Evaluation and Management of Pelvic Osteomyelitis in Stage IV Pressure Injuries: A Multidisciplinary Collaborative Approach.

Managing pelvic osteomyelitis (POM) in the setting of stage IV pressure injuries requires multidisciplinary evaluation as well as patient and caregiver engagement and is complicated by the lack of high-evidence data to guide best practices. In this review, we describe our approach to pressure injury and POM evaluation and management through multidisciplinary collaboration and highlight areas of future research that are necessary to enhance patient outcomes, reduce healthcare costs, and improve the quality of life of those affected by POM.

Circulating Tumor Cells Prediction in Hormone Receptor Positive HER2-Negative Advanced Breast Cancer: A Retrospective Analysis of the MONARCH 2 Trial.

BACKGROUND: The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials. PATIENTS AND METHODS: Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage IVindolent (pStage IVindolent, <5 predicted CTCs). Prognosis was tested in terms of progression-free-survival (PFS) and overall survival (OS) through Cox regression. RESULTS: Patients classified as predicted pStage IVaggressive and predicted pStage Stage IVindolent were, respectively, 183 (28%) and 461 (72%). After multivariable Cox regression, predicted CTCs were confirmed as independently associated with prognosis in terms of OS, together with ECOG performance status, liver involvement, bone-only disease, and treatment arm. Patients in the pStage Stage IVindolent subgroup treated with abemaciclib experienced the best prognosis both in terms of PFS and OS. The treatment effect of abemaciclib on OS was then explored through subgroup analysis, showing a consistent benefit across all subgroups. CONCLUSION: This study is the first analysis of CTCs modeling for stage IV disease stratification. These results show the need to expand biomarker profiling in combination with CTCs stratification for improved biomarker-driven drug development.

Survival among patients with untreated metastatic breast cancer: "What if I do nothing?"

PURPOSE: We sought to assess survival outcomes of patients with de novo metastatic breast cancer (dnMBC) who did not receive treatment irrespective of the reason. METHODS: Adults with dnMBC were selected from the NCDB (2010-2016) and stratified based on receipt of treatment (treated = received at least one treatment and untreated = received no treatments). Overall survival (OS) was estimated using the Kaplan-Meier method, and groups were compared. Cox proportional hazards models were used to identify factors associated with OS. RESULTS: Of the 53,240 patients with dnMBC, 92.1% received at least one treatment (treated), and 7.9% had no documented treatments, irrespective of the reason (untreated). Untreated patients were more likely to be older (median 68 y vs 61 y, p < 0.001), have higher comorbidity scores (p < 0.001), have triple-negative disease (17.8% vs 12.6%), and a higher disease burden (≥ 2 metastatic sites: 38.2% untreated vs 29.2% treated, p < 0.001). The median unadjusted OS in the untreated subgroup was 2.5 mo versus 36.4 mo in the treated subgroup (p < 0.001). After adjustment, variables associated with a worse OS in the untreated cohort included older age, higher comorbidity scores, higher tumor grade, and triple-negative (vs HR + /HER2-) subtype (all p < 0.05), while the number of metastatic sites was not associated with survival. CONCLUSIONS: Patients with dnMBC who do not receive treatment are more likely to be older, present with comorbid conditions, and have clinically aggressive disease. Similar to those who do receive treatment, survival in an untreated population is associated with select patient and disease characteristics. However, the prognosis for untreated dnMBC is dismal.

Prognostic value of the 21-Gene Breast Recurrence Score® assay for hormone receptor-positive/human epidermal growth factor 2-negative advanced breast cancer: subanalysis from Japan Breast Cancer Research Group-M07 (FUTURE trial).

PURPOSE: This study aimed to determine whether the 21-Gene Breast Recurrence Score® assay from primary breast tissue predicts the prognosis of patients with hormone receptor-positive and human epidermal growth factor 2-negative advanced breast cancers (ABCs) treated with fulvestrant monotherapy (Group A) and the addition of palbociclib combined with fulvestrant (Group B), which included those who had progression in Group A from the Japan Breast Cancer Research Group-M07 (FUTURE trial). METHODS: Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test and Cox regression analysis based on original recurrence score (RS) categories (Low: 0-17, Intermediate: 18-30, High: 31-100) by treatment groups (A and B) and types of ABCs (recurrence and de novo stage IV). RESULTS: In total, 102 patients [Low: n = 44 (43.1%), Intermediate: n = 38 (37.5%), High: n = 20 (19.6%)] in Group A, and 45 in Group B, who had progression in Group A were analyzed. The median follow-up time was 23.8 months for Group A and 8.9 months for Group B. Multivariate analysis in Group A showed that low-risk [hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.04-0.53, P = 0.003] and intermediate-risk (HR 0.22, 95% CI 0.06-0.78) with de novo stage IV breast cancer were significantly associated with better prognosis compared to high-risk. However, no significant difference was observed among patients with recurrence. No prognostic significance was observed in Group B. CONCLUSION: We found a distinct prognostic value of the 21-Gene Breast Recurrence Score® assay by the types of ABCs and a poor prognostic value of the high RS for patients with de novo stage IV BC treated with fulvestrant monotherapy. Further validations of these findings are required.

Morbidity and mortality in patients with stage IV pancreatic adenocarcinoma and acute cholangitis: Outcomes and risk prognostication.

BACKGROUND: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC. METHODS: We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality. RESULTS: One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0-5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3-92.5), 37 % (95 % CI, 29.3-46.6 %) and 18.9 % (95 % CI, 13.1-27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC. CONCLUSIONS: AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.

Survival outcomes of primary vs interval cytoreductive surgery for International Federation of Gynecology and Obstetrics stage IV ovarian cancer: a nationwide population-based target trial emulation.

BACKGROUND: The effect of primary cytoreductive surgery vs interval cytoreductive surgery on International Federation of Gynecology and Obstetrics stage IV ovarian cancer outcomes remains uncertain and may vary depending on the stage and the location of extraperitoneal metastasis. Emulating target trials through causal assessment, combined with propensity score adjustment, has become a leading method for evaluating interventions using observational data. OBJECTIVE: This study aimed to assess the effect of primary vs interval cytoreductive surgery on progression-free and overall survival in patients with International Federation of Gynecology and Obstetrics stage IV ovarian cancer using target trial emulation. STUDY DESIGN: Using the comprehensive French national health insurance database, we emulated a target trial to explore the causal impacts of primary vs interval cytoreductive surgery on stage IV ovarian cancer prognosis (Surgery for Ovarian cancer FIGO 4: SOFI-4). The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and to balance baseline characteristics between the groups. Subgroup analyses were conducted based on the stages and extraperitoneal metastasis locations. The study included patients younger than 75 years of age, in good health condition, who were diagnosed with stage IV ovarian cancer between January 1, 2014, and December 31, 2022. The primary and secondary outcomes were respectively 5-year progression-free survival and 7-year overall survival. RESULTS: Among the 2772 patients included in the study, 948 (34.2%) were classified as having stage IVA ovarian cancer and 1824 (65.8%) were classified as having stage IVB ovarian cancer at inclusion. Primary cytoreductive surgery was performed for 1182 patients (42.6%), whereas interval cytoreductive surgery was conducted for 1590 patients (57.4%). The median progression-free survival for primary cytoreductive surgery was 19.7 months (interquartile range, 19.3-20.1) as opposed to 15.7 months (interquartile range, 15.7-16.1) for those who underwent interval cytoreductive surgery. The median overall survival was 63.1 months (interquartile range, 61.7-65.4) for primary cytoreductive surgery in comparison with 55.6 months (interquartile range, 53.8-56.3) for interval cytoreductive surgery. The findings of our study indicate that primary cytoreductive surgery is associated with a 5.0-month increase in the 5-year progression-free survival (95% confidence interval, 3.8-6.2) and a 3.9-month increase in 7-year overall survival (95% confidence interval, 1.9-6.2). These survival benefits of primary over interval cytoreductive surgery were observed in both the International Federation of Gynecology and Obstetrics stage IVA and IVB subgroups. Primary cytoreductive surgery demonstrated improved progression-free survival and overall survival in patients with pleural, supradiaphragmatic, or extra-abdominal lymph node metastasis. CONCLUSION: This study advocates for the benefits of primary cytoreductive surgery over interval cytoreductive surgery for patients with stage IV ovarian cancer and suggests that extraperitoneal metastases like supradiaphragmatic or extra-abdominal lymph nodes should not automatically preclude primary cytoreductive surgery consideration in suitable patients.

Surgery for M1A Non-Small-Cell Lung Cancer With Additional Pulmonary Nodules in a Contralateral Lobe.

INTRODUCTION: Limited consensus exists on the optimal treatment strategy for clinical M1a non-small-cell lung cancer (NSCLC) presenting as a primary tumor with additional intrapulmonary nodules in a contralateral lobe ("M1a-Contra"). This study sought to compare long-term survival of patients with M1a-Contra tumors receiving multimodal therapy with versus without thoracic surgery. METHODS: Overall survival of patients with cT1-4, N0-3, M1a NSCLC with contralateral intrapulmonary nodules who received surgery as part of multimodal therapy ("Thoracic Surgery") versus systemic therapy with or without radiation ("No Thoracic Surgery") in the National Cancer Database from 2010 to 2015 was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching. RESULTS: Of the 5042 patients who satisfied study inclusion criteria, 357 (7.1%) received multimodal therapy including surgery. In multivariable-adjusted analysis, the Thoracic Surgery cohort had better overall survival than the No Thoracic Surgery cohort (HR: 0.66, 95% CI: 0.56-0.79, P < 0.001). In a propensity score-matched analysis of 386 patients, well-balanced on 12 common prognostic covariates, the Thoracic Surgery group had better 5-year overall survival than the No Thoracic Surgery group (P = 0.020). In propensity score-matched analyses stratified by clinical N status, Thoracic Surgery was associated with better overall survival than No Thoracic Surgery for patients with cN0 disease and cN1-2 disease. CONCLUSIONS: In this national analysis, multimodal treatment including surgery was associated with better overall survival than systemic therapy with or without radiation without surgery for patients with M1a-Contra tumors. These preliminary findings highlight the importance of further evaluation of surgery in a multidisciplinary treatment setting for M1a-Contra tumors.

Prognostic utility of circulating tumor DNA methylation analysis in stage IV colorectal cancer.

BACKGROUND AND OBJECTIVES: Our aim in this study was to investigate the usefulness of circulating tumor (ct) DNA methylation analysis for predicting long-term outcomes after resection in Stage IV colorectal cancer (CRC). METHODS: Methylation analyses were performed on 95 plasma samples from patients with CRC who underwent surgery. The methylation status (relative methylation value: RMV) of CpG within the promoter region of three genes (CHFR, SOX11, and CDO1) was assessed to quantitative methylation-specific PCR (qMSP) analysis. RESULTS: In the patients who had undergone resection of the primary tumor and metastatic organs with curative intent, the CHFR-RMV high group had significantly worse recurrence-free survival (RFS) compared with the CHFR-RMV low group (p = 0.001). Multivariate analysis revealed that CHFR-RMV was a significant independent prognostic factor (hazard ratio = 2.63 (1.29-5.36); p = 0.008). In the patients who had undergone resection of the primary tumor with metastatic organs with curative intent after neoadjuvant systemic chemotherapy, the SOX11-RMV high group had significantly worse RFS compared with the SOX11-RMV low group (p = 0.004). CONCLUSIONS: The current study showed the usefulness of ctDNA methylation analysis for predicting the possibility of curative resection and long-term outcomes after resection in Stage IV CRC. A future prospective study is needed to obtain more conclusive results.

International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape : Bertinoro Workshop, November 2022.

BACKGROUND: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. METHODS: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. RESULTS: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. CONCLUSION: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

The coagulation status in women of endometriosis with stage IV.

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

Consequences of Losing Incidental Pulmonary Nodules to Follow-Up: Unmonitored Nodules Progressing to Stage IV Lung Cancer.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death globally. Incidental pulmonary nodules represent a golden opportunity for early diagnosis, which is critical for improving survival rates. This study explores the impact of missed pulmonary nodules on the progression of lung cancer. METHODS: A total of 4,066 stage IV lung cancer cases from 2019 to 2021 in Danish hospitals were investigated to determine whether a chest computed tomography (CT) had been performed within 2 years before diagnosis. CT reports and images were reviewed to identify nodules that had been missed by radiologists or were not appropriately monitored, despite being mentioned by the radiologist, and to assess whether these nodules had progressed to stage IV lung cancer. RESULTS: Among stage IV lung cancer patients, 13.6% had undergone a chest CT scan before their diagnosis; of these, 44.4% had nodules mentioned. Radiologists missed a nodule in 7.6% of cases. In total, 45.3% of nodules were not appropriately monitored. An estimated 2.5% of stage IV cases could have been detected earlier with proper surveillance. CONCLUSION: This study underlines the significance of monitoring pulmonary nodules and proposes strategies for enhancing detection and surveillance. These strategies include centralized monitoring and the implementation of automated registries to prevent gaps in follow-up.

Assessing Feasibility and Outcomes of Robotic Single Port Transvaginal NOTES(RSP-vNOTES) Hysterectomy: A Case Series.

OBJECTIVE: To demonstrate the feasibility and short-term outcomes of Robot-Assisted Single Port vaginal NOTES (RSP-vNOTES) for total hysterectomy, with or without endometriosis resection for all stages. DESIGN: Retrospective case series. SETTING: Single academic tertiary care hospital in Houston, Texas, USA. PARTICIPANTS: 28 adult women with chronic pelvic pain who underwent RSP-vNOTES hysterectomy, with or without endometriosis resection. INTERVENTIONS: Hysterectomy with or without excision of endometriosis via single-port robot-assisted vNOTES platform (Intuitive Da Vinci SP Platform). MAIN RESULTS: 28 patients with a mean age of 40.1 years (range 24.0-54.0 years), mean BMI 28.5 kg/m2 (range 19.5-48.4 kg/m2), underwent RSP-vNOTES from November 11, 2023 to May 7, 2024. Five (17.9%) patients underwent solely a hysterectomy, while 23 (82.1%) patients underwent additional endometriosis resection; 28.6% with stage I, 25.0% stage II, 7.1% stage III, and 21.4% with stage IV. Mean total operative time was 188.7 minutes (range 135.0-427.0 minutes), with robot dock time of 2.9 minutes (range 1.0-10.0 minutes), robot console time of 97.3 minutes (range 51.0-221.0 minutes), and hysterectomy time of 55.3 minutes (range 24.0-170.0 minutes). Estimated blood loss averaged 32.1 mL (range 25.0-50.0mL). One case required a mini-laparotomy as the irregularly-shaped 1668g fibroid uterus was unable to be removed vaginally. Complications included one case of vaginal cuff cellulitis and one case of urinary tract infection. CONCLUSION: Our findings indicate that RSP-vNOTES, a novel single-port surgical approach, presents a promising alternative surgical platform in vaginal surgeries.

Prognostic Nutritional Index is Related to All-Cause Mortality in Patients With Stage IV Colorectal Cancer Treated With Capecitabine: Single-Center 24-Month Observational Study in Vietnam.

AIM: To determine the mortality rate and the predictive value of the prognostic nutritional index (PNI) for all-cause mortality during the 24 months in patients with stage IV colorectal cancer treated with capecitabine. METHODS: We conducted a study on 87 stage IV colorectal cancer patients treated with capecitabine. Before the day of treatment, all patients were measured CEA and CRP-hs levels and calculated neutrophil/lympho ratio (NLR) and PNI. Patients were monitored and collected drug side effects and mortality for 24 months. RESULTS: The mortality rate of study subjects was 60.9%. CRP-hs, NLR, and PNI were independent factors associated with 24-month mortality in patients with stage IV colorectal cancer (p < 0.05 to p < 0.01). At a cut-off value of 38.51, PNI was a predictor for mortality, with the area under the curve (AUC) of 0.88 and p < 0.001. CONCLUSIONS: PNI was a good predictor of all-cause mortality in patients with stage IV colorectal cancer treated with capecitabine for 24 months.

Stage IV Colorectal Cancer at Initial Presentation versus Progression during and after Treatment, Differences in Management: Management Differences for Initial Presentation versus Progression of Disease after Initial Treatment.

Stage IV colorectal cancer is a prevalent disease and understanding the appropriate treatment options is important. Medical oncologic treatment remains the mainstay of treatment in cases where curative resection is not possible. Surgical intervention is indicated if the primary tumor and associated metastases are amenable to curative resection or if obstructive, bleeding, or perforative complications arise from the tumor. New endoscopic techniques can provide palliation and benefit for patients who cannot undergo surgery and may speed time to chemotherapy initiation. Recently, immunotherapy has shown promise at managing, controlling, and regressing advanced disease, in some cases converting it to curative with resection. For patients that progress while on treatment, continued medical therapy remains the mainstay of treatment. Further research into the benefits of asymptomatic primary tumor resection without curative intent needs to be performed. Colorectal cancer, and more specifically metastatic colorectal cancer, continues to have improved 1- and 5-year survival rates and likely will continue to do so over the coming months and years.

HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico.

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3'UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex-age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16-7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.

Initial Impact of National CRC Screening on Incidence and Advanced Colorectal Cancer.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) aims to decrease CRC incidence and mortality. Biennial fecal immunochemical test screening started in the Netherlands in 2014 for individuals 55-75 years of age. This study investigated the effect of screening on stage-specific incidence, with focus on stage III and IV CRC. METHODS: Inhabitants diagnosed with CRC in 2009-2018 were included. CRC incidence per stage, year, and detection method (ie, screen-detected vs clinically detected) was evaluated. Patient, tumor, and treatment characteristics, and survival of patients with stage III and IV CRC, were compared according to the detection method. RESULTS: Included were 140,649 CRCs in 136,882 patients. An initial peak of stage I-III CRC diagnoses after initiation of screening was followed by a continuous decrease within screening-eligible ages. Total CRC incidence remained higher than before screening, although stage II and IV CRC incidence decreased below prescreening levels. Screen-detected CRCs were significantly more frequently located in the left-sided colon (stage III; 43.7% vs 30.9%; stage IV: 45.1% vs 36.1%), and the primary tumor resection rate was higher (stage III colon: 99.8% vs 99.0%, rectum: 97.3% vs 89.7%; stage IV colon: 65.4% vs 56.6%, rectum: 47.3% vs 33.5%). Patients with screen-detected stage IV CRC had significantly more often single-organ metastases (74.5% vs 57.0%; P < .001) and more frequently received treatment with curative intent (colon: 41.3% vs 27.4%; rectum: 33.8% vs 24.6%). Overall survival significantly improved for patients with screen-detected CRCs (stage III: P < .001; stage IV: P < .001). CONCLUSIONS: Five years after the start of a nationwide CRC screening program, a decrease in stage II and IV CRC incidence was observed. Patients with screen-detected stage III and stage IV CRC had less extensive disease and improved survival compared with those with clinically detected CRC.

Comparison between de novo and metachronous metastatic breast cancer: the presence of a primary tumour is not the only difference-a Dutch population-based study from 2008 to 2018.

PURPOSE: The aim of this study was to compare characteristics and survival of patients with de novo and metachronous metastatic breast cancer. METHODS: Data of patients with metastatic breast cancer were obtained from the Netherlands Cancer Registry. Patients were categorized as having de novo metastatic breast cancer (n = 8656) if they had distant metastases at initial presentation, or metachronous metastatic disease (n = 2374) in case they developed metastases within 5 or 10 years after initial breast cancer diagnosis. Clinicopathological characteristics and treatments of these two groups were compared, after which multiple imputation was performed to account for missing data. Overall survival was compared for patients treated with systemic therapy in the metastatic setting, using Kaplan Meier curves and multivariable Cox proportional hazards models. The hazard ratio for overall survival of de novo versus metachronous metastases was assessed accounting for time-varying effects. RESULTS: Compared to metachronous patients, patients with de novo metastatic breast cancer were more likely to be ≥ 70 years, to have invasive lobular carcinoma, clinical T3 or T4 tumours, loco-regional lymph node metastases, HER2 positivity, bone only disease and to have received systemic therapy in the metastatic setting. They were less likely to have triple negative tumours and liver or brain metastases. Patients with de novo metastases survived longer (median 34.7 months) than patients with metachronous metastases (median 24.3 months) and the hazard ratio (0.75) varied over time. CONCLUSIONS: Differences in clinicopathological characteristics and survival between de novo and metachronous metastatic breast cancer highlight that these are distinct patients groups.

Survival Outcomes of Patients with International Federation of Gynecology and Obstetrics Stage IV Ovarian Cancer: Cytoreduction Still Matters.

PURPOSE: There is still no consensus on the therapeutic strategies for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV ovarian cancer (OC). We aim to outline the clinical characteristics and optimal therapeutic strategies of patients with FIGO stage IV OC. METHODS: This single center retrospective study analyzed the clinical features and survival of patients with FIGO stage IV OC that underwent cytoreduction or received at least one course of chemotherapy between January 2014 and December 2020. RESULTS: One hundred and twenty patients were included. Surgery, especially optimal cytoreduction without residual mass improved the overall survival of patients in surgery group (P = .047, HR .432, 95% CI .181-.987). Secondly, the completion of chemotherapy improved median overall survival of patients either with (53.0 months vs 25.0 months, P < .001, HR 7.015, 95% CI 1.372-35.881) or without cytoreduction (43.0 months vs 6.0 months, P = .006, HR 5.969, 95% CI 1.115-31.952). In patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had better survival. CONCLUSIONS: In patients with FIGO stage IV, complete resection of intra-abdominal tumor foci and completion of chemotherapy provided considerable survival benefits to patients with FIGO stage IV OC. Among patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had a better prognosis.

Association of Surgery and Chemotherapy in Stage IV Gastroenteropancreatic Neuroendocrine Carcinoma.

INTRODUCTION: The survival benefit of chemotherapy for patients with metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) is well established. However, reasons for underutilization of chemotherapy are unknown. METHODS: The National Cancer Database (NCDB) was queried for metastatic GEP-NECs from 2009 to 2016. The cohort was stratified by patients who had received chemotherapy and who did not receive chemotherapy. Demographic, socioeconomic, clinical, and treatment characteristics were captured. Multivariable logistic regression examined factors associated with chemotherapy utilization. RESULTS: Of the 2367 stage IV GEP-NECs patients identified, 1647 (69.6%) received chemotherapy. Patients with primary site at colon and small bowel, age ≥75, no insurance, and ≥2 comorbidities were less likely to receive chemotherapy than patients with other primary sites, age <75, private insurance, and no comorbidities (P < 0.005). The small bowel and colon were the primary sites with the greatest percentage of patients who received surgery (46.4% and 41.8%, respectively). In these subgroup of patients, surgical intervention was also associated with lower probability of receiving chemotherapy (odds ratio = 0.60, P < 0.005). CONCLUSIONS: About 30% of patients with metastatic GEP-NECs did not receive chemotherapy. Primary site location and receipt of surgery were significantly associated with receipt of chemotherapy, with NECs in small bowel and colon being more likely to receive surgery and less likely to receive chemotherapy. While surgery may be considered on an individual basis, increasing efforts to ensure patients with colon or small bowel NECs receive guideline-concordant chemotherapy will positively impact survival. In addition, interventions to improve health insurance coverage to increase receipt of chemotherapy are warranted.

Surgical Management of the Primary Tumor in Stage IV Small Intestinal Neuroendocrine Tumors: To Operate or Not to Operate, That Is the Question.

PURPOSE OF REVIEW: Small intestinal neuroendocrine tumors (SI-NET) are rare tumors, often with distant metastases at diagnosis. The objective of this review is to provide an overview of the latest literature regarding surgical management of the primary tumor in stage IV SI-NET. RECENT FINDINGS: Primary tumor resection (PTR) seems to be associated with improved survival in patients with stage IV SI-NET, independent of treatment of distant metastases. A watch and wait approach of the primary tumor increases the risk of needing an emergency resection. PTR improves survival in patients with stage IV SI-NET, decreases the risk of emergency surgery, and should be considered in all patients with stage IV disease and unresectable liver metastasis.