Natural course of metastatic castration-resistant prostate cancer in the era of intensified androgen deprivation therapy in the hormone-sensitive setting.

BACKGROUND: Androgen deprivation therapy (ADT) intensification (ADTi) (i.e., ADT with androgen receptor pathway inhibitor or docetaxel, or both) has significantly improved survival outcomes of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of prior ADTi in the mHSPC setting on the disease presentation and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) is not well characterized. In this study, our objective was to compare the disease characteristics and survival outcomes of patients with new mCRPC with respect to receipt of intensified or nonintensified ADT in the mHSPC setting. METHODS: In this institutional review board-approved retrospective study, eligibility criteria were as follows: patients diagnosed with mCRPC, treated with an approved first-line mCRPC therapy, and who received either intensified or nonintensified ADT in the mHSPC setting. Progression-free survival (PFS) was defined from the start of first-line therapy for mCRPC to progression per Prostate Cancer Working Group 2 criteria or death, and overall survival (OS) was defined from the start of first-line therapy for mCRPC to death or censored at the last follow-up. A multivariable analysis using the Cox proportional hazards model was used, adjusting for potential confounders. RESULTS: Patients (n = 387) treated between March 20, 2008, and August 18, 2022, were eligible and included: 283 received nonintensified ADT, whereas 104 were treated with ADTi. At mCRPC diagnosis, patients in the ADTi group were significantly younger, had more visceral metastasis, lower baseline prostate-specific antigen (all p < 0.01), and lower hemoglobin (p = 0.027). Furthermore, they had significantly shorter PFS (median 4.8 vs. 8.4 months, adjusted hazard ratio [HR]: 1.46, 95% confidence interval [95% CI]: 1.07-2, p = 0.017) and OS (median 21.3 vs. 33.1 months, adjusted HR: 1.53, 95% CI: 1.06-2.21, p = 0.022) compared to patients in the nonintensified ADT group. CONCLUSION: Patients treated with ADTi in the mHSPC setting and experiencing disease progression to mCRPC had more aggressive disease features of mCRPC (characterized by a higher number of poor prognostic factors at mCRPC presentation). They also had shorter PFS on first-line mCRPC treatment and shorter OS after the onset of mCRPC compared to those not receiving ADTi in the mHSPC setting. Upon external validation, these findings may impact patient counseling, prognostication, treatment selection, and design of future clinical trials in the mCRPC setting. There remains an unmet need to develop novel life-prolonging therapies with new mechanisms of action to improve mCRPC prognosis in the current era.

Meta-analysis of sex and racial subgroup participation rates and differential treatment effects for trials in solid tumor malignancies leading to US Food and Drug Administration registration between 2010 and 2021.

BACKGROUND: The lack of sociodemographic diversity in clinical trials limits the generalizability of results. The authors examined participation rates and effect modification by sex and race in oncology trials. METHODS: The authors extracted outcome data stratified by sex and race for registration trials supporting US Food and Drug Administration (FDA) approval (2010-2021). Effect modification by race and sex was examined using quantitative and qualitative methods. A random-effects meta-analysis and pairwise comparison of progression-free survival (PFS) and overall survival (OS) outcomes was conducted by sex and race. RESULTS: Ninety-five trials with 123 end points and 54,365 patients provided information on sex. Trial patients were more often male (n = 35,482; 65% vs. 56% male patients in US Surveillance, Epidemiology, and End Results [SEER] data), although the proportion of male patients was similar after adjusting by tumor type (60% in FDA data vs. 58% in SEER data). There was no difference in pooled outcomes among male versus female patients (PFS: hazard ratio, 0.99; 95% confidence interval, 0.92-1.07; p = .89; OS: hazard ratio, 0.99; 95% confidence interval, 0.93-1.07; p = .90). In total, 111 trials including 74,217 patients provided information on race, and 68% of patients identified as White, compared with 72.3% in US SEER incidence data. Black patients were under-represented compared with US SEER incidence data, although ethnicity was poorly reported throughout the data set. In the authors' network meta-analysis by race, there were no statistically significant differences in PFS or OS outcomes. CONCLUSIONS: No significant differences in PFS or OS outcomes were identified when the analyses were stratified by sex or race. Certain racial minorities remain under-represented, and clearer reporting of race and ethnicity is needed. Representation of female patients in FDA trials is similar to that in SEER data after adjusting for tumor type.

Cabozantinib with immune checkpoint inhibitor versus cabozantinib monotherapy in patients with metastatic clear cell renal cell carcinoma progressing after prior immune checkpoint inhibitor.

INTRODUCTION: Rechallenge with antibodies targeting programmed cell death protein-1 or its ligand (PD-1/L1) after discontinuation or disease progression in solid tumors following a prior PD-1/L1 treatment is often practiced in clinic. This study aimed to investigate if adding PD-1/L1 inhibitors to cabozantinib, the most used second-line treatment in real-world patients with metastatic clear cell renal cell carcinoma (mccRCC), offers additional benefits. METHODS: Using de-identified patient-level data from a large real-world US-based database, patients diagnosed with mccRCC, who received any PD-1/L1-based combination in first-line (1L) setting, followed by second-line (2L) therapy with either cabozantinib alone or in combination with PD-1/L1 inhibitors were included. Patients given a cabozantinib-containing regimen in 1L were excluded. The study end points were real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS) by 2L. RESULTS: Of 12,285 patients with metastatic renal cell carcinoma in the data set, 348 patients met eligibility and were included in the analysis. After propensity score matching weighting, cabozantinib with PD-1/L1 inhibitors versus cabozantinib (ref.) had similar rwTTNT and rwOS in the 2L setting. Hazard ratios and 95% confidence interval (CI) for rwTTNT and rwOS are 0.74 (95% CI, 0.49-1.12) and 1.15 (95% CI, 0.73-1.79), respectively. CONCLUSION: In this study, the results align with the phase 3 CONTACT-03 trial results, which showed no additional benefit of adding PD-L1 inhibitor to cabozantinib compared to cabozantinib alone in 2L following PD-1/L1-based therapies in 1L. These results from real-world patients strengthen the evidence regarding the futility of rechallenge with PD-1/L1 inhibitors.

Survival outcomes of neoadjuvant versus adjuvant therapy in patients with T1c, node-negative, human epidermal growth factor receptor 2-positive breast cancer: A Surveillance, Epidemiology, and End Results population-based study.

BACKGROUND: Persistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node-negative, human epidermal growth factor receptor 2-positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking. METHODS: Data on patients with T1cN0M0-stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well-balanced cohorts for the NAT and AT groups. Kaplan-Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT. RESULTS: After PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35-0.77; p < .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37-0.98; p = .041). A logistic regression model revealed that White race and hormone receptor-negative status independently predicted pCR. CONCLUSIONS: For patients with T1cN0M0-stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.

Outcome of malignant lymphoma in Ukraine. Analysis of 563 cases registered in the Ukrainian Lymphoma Registry in 2019-2021.

We report the outcome of 563 cases of newly diagnosed lymphoma registered in 2019-2021, including 176 cases (31.2%) of Hodgkin lymphoma (HL), 130 (23.1%) of diffuse large B-cell lymphoma (DLBCL), 28 (5%) of follicular lymphoma (FL), 16 (2.9%) of mantle cell lymphoma (MCL) and 20 (3.5%) of peripheral T-cell lymphoma (PTCL). After a median follow-up of 30.1 months (95% CI: 28.8-31.3), the 3-year overall survival rates were 95%, 83%, 86%, 100%, 61% and 42% for HL, DLBCL, CLL, FL, MCL and PTCL respectively. These data offer valuable information on the curability of lymphoma patients in Ukraine, in a real-world setting.

Impact of radioiodine therapy on recurrence and survival outcomes in intermediate-risk papillary thyroid carcinoma -A systematic review and meta-analysis.

OBJECTIVE: The utility of radioiodine (RAI) therapy in intermediate-risk papillary thyroid carcinoma (PTC) remains a topic of ongoing discussion. This systematic review and meta-analysis aimed to consolidate existing evidence on the impact of postoperative RAI therapy on recurrence and survival outcomes in intermediate-risk PTC. METHODS: A literature search was performed using relevant keywords in PubMed, Scopus, and EMBASE. Articles from January 2008 to March 2023 were included. Odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates were generated using meta-analysis. RESULTS: Eleven articles comprising 56,266 intermediate-risk PTC patients were included. 41,530 (73.8%) patients underwent postoperative RAI therapy, while 14,736 (26.2%) patients were kept on no-RAI (NOI) follow-up. No significant reduction in rates of structural disease recurrence was noted with RAI therapy in comparison to NOI follow-up (pooled univariate OR, 0.73, 95% confidence interval [CI], 0.29-1.87, I2 = 75%). RAI therapy was not a significant predictor of better recurrence-free survival (pooled multivariate HR, 0.21; 95% CI, 0.01-3.74, I2 = 94%). Interestingly, RAI therapy was associated with an overall survival benefit compared to NOI follow-up (pooled multivariate HR, 0.63; 95% CI, 0.48-0.82, I2 = 79%). CONCLUSIONS: This meta-analysis did not establish a conclusive benefit of RAI therapy in preventing structural disease recurrence or improving recurrence-free survival in intermediate-risk PTC. However, these results need to be interpreted with caution owing to significant heterogeneity in the existing literature. A prospective, randomised clinical trial is the need of the hour to better understand the effect of RAI therapy on long-term outcomes.

Sentinel lymph node biopsy for breast cancer during pregnancy: A comprehensive update.

BACKGROUND: Pregnant patients diagnosed with breast cancer (PrBC) may receive substantially different treatments compared to general population, considering that certain treatment options cannot be applied during pregnancy due to their potential harmful effects to the foetus. Regarding the use of sentinel lymph node biopsy (SLNB) in pregnant patients, potential concerns include foetal harm from radiation exposure, possible teratogenic effects of blue dyes and maternal anaphylaxis to isosulfan. OBJECTIVE: The main objective of the present systematic review is to summarize and present current knowledge and up-to-date evidence about the safety and efficacy of SLNB in PABC. METHODS: MEDLINE, Google Scholar and UpToDate databases were searched up to 22 January 2023. Articles studying the safety and effectiveness of SLNB in patients for PrBC were eligible for inclusion in the present review. RESULTS: In total, 63 articles that met the inclusion criteria were included in this study. Forty-seven articles were strongly in favour of performing SLNB in PABC, 4 articles were partially in favour, 10 articles were strongly against and 2 articles were partially against performing SLNB in PABC. Sub-categorization based on type of study showed that the majority of studies in favour were of higher level of evidence than those against. Furthermore, there were overall 12 studies reporting on outcomes. There were overall 382 women with PrBC that underwent SLNB. Full data were reported for 237 cases. Overall live birth rate was 95.8%, while overall neonatal complication rate was 3.4%. No case of maternal side effects or anaphylactic reaction, maternal death, stillbirth and neonatal death was reported (0%). CONCLUSIONS: Sentinel lymph node biopsy seems to be safe and effective technique for breast cancer during pregnancy.

Pre-treatment [18F]FDG PET/CT biomarkers for the prediction of antibody-drug conjugates efficacy in metastatic breast cancer.

PURPOSE: This study aimed to evaluate the association between pretreatment [18F]FDG PET/CT-derived biomarkers and outcomes in metastatic breast cancer (mBC) patients treated with antibody-drug conjugates (ADCs) Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd). METHODS: A retrospective bicentric analysis was conducted on triple-negative mBC (mTNBC) patients treated with SG and HER2-low mBC patients treated with T-DXd, who underwent [18F]FDG PET/CT scans before therapy. Key biomarkers, including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV) and maximum tumor dissemination (Dmax), were measured. Their prognostic value for progression-free survival (PFS) and overall survival (OS) was assessed using Cox models and Kaplan-Meier curves. RESULTS: 128 patients were included: 71 mTNBC treated with SG and 57 HR-positive and -negative HER2-low mBC treated with T-DXd. Median follow-up was 12.9 months. In the SG cohort, median PFS and OS were 4.8 and 8.9 months, respectively. High Dmax (HR 2.1, 95% CI 1.1-4.3) and high TMTV (HR 2.9, 95% CI 1.2-6.6) were independently associated with shorter OS. In the T-DXd cohort, median PFS and OS were 5.8 and 9.0 months, respectively. High Dmax (HR 2.1, 95% CI 1.2-3.9) and high TMTV (HR 2.4, 95% CI 1.0-6.5) independently correlated with shorter PFS and shorter OS, respectively. CONCLUSION: Pretreatment [18F]FDG PET/CT-derived biomarkers, namely TMTV and Dmax, have significant prognostic value in patients with mTNBC and HER2-low mBC treated with SG and T-DXd. These biomarkers improve prognostic prediction and may optimize treatment strategies, warranting their clinical use, but larger studies are needed to validate these findings.

Revisiting the association between pretreatment thrombocytosis and cancer survival outcomes: an umbrella review of meta-analyses.

BACKGROUND: Although associations have been reported linking pretreatment thrombocytosis to cancer survival outcomes, the validity and strength of existing observational evidence have been contested. This study aimed to conduct an umbrella review to comprehensively appraise the strength, validity and credibility of these reported associations. METHODS: We searched Medline, Embase and Cochrane Database of Systematic Reviews from inception to 8 April 2023 to retrieve meta-analyses of observational studies. Meta-analyses were re-performed using a random-effect model and the strength of evidence was graded as convincing, highly suggestive, suggestive and weak according to seven pre-defined quantitative criteria reflecting statistical significance, amount of data, heterogeneity, and evidence of bias. The quality of review was appraised using the AMSTAR2 checklist. The umbrella review was reported adhering to the PRISMA guideline and was registered on PROSPERO (CRD42023455391). RESULTS: A total of 21 unique meta-analyses investigating ten cancer subtypes were included. All meta-analyses reported inferior survival outcome in cancer patients with pretreatment thrombocytosis, and 18 of them (85.7%) yielded statistically significant results (P < 0.05). Consistent effects were observed across meta-analyses that adopted different cut-off values (i.e. platelet count > 300 or 400 × 109 /L) to define thrombocytosis. Although evidence appraisal did not identify convincing evidence (Class I), the associations of thrombocytosis with inferior overall survival of lung, gastric, colorectal cancer and malignant mesothelioma were classified as highly suggestive evidence (Class II). According to AMSTAR2 ratings, no meta-analysis was identified with high or moderate quality. CONCLUSIONS: Our findings consolidated the association between pretreatment thrombocytosis and poor survival outcomes in various cancers. Nonetheless, the absence of convincing associations indicates a need for further large-scale, high-quality evidence to confirm whether platelets can serve as a prognostic predictor or a therapeutic target.

Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study.

BACKGROUND: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. METHODS: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. RESULTS: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). CONCLUSIONS: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3 years (1.8-6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.

Cervical squamous cell carcinoma outcomes across continents: A retrospective study.

OBJECTIVE: To assess the influence of geographies and race on the survival outcomes in patients diagnosed with cervical squamous cell carcinoma (CSCC) across three continents. METHODS: This multicontinental retrospective study was conducted in 8 hospitals across Asia, Europe, and North America (NA). Clinicopathologic data of 595 patients with presumed early stages of CSCC, treated surgically, with curative intent was collected. Descriptive analysis and Cox regression models were produced. RESULTS: A total of 595 patients, consisting of 445 (74.8 %) white, 75 (12.6 %) Blacks, and 75 (12.6 %) Asian patients were included. Geographical distribution comprised 69 % of patients from NA, 22 % from Europe, and 9 % from Asia. The median age at diagnosis was 46 years. The median overall survival (OS) and relapse-free survival (RFS) were 22.09 years and 21.19 years, respectively. Patient characteristics varied significantly across geographical regions, except for consensus tumor grade. Patients in Europe from middle-income countries with limited CC screening had a substantially higher risk of death than those in NA (HR, 1.79; 95 % CI, 1.13 to 2.79; p = 0.015). Patients from single center in Japan had higher risk of relapse than those from the four heterogeneous NA centers (sub-distribution hazard ratio, 2.19; 95 % CI, 1.22 to 3.95; p = 0.009), although OS did not differ significantly. Race remained statistically insignificant for survival outcomes across the three continents but seemed to influence survival outcomes in NA centers. CONCLUSION: Our study highlights impact of geographies and races on CSCC survival outcomes, emphasizing the need of considering these factors when developing targeted interventions against CSCC.

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

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

Association of Surgical Approaches and Outcomes in Total Mesorectal Excision and Margin Status for Rectal Cancer.

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer. METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected from the US Rectal Cancer Consortium database (2007-2017). Quasi-Poisson regression analysis with backward selection was used to investigate the relationship between the surgical approach and outcomes of interest. RESULTS: Among the 664 patients included in the study, the distribution of surgical approaches was as follows: 351 (52.9%) underwent TME via the open approach, 159 (23.9%) via the robotic approach, and 154 (23.2%) via the laparoscopic approach. There were no significant differences in baseline demographics among the three cohorts. The laparoscopic cohort had fewer patients with low rectal cancer (<6 cm from the anal verge) than the robotic and open cohorts (Lap 28.6% versus Rob 59.1% versus Open 45.6%, P = 0.015). Patients who underwent Rob and Lap TME had lower intraoperative blood loss compared with the Open approach (Rob 200 mL [Q1, Q3: 100.0, 300.0] versus Lap 150 mL [Q1, Q3: 75.0, 250.0] versus Open 300 mL [Q1, Q3: 150.0, 600.0], P < 0.001). There was no difference in the operative time (Rob 243 min [Q1, Q3: 203.8, 300.2] versus Lap 241 min [Q1, Q3: 186, 336] versus Open 226 min [Q1, Q3: 178, 315.8], P = 0.309) between the three approaches. Postoperative length of stay was shorter with robotic and laparoscopic approach compared to open approach (Rob 5.0 d [Q1, Q3: 4, 8.2] versus Lap 5 d [Q1, Q3: 4, 8] versus Open 7.0 d [Q1, Q3: 5, 9], P < 0.001). There was no statistically significant difference in the quality of TME between the robotic, laparoscopic, and open approaches (79.2%, 64.9%, and 64.7%, respectively; P = 0.46). The margin positivity rate, a composite of circumferential margin and distal margin, was higher with the robotic and open approaches than with the laparoscopic approach (Rob 8.2% versus Open 6.6% versus Lap 1.9%, P = 0.17), Rob versus Lap (odds ratio 0.21; 95% confidence interval 0.05, 0.83) and Rob versus Open (odds ratio 0.5; 95% confidence interval 0.22, 1.12). There was no difference in long-term survival, including overall survival and recurrence-free survival, between patients who underwent robotic, laparoscopic, or open TME (Figure 1). CONCLUSIONS: In patients undergoing surgery with curative intent for rectal cancer, we did not observe a difference in the quality of TME between the robotic, laparoscopic, or open approaches. Robotic and open TME compared to laparoscopic TME were associated with higher margin positivity rates in our study. This was likely due to the higher percentage of low rectal cancers in the robotic and open cohorts. We also reported no significant differences in overall survival and recurrence-free survival between the aforementioned surgical techniques.

Patients With Surgically Resectable Lung Cancer Who Opt for Radiation Have Worse Outcomes.

BACKGROUND: Surgery has been the standard procedure for resectable primary LC. Survival after stereotactic body radiation therapy, another treatment, is significantly biased due to preponderance of data from patients deemed unsuitable for surgery. We examined survival of patients refusing surgery in favor of radiation therapy. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify patients with primary Stage I NSCLC diagnosed between 2007 and 2016. Patients were excluded if it was unknown if they were recommended for surgery or if surgery was contraindicated. Multiple predictors were assessed: radiation versus surgery, age at diagnosis, sex, race/ethnicity, health insurance status, marital status, tumor size, and histology. A multivariate analysis was performed to estimate hazard ratios and generate Kaplan-Meier survival curves. RESULTS: When adjusted for confounding variables, survival was greater for patients undergoing surgical resection than those refusing surgery in favor of radiation (HRadj 2.66; 95% CI: 2.27-3.11, p < 0.001) or for those receiving no standardized treatment (HRadj 4.43; 95% CI: 3.57-5.50, p < 0.001). CONCLUSIONS: SBRT is an effective treatment for inoperable early LC but there is limited data comparing outcomes against surgical resection. When eligible for both, patients refusing surgery and choosing radiation had worse survival when adjusting for variables including age, tumor size, and histology, and suggests that surgical resection is a superior treatment modality.

Outcomes of Lung Transplantation in Patients With Right Ventricular Dysfunction: A Single-Center Retrospective Analysis Comparing ECMO Configurations in a Bridge-to-Transplant Setting.

This study aimed to assess the lung transplantation (LT) outcomes of patients with right ventricular dysfunction (RVD), focusing on the impact of various extracorporeal membrane oxygenation (ECMO) configurations. We included adult patients who underwent LT with ECMO as a bridge-to-transplant from 2011 to 2021 at a single center. Among patients with RVD (n = 67), veno-venous (V-V) ECMO was initially applied in 79% (53/67) and maintained until LT in 52% (35/67). Due to the worsening of RVD, the configuration was changed from V-V ECMO to veno-arterial (V-A) ECMO or a right ventricular assist device with an oxygenator (Oxy-RVAD) in 34% (18/67). They showed that lactic acid levels (2-6.1 mmol/L) and vasoactive inotropic score (6.6-22.6) increased. V-A ECMO or Oxy-RVAD was initiated and maintained until LT in 21% (14/67) of cases. There was no significant difference in the survival rates among the three configuration groups (V-V ECMO vs. configuration changed vs. V-A ECMO/Oxy-RVAD). Our findings suggest that the choice of ECMO configuration for LT candidates with RVD should be determined by the patient's current hemodynamic status. Vital sign stability supports the use of V-V ECMO, while increasing lactic acid levels and vasopressor needs may require a switch to V-A ECMO or Oxy-RVAD.

Survival outcomes of rare cutaneous malignancies within an insured cohort of patients, 1988-2018.

BACKGROUND: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). OBJECTIVE: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients. METHODS: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021. RESULTS: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC. LIMITATIONS: Retrospective nature of the analysis and small sample size. CONCLUSION: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage.

Exploring the connection between microsatellite instability and inflammatory indicators in cancers.

Aim: This study aimed to investigate the association between microsatellite instability (MSI) status and inflammatory indicators in patients with cancer. Patients & methods: A total of 204 patients with various cancer diagnoses, including 102 with MSI-high (MSI-H) and 102 with microsatellite stable tumors, were enrolled. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP)-to-albumin ratio and systemic immune-inflammation index were evaluated. Results: In microsatellite stable patients, NLR, LMR, PLR and systemic immune-inflammation index were significantly linked to worse survival in univariate analysis, and having a LMR ≤2.6 negatively affected survival in multivariate analysis, although these indicators did not affect the survival of MSI-H patients. Conclusion: The impact of chronic inflammation on survival varies with MSI status. Further research is needed for targeted therapies in different tumors.

Pembrolizumab plus chemotherapy for first-line treatment of advanced triple-negative breast cancer.

Aim: A systematic review and network meta-analysis (NMA) was performed to evaluate the efficacy of first-line treatments for locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) patients.Materials & methods: Databases were searched for randomized controlled trials evaluating first-line treatments for locally recurrent unresectable or metastatic TNBC patients. NMA was performed to estimate relative treatment effects on overall and progression-free survival between pembrolizumab + chemotherapy and other interventions.Results: NMA including eight trials showed that the relative efficacy of pembrolizumab + chemotherapy was statistically superior to that of other immunotherapy- or chemotherapy-based treatment regimens.Conclusion: Pembrolizumab + chemotherapy confers benefits in survival outcomes versus alternative interventions for the first-line treatment of locally recurrent unresectable or metastatic TNBC patients.

Clinical value of initial treatments for patients with advanced triple-negative breast cancerWhat is this article about? Around 15% of breast cancer patients have the triple-negative breast cancer (TNBC) subtype, which has the worst prognosis. Treatments targeting the immune system, such as pembrolizumab, were recently found to improve the outcomes of patients with cancer that is at an advanced stage or resistant to standard therapies. However, clinical trials evaluating the efficacy of cancer treatments typically compare only two alternative treatments. Therefore, we conducted this study to understand the relative efficacy of several commonly used initial treatments for advanced TNBC by indirectly comparing the results of all available clinical trials that were sufficiently similar. We identified trials by systematically searching the medical literature and analyzed the results of several clinical trials together to estimate the efficacy of pembrolizumab + chemotherapy compared with several other initial treatment regimens for patients with advanced TNBC.What were the results? We identified eight randomized controlled trials evaluating treatment regimens containing chemotherapeutic or immunotherapeutic agents in patients with previously untreated advanced TNBC. Considering all these trials together, pembrolizumab + chemotherapy was found to prolong patient survival to a greater extent than several other treatment regimens including carboplatin, docetaxel, paclitaxel, nab-paclitaxel/paclitaxel, bevacizumab + paclitaxel, ixabepilone + paclitaxel and ixabepilone + bevacizumab depending on the specific set of trials analyzed.What do the results of the study mean? These results indicate that pembrolizumab + chemotherapy has beneficial effects on patient survival compared with other initial treatment regimens for patients with advanced TNBC.

Contemporary results from the PelvEx collaborative: improvements in surgical outcomes for locally advanced and recurrent rectal cancer.

AIM: The PelvEx Collaborative collates global data on outcomes following exenterative surgery for locally advanced and locally recurrent rectal cancer (LARC and LRRC, respectively). The aim of this study is to report contemporary data from within the collaborative and benchmark it against previous PelvEx publications. METHOD: Anonymized data from 45 units that performed pelvic exenteration for LARC or LRRC between 2017 and 2021 were reviewed. The primary endpoints were surgical outcomes, including resection margin status, radicality of surgery, rates of reconstruction and associated morbidity and/or mortality. RESULTS: Of 2186 patients who underwent an exenteration for either LARC or LRRC, 1386 (63.4%) had LARC and 800 (36.6%) had LRRC. The proportion of males to females was 1232:954. Median age was 62 years (interquartile range 52-71 years) compared with a median age of 63 in both historical LARC and LRRC cohorts. Compared with the original reported PelvEx data (2004-2014), there has been an increase in negative margin (R0) rates from 79.8% to 84.8% and from 55.4% to 71.7% in the LARC and LRRC cohorts, respectively. Bone resection and flap reconstruction rates have increased accordingly in both cohorts (8.2%-19.6% and 22.6%-32% for LARC and 20.3%-41.9% and 17.4%-32.1% in LRRC, respectively). Despite this, major morbidity has not increased. CONCLUSION: In the modern era, patients undergoing pelvic exenteration for advanced rectal cancer are undergoing more radical surgery and are more likely to achieve a negative resection margin (R0) with no increase in major morbidity.