Clinical impact of delaying initiation of adjuvant chemotherapy in patients with early triple negative breast cancer.

PURPOSE: The optimal time to initiation of adjuvant chemotherapy (TTAC) for triple negative breast cancer (TNBC) patients is unclear. This study evaluates the association between TTAC and survival in TNBC patients. METHODS: We conducted a retrospective study using data from a cohort of TNBC patients diagnosed between January 1, 2010 to December 31, 2018, registered in the Tumor Centre Regensburg was conducted. Data included demographics, pathology, treatment, recurrence and survival. TTAC was defined as days from primary surgery to first dose of adjuvant chemotherapy. The Kaplan-Meier method was used to evaluate impact of TTAC on overall survival (OS) and 5-year OS. RESULTS: A total of 245 TNBC patients treated with adjuvant chemotherapy and valid TTAC data were included. Median TTAC was 29 days. The group receiving systemic therapy within 22 to 28 days after surgery had the most favorable outcome, with median OS of 10.2 years. Groups receiving systemic therapy between 29-35 days, 36-42 days, and more than 6 weeks after surgery had significantly decreased median survival, with median OS of 8.3 years, 7.8 years, and 6.9 years, respectively. Patients receiving therapy between 22-28 days had significantly better survival compared to those receiving therapy between 29-35 days (p = 0.043), and patients receiving therapy after 22-28 days also demonstrated significantly better survival compared to those receiving therapy after more than 43 days (p = 0.033). CONCLUSION: Timing of adjuvant systemic therapy can influence OS in TNBC patients. Efforts should be made to avoid unnecessary delays in administering chemotherapy to ensure timely initiation of systemic therapy and optimize patient outcomes.

Neutral Adducts of Molybdenum Hexafluoride: Structure and Bonding in MoF6(NC5H5) and MoF6(NC5H5)2.

The first Lewis acid base adducts of MoF6 and an organic base have been synthesized, i. e., MoF6(NC5H5) and MoF6(NC5H5)2. These adducts are structurally characterized with X-ray crystallography, showing that both adducts adopt capped trigonal prismatic structures. The MoF6(NC5H5) and MoF6(NC5H5)2 adducts are fluxional on the NMR time scale at room temperature. Two different fluorine environments could be resolved by 19F NMR spectroscopy at -80 °C for the 1 : 2 adduct, MoF6(NC5H5)2, whereas MoF6(NC5H5) remains fluxional at that temperature. Density functional theory (DFT) calculations aide the assignment of the infrared and Raman spectra. Natural Bond Order and Molecular Electrostatic Potential analyses elucidate the structures and properties of the MoF6 pyridine adducts. Regions of significantly higher molecular electrostatic potential, i. e., σ-holes, in trigonal prismatic compared to octahedral MoF6 rationalize the capped trigonal prismatic geometry of the adducts. Whereas MoF6(NC5H5) is stable at room temperature under exclusion of moisture, MoF6(NC5H5)2 decomposes at 60 °C in pyridine solvent, and the solid slowly decomposes at room temperature after 24 h.

Fluoride-Ion Donor Properties of AsF5.

Arsenic pentafluoride undergoes ligand-induced autoionization in the presence of 1,10-phenanthroline (phen) in a SO2ClF solution to form the donor-stabilized [AsF4(phen)][AsF6] salt. Reacting [AsF4(phen)][AsF6] with the strong Lewis acid SbF5·SO2 yields the mixed arsenic-antimony salt [AsF4(phen)][Sb2F11]. These salts are the first examples of crystallographically characterized donor-stabilized [AsF4]+ cations. The analogous reaction of AsF5 and 2,2'-bipyridine (bipy) does not result in autoionization but leads to the formation of the neutral 2:1 adduct (AsF5)2·bipy. The gas-phase and solution fluoride-ion affinities of [AsF4]+ and [SbF4]+ were calculated, revealing them to be incredibly strong Lewis acids. Density functional theory calculations and natural bond orbital analysis show that significant electron-pair donation from phen to the As center in [AsF4(phen)]+ occurs and quenches the extreme electrophilicity of the [AsF4]+ cation.

Transanal total mesorectal excision: short- and long-term results of four certified colorectal cancer centers in Germany.

BACKGROUND: Transanal total mesorectal excision (TaTME), a novel approach for treating low rectal cancer, holds promise. However, concerns exist in certain countries about their oncologic safety due to less-than-optimal outcomes on global studies. This research seeks to evaluate the long-term oncologic outcomes focusing on local recurrence rate and overall survival after TaTME surgery in Germany. PATIENTS AND METHODS: This study analyzed data from patients who underwent elective TaTME surgery between 2014 and 2021 in four certified colorectal cancer centers in Germany. Primary endpoints were 3-year local recurrence rate and local recurrence-free survival (LRFS). Secondary outcomes encompassed overall survival (OS), operative time, completeness of local tumor resection, lymph node resection, and postoperative complications. RESULTS: A total of 378 patients were analyzed (mean age 61.6 years; 272 males, 72%). After a median follow-up period of 2.5 years, 326 patients with UICC-stages I-III and tumor operability included in survival analyses. Local recurrence was observed in 8 individuals, leading to a 3-year cumulative local recurrence rate of 2.2% and a 3-year LRFS rate of 88.1%. The 3-year OS rate stood at 88.9%. Within 30 days after surgery, anastomotic leakage occurred in 19 cases (5%), whereas a presacral abscess was present in 12 patients (3.2%). CONCLUSION: TaTME proves effective in addressing the anatomical and technical challenges of low rectal surgery and is associated with pleasing short- and long-term results. However, its safe integration into surgical routine necessitates sufficient knowledge and a previously completed training program.

Treatment in certified cancer centers is related to better survival in patients with colon and rectal cancer: evidence from a large German cohort study.

BACKGROUND: Certified cancer centers aim to ensure high-quality care by establishing structural and procedural standards according to evidence-based guidelines. Despite the high clinical and health policy relevance, evidence from a nation-wide study for the effectiveness of care for colorectal cancer in certified centers vs. other hospitals in Germany is still missing. METHODS: In a retrospective cohort study covering the years 2009-2017, we analyzed patient data using demographic information, diagnoses, and treatments from a nationwide statutory health insurance enriched with information on certification. We investigated whether patients with incident colon or rectal cancer did benefit from primary therapy in a certified cancer center. We used relative survival analysis taking into account mortality data of the German population and adjustment for patient and hospital characteristics via Cox regression with shared frailty for patients in hospitals with and without certification. RESULTS: The cohorts for colon and rectal cancer consisted of 109,518 and 51,417 patients, respectively, treated in a total of 1052 hospitals. 37.2% of patients with colon and 42.9% of patients with rectal cancer were treated in a certified center. Patient age, sex, comorbidities, secondary malignoma, and distant metastases were similar across groups (certified/non-certified) for both colon and rectal cancer. Relative survival analysis showed significantly better survival of patients treated in a certified center, with 68.3% (non-certified hospitals 65.8%) 5-year survival for treatment of colon cancer in certified (p < 0.001) and 65.0% (58.8%) 5-year survival in case of rectal cancer (p < 0.001), respectively. Cox regression with adjustment for relevant covariates yielded a lower hazard of death for patients treated in certified centers for both colon (HR = 0.92, 95% CI = 0.89-0.95) and rectal cancer (HR = 0.92, 95% CI = 0.88-0.95). The results remained robust in a series of sensitivity analyses. CONCLUSIONS: This large cohort study yields new important evidence that patients with colorectal cancer have a better chance of survival if treated in a certified cancer center. Certification thus provides one powerful means to improve the quality of care for colorectal cancer. To decrease the burden of disease, more patients should thus receive cancer care in a certified center.

Interaction Modes Between SF4 and Ketones; Study of Intermediates in Deoxofluorination Reactions.

Interactions between ketones and SF4 are studied for the simplest ketone, acetone, and the bulky polycyclic 2-adamantanone. Acetone forms the 1 : 2 adduct SF4 ⋅ [O=C(CH3 )2 ]2, as well as the dimeric 1 : 1 adducts [SF4 ⋅ O=C(CH3 )2 ]2 as identified by low-temperature Raman spectroscopy and, for the latter, X-ray crystallography. In both adducts, SF4 acts as a double chalcogen-bond donor to two keto groups. In contrast 2-adamantanone does not form an isolable solid adduct with SF4 ; in the presence of HF, however, it forms SF4 ⋅ O=C10 H14 O ⋅ HF, which comprises chains with weak S-O and S-FH chalcogen bonds in the crystal structure. Sulfur tetrafluoride in this compound is readily lost at -85 °C, leading to the isolation of C10 H14 O ⋅ HF at low temperature. Density functional theory (DFT) calculations aid in vibrational assignments and serve to describe the interactions of the keto group with SF4 and HF, as well as interactions between SF4 with HF. It is found that separate and combined CO-HF and CO-SF4 chalcogen bonds do not polarize the C=O group to any significant degree.

Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Primary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. METHODS: Clinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. RESULTS: The median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan-Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). CONCLUSIONS: With multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

Impact of cavity shaving on residual tumor rates in patients with primary invasive carcinoma and carcinoma in situ in breast conserving surgery.

BACKGROUND: Several international studies reported relatively high re-excision rates due to residual tumor in breast conserving surgery (BCS). Cavity shaving (CS) is a surgical strategy to reduce re-excision rates. This study aimed to investigate the effect of circumferential cavity shaving during BCS to reduce residual tumor. MATERIAL AND METHODS: A total of 591 patients with early invasive carcinoma or carcinoma in situ of the breast (ICD-10, C50 or D05) who were diagnosed between 01/01/2017 and 31/12/2019 and underwent BCS in a certified breast cancer center of the University Regensburg were analyzed regarding surgical excision methods. Patients with CS during BCS and patients with targeted re-excision in a specific direction depending on the result of intraoperative mammography or sonography during BCS were compared. The risk of pathologic residual tumor (R1) was compared between both groups by means of a multivariable binary logistic regression model to determine if there is a benefit of a certain surgical method to avoid a second intervention for re-excision. We adjusted for age, tumor size, nodal status, histologic type, surgeon, breast side, and neoadjuvant chemotherapy. RESULTS: 80 (n = 13.54%) patients had CS and 511 (n = 86.46%) had a targeted re-excision in a specific direction during BCS according to intraoperative mammography or sonography. After comparing both techniques in a multivariable regression model, there was no significant difference regarding risk of residual tumor (p = 0.738) in the total cohort. However, CS showed a tendency to be favorable regarding rates of residual tumor in patients with invasive breast cancer between 60 and 70 years (p = 0.072) and smaller T1-tumors (p = 0.057) compared to targeted intraoperative re-excision following mammographic or sonographic assessment. CONCLUSION: CS showed a tendency to reduce residual tumor compared to the standard technique of intraoperative re-excision in specific subgroups, although no statistical significance was reached. Further studies are needed to overcome potential limitations like surgeon-based bias and missing standardized definitions of CS to reduce residual tumor rates.

[Methodology and Attribution Success of a Data Linkage of Clinical Registry Data with Health Insurance Data]. / Methodik und Zuordnungserfolg eines Linkage von Daten klinischer Krebsregister mit Abrechnungsdaten gesetzlicher Krankenkassen.

BACKGROUND: The aim of the project "Effectiveness of care in oncological centres" (WiZen), funded by the innovation fund of the federal joint committee, is to investigate the effectiveness of certification in oncology. The project uses nationwide data from the statuory health insurance AOK and data from clinical cancer registries from three different federal states from 2006-2017. To combine the strengths of both data sources, these will be linked for eight different cancer entities in compliance with data protection regulations. METHODS: Data linkage was performed using indirect identifiers and validated using the health insurance's patient ID ("Krankenversichertennummer") as a direct identifier and gold standard. This enables quantification of the quality of different linkage variants. Sensitivity and specificity as well as hit accuracy and a score addressing the quality of the linkage were used as evaluation criteria. The distributions of relevant variables resulting from the linkage were validated against the original distributions in the individual datasets. RESULTS: Depending on the combination of indirect identifiers, we found a range of 22,125 to 3,092,401 linkage hits. An almost perfect linkage could be achieved by combining information on cancer type, date of birth, gender and postal code. A total of 74,586 one-to-one linkages were achieved with these characteristics. The median hit quality for the different entities was more than 98%. In addition, both the age and sex distributions and the dates of death, if any, showed a high degree of agreement. DISCUSSION AND CONCLUSION: SHI and cancer registry data can be linked with high internal and external validity at the individual level. This robust linkage enables completely new possibilities for analysis through simultaneous access to variables from both data sets ("the best of both worlds"): Information on the UICC stage that stems from the registries can now be combined, for instance, with comorbidities from the SHI data at the individual level. Due to the use of readily available variables and the high success of the linkage, our procedure constitutes a promising method for future linkage processes in health care research.

Is treatment in certified cancer centers related to better survival in patients with pancreatic cancer? Evidence from a large German cohort study.

BACKGROUND: Treatment of cancer patients in certified cancer centers, that meet specific quality standards in term of structures and procedures of medical care, is a national treatment goal in Germany. However, convincing evidence that treatment in certified cancer centers is associated with better outcomes in patients with pancreatic cancer is still missing. METHODS: We used patient-specific information (demographic characteristics, diagnoses, treatments) from German statutory health insurance data covering the period 2009-2017 and hospital characteristics from the German Standardized Quality Reports. We investigated differences in survival between patients treated in hospitals with and without pancreatic cancer center certification by the German Cancer Society (GCS) using the Kaplan-Meier estimator and Cox regression with shared frailty. RESULTS: The final sample included 45,318 patients with pancreatic cancer treated in 1,051 hospitals (96 GCS-certified, 955 not GCS-certified). 5,426 (12.0%) of the patients were treated in GCS-certified pancreatic cancer centers. Patients treated in certified and non-certified hospitals had similar distributions of age, sex, and comorbidities. Median survival was 8.0 months in GCS-certified pancreatic cancer centers and 4.4 months in non-certified hospitals. Cox regression adjusting for multiple patient and hospital characteristics yielded a significantly lower hazard of long-term, all-cause mortality in patients treated in GCS-certified pancreatic centers (Hazard ratio = 0.89; 95%-CI = 0.85-0.93). This result remained robust in multiple sensitivity analyses, including stratified estimations for subgroups of patients and hospitals. CONCLUSION: This robust observational evidence suggests that patients with pancreatic cancer benefit from treatment in a certified cancer center in terms of survival. Therefore, the certification of hospitals appears to be a powerful strategy to improve patient outcomes in pancreatic cancer care. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04334239 ).

Protective effect of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer.

OBJECTIVE: The aim of this study was to investigate the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. METHODS: In this population-based cohort study we analysed from clinical cancer registries to determine DFS of women with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB1 cervical cancer with respect to conization preceding radical hysterectomy performed between January 2010 and December 2015. RESULTS: Out of 993 datasets available for the analysis, 235 patients met the inclusion criteria of the current study. The median follow-up was 5.4 years. During the study period, 28 (11.9%) recurrences were observed. All of these occurred in patients with FIGO stage IB1. For further evaluation, patients with FIGO IB1 tumors <2 cm were further analysed and divided into two groups, based on pre-operative conization. Pre-operative conization was associated with a reduced rate of recurrence (p = 0.007), with only three (5.2%) recurrences in this group (CO) compared to 25 recurrences (21.0%) in the group without conization (NCO) preceding radical hysterectomy. DFS was estimated at 79.0% and 94.8% in NCO and CO, respectively (p = 0.008). After adjustment for other prognostic covariates, conization remained a favourable prognostic factor for DFS (HR 0.27; 95% CI 0.08-0.93, p = 0.037). Lymph node involvement was the only unfavourable factor (HR 4.38; 95% CI 1.36-14.14, p = 0.014) in the multivariable analysis. CONCLUSIONS: Pre-operative conization is associated with improved DFS in early-stage cervical cancer independently of the surgical approach.

Transanal total mesorectal excision: short- and long-term results of the first hundred cases of a certified colorectal cancer center in Germany.

BACKGROUND: Since 2010, laparoscopic transanal total mesorectal excision (TaTME) has been increasingly used for low and very low rectal cancer. It is supposed to improve visibility and access to the dissection planes in the pelvis. This study reports on short- and long-term outcomes of the first 100 consecutive patients treated with TaTME in a certified German colorectal cancer center. PATIENTS AND METHODS: Data were derived from digital patient files and official cancer registry reports for patients with TaTME tumor surgery between July 2014 and January 2020. The primary outcome was the 3-year local recurrence rate and local recurrence-free survival (LRFS). Secondary endpoints included overall survival (OAS), disease-free survival (DFS), operation time, completeness of local tumor resection, lymph node resection, and postoperative complications. The Kaplan-Meier method was employed for the survival analyses; competing risks were considered in the time-to-event analysis. RESULTS: During the observation period, the average annual operation time decreased from 272 to 178 min. Complete local tumor resection was achieved in 97% of the procedures. Major postoperative complications (Clavien-Dindo 3-4) occurred in 11% of the cases. At a median follow-up time of 2.7 years, three patients had suffered from a local recurrence. Considering competing risks, this corresponds to a 3-year cumulative incidence rate for local recurrence of 2.2% and a 3-year LRFS of 81.9%. 3-year OAS was 82.9%, and 3-year DFS was 75.7%. CONCLUSION: TaTME is associated with favorable short and long-term outcomes. Since it is technically demanding, structured training programs and more research on the topic are indispensable.

Ten-year single-center experience with treatment of primary diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

PURPOSE: This single-center study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). METHODS: Prospectively collected data from a single institution data registry was retrospectively investigated. Eighty-four patients with primary malignant peritoneal mesothelioma underwent CRS and HIPEC with cisplatin and doxorubicin either for 60 min or 90 min of duration from 2011 to 2021. The primary endpoint was overall survival. The secondary endpoint was the evaluation of prognostic factors for overall survival. The tertiary endpoint was to assess the effect of neoadjuvant chemotherapy on survival. RESULTS: The median follow-up was 5.0 years (95%-CI 4.6-5.5). The median age was 59.2 years (IQR: 47-66). Eighty-two patients (97.6%) had epithelioid tumors. The median peritoneal cancer index was 18.0 (IQR: 13-27). Sixty-six patients (78.6%) had complete or near-complete cytoreduction (CCR 0 or CCR 1). Seventy patients (83.3%) received HIPEC for 60 min and 14 patients (16.7%) received it for 90 min. Twenty-two patients (26.2%) had grade 3 to 4 complications. Acute kidney injury (AKI) stage I-III occurred in 30 (35.7%) patients. Three patients (3.6%) died perioperatively. The overall median survival was 38.4 months (95%-CI 23.6-54.3), and the 5-year survival rate was 42%. Survival was independently associated with age, female gender, and thrombocytosis. Preoperative chemotherapy did not emerge as an adverse prognostic factor. CONCLUSION: In well-selected patients with DMPM, prolonged survival is achievable with CRS and HIPEC in specialized centers.

Factors influencing treatment decision and guideline conformity in high-grade endometrial cancer patients: a population-based study.

PURPOSE: Treatment according to guidelines has been demonstrated to improve survival in a number of different cancer entities. Deviations from guidelines depend on several factors, including the patient's preferences, age and comorbidities. The aim of this study was to assess the adherence to guideline recommendations concerning surgical and adjuvant treatment in endometrial cancer. Furthermore, we sought to evaluate the reasons for non-adherence to guidelines by further examining the influence of comorbidities and age. METHODS: The influence of age, comorbidities, tumor stage and histological subtype on guideline adherence was evaluated by multivariable logistic regression in a cohort of 353 high-grade endometrial cancer patients. High-grade endometrial cancer was defined as carcinosarcoma, Type II (serous, clear cell, mixed cell carcinoma) and Type I G3 histology. RESULTS: Extensive surgical procedures, particularly systematic LNE, were less frequently applied in patients with comorbidities (p = 0.015) or higher age (p < 0.01). Guideline adherence was not affected by comorbidities (p = 0.563), but was significantly reduced with higher age (p < 0.01). In a multivariable model, higher age (p < 0.01), obesity (p = 0.011), higher FIGO Stage (p < 0.01) and histologic subtype (p < 0.01) significantly decreased OS. Surgery (p < 0.001), chemotherapy (p < 0.01) and systematic LNE (p = 0.011) were associated with higher OS. CONCLUSION: Age seems to be the strongest independent factor leading to guideline deviation. Comorbidities were associated with less aggressive treatment, but not with deviations from guidelines.

Small-area analysis on socioeconomic inequalities in cancer survival for 25 cancer sites in Germany.

Socioeconomic inequalities in cancer survival have been reported in various countries but it is uncertain to what extent they persist in countries with relatively comprehensive health insurance coverage such as Germany. We investigated the association between area-based socioeconomic deprivation on municipality level and cancer survival for 25 cancer sites in Germany. We used data from seven population-based cancer registries (covering 32 million inhabitants). Patients diagnosed in 1998 to 2014 with one of 25 most common cancer sites were included. Area-based socioeconomic deprivation was assessed using the categorized German Index of Multiple Deprivation (GIMD) on municipality level. We estimated 3-month, 1-year, 5-year and 5-year conditional on 1-year age-standardized relative survival using period approach for 2012 to 2014. Trend analyses were conducted for periods between 2003-2005 and 2012-2014. Model-based period analysis was used to calculate relative excess risks (RER) adjusted for age and stage. In total, 2 333 547 cases were included. For all cancers combined, 5-year survival rates by GIMD quintile were 61.6% in Q1 (least deprived), 61.2% in Q2, 60.4% in Q3, 59.9% in Q4 and 59.0% in Q5 (most deprived). For most cancer sites, the most deprived quintile had lower 5-year survival compared to the least deprived quintile even after adjusting for stage (all cancer sites combined, RER 1.16, 95% confidence interval 1.14-1.19). For some cancer sites, this association was stronger during short-term follow-up. Trend analyses showed improved survival from earlier to recent periods but persisting deprivation differences. The underlying reasons for these persisting survival inequalities and strategies to overcome them should be further investigated.

Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases.

BACKGROUND: The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed. PATIENTS AND METHODS: We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97 years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases. RESULTS: The median follow-up was 7.2 years, with a confidence interval (CI) of 7.1-7.3 years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80-2.85, p = 0.208) for OS and 1.12 (95% CI 0.63-1.97, p = 0.705) for RFS. CONCLUSION: Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

Stabilisation of [WV F4 ]+ by N- and P-Donor Ligands: Second-Order Jahn-Teller Effects in Octacoordinate d1 Complexes.

The first isolated examples of cationic fluoridotungsten(V) complexes are reported as octacoordinate [WF4 (L)4 ]+ (L=C5 H5 N, P(CH3 )3 ). The [WF4 (NC5 H5 )4 ]+ cation is synthesised as its [O3 SCF3 ]- salt upon reaction of WF5 (NC5 H5 )2 with [(CH3 )3 Si(NC5 H5 )][O3 SCF3 ] in excess C5 H5 N, whereas [WF4 {P(CH3 )3 }4 ]+ is accessed directly from WF6 upon reaction with (CH3 )3 SiO3 SCF3 and excess P(CH3 )3 . These salts were characterised by X-ray crystallography and Raman spectroscopy in the solid state. New geometry indices for octacoordinate complexes (τ8 and τ8 ') are introduced, allowing for the facile differentiation of trigonal-dodecahedral (TD) and square-antiprismatic (SA) geometries. This has disambiguated the SA geometries of [WF4 (L)4 ]+ and the geometries of a series of previously reported d0 and d1 MA4 B4 complexes. Computational (DFT-B3LYP) studies of [WF4 (PH3 )4 ]2+/+ and related model systems demonstrate the occurrence of a second-order Jahn-Teller (SOJT) distortion from TD in d0 complexes to SA in d1 complexes, with the degree of SOJT stabilisation being most significant in 5d complexes containing fluorido ligands and monodentate neutral donors.

Donor-Stabilised [SbF4 ]+ : SbF5 as a Fluoride-Ion Donor.

Antimony pentafluoride is a strong Lewis acid and fluoride-ion acceptor that has not previously demonstrated any discreet fluoride-ion donor properties. The first donor-stabilised [SbF4 ]+ cations were prepared from the autoionisation of SbF5 in the presence of bidentate N-donor ligands 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) as their [SbF6 ]- salts. The [SbF4 (N-N)][Sb2 F11 ] (N-N=bipy, phen) salts were synthesised by the addition of one equivalent of SbF5 ⋅SO2 to [SbF4 (N-N)][SbF6 ] in liquid SO2. The salts show remarkable stability and were characterised by Raman spectroscopy and multinuclear NMR spectroscopy. The crystal structures of [SbF4 (phen)][SbF6 ] ⋅ 3CH3 CN and [SbF4 (phen)][SbF6 ] ⋅ 2SO2 were determined, showing distorted octahedral cations. DFT calculations and NBO analyses reveal that significant degree of electron-pair donation from N to Sb stabilizes [SbF4 ]+ with the Sb-N bond strength being approximately two thirds of that of the Sb-F bonds in these cations and the cationic charge being primarily ligand-centred.

Chalcogen versus Dative Bonding in [SF3]+ Lewis Acid-Base Adducts: [SF3(NCCH3)2]+, [SF3(NC5H5)2]+, and [SF3(phen)]+ (phen = 1,10-phenanthroline).

The Lewis-acid behavior of [SF3][MF6] (M = Sb, As) salts toward mono- and bidentate nitrogen bases was explored. Reactions of [SF3][MF6] with excesses of CH3CN and C5H5N yielded [SF3(L)2]+ (L = CH3CN, C5H5N) salts, whereas the reaction of [SF3][SbF6] with equimolar 1,10-phenanthroline (phen) in CH3CN afforded [SF3(phen)][SbF6]·2CH3CN. Salts of these cations were characterized by low-temperature X-ray crystallography and Raman spectroscopy in the solid state as well as by 19F NMR spectroscopy in solution. In the solid state, the geometries of [SF3(NC5H5)2]+ and [SF3(phen)]+ are square pyramids with negligible cation-anion contacts, whereas the coordination of CH3CN and [SbF6]- to [SF3]+ in [SF3(NCCH3)2][SbF6] results in a distorted octahedral coordination sphere with a minimal perturbation of the trigonal-pyramidal SF3 moiety. 19F NMR spectroscopy revealed that [SF3(L)2]+ is fluxional in excess L at -30 °C, whereas [SF3(phen)]+ is rigid in CH2Cl2 at -40 °C. Density functional theory (DFT-B3LYP) calculations suggest that the S-N bonds in [SF3(NC5H5)2]+ and [SF3(phen)]+ possess substantial covalent character and result in a regular AX5E VSEPR geometry, whereas those in [SF3(NCCH3)2]+ are best described as S···N chalcogen-bonding interactions via σ-holes on [SF3]+, which is consistent with the crystallographic data.

Lewis Acid Behavior of MoF5 and MoOF4: Syntheses and Characterization of MoF5(NCCH3), MoF5(NC5H5)n, and MoOF4(NC5H5)n (n = 1, 2).

The Lewis acid-base adducts MoF5(NC5H5)n and MoOF4(NC5H5)n (n = 1, 2) were synthesized from the reactions of MoF5 and MoOF4 with C5H5N and structurally characterized by X-ray crystallography. Whereas the crystal structures of MoF5(NC5H5)2 and MoOF4(NC5H5)2 are isomorphous containing pentagonal-bipyramidal molecules, the fluorido-bridged, heptacoordinate [MoF5(NC5H5)]2 dimer differs starkly from monomeric, hexacoordinate MoOF4(NC5H5). For the weaker Lewis base CH3CN, only the 1:1 adduct, MoF5(NCCH3), could be isolated. All adducts were characterized by Raman spectroscopy in conjunction with vibrational frequency calculations. Multinuclear NMR spectroscopy revealed an unprecedented isomerism of MoOF4(NC5H5)2 in solution, with the pyridyl ligands occupying adjacent or nonadjacent positions in the equatorial plane of the pentagonal bipyramid. Paramagnetic MoF5(NC5H5)2 was characterized by electron paramagnetic resonance (EPR) spectroscopy as a dispersion in solid adamantane as well as in a diamagnetic host lattice of MoOF4(NC5H5)2; EPR parameters were computed using ZORA with the BPW91 functional using relativistic all-electron wave functions for Mo and simulated using EasySpin. Density functional theory calculations (B3LYP) and natural bond orbital analyses were conducted to elucidate the distinctive bonding and structural properties of all adducts reported herein and explore fundamental differences observed in the Lewis acid behavior of MoF5 and MoOF4.