Study protocol: randomized phase III trial of neo-adjuvant and adjuvant chemotherapy vs. immediate surgery and adjuvant chemotherapy for localized soft tissue sarcoma: Japan Clinical Oncology Group study JCOG2102 (NACLESS).

The optimal timing of surgery and the number of courses of perioperative chemotherapy for high-risk soft tissue sarcoma patients are still controversial. Tumour growth during neoadjuvant chemotherapy led to limb amputation in some patients. This study aims to confirm the non-inferiority of surgery and three courses of adjuvant chemotherapy with adriamycin (30 mg/m2, days 1 and 2) plus ifosfamide (2 g/m2, days 1-5) compared with our standard treatment of three courses of neoadjuvant chemotherapy and surgery followed by two courses of adjuvant chemotherapy with adriamycin plus ifosfamide for localized high-risk soft tissue sarcoma patients. This is a multi-center, two-arm, open-label, randomized phase III trial. The primary aim is to confirm the non-inferiority in overall survival (margin: hazard ratio of 1.61). This is the first randomized controlled trial to compare neoadjuvant chemotherapy and immediate surgery for soft tissue sarcoma. This trial was initiated on 16 November 2022 and registered with the Japan Clinical Trials Registry (jRCTs031220446).

Clinical characteristics and treatment management of combined large cell neuroendocrine carcinoma, a subtype of large cell neuroendocrine carcinoma.

Combined large cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine carcinoma, accounting for approximately 10% of large cell neuroendocrine carcinoma (LCNEC). Mainly composed of coexisting adenocarcinoma components, with strong invasiveness and poor prognosis. The treatment regimen for CLCNEC mainly refers to complete surgical resection as the first choice in the early stage, while patients with stage II or higher require adjuvant treatment. At present, research on CLCNEC is mostly small sample and retrospective, and there is no consensus on whether molecular typing and treatment should be carried out. There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC.

Phase II trial evaluating the long-term efficacy and peripheral sensory neuropathy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer.

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and two divided doses oral capecitabine (2000 mg/m2/day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer.

Maturity and density of tertiary lymphoid structures associate with tumor metastasis and chemotherapy response.

Background: Tertiary Lymphoid Structures (TLSs) are abnormal clusters of immune cells that form in tissues not normally associated with the immune system, usually in cases of long-lasting inflammation, like cancer. TLSs have been suggested as a potential prognostic indicator in various cancer types. Methods: We retrospectively enrolled 223 gastric cancer (GC) patients who had surgical resections in this study. We utilized hematoxylin and eosin (HE) staining to detect the presence, abundance, and maturity of TLSs. In serial sections, we used immunohistochemistry to examine the cellular composition of TLSs. Results: The pathological review identified TLSs in 95.1% of the tumors, lymphoid aggregates in 79.8%, primary follicles in 45.7%, and lymphoid aggregates in 95.1% of the cases. Based on Kaplan-Meier curves, the maturation and abundance of TLSs contributed to longer disease-free survival (DFS) and overall survival (OS). In addition, the density of TLSs was strongly associated with the occurrence of tumor metastases and the response to adjuvant chemotherapy. Conclusions: We validated the prognostic value of TLSs in GC patients in both independent cohorts, and the maturity and density of TLS correlated with tumor metastasis. In addition, TLS may reflect sustained antitumor potency, which has important implications for adjuvant chemotherapy.

Successful treatment of osteosarcoma in a pregnant woman with survival of the gestational product: A case report and literature review.

Osteosarcoma (OS) is the most prevalent bone neoplasm of mesenchymal origin, accounting for 20% of all bone tumors worldwide. It mainly affects the marrow of long bones, and its diagnosis is more common among adolescents and the geriatric population. Histologically, it is characterized by high cellular variability, abundant osteoid and fibrotic material. In the early stages, it presents with only local symptoms such as pain, edema and limited joint mobility. This neoplasm, when detected promptly, is associated with a favorable prognosis and can be effectively treated through surgical removal and adjuvant therapy. The development of tumors in pregnant women is rare, and the occurrence of osteosarcoma is even more exceptional, with only 10 cases documented in the literature. Given its rarity, the present study describes the case of a female patient with OS diagnosed in the first trimester of pregnancy, where the patient responded well to treatment, resulting in no adverse effects on the pregnancy outcome.

Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy-a systematic review and meta-analysis.

Background: More and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection. Methods: We conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria. Results: A total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75∼0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [<2-cm subgroup: HR = 0.72, 95% CI (0.5∼0.94), P = 0.01; ≥2-cm subgroup: HR = 0.79, 95% CI (0.65∼0.96), P = 0.02] and the margin status [R0 subgroup: HR = 0.83, 95% CI (0.77∼0.88), P < 0.00001; R2 subgroup: HR = 0.75, 95% CI (0.61∼0.92), P = 0.007]. AC also benefited the patients with a stage N0 [HR = 0.79, 95% CI (0.74~0.84), P < 0.00001], N1 [HR = 0.78, 95% CI (0.72∼0.85), P < 0.00001], or poorly/undifferentiated tumor [HR = 0.76, 95% CI (0.66∼0.87), P < 0.0001] in survival but not in patients with a stage N2 [HR = 0.69, 95% CI (0.43∼1.09), P = 0.11] or well/moderately differentiated tumor [HR = 0.97, 95% CI (0.66∼1.42), P = 0.87]. Conclusions: Although AC showed survival benefit for patients with PC undergoing radical pancreatectomy after NAT, we still need to consider the lymph node stage and the degree of differentiation of the tumor when we gave AC to a patient. High-quality prospective randomized controlled studies are required to well disclose the value of AC in patients with PC undergoing radical pancreatectomy after NAT. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023461365.

Salinomycin induces apoptosis and potentiates the antitumor effect of doxorubicin against feline mammary tumor 2.5D organoids.

Feline mammary tumors (FMT) are the third most common form of neoplasm in cats. The prognosis of FMT is poor due to its high malignancy and metastatic potential. The outcomes of treatment using the common anticancer drug doxorubicin (DOX) are unsatisfactory, with resistance inevitably leading to treatment failure and disease recurrence. Salinomycin (SAL), an antibiotic, has been reported to exert anticancer effects on both human and canine mammary tumors. To recapitulate the genetic and molecular imprints of the original tumor sample, we generated four strains of patient-derived FMT 2.5D organoids (FMTO) to examine the anti-tumor potential of SAL. Our results revealed that SAL decreased cell viability in a dose-dependent manner. Treatment of FMTO with SAL-induced cell apoptosis, represented by an upregulation of P21, Caspase-8, and Caspase-9, and increased activity of Caspase-3/7. The combination of low-dose SAL with DOX (SD) potentiated the cytotoxicity of the latter in both DOX-resistant and DOX-sensitive strains, promoting cell apoptosis and cell-cycle arrest. In vivo, experiments using FMTO-derived xenografts engrafted into mice revealed decreased tumor growth following SAL administration. In conclusion, SAL showed anticancer activity against FMTO and potentiated the anticancer effect of DOX by inhibiting cell proliferation and inducing apoptosis and cell cycle arrest. These results suggest that SAL may represent a new adjuvant treatment option for patients with FMT.

Adjuvant therapy de-escalation for stage I uterine leiomyosarcoma: A systematic review and meta-analysis.

OBJECTIVE: To examine the association between adjuvant chemotherapy and survival outcomes in patients with stage I uterine leiomyosarcoma (uLMS). METHODS: This comprehensive systematic review and meta-analysis through December 31, 2023 (PROSPERO registration number: CRD42024504776) investigated studies that examined survival outcomes in patients with stage I uLMS using 4 public search engines (PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials). Two investigators searched the studies independently, and survival outcomes (overall survival [OS] and disease-free survival [DFS]) were compared between the adjuvant chemotherapy and observation groups. Utilization rate of adjuvant chemotherapy and the regimens used were also assessed. Kaplan-Meier survival curves in the two treatment groups were evaluated using ImageJ software. RESULTS: From 1988 to 2022, 16 eligible studies including a total of 5690 patients met the inclusion criteria and evaluated the effect of adjuvant chemotherapy on survival outcomes in patients with stage I uLMS. Adjuvant chemotherapy was utilized in 38.5 % of patients (range, 14.8 % to 70.0 %). Eight studies from 2017 to 2022 compared the survival outcomes between adjuvant chemotherapy and observation. OS was comparable between the two groups in both unadjusted (n = 6, hazard ratio [HR] 1.02, 95 % confidence interval [CI] 0.77-1.35, P = 0.88) and adjusted (n = 4, HR 0.90, 95 %CI 0.56-1.43, P = 0.65) pooled analyses. DFS was also similar between adjuvant chemotherapy and observation in both unadjusted (n = 4, HR 0.78, 95 %CI 0.53-1.13, P = 0.18) and adjusted (n = 2, HR 1.14, 95 %CI 0.67-1.94, P = 0.64) pooled analyses. Adjuvant chemotherapy regimens utilized included doxorubicin, ifosfamide, cisplatin, gemcitabine, and docetaxel as monotherapies or combination therapies. CONCLUSIONS: In this contemporaneous systematic review and meta-analysis, less than 40 % of patients received adjuvant chemotherapy for stage I uLMS and adjuvant chemotherapy which was not associated with improved survival. These results support the current National Comprehensive Cancer Network clinical practice guidelines that recommends de-escalating adjuvant chemotherapy in stage I uLMS after complete resection.

The Role of Medicaid Expansion on the Receipt of Adjuvant Chemotherapy in Patients With Lung Cancer.

OBJECTIVE: We aimed to utilize a nationally representative database to study the effect of Medicaid expansion on the receipt of adjuvant chemotherapy in eligible patients. MATERIALS AND METHODS: Retrospective review of the National Cancer Database (NCDB) was performed between 2006 and 2019. Patients with clinical T1-T3, N1, and M0 were included. Patients with nodal disease or tumors > 4 cm were eligible for adjuvant therapy. Demographic and clinical information were collected. A difference-in-difference analysis was performed to compare changes in the rate of adjuvant chemotherapy. RESULTS: Total 9954 eligible patients were treated in states that expanded Medicaid coverage in January 2014 or later, with 4809 patients treated in the pre-expansion years (2012-2013) and 5145 patients treated in the postexpansion years (2017-2018). Following Medicaid expansion, eligible patients were more likely to receive adjuvant therapy (70.2% vs. 62.3%; P < .001). Compared with the pre-expansion period, patients who received adjuvant therapy were more likely to use Medicaid insurance postexpansion (7.8% vs. 5%, P < .001). Among patients using Medicaid coverage only, a greater percentage started adjuvant therapy within 8 weeks of resection following Medicaid expansion (46.6% vs. 38.3%, P = .048). The observed difference-in-difference in the change in adjuvant therapy rate from the pre-expansion period to the postexpansion period between expansion and nonexpansion states was 1.25% (95% Bootstrap CI -0.36% to -3.18%). There was a modest survival benefit in expansion states postexpansion. CONCLUSION: Medicaid expansion appears to be associated with increased access to care, as shown by the increased receipt of adjuvant systemic therapy in eligible patients.

C-Reactive Protein-to-Albumin Ratio as a Predictive Indicator for Evaluating Tolerability in S-1 Adjuvant Chemotherapy after Curative Surgery for Pancreatic Cancer: An External Validation Cohort Study.

BACKGROUND: S-1 in adjuvant chemotherapy (AC) administration after pancreatic cancer (PC) surgery has been standardized in Japan. The Ehime study confirmed that a postoperative higher C-reactive protein-to-albumin ratio (CAR) value predicted the risk of adverse event (AE)-related S-1 non-completion as an AC in patients with PC after curative surgery. This study aimed to investigate the index to predict S-1 tolerance among patients who underwent curative surgery for PC (the Dokkyo study). METHODS: This retrospective validation cohort study included 172 patients at the Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Japan, from January 2010 to December 2022. All patients underwent nutritional screening using the postoperative CAR. S-1 completion status and its effect on prognosis were systematically followed up and investigated. We conducted a statistical analysis of predictive markers to investigate their association with S-1 completion. RESULTS: Patients were categorized into the S-1 completion (N = 91) and non-completion (N = 81) groups. The S-1 completion group demonstrated a significantly lower CAR than the S1 non-completion group. Moreover, the current study revealed a significant difference in the S-1 completion rate, applying the CAR cutoff value of 0.05 established in the Ehime study. Additionally, univariate and multivariate analyses confirmed that a CAR of <0.05 was significantly associated with S-1 completion. CONCLUSIONS: The Dokkyo study confirmed the results observed in the Ehime study. Consequently, an increased postoperative CAR value appeared as a universal applicable marker for the risk factor of AE-related S-1 non-completion after curative surgery for patients with PC.

Long term safety of controlled ovarian stimulation for fertility preservation prior to chemotherapy treatment in breast cancer patients.

OBJECTIVE: To evaluate the long-term safety of controlled ovarian stimulation for fertility preservation prior to breast cancer chemotherapy treatment DESIGN: Retrospective observational cohort SUBJECTS: 213 women aged 18-43 years with newly diagnosed stage I-III breast cancer treated with systemic chemotherapy during 2015-2019. Of those, 74 underwent controlled ovarian stimulation for fertility preservation recipients and 141 did not (controls). EXPOSURE: Controlled ovarian stimulation for fertility preservation MAIN OUTCOME MEASURES: Invasive disease-free survival, calculated from the time of surgery to the time of detection of breast cancer recurrence or death, whichever came first. RESULTS: At diagnosis, fertility preservation recipients were significantly younger than controls (32.7 vs 38.5 years), were less likely to be partnered (44.4% vs 90.1%) or parous (38.9% vs 95%) and were more likely to harbor a BRCA germline mutation (36.5% vs 14.2%). Disease characteristics and treatment modalities were comparable between groups, apart from tumor staging, with maximal tumor diameter being over 5 cm in 22.2% of fertility preservation recipients as opposed to 5.7% of controls (P<0.05). Mean follow-up was 60.9 and 65.4 months for fertility preservation recipients and controls, respectively. 5-year-invasive disease free survival was 80% for fertility preservation recipients and 86% for controls (p=0.20). In a multivariate analysis adjusted for statistically significant covariates, invasive disease free survival remained similar between the groups (Hazards Ratio (HR), 0.86, 95CI 0.4-1.87, p = 0.71). Invasive disease free survival rates were not statistically different in clinically relevant subgroups including patients receiving neoadjuvant chemotherapy (HR 1.57, CI 95 0.62-3.99, p=0.34), and those co-treated with tamoxifen during stimulation due to an ER-positive disease (HR 1.66, 95CI 0.67-3.49, p=0.23). CONCLUSIONS: Fertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emerging clinically relevant subgroups.

Breast Cancer Adjuvant Radiotherapy and Chemotherapy Sequencing: Sequential, Concomitant, or What Else? A Comprehensive Review of the Adjuvant Combinations Journey.

Background: To date, in breast cancer (BC) treatment, adjuvant chemotherapy (A-CT) has preceded adjuvant radiotherapy (A-RT). In the last twenty years, the adjuvant treatment of BC has quickly evolved due to better knowledge of its molecular biology, genetic profile, and α/ß ratio of 3/4 Gy for tumor and normal tissue radiosensitivity. Thus, new schedules with hypofractionated radiotherapy have been tested, and a third generation of A-CT has been introduced, raising the question of whether it is time to rethink the sequencing between these two approaches. Methods: In the last 20 years, many attempts have been made worldwide to optimize the best sequencing strategy between these two approaches in terms of sequential CT-RT and RT-CT and concomitant and sandwich modalities using drugs and schedules. This paper presents a comprehensive review of the state of the art, analyzing all the available studies to assess the sequencing between A-CT and A-RT with different generations of chemotherapy schedules. Results: More than 8000 patients from 30 studies treated with adjuvant chemotherapy and whole breast radiotherapy who were enrolled in randomized, retrospective, and prospective studies were analyzed. Sequential, concomitant, and sandwich modalities of chemotherapy with conventional or hypofractionated RT schedules from the most important studies were included. The most used sequence was adjuvant chemotherapy followed by conventional or hypofractionated radiotherapy. In the concomitant approach, i.v. CMF has been the most important adopted schedule, while the concomitant use of anthracyclines and taxanes with conventional or hypofractionated radiotherapy has been found to be more toxic. One study analyzed the benefit in terms of reducing adjuvant treatment time with upfront hypofractionated radiotherapy and third-generation chemotherapy. Conclusions: At present, the best sequencing strategy has not yet been defined. This comprehensive review is a journey among the most important randomized, retrospective, and prospective studies that highlights the past, current, and novel time sequencing proposals between A-CT and A-RT to assess the state of the art and provide useful information for future adjuvant approaches in breast cancer treatment.

Effect of training based on Orem's self-care deficit theory on breast cancer patients' management of chemotherapy-related side effects and self-care behaviors: A randomized controlled trial.

PURPOSE: To examine the effects of training based on Orem's self-care deficit theory on breast cancer patient's physical, social, and psychological well-being and self-care behaviors during chemotherapy. METHODS: This randomized controlled trial was based on a pretest-posttest experimental design. The study sample consisted of 62 breast cancer patients (n = 31 for each of the intervention and control groups) receiving cyclophosphamide-epirubicin or cyclophosphamide-adriamycin treatment in the medical oncology department of a university hospital in Tekirdag, Turkey. The breast cancer patients in the intervention group received training based on Orem's self-care deficit theory regarding physical, social, and psychological well-being and self-care behaviors during chemotherapy. The researcher conducted two face-to-face follow-ups (during the second and third chemotherapy cycles, 3 weeks apart) and a posttest assessment. Pretest and posttest symptom scores and self-care survey results were compared for both groups. RESULTS: The Nightingale Symptom Assessment Scale (N-SAS) first follow-up, second follow-up, and posttest scores showed that the intervention group experienced fewer negative changes in quality of life than the control group based on the physical, social, and psychological subdimension and total scale scores (p < .05). The most positive changes in the intervention group's self-care behaviors were observed for items about caring for and protecting hair, using protective gloves when doing chores, monitoring weight, and limiting social meetings when blood values were low to protect against possible infection. CONCLUSION: Training based on Orem's self-care deficit theory positively influenced breast cancer patients' management of chemotherapy-related side effects and self-care behaviors. Chemotherapy-related side effects should be evaluated frequently. Moreover, patients' needs should be determined, and training should be tailored to their needs.

Phase II Trial of Adjuvant S-1 Following Neoadjuvant Chemotherapy and Surgery in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: The PIECE Trial.

BACKGROUND: Neoadjuvant chemotherapy followed by surgery (NAC-S) is the standard therapy for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan. OBJECTIVE: The aim of this phase II trial was to assess the efficacy and safety of the addition of adjuvant S-1 after R0 resection in ESCC patients who received NAC-S. PATIENTS AND METHODS: Key eligibility criteria included clinical stage IB-III (without T4 disease) ESCC, age 20-75 years, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received adjuvant therapy with four cycles of S-1 (80 mg/m2/day) administered orally for 4 weeks of 6-week cycles. The primary endpoint was 3 year relapse-free survival (RFS). If the lower confidence limit for 3 year RFS was >50%, we judged that the primary endpoint of this study was met. RESULTS: A total of 52 patients were enrolled between January 2016 and January 2019. Two patients were excluded from analysis; five patients were determined to have R1 or R2 resection, and seven patients did not receive adjuvant S-1. The 3-year RFS and overall survival rates in the intention-to-treat population were 72.3% (90% confidence interval [CI] 59.9-81.5) and 85.0% (90% CI 73.9-91.6), indicating that the primary endpoint was met. Grade ≥3 adverse events with an incidence ≥10% included neutropenia (13.2%), anorexia (13.2%), and diarrhea (10.5%). There were no treatment-related deaths. CONCLUSION: Adjuvant S-1 after NAC-S showed promising efficacy with a manageable safety profile for patients with resectable ESCC and warrants further evaluation in larger studies.

Comparison of postoperative prognoses for resectable colorectal cancer with vs. without oncologic emergency using propensity score­matched analyses: A single-center retrospective observational study.

While oncological emergencies in colorectal cancer present distinct challenges, existing literature offers conflicting evidence regarding long-term outcomes. Therefore, the present study compared the postoperative prognoses between patients with and without oncological emergencies. A retrospective evaluation was conducted on patients who had undergone radical surgery for pathological stages II and III colorectal cancer at a single center between January 2012 and December 2020. Patients were classified into the non-emergency and oncological emergency groups. The status of oncologic emergency was divided into obstruction and perforation. The outcomes were compared using propensity score matching. The primary objective was to compare the postoperative prognoses between non-emergency and oncological emergency situations. The secondary objectives included comparing prognoses between obstruction and perforation, identifying the type of recurrence depending on the status of oncologic emergency, and assessing the effect of adjuvant chemotherapy for oncologic emergencies. This study included 524 patients. After propensity score matching, the prognoses of oncological emergencies were worse compared with those without any emergency, whereas those of obstruction and perforation did not significantly differ. Regarding the type of recurrence, peritoneal dissemination in obstruction and local recurrence in perforation was more common compared with that in non-emergency cases. Adjuvant chemotherapy improved the recurrence-free survival for cases with oncological emergencies. The prognoses in cases with oncological emergencies could be worse compared with those without any emergency, whereas obstruction and perforation outcomes can be comparable. The administration of adjuvant chemotherapy should be strongly considered for oncological emergencies.

Nuclear TOP1MT Confers Cisplatin Resistance via Pseudogene in HNSCC.

Cisplatin resistance is one of the major causes of treatment failure in head and neck squamous cell carcinoma (HNSCC). There is an urgent need to uncover the underlying mechanism for developing effective treatment strategies. A quantitative proteomics assay was used to identify differential proteins in cisplatin-resistant cells. Mitochondrial topoisomerase I (TOP1MT) localization was determined using laser confocal microscopy and nucleocytoplasmic separation assay. Chromatin immunoprecipitation sequencing, dual-luciferase reporter assay, and RNA immunoprecipitation were used to identify the interaction between pseudogenes, miRNAs, and real genes. In vivo experiments verified the interaction between TOP1MT and pseudogenes on cisplatin resistance. TOP1MT was identified as a driving factor of cisplatin resistance in vitro, in vivo, and in HNSCC patients. Moreover, TOP1MT exceptionally translocated to the nucleus in cisplatin-resistant HNSCC cells in a signal peptide-dependent manner. Nuclear TOP1MT (nTOP1MT) transcriptionally regulated the mitochondrial functional pseudogene MTATP6P1, which bound to miR-137 and miR-491-5p as a competing endogenous RNA (ceRNA) and promoted the expression of MTATP6. An increase in MTATP6 enhanced mitochondrial oxidative phosphorylation (OXPHOS), which conferred cisplatin resistance in HNSCC. Our findings revealed that nTOP1MT transcriptionally activated MTAPT6P1 and increased MTATP6 expression via ceRNA, which facilitated OXPHOS and cisplatin resistance. These results provide novel insight for overcoming cisplatin resistance in HNSCC.

Sex differences in recovery from postoperative sarcopenia during adjuvant CAPOX therapy for colorectal cancer.

BACKGROUND: Women are predisposed to develop intolerance to cancer chemotherapy. Sarcopenia and chemotherapy are mutually related. Women are generally intolerable to chemotherapeutics such as 5-fluorouracil. Although adjuvant oxaliplatin-based chemotherapy, e.g. CAPOX is commonly used to treat colorectal cancer, its effects on patients in terms of sarcopenia and sex remain unknown. We investigated sex disparities in the impacts of CAPOX on body composition in this study. METHODS: We conducted a prospective study on diagnostic metrics used for sarcopenia in colorectal cancer patients receiving adjuvant CAPOX. Evaluations of the nutritional status by the Mini-Nutritional Assessment (MNA), gait speed, grip strength, skeletal muscle mass, fat mass, and bone mineral content using a body composition analyzer were performed in the first, fourth, and eighth cycles of CAPOX (first, second, and third measurements, respectively). RESULTS: Among 80 eligible patients, 61 completed four CAPOX cycles. The median differences in MNA, gait, grip strength, muscle mass, fat mass, and bone mineral content between the first and second measurements for men (n = 35) and women (n = 26) were + 10.5% and + 2.9% (p = 0.067), + 4.5% and - 2.6% (p = 0.16), + 1.8% and + 2.8% (p = 0.66), + 2.7% and + 1.3% (p = 0.021), + 4.5% and + 3.5% (p = 0.59), and + 3.3% and + 0.0% (p = 0.006), There were no sex differences in comparisons of the above metrics between the first and third measurements in 34 patients who completed eight CAPOX cycles (19 wen and 15 women). CONCLUSIONS: Early cycles of adjuvant CAPOX may have a negative impact on the postoperative recovery of several metrics for diagnosing sarcopenia in women.

Astragalus polysaccharides improve adjuvant chemotherapy-induced fatigue for patients with early breast cancer.

This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.