5-year Relapse-free Survival Research Articles

The prognostic value of boost dose in residual cervical lymph nodes in nasopharyngeal carcinoma patients after intensity-modulated radiotherapy: a retrospective study

BackgroundThe administration of a boost dose to residual cervical lymph nodes (RCLN) following radiotherapy for nasopharyngeal carcinoma (NPC) remains a controversial contentious issue. This study explored the prognosis of NPC patients with such residuals and evaluated the impact of an intensity-modulated radiotherapy (IMRT) boost on outcome.MethodsTwo thousand six hundred thirty-three NPC patients following radical IMRT were retrospectively conducted. Clinical data of 1057 NPC patients with RCLN after radical IMRT were analyzed and 199 patients received boost radiation. To balance possible confounders between groups, propensity score matching (PSM) was carried out (ratio: 1:2). Risk classification was according to postradiotherapy Epstein-Barr virus (EBV) DNA and N category.ResultsPatients with positive RCLN findings exhibited considerably lower 3-year relapse-free survival (RRFS), overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) rates compared to those with negative findings (98.0% vs. 92.8%; 93.5% vs. 85.0%; 87.0% vs. 68.4%; 92.8% vs. 81.9%, all P < 0.001). Multivariate analysis indicated that N category and postradiotherapy EBV DNA levels as high-risk factors for RCLN. In the matched cohort, the boost radiation group showed improved 3-year OS (89.4% vs. 80.0%, P < 0.001), RRFS (95.0% vs. 89.8%, P = 0.019), PFS (73.8% vs. 63.7%, P = 0.004), and DMFS (85.2% vs. 74.2%, P = 0.001). Multivariate analysis confirmed boost radiation as a critical protective prognostic factor.ConclusionFor NPC patients with RCLN, adding a boost dosage following radical IMRT results in desirable tumor control and a positive clinical outcome. Individuals with detectable EBV DNA and N2-3 category may benefit from the boost radiation.

Risk Factors and Long-Term Outcomes of Acute Kidney Disease in Hematopoietic Stem Cell Transplant—Cohort Study

Background: Acute kidney disease (AKD) is a recent definition reflecting ongoing physiopathological processes of an acute renal injury (AKI). Information on AKD in hematopoietic stem cell transplant (HSCT) is scarce and there is no available data on long-term outcomes. We aimed to determine the cumulative incidence of AKD in the first 100 days after HSCT; to identify risk factors for AKD in HSCT; and to determine the impact of AKD in 3-year overall survival and relapse-free survival in HSCT. Methods: A retrospective cohort study was conducted, considering AKD when AKI was present and the patient continued to meet the KDIGO criteria (creatinine and/or urinary output criteria) for 7 days or more. Survival analysis methods considering competing events were used for risk factors and disease-free survival, Cox proportional regression for overall survival, and stepwise regression methods for multivariable models. Results: We enrolled 422 patients. AKD incidence was 22.9% (95% CI: 19.2–27.4%). Higher body mass index (HR: 1.05, 95% CI 1.01–1.10; p = 0.034), HCT-CI score ≥ 2 (HR: 1.83, 95% CI 1.11–3.13; p = 0.027), allogeneic transplantation (HR:2.03, 95% CI 1.26–3.33; p = 0.004), higher C-reactive protein (HR:1.01, 95% CI 1.01–1.02; p &lt; 0.001), and exposure to nephrotoxic drugs (HR: 4.81, 95% CI 1.54–4.95; p = 0.038) were independently associated with AKD. AKD had a significant impact on overall survival (HR: 1.75; 95% CI 1.27–2.39; p = 0.001). Conclusion: An awareness of the risk factors for AKD allows the identification of high-risk patients, enabling the timely implementation of preventive measures to alleviate the progression and impact of the disease.

Functions and clinical significance of KCNB1 in esophageal squamous cell carcinoma.

Voltage-gated potassium channel subfamily B member 1 (KCNB1) encodes the α-subunit of the Kv2.1 channel and mediates transmembrane potassium transport. The functions and mechanisms underlying KCNB1 activation have been examined in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. Therefore, the present study investigated the involvement of KCNB1 in tumor progression and the clinicopathological significance of its expression in ESCC. Knockdown experiments using KCNB1 small interfering RNA were performed on the human ESCC cell lines, KYSE70 and TE5, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. Gene expression profiles were examined using a microarray analysis. An immunohistochemical (IHC) analysis was performed on 129 primary tumor samples from ESCC patients who underwent curative esophagectomy. Cell proliferation, G2-M phase progression, migration, and invasion were inhibited, and apoptosis was induced in KCNB1-depleted cells. Microarray results showed that KCNB1 gene expression affected Ephrin receptor signaling by suppressing EPHB1, EPHB2, and ERK1/2 gene expression. IHC results revealed a relationship between high KCNB1 expression and a poor prognosis. High KCNB1 expression was extracted as an independent prognostic factor in a multivariate analysis of 5-year relapse-free survival in ESCC patients (p = 0.0197). Cell proliferation is controlled by KCNB1 through its regulation of ERK1/2 gene expression via ephrin receptor signaling. A relationship was observed between KCNB1 and the prognosis of ESCC patients, indicating its potential as a biomarker for cancer progression and in targeted therapy for ESCC.

Risk factors for relapse based on the molecular profiling of Japanese patients with stage II colorectal cancer.

215 Background: The association between the molecular profiles and prognosis of Stage II colorectal cancer (CRC) remains unclear. This study aimed to evaluate the long-term outcomes of Stage II CRC based on the molecular profiling and to examine the risk factors for relapse. Methods: We retrospectively enrolled Japanese patients with pStage II CRC without pre- and/or postoperative adjuvant therapy and whose surgically resected specimens were evaluated using gene expression and whole exome analyses from January 2014 to December 2018. We evaluated the 5-year overall survival (OS) and relapse-free survival (RFS), and examined the risk factors for RFS. Results: We evaluated 322 patients with pStage II CRC, including 126 (39.1%) with right colon cancer, 133 (41.3%) with left colon cancer and 63 (19.6%) with rectal cancer. There were 87 patients (27.0%) with pT4, 175 (54.3%) with venous invasion, 120 (37.3%) with lymphatic invasion, and 68 (21.1%) with perineural invasion. Whole exome analyses revealed that there were 48 patients (14.9%) with MSI-High, and the presence of mutations in key genes for colorectal cancer development was as follows: APC , 245 (76.1%); TP53 , 208 (64.6%); KRAS , 134 (6.5%); PIK3CA , 64 (19.9%); FBXW7 , 27 (8.4%); and BRAF , 21 (6.5%). The 5-year OS and RFS rates were 98.0% and 90.7%, respectively. According to the consensus molecular subtype (CMS) classification based on gene expression, 76 patients (23.6%) had CMS4 and a significantly lower RFS than the other patients (5-year RFS: 83.8% vs. 92.9%, p=0.017). The independent risk factors for RFS were perineural invasion (Hazard ratio [HR] 5.316, p&lt;0.001) and CMS4 (HR 2.399, p=0.020). Conclusions: Molecular profiling of Stage II CRC to assess the risk factors for relapse may contribute to the indication and drug selection for postoperative adjuvant chemotherapy and lead to personalized treatment to improve prognosis.

Therapeutic value of para-aortic lymph node dissection in gastric cancer with extensive lymph node metastasis: Integrated analysis of three phase II trials (JCOG2212A).

419 Background: Gastric cancer (GC) sometimes forms metastatic bulky nodes around celiac artery or its branches (Bulky N), or metastasizes to para-aortic node (PAN) without any other distant metastasis. These severe nodal metastases are seldom cured by surgery alone. Japan Clinical Oncology Group (JCOG) defined these tumors as an extensive lymph node metastasis (ELM), and has developed multidisciplinary treatment through 3 phase II trials (JCOG0001, 0405, and 1002). JCOG0405 and 1002 reported the efficacy of D2 gastrectomy and PAN dissection (PAND) after neoadjuvant chemotherapy for GC with ELM with favorable survival outcomes. However, it remains unclear whether PAND truly contributed to the survival. The aim of this study was to clarify an optimal lymph node dissection area for GC with ELM. Methods: Therapeutic value index (TI) was investigated using an integrated dataset of JCOG0001, 0405, and 1002. Irinotecan and cisplatin, S-1 and cisplatin, or docetaxel, cisplatin and S-1 were used as neoadjuvant chemotherapy in JCOG0001, 0405, or 1002, respectively. Patients were classified into Bulky N group (only bulky N without PAN) and PAN group (PAN regardless of bulky N). TI was calculated by the following formula: proportion of metastasis (%) × 5-year relapse-free survival (5y-RFS, %) of patients with metastasis in the respective lymph node area / 100. Subgroup analysis by pathological response was also examined using the Japanese Classification of Gastric Carcinoma (JCGC) criteria. Grade ≥ 2a in JCGC criteria was defined as major pathological response (MPR). Results: A total of 122 patients were analyzed (Bulky N group: 68, PAN group: 54). Proportion of metastasis in peri-gastric (PG), supra-pancreatic (SP), and PAN areas were 80.9%, 54.4%, and 15.2% in Bulky N group, and 79.6%, 51.9%, and 44.4% in PAN group, respectively. 5y-RFS of patients with metastasis in PG, SP, and PAN areas were 38.2%, 29.7%, and 30% in Bulky N group and 23.3%, 7.1%, and 4.2% in PAN group, respectively. 30.9% of Bulky N group and 27.8% of PAN group showed MPR.TIs in each lymph node area are shown in the table. Conclusions: TI of PAN was extremely low in PAN group, especially in recent 2 trials (JCOG0405 and 1002) and when neoadjuvant chemotherapy was effective. These results suggest that advances in chemotherapy may make PAND unnecessary for GC with PAN metastasis in the future. Therapeutic value index in each lymph node area. PG area SP area PAN area Population N Bulky N group PAN group Bulky N group PAN group Bulky N group PAN group Overall 122 30.9 18.5 15.0 3.7 5.6 1.9 JCOG0001 36 25.0 12.5 18.2 12.5 4.5 6.3 JCOG0405 42 40.9 25.0 15.4 0.0 3.8 0.0 JCOG1002 44 26.9 16.7 16.2 0.0 4.5 0.0 MPR 36 19.0 33.3 4.8 0.0 4.8 0.0 PG, peri-gastric; SP, supra-pancreatic; PAN, para-aortic node; MPR, major pathological response.

Socioeconomic characteristics and relapse-free and overall survival from childhood cancer - a nationwide study based on data from the Danish Childhood Cancer Registry.

Over the past decades, childhood cancer survival has increased substantially in Europe, including Denmark. However, families with fewer social resources may have benefitted less from these improvements. In this nationwide register-based study, we assessed associations between parental socioeconomic position (SEP) and 5-year relapse-free survival (RFS) and overall survival (OS) in childhood cancer patients. All children aged <16 years diagnosed with cancer in Denmark between 1998 and 2017 were identified in the Danish Childhood Cancer Registry (N = 3245). Parents, with whom the children resided, were identified, and data on the parents' education, cohabitation status, affiliation to work market, country of origin, and vital status of the children were obtained through individual-level linkage across Danish nationwide registries. Cox proportional hazards models were used to estimate the association between SEP indicators and 5-year RFS and OS. Tendencies towards lower 5-year RFS and OS were observed among children whose parents were unemployed/not in workforce (RFS: HR [hazard ratio] = 1.14, 95% CI [confidence interval]: 0.90-1.45, OS: HR = 1.28, 95% CI: 0.95-1.71) or from non-Western countries (RFS: HR = 1.21 95% CI: 0.96-1.52, OS: HR = 1.44, 95% CI: 1.09-1.90). Results by diagnostic groups revealed particularly low OS for children with non-central nervous system tumors whose parents were from non-Western countries (HR = 1.92, 95% CI: 1.24-2.97). Targeted strategies are needed to promote social equity and ensure optimal diagnosis, care, and management of childhood cancer across social groups.

Short- and Long-term Outcomes of One-stage Radical Resection and Anastomosis without Preoperative Decompression and Diverting Stoma between Incomplete Obstructive and Non-obstructive Left-sided Colorectal Cancer: A Retrospective Observational Study

This study aimed to evaluate the safety and long-term outcomes of a one-stage resection and anastomosis approach without preoperative decompression in patients with left-sided incomplete obstructive colorectal cancer. We conducted a retrospective analysis of 571 patients diagnosed with pT3-4NanyM0 left-sided colorectal cancer who underwent radical resection and primary anastomosis without preoperative decompression or a diverting stoma from April 2012 to December 2019. Of these, 97 (17%) patients presented with incomplete obstruction, while 474 (83%) had no obstruction. Incomplete obstruction was characterized by the inability of a small-caliber endoscope to pass through the tumor without necessitating emergency surgery or decompression due to bowel obstruction. We compared perioperative short-term outcomes, as well as the 5-year overall survival rate and the 5-year relapse-free survival rate between the two groups. Patients in the incomplete obstruction group experienced significantly longer median intervals between admission and surgery (6 vs. 2 days, P<0.001), higher complication rates (25.8% vs. 15%, P=0.016), and longer median postoperative hospital stays (10 vs. 9 days, P=0.002). However, the rates of anastomotic leakage (2.1% vs. 2.3%, P=1), the 5-year overall survival (91.5% vs. 93.7%, P=0.436), and the 5-year relapse-free survival (80.2% vs. 85.6%, P=0.195) were comparable between the groups. The outcomes regarding anastomotic leakage and long-term survival for one-stage resection and anastomosis without preoperative decompression in cases of incomplete obstructive colorectal cancer are promising. This management strategy appears feasible and safe with appropriate preoperative bowel preparation.

Digital Profiling of Immune Biomarkers in Breast Cancer: Relation to Anthracycline Benefit.

Assessment of the tumor immune microenvironment can be used as a prognostic tool for improved survival and as a predictive biomarker for treatment benefit, particularly from immune modulating treatments including cytotoxic chemotherapy. Using Digital Spatial Profiling (DSP), we studied the tumor immune microenvironment of 522 breast cancer cases by quantifying 35 immune biomarkers on tissue microarrays from the MA.5 phase III clinical trial. In this trial, node-positive breast cancer patients were randomized to receive either a non-anthracycline chemotherapy (CMF) or anthracycline-containing cytotoxic chemotherapy (CEF). Donor block hematoxylin and eosin (H&E)-stained sections were scored for the level of stromal tumor infiltrating lymphocytes (sTILs), according to the international guidelines. We hypothesized that patients with higher levels of tumor immune infiltration, assessed by either DSP or H&E staining, would benefit from CEF (relative to CMF) more than patients with lower immune infiltration. Unsupervised hierarchical clustering of digitally scored biomarkers revealed two patient clusters: immune infiltrated vs. ignored. Following a pre-specified statistical plan crafted to meet ReMARK guidelines, we found that the DSP-derived Immune Cluster assignment did not predict an improved 10-year relapse-free survival for patients receiving CEF compared to CMF. However, a secondary hypothesis revealed a significant predictive value for H&E-sTILs assessed on full-faced sections for CEF benefit over CMF in the entire cohort and the HER2-enriched subset. As exploratory analyses, supervised clustering of DSP scored biomarkers suggested that low levels of TIM-3 and high levels of HLA-DR and PD-L1 are associated with sensitivity to CEF. Although novel high-plex techniques provide a detailed insight into the tumor microenvironment, conventional H&E staining remains a powerful tool that can be applied onto full-faced sections to assess the value of immune microenvironment, particularly sTILs, in predicting benefits from immunogenic chemotherapies.

Superior Regional Control and Laryngeal Function Preservation With Radiotherapy Versus Partial Laryngectomy: A Propensity Score-Matched Analysis of562Early Glottic Cancer Patients.

We aimed to compare the outcomes of patients with T1-T2N0M0 glottic squamous cell carcinoma who underwent either partial laryngectomy (PL) or radiotherapy (RT). A retrospective analysis of 562 patients treated with RT (n = 151) or PL (n = 411) was conducted. The Kaplan-Meier method was used to estimate outcomes. The risk factors were identified using univariate and multivariate Cox regression analyses. Propensity score matching (PSM) was used to adjust for baseline variations. Post-PSM, the 5-year overall survival (89.4% vs. 88.4%, p = 0.879), 5-year cancer-specific survival (91.9% vs. 90.1%, p = 0.554), and 5-year local relapse-free survival (87.2% vs. 89.3%, p = 0.487) rates did not differ significantly between the two groups. However, the 5-year regional relapse-free survival rate was significantly higher in the RT group than that in the PL group (99.3% vs. 93.3%, p = 0.009). Recurrence was most likely to occur in the lymph nodes at levels II and III. Supraglottic engagement has emerged as an independent prognostic factor for regional relapse in T2 stage diagnosed PL. The RT group demonstrated significantly superior speech function (mean: 6.065) compared to the PL group (mean: 10.650, p < 0.0001). RT yielded survival rates, local control, and laryngeal preservation comparable to PL. RT is associated with a higher regional control rate in T2 patients. Supraglottic involvement is an independent risk factor for regional relapse in patients with T2 disease after PL. The RT group exhibited extremely low complication rates and significantly improved speech function.

Post-transplant TKIs for Ph+ ALL: practices to date and clinical significance.

Post-transplant tyrosine kinase inhibitors (TKIs) show promise in preventing relapse after allogeneic hematopoietic cell transplantation (allo-HCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, their real-world use and efficacy remain unclear. A comprehensive study across seven centers included Ph+ALL patients who underwent allo-HCT between 2002 and 2022. Post-transplant TKIs were administered in 28% of patients (49 of 173 transplanted in complete remission): 7% as prophylaxis during complete molecular remission (CMR), and 21% in response to measurable residual disease (MRD) positivity. Median first post-transplant TKI duration was 13.7 months for the prophylactic group and 4.0 months for the MRD-triggered group. Prophylactic TKIs appear particularly beneficial for patients not in CMR at allo-HCT, showing a trend towards higher 5-year relapse-free survival (RFS) compared to those not receiving prophylactic TKIs (100% vs. 73%; P = 0.11). Significant RFS differences were observed between the prophylactic, non-TKI, and MRD-triggered groups. However, patients with white blood cell counts <15000/µl at diagnosis and no additional chromosomal abnormalities-an MRD-triggered high efficacy cluster-demonstrated comparable 5-year RFS regardless of TKI strategy (100% vs. 85% vs. 80%; P = 0.87). This cluster highlights the potential effectiveness of MRD-triggered TKI administration in select low-risk patients, suggesting tailored TKI strategies based on risk factors.

Clinical features and prognostic nomogram for therapy-related acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

Therapy-related acute myeloid leukemia (t-AML), which develops after cytotoxic therapy, has a poorer prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure, its efficacy varies among patients. In this retrospective study, we analyzed 154 patients with t-AML who underwent hematopoietic stem cell transplantation (HSCT) at our institution to determine their clinical characteristics and develop a prognostic nomogram. The median ages at t-AML diagnosis prior disease diagnosis was 42 and 39 years, respectively. Multivariate analysis identified key prognostic indicators: leukocyte count at AML diagnosis ≥ 7 × 10ˆ9/L, genetic abnormalities before HSCT, platelet engraftment ≥ 28 days, age at prior disease ≥ 45 years, and relapse of prior disease. We developed a prognostic nomogram for LGPAR by categorizing patients into low, medium, and high-risk groups. The 3-year and 5-year overall survival (OS) rates for these groups were 92.6%, 84.4%, 14%, and 92.6%, 76.6%, and 7%, respectively. The 3-year and 5-year relapse-free survival (RFS) rates were 80%, 75.9%, 10.7% and 80%, 72.6%, and 10.7% for the respective risk groups. The 3-year and 5-year non-relapse mortality (NRM) rates were 0%, 5.6%, 63.3% and 0%, 9.3%, and 63.3% for these groups, respectively. This novel prognostic nomogram culminates in the development of a clinical decision-support tool for patients with t-AML undergoing allo-HSCT.

Single or Double Induction With 7 + 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia.

To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m2 with 90 mg/m2 daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction. Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m2 daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle. Eight hundred and sixty-four patients with a median age of 52 years were randomly assigned. After a preplanned interim analysis showing no significant difference in response between 60 and 90 mg/m2, all consecutive patients received 60 mg/m2 daunorubicin once daily. The proportion of good early responders was 44% versus 48% (P = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction (P = .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m2 once daily was 54% versus 50% (P = .561), and the 3-year overall survival (OS) was 65% versus 58% (P = .242). Among 389 good responders, CRc rates at the end of induction were 87% after single induction and 85% after double induction. The 3-year RFS was 51% versus 60% (hazard ratio [HR], 1.3; P = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P = .937). The use of 90 mg/m2 daunorubicin once daily in the context of classical 7 + 3 induction does not significantly improve early response and does not lead to higher remission rates or longer survival than 60 mg/m2 once daily. In patients with a good early response after first induction, a second induction has only a limited impact on RFS and does not result in an OS benefit.

Efficacy of Neoadjuvant Hypofractionated Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer: A Single-Center Retrospective Analysis.

Background/Objectives: The application of long-course chemoradiotherapy (LCRT) in elderly patients with locally advanced rectal cancer (LARC) can be challenging due to increased risks of complications associated with comorbidities and reduced functional status. This study aimed to assess the efficacy of neoadjuvant hypofractionated chemoradiotherapy (HCRT) in elderly patients with mid-to-low LARC. Methods: We performed a retrospective review of patients diagnosed with LARC from January 2013 to December 2020 and included those aged 70 years or older. Patients were categorized into three groups based on their treatment strategies: neoadjuvant HCRT (33 or 35 Gy in 10 fractions), neoadjuvant LCRT, and upfront surgery. Comparative analyses were performed on clinicopathological characteristics, short-term outcomes, and long-term survival outcomes among these groups. Results: Among the 296 patients included, 30 (10.1%) received HCRT, 195 (65.9%) underwent standard LCRT, and 71 (24.0%) underwent upfront surgery. The baseline characteristics showed that the HCRT group had a higher American Society of Anesthesiologists (ASA) score (ASA score 3 or 4, HCRT 43.3% vs. LCRT 16.9% vs. upfront surgery 15.5%, p = 0.002). The HCRT group showed a significantly lower incidence of radiotherapy-related complications than the LCRT group (16.7% vs. 48.7%, p = 0.001). However, the rate of pathological complete response was significantly lower in the HCRT group (10.0% vs. 15.4%, p = 0.002). The 3-year relapse-free survival (83.0% vs. 77.2% vs. 83.2%; p = 0.411), 3-year local recurrence-free survival (93.1% vs. 93.2% vs. 93.5%; p = 0.464), and 5-year overall survival (65.1% vs. 67.0% vs. 67.7%; p = 0.682) were not significantly different between the three groups. Multivariate analysis also showed that the treatment strategy was not associated with survival outcomes. Conclusions: Neoadjuvant HCRT demonstrated reduced radiotherapy-related complications and acceptable long-term oncologic outcomes. Therefore, neoadjuvant HCRT may be considered as a viable alternative for elderly patients with LARC.

Prognostic value of HER2 2+ expression in patients with TNBC receiving adjuvant capecitabine.

In triple-negative breast cancer (TNBC) patients receiving adjuvant capecitabine, the impact of HER2 expression on survival outcomes is unclear. Between June 2017 and December 2023, 112 patients with TNBC who received adjuvant capecitabine due to residual masses after neoadjuvant chemotherapy (NACT) in three hospitals were identified. HER2 is analyzed through immunohistochemistry (IHC) and/or in situ hybridization in the core biopsy and/or post-surgical histopathologies. Relapse-free survival (RFS) and overall survival (OS), according to HER2 expression (0, 1 + , 2 +) status, were calculated (Kaplan-Meier method). Seventy-eight (69.6%) patients had HER2 zero, 20 (17.9%) patients had HER2 + 1, and 14 (12.5%) patients had HER2 + 2/ISH- BC. The 5-year OS was 62.6%, and the 5-year RFS was 55.8%. HER2 2 + expression was associated with worse OS (27.5 vs. 84.5months; HR 4.82, 95% CI 2.15-10.80, p < 0.001) and worse RFS (11.90months vs. not reached; HR 4.30, 95% CI 2.06-8.99, p < 0.001) compared with HER2 0/1 + expression. The 5-year OS rates were 32.7% and 72.1%, and the 5-year RFS rates were 30.6% and 64.7% in the HER2 2 + and HER2 0/1 + groups, respectively. No statistically significant differences were detected in clinicopathologic features or pathologic responses to NACT according to the HER2 expression level. Despite the use of the adjuvant capecitabine in HER2 2 + TNBC patients, these poor results will pave the way for further investigations of anti-HER2 therapeutic agents in adjuvant treatment.

The efficacy of adjuvant chemotherapy for curative resected biliary tract cancers: a systematic review and network meta-analysis of randomized clinical trials.

Despite complete resection, recurrence rate of biliary duct cancer (BTC) remains high, leading to poor prognosis. Postoperative adjuvant chemotherapy (ACT) following radical resection may substantially reduce the recurrence risk by eradicating micrometastatic lesions. However, the benefits of postoperative ACT and the optimal ACT strategy are still unclear for BTC. The objectives of this study are to evaluate the prognostic value of ACT and compare the effectiveness of different ACTs among BTC patients after curative resection. A comprehensive literature search was conducted across PubMed, Cochrane Library, Web of Science and EMBASE database to identify randomized controlled trials (RCTs) comparing the benefits of ACT versus no intervention or other ACTs in BTC patients after curative resection. A random-effects network meta-analysis was performed to compare overall survival (OS) and relapse-free survival (RFS). The quality of evidence was rated using the GRADE-framework. Eight RCTs comprising 1803 patients were included in the meta-analysis. ACT was associated with significant improvements in 5-year all-cause mortality (4 RCTs, HR 0.93; 95%CI 0.87-1.00, marginally significant; low-certainty evidence), RFS (5 RCTs, HR 0.87; 95%CI 0.78-0.98; moderate-certainty evidence) and OS (7 studies, HR 0.85; 95%CI 0.75-0.96; low-certainty evidence) compared with observation. ACT had significantly better survival benefits on patients with negative margin(R0), lymph node positive (N+) and TNM-stage I/II (P<0.05). Further network meta-analysis demonstrated fluorouracil-based ACT was significantly inferior to gemcitabine-based ACT (HR 1.20, 95%CI 1.10-1.25) in improving RFS. However, both were superior to observation (P<0.05). No statistical difference in OS was observed between gemcitabine-based and fluorouracil-based chemotherapy (HR 1.00, 95%CI 0.86-1.20). In subgroup analysis, fluorouracil-based ACT but not gemcitabine-based ACT achieved significantly better OS benefits on patients with N+ (HR 0.67; 95%CI 0.52-0.86) and R0 (HR 0.69; 95%CI 0.54-0.88). Compared with observation, ACT should be routinely recommended to improve survival outcomes in BTC patients after curative resection, especially for those with R0, N+and TNM stage I/II. Gemcitabine-based ACT performed better than other chemotherapies on improving RFS. This network meta-analysis provides precise information for determining the best adjuvant treatment for resected BTC. Further thorough and high quality RCTs are needed.

Acute Promyelocytic Leukemia Asian Consortium study of arsenic trioxide in newly-diagnosed patients: impact and outcome.

The Acute Promyelocytic Leukemia Asian Consortium analyzed a contemporaneous cohort of newly-diagnosed APL patients treated with and without frontline arsenic trioxide (ATO) in six centers. The objectives were to define the impact of ATO on early deaths and relapses, and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 (range: 18.1-91.8) years (low/intermediate risk, N=448; high-risk, N=199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (N=436); ATRA/intravenous-ATO/chemotherapy (ATRA/i.v.-ATO; N=61); and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; N=150). The ATRA/chemotherapy group, compared with the ATO-containing (ATRA/i.v.-ATO and oral-AAA) groups, had significantly more frequent early deaths within 60 days (8.3% versus 3.3%; P=0.05); inferior 60-day survival (91.7% versus 98.4%/96%; P<0.001); inferior 5-year relapse-free survival (RFS) (76.9% versus 92.8%/97.8%; P<0.001) and inferior 5-year overall survival (OS) (84.6% versus 91.4%/92.3%; P=0.03). Addition of oral-ATO maintenance could partly mitigate the inferior 5-year RFS resulting from omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance versus ATRA/chemotherapy/ATO maintenance versus ATRA/i.v.-ATO versus oral-AAA: 71.1% versus 87.9% versus 92.8% versus 97.8%, P<0.001). The favorable survival impacts of ATO were observed in both low/intermediate-risk and high-risk patients, so that conventional risks (high leucocyte and low platelet counts) were overcome. Therefore, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. Its benefits were most obvious in frontline treatment, but were still observed during maintenance. (ClinicalTrials.gov Identifier: NCT04251754).

Long-term outcomes of S-1 and oxaliplatin neoadjuvant chemotherapy with total mesorectal excision and lateral lymph node dissection for rectal cancer

PurposeChemoradiotherapy (CRT) for rectal cancer is limited by its harmful side effects and its insufficient benefit on lateral lymph node metastases. The purpose of this study was to evaluate the long-term outcomes of S-1 and oxaliplatin with total mesorectal excision (TME) and lateral lymph node dissection (LLND) without radiation for rectal cancer.MethodsThe inclusion criteria were patients with stage II or III rectal cancer located within 10 cm from the anal verge. Fifty-two patients who underwent neoadjuvant chemotherapy (NAC) followed by TME and LLND were evaluated. The primary endpoint was the 3-year local recurrence. The secondary endpoints were the 3-year rates of relapse-free survival and overall survival. Expected post-NAC and surgical outcomes were prospectively analyzed.ResultsThe overall recurrence rate was 15.4%, with eight patients developing distant recurrences. The local recurrence rate was 7.7% (n = 4). Among the 4 patients with local recurrence, 3 (5.8%) patients had central pelvis recurrence, and 1 (1.9%) patient had lateral pelvic recurrence. The 3-year survival rate was 98.1%, and the 3-year relapse-free survival rate was 84.6%. The risk factors for local recurrence were mucinous carcinoma (p = 0.016) and a positive resection margin (p = 0.009). Pathological mesorectal lymph node metastasis and local recurrence were independent risk factors for poor survival.ConclusionsAlthough preoperative chemotherapy and TME with LLND are sufficient to control local recurrence, some cases will require more aggressive chemotherapy with radiation therapy.

Long-Term Outcomes of Reduced-Toxicity Conditioning Using 8-Gray Total Body Irradiation, Fludarabine, and Cyclophosphamide in Children, Adolescents, and Young Adults With Hematological Malignancies.

Recent studies have indicated that total body irradiation (TBI)-based reduced-toxicity conditioning (RTC) may be a potential treatment modality, especially in adults with leukemia. However, its efficacy and safety in children with hematological malignancies remain unclear. To investigate the long-term outcomes and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) using an 8-Gray (Gy) TBI/fludarabine (FLU)/cyclophosphamide (CY) RTC in children with hematological malignancies. We included 66 consecutive patients with leukemia, lymphoma, or myelodysplastic syndrome in this retrospective cohort study. Participants were < 25years old and received an 8-Gy TBI/FLU/CY RTC regimen followed by the first allo-HSCT at Shinshu University Hospital between March 2004 and March 2021. The 5-year overall and relapse-free survival probabilities were 88.2% and 76.5%, respectively, in the lymphoid malignancy group. The myeloid malignancy group had probabilities of 72.4% and 58.6%, respectively. The 5-year cumulative incidences of relapse and non-relapse mortality were 20.6% and 2.9%, respectively, in the lymphoid malignancy group. These incidences were 37.9% and 3.4%, respectively, in the myeloid malignancy group. All patients had engraftment without early relapse and none developed grade 5 regimen-related toxicity within 28days after allo-HSCT. Nonetheless, two patients had congenital abnormalities caused by chromosomal aberrations and died without relapse. 8-Gy TBI/FLU/CY RTC was safe in children with hematological malignancies, regardless of the donor source. However, safety concerns were noted in cases of chromosomal aberration-induced congenital abnormalities. Additionally, patients in the lymphoid and myeloid malignancy groups had favorable prognoses.

Characteristics, treatment patterns and survival of patients with high-risk early hormone receptor-positive breast cancer in French real-world settings: an exploratory study of the CANTO cohort

Patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (HR+ BC) with unfavorable features have an increased risk of relapse and are currently candidate for additional treatment strategies. We evaluated the real-world clinicopathological characteristics, treatment patterns and survival outcomes of these patients within the CANcer TOxicities study (CANTO, NCT01993498). This is a retrospective analysis of the prospective data collected within CANTO between 2012 and 2022. Patients with high-risk HR+ BC were defined either by the identification of at least four positive axillary lymph nodes (LNs) or one to three positive axillary LNs with a tumor size ≥5 cm or histologic grade 3 (cohort 1). The definition 1-3 positive LNs with Ki-67 ≥20% was also considered (cohort 2). The Kaplan-Meier method was used for survival analysis. Patients with high-risk HR+ BC represented 15.0%-19.6% of HR+ BC (cohort 1 and 2, respectively) in the CANTO cohort. Of the 1266 patients in cohort 1, 617 patients (49.0%) had ≥4 LNs, 327 (26.0%) had tumor ≥5 cm and 727 (57.6%) had grade III tumors. 79.9% had a favorable Charlson comorbidity score and 88.1% stage II/IIIA. Patients with ≥10 LNs accounted for 11.8%. (Neo)adjuvant chemotherapy was administered in 94.2%. Endocrine therapy was prescribed in 97.3%, mostly with aromatase inhibitors and discontinued in 34.3%, mainly for adverse events. Patients enrolled at least 6 years before data extraction had a 5-year invasive disease-free survival and 5-year distant relapse-free survival of 79.9% [95% confidence interval (CI) 77.2% to 82.4%] and 83.5% (95% CI 80.9% to 85.7%), respectively. This real-world study confirms that patients with HR+ BC and unfavorable clinicopathological features are at risk of relapse early in their adjuvant treatment trajectory, despite (neo)adjuvant chemotherapy. It is imperative to implement innovative treatment approaches for high-risk patients, ideally adding them as early as possible to the adjuvant treatment.

FLT3 inhibitors and hematopoietic cell transplantation prolong survival in patients with FLT3-ITD-positive AML.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting. We retrospectively analyzed 139 patients with FLT3-ITD-positive AML between 2012 and 2021. The median age was 63 years. In the propensity score-matched cohort, FLT3 inhibitors improved overall survival (OS) compared with patients treated without FLT3 inhibitors (3-year OS: 33.7% vs. 25.8%, p = 0.021). Patients who underwent HCT had superior outcomes to those without HCT (3-year OS: 45.3% vs. 2.2%, p < 0.0001). The combination of FLT3 inhibitors and HCT resulted in the highest OS and relapse-free survival (RFS) rates (3-year OS: 62.4%; 3-year RFS: 44.4%). Disease status before transplantation did not predict the prognosis, but use of FLT3 inhibitors increased survival in patients without complete remission before HCT. These results demonstrate the clinical impact of FLT3 inhibitors on survival outcomes in patients with FLT3-ITD-positive AML, particularly when combined with HCT. FLT3 inhibitors can improve the prognosis of AML with FLT3 mutations, especially in patients who undergo HCT.