observation might be a valid strategy for asymptomatic patients without extrapulmonary diseases. Further research is warranted to identify the optimal patients and therapeutic regimens to prolong OS in HNACC. [ABSTRACT FROM AUTHOR]

Background: The clinical benefit of systemic chemotherapy for recurrent/metastatic retroperitoneal/intra-abdominal soft tissue sarcoma (STS) compared to its benefits for other primary lesions has not been known or sufficiently evaluated. Methods and Patients: We retrospectively reviewed the cases of the STS patients who consulted a department of medical oncology in Tokyo between June 2011 and March 2018, and we extracted the cases of patients with primary sites at the retroperitoneum/intra-abdomen (cohort R) or extremities/trunk (cohort E) who received systemic chemotherapy in a recurrent/metastatic setting, comparing the cohorts' characteristics, chemotherapy details, and prognoses. Results: Of all 337 STS patients, we enrolled 49 patients in cohort R and 75 patients in cohort E. Liposarcoma was more frequently observed in cohort R (51.0%) than cohort E (22.7%). The median chemotherapy treatment line was two lines (range: 1–6) in cohort R and three lines (range: 1–9) in cohort E. The doxorubicin usage rates differed in recurrent/metastatic settings (90.0% in cohort R and 55.0% in cohort E), due mainly to the higher rate of a perioperative chemotherapy treatment history in cohort E (52.0% vs. 6.1% in cohort R). The median overall survival from the start of salvage chemotherapy was 31.9 months (cohort R; 95% CI: 20.9–42.8) and 27.1 months (cohort E; 95% CI: 21.6–32.5) (p = 0.549). Conclusion: There were differences in the distributions of pathology and antitumor drugs used in a salvage setting between retroperitoneal/intra-abdominal and extremities/trunk STS patients in recurrent/metastatic settings, but the prognoses with salvage chemotherapy were similar in the two cohorts. [ABSTRACT FROM AUTHOR]

Purpose: There have been few reports on the evaluation of cancer cachexia based on skeletal muscle mass index (SMI) in patients with head and neck cancer. Patients and Methods: One hundred and ninety-two head and neck cancer patients were enrolled. In definitive and adjuvant chemoradiotherapy settings, clinical outcomes were compared between cachexia and non-cachexia patients. Results: Forty patients were diagnosed with cachexia (20.8%). In the definitive setting, overall survival (OS) was significantly shorter in the cachexia group (3-year OS: 50.0% vs 88.5%; p < 0.01), and multivariate analysis identified UICC stage IV, baseline albumin of < 4 and cachexia as poor prognostic factors. However, cachexia was not significant in the adjuvant setting. Conclusion: Cancer cachexia was negatively associated with prognosis in patients with HNC who received definitive chemoradiotherapy. Nutritional intervention during chemoradiotherapy may improve survival in these patients. [ABSTRACT FROM AUTHOR]

Background: In the CheckMate-141 trial, nivolumab conferred a survival benefit in patients with recurrent or metastatic refractory squamous cell carcinoma (SCC) head and neck cancer (HNC). Here, we examined the efficacy of nivolumab in patients with histological subtypes or primary sites of HNC not included in the CheckMate-141 trial. Methods: This was a retrospective analysis of data collected prospectively from 97 patients who were treated with nivolumab for recurrent or metastatic HNC at our institution. The patients were assigned to three groups based on HNC primary site: 1) oral cavity, pharynx, and larynx, which were included in CheckMate-141 (n = 68), 2) nasopharynx (excluded in CheckMate-141, n = 7) and 3) other primary sites excluded in CheckMate-141 (n = 22) and assigned to two groups according to histological subtype: 1) SCC (included in CheckMate-141, n = 83) and 2) non-SCC (all sites excluded in CheckMate-141, n = 14). Survival outcomes and nivolumab treatment response were compared between the primary site and histological subgroups. Results: The median number of nivolumab treatments was 7 cycles (range, 1– 53 cycles) and the median follow-up time was 9.1 months (range, 0.66– 33.0 months). There were no significant differences in response rates between the three primary site subgroups (CheckMate-141 sites 22%, nasopharynx 43%, others 18%; p=0) or the two histological subtype subgroups (SCC 25%, non-SCC  7%, p=0). Similarly, overall survival and progression-free survival were comparable for patients stratified by primary site or histological subtype. Conclusion: No significant difference in response rates or survival outcomes was detected between nivolumab-treated HNC patients with primary sites and histological subtypes that were included versus excluded in the CheckMate-141 trial. These data provide a potential rationale for nivolumab therapy for all HNC patients in clinical practice. [ABSTRACT FROM AUTHOR]

The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cells in their chemoresistance and their tumorigenic and metastatic activities. In this review, we focus on recent reports regarding the identification of CSC markers and the molecular mechanism of CSC phenotypes to understand the basic properties and molecular target of CSCs. In addition, we especially focus on the CSCs of breast cancer since the use of neoadjuvant chemotherapy can lead to the enrichment of CSCs in patients with that disease. The identification of CSC markers and an improved understanding of the molecular mechanism of CSC phenotypes should lead to progress in cancer therapy and improved prognoses for patients with cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Second-line systematic therapy options for soft-tissue sarcoma (STS) have remained unchanged for decades due to the rarity and various histological types associated with STS. Challenges with molecular-targeted treatments for STS led to the approval of pazopanib and its wide use for STS. However, predictive markers of pazopanib treatment for STS have not been identified. Baseline neutrophil-to-lymphocyte ratio (NLR) is known as a candidate biomarker for several cancers. In this retrospective study, we investigated the use of the NLR as a predictor for the efficacy and prognosis of pazopanib in patients with STS. Our findings could be useful for the development of biomarker-targeted therapies for STS. Pazopanib with trabectedin and eribulin is widely used to treat soft-tissue sarcoma (STS). We have shown that baseline neutrophil-to-lymphocyte ratio (NLR) may predict the efficacy and patient prognosis of eribulin. Changes in NLR, but not baseline NLR, can predict patient prognosis of trabectedin. However, prognostic factors of pazopanib for STS have not been identified. We present a retrospective analysis of 141 patients treated with pazopanib for recurrent or metastatic non-round cell STS. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit (DCB), overall survival (OS), and progression-free survival. L-sarcoma histology (odds ratio [OR] = 0.31, 95% CI = 0.12–0.79; p = 0.014) and pre-treatment NLR < 3.0 (OR = 2.03, 95% CI = 1.02–6.67; p = 0.045) were independent predictive factors of DCB. Pre-treatment NLR < 3.0 (hazard ratio [HR] = 0.55, 95% CI = 0.36–0.84; p = 0.0057), liposarcoma histology (HR = 1.78, 95% CI = 1.09–2.91; p = 0.022), primary extremity site (HR = 0.48, 95% CI = 0.31–0.75; p = 0.0010), ECOG PS ≥ 1 (HR = 1.62, 95% CI = 1.08–2.42; p = 0.019), and CRP < 0.3 (HR = 0.52, 95% CI = 0.33–0.82; p = 0.0050) were independent predictive factors of OS. These findings indicate that baseline NLR predicts the efficacy and patient prognosis of pazopanib for STS. [ABSTRACT FROM AUTHOR]

Background Precision medicine using next gene sequencing (NGS) of tumor tissues has become mainstream of cancer therapy. Liquid biopsy is minimally invasive Method of sampling to assess tumor genotypes, and would be useful for detecting targetable mutations, follow-up during therapy, and detecting relapse, but more data are needed to clarify its significance. We show some preliminary data for liquid biopsy to detect actionable mutations in various cancer patients. Method We analyzed peripheral blood (14 ml) of patients with various cancers resistant to or without standard therapy and purified circulating cell-free DNA and RNA, then sequenced with customized Oncomine Pan-cancer cell free assay to detect actionable mutations in 95 genes. Data would be confirmed with sequencing of cancer tissues if possible, and be followed during therapy. Results From September 2018 to February 2019, 41 patients were analyzed. Of the 41 patients, primary loci of cancer are breast (n = 12), pancreas (n = 7), soft tissue sarcoma (n = 6), uterine (n = 5), head and neck (n = 3), ovary (n = 3), urothelial (n = 2), others (n = 3). The median age was 57 (25-78) years, performance status was 0-1 in all patients. No actionable mutation was detected in 7 patients. In other 34 patients, some significant mutations could be detected. Of those mutations, TP53 mutations were detected in 20 patients, PIK3CA mutations in 10, KRAS mutations in 7, AKT1 mutation in 1, BRAF mutation in 1, MTOR mutation in 1, FGFR3 amplification in 3. Conclusion The results suggest that actionable or druggable mutation can be detected by liquid biopsy using NGS. Further validation with tumor tissue examination and targeting therapy is needed. [ABSTRACT FROM AUTHOR]