The controlling nutritional status (CONUT) score is a nutritional index calculated from serum albumin and total cholesterol levels and lymphocyte counts. Its role in predicting clinical outcomes of diffuse large B-cell lymphoma (DLBCL) has not been evaluated. In this retrospective study, data from 476 patients with DLBCL were analyzed. The cutoff value of the CONUT score was set as 4. CONUT score significantly stratified the overall survival (OS) and the progression-free-survival (PFS) (5-year OS, 49.0% vs 83.2%, P < .001; 5-year PFS, 46.1% vs 73.1%, P < .001) of the patients. Among patients at high-intermediate or high risk, as per the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), 5-year OS was lower in patients with high CONUT scores than in those with low CONUT scores (highintermediate risk, 51.2% vs 75.5%, P < .001; high risk, 29.9% vs 63.3%, P = .007). Additionally, in patients with high CONUT scores, maintenance of relative dose intensity (RDI) of chemotherapy did not affect the 5-year OS (RDI > 80% vs RDI ≤ 80%: 59.8% vs 50.9%, P = .73). In the present study, we have demonstrated that the CONUT score is an independent prognostic factor in patients with DLBCL.

Identification of gastric tumor-initiating cells (TICs) is essential to explore new therapies for gastric cancer patients. There are reports that gastric TICs can be identified using the cell surface marker CD44 and that they form floating spheres in culture, but we could not obtain consistent results with our patient-derived tumor xenograft (PDTX) cells. We thus searched for another marker for gastric TICs, and found that CD49fhigh cells from newly-dissected gastric cancers formed tumors with histological features of parental ones while CD49flow cells did not when subcutaneously injected into immunodeficient mice. These results indicate that CD49f, a subunit of laminin receptors, is a promising marker for human gastric TICs. We established a primary culture system for PDTX cells where only CD49fhigh cells could grow on extracellular matrix (ECM) to form ECM-attaching spheres. When injected into immunodeficient mice, these CD49fhigh sphere cells formed tumors with histological features of parental ones, indicating that only TICs could grow in the culture system. Using this system, we found that some sphere-forming TICs were more resistant than gastric tumor cell lines to chemotherapeutic agents, including doxorubicin, 5-fluorouracil and doxifluridine. There was a patient-dependent difference in the tumorigenicity of sphere-forming TICs and their response to anti-tumor drugs. These results suggest that ECM plays an essential role for the growth of TICs, and that this culture system will be useful to find new drugs targeting gastric TICs.

Transcriptome analysis of circulating tumor cells (CTCs), which migrate into blood vessels from primary tumor tissues, at the single-cell level offers critical insights into the biology of metastasis and contributes to drug discovery. However, transcriptome analysis of single CTCs has only been reported for a limited number of cancer types, such as multiple myeloma, breast, hepatocellular, and prostate cancer. Herein, we report the transcriptome analysis of gastric cancer single-CTCs. We utilized an antigen-independent strategy for CTC isolation from metastatic gastric cancer patients involving a size-dependent recovery of CTCs and a single cell isolation technique. The transcriptomic profile of single-CTCs revealed that a majority of gastric CTCs had undergone epithelial-mesenchymal transition (EMT), and indicated the contribution of platelet adhesion toward EMT progression and acquisition of chemoresistance. Taken together, this study serves to employ CTC characterization to elucidate the mechanisms of chemoresistance and metastasis in gastric cancer.

No standard therapy for peripheral T-cell lymphomas (PTCLs) has been established, and treatment outcomes are poor. Upfront stem cell transplantation has been investigated in several studies, some of which have reported promising outcomes. However, some patients maintain long-term remission after chemotherapy alone. It is thus important to predict sensitivity to first-line chemotherapy to optimize treatment strategies. In the present study, we retrospectively analyzed time to treatment failure (TTF) of first-line chemotherapy in 59 patients with PTCLs. On multivariate analysis for TTF, elevated lactate dehydrogenase level, hypoalbuminemia, and high neutrophil-to-lymphocyte ratio were significant prognostic factors. Using these three factors, we also developed a new model that effectively distinguished patient outcomes. The TTF rate at 1 year from diagnosis was 71.4% in patients with score 0 (0 factor), 31.8% with score 1 (1 factor) and 4.5% with score 2 (2-3 factors) (P< 0.001). The prognostic power was superior to that of the Prognostic Index for PTCL-unspecified score. Patients with scores of 1 and 2 had poor TTF, and may be candidates for upfront stem cell transplantation if they respond to first-line chemotherapy. Further investigation in a larger cohort is warranted to determine the general applicability of this score.

Background: The previous second-line treatment for HER2-positive metastatic breast cancer were adotrastuzumab emtansine (T-DM1); however, its activity is decreased in tumors with heterogenous, reduced, or loss of HER2 expression. Trastuzumab deruxtecan (T-DXd) has recently been developed as a novel antibody-drug conjugate to overcome resistance to T-DM1. However, clinical evidence on its ability to overcome this resistance is limited. Materials and methods: We retrospectively analyzed data for patients with HER2-positive metastatic breast cancer who received T-DXd at our institution from April 2020 to March 2021. We evaluated the associations between clinicopathological and molecular biomarkers and the efficacy of T-DXd. Results: Twenty-two patients were enrolled in this study. The median progression-free survival (PFS) was 9.7 months (95% confidence interval [CI], 7.0enot reached [NR]), and the objective response rate (ORR) was 61.9%. The ORR and PFS were comparable between patients with HER2 immunohistochemistry scores of 3þ and 2þ/1þ at initial diagnosis (ORR: 50.0% vs. 72.7%, p ¼ 0.39; median PFS, 9.7 months [95%CI, 2.6eNR] vs. 8.3 months [95%CI, 7.1eNR]; hazard ratio, 1.86 [95%CI, 0.53e6.57], p ¼ 0.34). Two patients with heterogenous HER2 expression had a partial response or long stable disease (!6 months). Three of four patients with re-biopsy samples after anti-HER2 targeted therapy and with latest HER2 immunohistochemistry scores of 1þ experienced partial responses (75.0%) to T-DXd, but none had responded to prior T-DM1. Conclusions: T-DXd demonstrated favorable activity in clinical practice. Moreover, T-DXd showed meaningful benefit in patients with heterogeneity, reduction, or loss of HER2 expression.

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Somatic mutations in human epidermal growth factor receptor 2 (HER2) are present in approximately 3% of breast cancers. Some HER2 mutations are activating, and they represent a mechanism of resistance to conventional anti-HER2 therapies such as trastuzumab and lapatinib. Consistently, in patients with HER2-amplified breast cancer, these mutations are predominantly observed in metastatic tumors obtained after exposure to anti-HER2 systemic therapies, possibly after clonal selection. Therefore, it is rare to find co-existent HER2 mutation and amplification in the early clinical course, and thus, the clinical relevance of HER2 mutation to the sensitivity to HER2-targeted drugs, particularly antibody-drug conjugates (ADCs) such as ado-trastuzumab emtansine (T-DM1) and the recently approved fam-trastuzumab deruxtecan (T-DXd), remains unclear. In this study, we described a patient with de novo metastatic breast cancer who exhibited both HER2 amplification and the L755S mutation in the untreated primary breast tumor obtained at the initial diagnosis, and the lesion responded to T-DM1 and T-DXd after exhibiting clinical resistance to other HER2-targeted drugs. Our current case findings suggested that anti-HER2 ADCs should be prioritized over conventional trastuzumab-or lapatinib-based therapies for patients with HER2-amplified and co-mutated tumors. The Oncologist 2021;9999:• • KEY POINTS • Although HER2 mutations were implicated in resistance to anti-HER2 monoclonal antibodies or HER2 TKIs in preclinical studies, their clinical impact on sensitivity to anti-HER2 drugs is unclear owing to the rarity of concomitant HER2 mutation and HER2 amplification. • A case of de novo metastatic breast cancer harboring both HER2 amplification and the L755S mutation in an untreated breast primary tumor displayed clinical resistance to standard trastuzumab-or lapatinib-based therapies but good responses to T-DM1 and T-DXd. • Anti-HER2 ADCs such as T-DM1 and T-DXd may be prioritized over conventional trastuzumab-or lapatinibcontaining therapies for patients with HER2-amplified and co-mutated tumors.

Background/Aim: To maximize the effect of perioperative chemotherapy in breast cancer, it is critical to keep the relative dose intensity (RDI) high. While bi-weekly doxorubicin and cyclophosphamide, dose-dense AC (ddAC), instead of tri-weekly conventional AC (cAC) followed by a taxane has been adopted as standard perioperative chemotherapy, postponement or discontinuation are sometimes experienced during ddAC or subsequent taxane phase. This study aimed at evaluating whether ddAC, compared to cAC, was associated with reduced RDI. Patients and Methods: We compared ddAC and cAC, both followed by a taxane, for perioperative breast cancer regarding the proportion of completion of planned treatment (%completion), defined as an RDI ≥85% for both AC and taxane phases. Results: There was no remarkable difference between the groups in patient characteristics after propensity score matching (n=46 in ddAC, and n=86 in cAC). The %completion was similar between the groups (67.4% vs. 65.1%). Most other endpoints related to RDI were similar between groups. The incidence of pneumonia was higher in the ddAC group (13% vs. 3%) including one Pneumocystis jiroveci pneumonia. Conclusion: ddAC followed by a taxane can be considered with sufficient supportive measures and precautions for pneumonia.Breast cancer is the most common cancer in women worldwide (1). The survival benefit of perioperative, adjuvant or neoadjuvant, chemotherapy has been established in patients with early-stage and locally-advanced breast cancer (2). The standard and one of the most commonly employed perioperative chemotherapy regimens is doxorubicin plus cyclophosphamide (AC) followed by a taxane (docetaxel or paclitaxel) (3,4).The effect of chemotherapy is generally correlated with dose intensity, defined as the total amount of drug given in a fixed unit of time, and most commonly expressed as milligrams per meter squared per week (mg/m 2 /week) (5). Relative dose intensity (RDI) is defined as the ratio of the actual dose intensity over the standard or planned dose intensity. The RDI of perioperative chemotherapy for breast cancer has been reported to affect disease-free survival (DFS) and overall survival (OS) (5). A randomized controlled trial suggested that early-stage breast cancer patients treated with a cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) regimen delivered with an RDI of ≥85% had a significantly better survival than those treated with the same regimen but delivered with an RDI of <85% (6). The survival benefits of receiving a higher RDI have been confirmed subsequently in several observational studies (5, 7), and clinical guidelines recommend keeping an RDI of at least 85% for optimal treatment (8).To increase dose intensity, a dose-dense (dd)AC regimen was developed; it shortens the interval of AC therapy from 6217