Pretreatment CRP–Albumin–Lymphocyte (CALLY) Index as a Prognostic Biomarker of Survival and Recurrence‐Free Survival in Patients With Early‐Stage Cervical Cancer After Radical Hysterectomy: A Multicenter Retrospective Cohort Study

Low grade appendiceal mucinous neoplasms (LAMN) are indolent tumors that lack invasive potential but may present as pseudomyxoma peritonei. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves both overall and recurrence free survival. While systemic chemotherapy is generally considered ineffective for LAMN, little literature is available to support this notion. We evaluated outcomes for individuals with LAMN who did and did not receive systemic chemotherapy in combination with CRS+HIPEC. A multicenter retrospective cohort study was performed using the US HIPEC Collaborative that included patients with LAMN who underwent CRS+HIPEC. The overall survival (OS) and recurrence-free survival (RFS) of patients who did and did not receive systemic chemotherapy were compared. Survival and variables associated with survival were evaluated with the Kaplan-Meier analysis and cox regression, respectively. Among the 529 included patients with LAMN, 63 (11.9%) received systemic chemotherapy and CRS+HIPEC, while 466 (88.1%) were treated with only CRS+HIPEC. Patients selected for systemic chemotherapy had a higher burden of disease (mean peritoneal cancer index: 18.8 +/- 8.6 versus 14.3 +/- 8.8, p<0.001). Patients who were not treated with chemotherapy had better mean OS and RFS (OS: 104.3 +/- 6.2 months, RFS: 84.9 +/- 6.6 months) compared to those who underwent systemic chemotherapy (OS: 70.2 +/- 6.8 months, RFS: 38 +/- 5.9 months, p<0.001). Increasing pre-operative CEA level (HR 1.012, p<0.001), higher completeness of cytoreduction score (reference CCR 0, CCR2 HR 34.175, p=0.001 and CCR3 HR 52.041, p=0.001), and treatment with systemic chemotherapy (HR 4.196, p=0.045) were associated with worse OS. In this multicenter retrospective study, the receipt of perioperative chemotherapy was associated with worse long-term outcomes among patients with LAMN undergoing CRS-HIPEC. Systemic chemotherapy may lead to patient deconditioning and contribute to worse long-term outcomes. It should not be recommended outside of a clinical trial.

Objectives: This study aimed to compare the 5-year disease-free survival (DFS) and overall survival (OS) of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for IA1 with lymphovascular space invasion (LVSI)-IIA2 cervical cancer and to analyze the Cox proportional hazard ratio (HR) of LRH among the total study population and different subgroups.Methods: This was a multicenter retrospective cohort study. The oncological outcomes of LRH (n = 4,236) and ARH (n = 9,177) were compared. The HRs and 95% confidence intervals for the effect of LRH on 5-year OS and DFS were estimated by Cox proportional hazards models.Results: Overall, there was no difference in DFS between LRH and ARH in the unadjusted analysis (HR 1.11, 95% CI: 0.99–1.25, p = 0.075). The risk-adjusted analysis revealed that LRH was independently associated with inferior DFS (HR 1.25, 95% CI: 1.11–1.40, p < 0.001). There was no difference in OS between the two groups in the unadjusted analysis (HR 1.00, 95% CI: 0.85–1.17, p = 0.997) or risk-adjusted analysis (HR 1.15, 95% CI: 0.98–1.35, p = 0.091). For patients with FIGO stage IB1 and tumor size <2 cm, LRH was not associated with lower DFS or OS (p = 0.637 or p = 0.107, respectively) in risk-adjusted analysis. For patients with FIGO stage IB1 and tumor size ≥2 cm, LRH was associated with lower 5-year DFS (HR 1.42, 95% CI: 1.19–1.69, p < 0.001) in risk-adjusted analysis, but it was not associated with lower 5-year OS (p = 0.107). For patients with FIGO stage IIA1 and tumor size <2 cm, LRH was not associated with lower 5-year DFS or OS (p = 0.954 or p = 0.873, respectively) in risk-adjusted analysis. For patients with FIGO stage IIA1 and tumor size ≥2 cm, LRH was associated with lower DFS (HR 1.48, 95% CI: 1.16–1.90, p = 0.002) and 5-year OS (HR 1.69, 95% CI: 1.22–2.33, p = 0.002) in risk-adjusted analysis.Conclusion: The 5-year DFS of LRH was worse than that of ARH for FIGO stage IA1 with LVSI-IIA2. LRH is not an appropriate option for FIGO stage IB1 or IIA1 and tumor size ≥ 2 cm compared with ARH.

Robotic versus vaginal radical trachelectomy for reproductive-aged women with early cervical cancer: a multi-center Canadian study (097)

Triple-negative breast cancer (TNBC) (ER-/PGR-/erb-2-) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2- breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27-2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17-3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8-80.8%] vs. 86.5% [95% CI: 84.6-88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9-81.8%] vs. 86.0% [95% CI: 84.1-87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number of guideline violations.

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

Scores and Misses With New Technology—Walking the Narrow Path of Evidence

In the treatment of cervical cancer, the extent of lymphadenectomy is a matter of debate. The goal of the current study was to examine the question of whether the number of retrieved lymph nodes (RLN) can influence survival of patients with early stage cervical cancer. The medical records of 180 FIGO stage IB-IIA cervical cancer patients treated with primary radical surgery were reviewed. Patients were divided into two groups: those with ≤40 RLN and those with > 40 RLN. Patients were also assigned to either the bulky (tumor size>4 cm) cervical cancer group or the non-bulky (tumor size≤4 cm) cervical cancer group. The number of RLN had a statistically significant effect on both disease-free survival (P = 0.04) and overall survival (P = 0.02) of all patients. Patients with>40 RLN had better prognoses than those with≤40 RLN. In the bulky cervical cancer group, the number of RLN was an independent prognostic factor. In multivariate analysis for the bulky cervical cancer group, >40 RLN had a significant positive effect on disease-free survival (adjusted hazard ratio, 0.36; 95% confidence interval, 0.13-0.97) and overall survival (adjusted hazard ratio, 0.23; 95% confidence interval, 0.06-0.90). However, number of RLN was not an independent prognostic factor in the non-bulky cervical cancer group. A more extensive lymphadenectomy increased the survival of bulky cervical cancer patients. This finding may be helpful in determining surgical extent before surgery for cervical cancer.

To compare oncological outcomes of radical hysterectomy (RH) and radiochemotherapy (R-CT) for stage IIIC1 (FIGO 2018) cervical adenocarcinoma patients. Based on the Chinese Cervical Cancer Clinical Diagnosis and Treatment Project Database, we retrospectively reviewed 236 cases of FIGO stage IIIC1 cervical adenocarcinoma diagnosed between 2005 and 2019. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were compared between the two treatment groups using multivariate Cox regression models and the log-rank test, both in the overall study population and after propensity score matching (PSM). From 63 926 patients, we selected 236 cases, including 203 in the RH group and 33 in the R-CT group. In the overall study population, R-CT was associated with significantly worse 5-year OS (51.8% vs. 67.2%, p < 0.05) and 5-year DFS (43.1% vs. 60.1%, p < 0.05) compared to RH. Multivariate analysis revealed that R-CT was an independent risk factor for 5-year DFS (hazard ratio [HR] = 2.226, 95% confidence interval [CI] 1.141-4.343, p < 0.05) but not for 5-year OS (HR = 1.834, 95% CI: 0.829-4.061, p > 0.05) in FIGO stage IIIC1 cervical adenocarcinoma. After matching (n = 26 in R-CT group vs. 73 in RH group), the R-CT group showed significantly lower 5-year OS (50.3% vs. 77.4%, p < 0.05) and DFS (38.2% vs. 65.0%, p < 0.05) compared to the RH group. In the matched cohort, R-CT remained an independent risk factor for 5-year DFS (HR = 2.299, 95% CI: 1.113-4.750, p < 0.05) but not for 5-year OS (HR = 1.926, 95% CI: 0.792-4.682, p > 0.05). Among patients with stage FIGO 2018 IIIC1 cervical cancer adenocarcinoma, R-CT was not associated with better oncological outcomes than RH. Radiotherapy should not be the only recommended treatment.

6006 Background: The goal of this study was to assess disease-free survival (DFS) and disease-specific survival (DSS) in patients with early-stage cervical cancer who underwent bilateral sentinel lymph node (BSLN) biopsy alone versus bilateral pelvic lymphadenectomy (BPL). Methods: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was performed. All patients with early stage cervical cancer (IA to IIB FIGO stage), negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrency and disease-specific deaths were determined by Cox proportional hazard models. Kaplan-Meier survival curves were compared by applying log-rank test. Results: Between January 2005 and July 2012, 259 patients met the inclusion criteria: 85 patients underwent only bilateral SLN biopsy whereas 174 patients underwent BPL. None had positive SLN at ultrastaging or positive non-SLN at final pathologic examination. Between the both groups, there was no differences in histology, final FIGO stage and type of surgical approach. In the BPL group, patients had more frequently tumor size larger than 20 mm (22.9% vs 10.7%, p = 0.02) and postoperative radiochemotherapy (10.7% vs 1.6%, p = 0.01). The median follow-up was 47 months (4-127). During the follow-up, 21 patients (8.1%) experienced reccurencies, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. The 5-year DFS and the DSS were similar between BSLN and BPL groups, 94.1% vs 97.7%, p = 0.14 and 88.2% vs 93.7%, p = 0.14 respectively. After controlling for final FIGO stage and margin status, BSLN compared to BPL was not associated with DFS (HR = 1.76, 95%CI = [0.69 – 4.53], p = 0.24) and DSS (HR = 2.5, 95%CI = [0.64 – 9.83], p = 0.19). Only final FIGO stage was independent predictor of DSS. Conclusions: SLN biopsy alone is oncologically safe in early-stage cervical cancer. Full lymphadenectomy could be omitted in case of bilateral negative SLN. Worse prognosis was associated with higher FIGO stage disease.

Comprehensive assessment of postoperative recurrence and survival in patients with cervical cancer

The aim of the study was to compare recurrence-free survival (RFS) and overall survival (OS) of patients with early stage cervical cancer in dependence of surgical approach and treatment center. A population-based cohort study including women with early stage IA1-IIB2 cervical cancer treated by radical hysterectomy between January 2010 and December 2015 was performed. The median follow-up time was 5.6years. After exclusions, 413patients were eligible for analysis: 111 (26.9%) underwent minimal-invasive surgery (MIS) and 302 (73.1%) open surgery. Both treatment groups were well balanced regarding the clinical and pathological characteristics. The mean age of the patients was 51.0years. MIS was associated with improved RFS and OS compared with the open surgery. The 5-year RFS rates were 89.2% in the MIS group and 73.4% in the open surgery group (p = 0.004). The 5-year OS rates were 93.7% in the MIS group and 81.8% in the open surgery group (p = 0.016). After adjustment for other prognostic covariates, the MIS was further associated with improved RFS (HR = 0.45, 95% CI 0.24-0.86; p = 0.015) but not with OS. Nevertheless, after adjustment for treatment center, the surgical approach was not associated with significant difference in RFS (HR = 0.61, 95% CI 0.31-1.19; p = 0.143). Overall survival of patients treated in university cancer centers was significantly increased compared to patients treated in non-university cancer centers. The treatment center remains a strong prognostic factor regarding RFS (HR = 0.49, 95% CI 0.28-0.83; p = 0.009) and OS (HR = 0.50, 95% CI 0.26-0.94; p = 0.031). The treatment center but not the surgical approach was associated with the survival of patients treated with radical hysterectomy for early stage cervical cancer.

Simple SummaryAdjuvant chemotherapy following radical cystectomy is a common therapy for muscle invasive bladder cancer (MIBC) patients. No applicable biomarkers exist to predict which patients will benefit from chemotherapy. Three immune cell markers, the chemokine CC motif ligand 2 (CCL2), the pan macrophage marker CD68, and the M2 macrophage marker CD163, were examined using immunohistochemistry to determine their predictive value for chemotherapy responses in different nodal stage and tumor stage subgroups. The presence of tumor-infiltrating immune cells, characterized by the markers CD68, CD163, and CCL2, was associated with a superior prognosis, and chemotherapy may not add an advantage for prognosis. However, a depleted immune microenvironment, here represented as a reduction or loss of macrophages, helped to predict the benefit of chemotherapy in N1 + 2 stage patients. Altogether, it is meaningful to consider the abundance of immune cells, such as macrophages, to better predict the response to chemotherapy for bladder cancer (BCa) patients after radical treatment.Bladder cancer (BCa) is the tenth most commonly diagnosed malignant cancer worldwide. Although adjuvant chemotherapy following radical cystectomy is a common therapy for muscle invasive bladder cancer patients, no applicable biomarkers exist to predict which patients will benefit from chemotherapy. In this study, we examined three immune cell markers, the chemokine CC motif ligand 2 (CCL2), the pan macrophage marker cluster of differentiation 68 (CD68) and the M2 macrophage marker cluster of differentiation 163 (CD163), using immunohistochemistry to determine their predictive value for the chemotherapy response in different nodal stage (pN0 vs. pN1 + 2) and tumor stage subgroups (pT2 vs. pT3 + 4). The prognosis was studied in terms of the overall survival (OS), disease-specific survival (DSS), and recurrence-free-survival (RFS) in 168 muscle invasive BCa patients. Chemotherapy was associated with a poorer prognosis in patients with a higher expression of the immune markers CCL2 (RFS), CD68 (DSS and RFS), and CD163 (DSS and RFS) in the N0 group and with poorer survival in patients with a higher expression of the immune markers CCL2 (OS, DSS, and RFS), CD68 (OS, DSS, and RFS), and CD163 (OS, DSS, and RFS) in the pT2 group when compared with treatments without chemotherapy. In contrast, chemotherapy was associated with a better prognosis in patients with a low expression of the immune markers CCL2 (DSS and RFS), CD68 (OS, DSS, and RFS), and CD163 (OS) in the N1 + 2 group. In addition, chemotherapy was associated with improved survival in patients with a low expression of the immune marker CD68 (OS and DSS) and there was a trend for a better prognosis in patients with a low expression of CD163 (OS) in the pT3 + 4 group compared to patients not treated with chemotherapy. Interestingly, CD68 appeared to be the most applicable immune marker to stratify patients by the outcome of chemotherapy in the nodal stage and tumor stage groups. Overall, we suggest that, in addition to the clinical factors of tumor stage and nodal stage, it is also meaningful to consider the abundance of immune cells, such as macrophages, to better predict the response to chemotherapy for BCa patients after radical treatment.

BackgroundPrevious studies have shown that fibrinogen-to-albumin ratio (FAR) is a novel prognostic immune biomarker in various diseases. In this study, we investigated the role of FAR in the prognosis of patients with stage IB-IIA cervical cancer (CC).MethodsA total of 278 eligible participants with newly diagnosed CC (stage IB-IIA) who had undergone radical hysterectomy followed by adjuvant chemotherapy were enrolled in this study. Demographics, clinicopathological variables, and laboratory tests were obtained from the medical records. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were evaluated by univariate and multivariate Cox proportional regression analyses. The association between OS, RFS, and FAR was assessed by the Kaplan–Meier method using log-rank test.ResultsFAR was associated with age, International Federation of Gynecology and Obstetrics (FIGO) stage, depth of the invasion, and C-reactive protein (CRP) level (P < 0.05). Preoperative FAR was an effective predictor for OS in CC patients with a cut-off value of 7.75 and an area under the curve (AUC) of 0.707 (P < 0.001). The univariate and multivariate Cox analyses indicated that FIGO stage and FAR were two independent risk factors for both OS and RFS (P < 0.05). Kaplan–Meier analysis confirmed that patients with high FAR levels showed significantly lower RFS (P = 0.004) and OS (P = 0.003) than those with low FAR levels.ConclusionsThis study indicated that elevated preoperative FAR might be a novel prognostic factor for CC patients with stage IB-IIA.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a form of rare primary liver cancer that combines intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma. To investigate overall survival (OS) and recurrence-free survival (RFS) after radical resection in patients with cHCC-CCA, and the clinicopathological factors affecting prognosis in two center hospitals of China. We reviewed consecutive patients with cHCC-CCA who received radical resection between January 2005 and September 2021 at Peking Union Medical College and the 5th Medical Center of the PLA General Hospital retrospectively. Regular follow-up and clinicopathological characteristics were systematic collected for baseline and prognostic analysis. Our study included 95 patients who received radical resection. The majority of these patients were male and 82.7% of these patients were infected with HBV. The mean tumor size was 4.5 cm, and approximately 40% of patients had more than one lesion. The median OS was 26.8 (95%CI: 18.5-43.0) mo, and the median RFS was 7.27 (95%CI: 5.83-10.3) mo. Independent predictors of OS were CA19-9 ≥ 37 U/mL (HR = 8.68, P = 0.002), Child-Pugh score > 5 (HR = 5.52, P = 0.027), tumor number > 1 (HR = 30.85, P = 0.002), tumor size and transarterial chemoembolization (TACE) after surgery (HR = 0.2, P = 0.005). The overall postoperative survival of cHCC-CCA patients is poor, and most patients experience relapse within a short period of time after surgery. Preoperative tumor biomarker (CA19-9, alpha-fetoprotein) levels, tumor size, and Child-Pugh score can significantly affect OS. Adjuvant TACE after surgery prolongs RFS, suggesting that TACE is a possible option for postoperative adjuvant therapy in patients with cHCC-CCA.

BackgroundDiffusion Weighted (DW) Magnetic Resonance Imaging (MRI) has been studed in several cancers including cervical cancer. This study was designed to investigate the association of DW-MRI parameters with baseline clinical features and clinical outcomes (local regional control (LRC), disease free survival (DFS) and disease specific survival (DSS)) in cervical cancer patients treated with definitive chemoradiation.Methods This was a retrospective study approved by an institutional review board that included 66 women with cervical cancer treated with definitive chemoradiation who underwent pre-treatment MRI at our institution between 2012 and 2013. A region of interest (ROI) was manually drawn by one of three radiologists with experience in pelvic imaging on a single axial CT slice encompassing the widest diameter of the cervical tumor while excluding areas of necrosis. The following apparent diffusion coefficient (ADC) values (×10−3 mm2/s) were extracted for each ROI: Minimum - ADCmin, Maximum - ADCmax, Mean - ADCmean, and Standard Deviation of the ADC - ADCdev. Receiver operating characteristic (ROC) curves were built to choose the most accurate cut off value for each ADC value. Correlation between imaging metrics and baseline clinical features were evaluated using the Mann Whitney test. Confirmatory multi-variate Cox modeling was used to test associations with LRC (adjusted by gross tumor volume – GTV), DFS and DSS (both adjusted by FIGO stage). Kaplan Meyer curves were built for DFS and DSS. A p-value < 0.05 was considered significant.Women median age was 52 years (range 23–90). 67 % had FIGO stage I-II disease while 33 % had FIGO stage III-IV disease. Eighty-two percent had squamous cell cancer. Eighty-eight percent received concurrent cisplatin chemotherapy with radiation. Median EQD2 of external beam and brachytherapy was 82.2 Gy (range 74–84).ResultsWomen with disease staged III-IV (FIGO) had significantly higher mean ADCmax values compared with those with stage I-II (1.806 (0.4) vs 1.485 (0.4), p = 0.01). Patients with imaging defined positive nodes also had significantly higher mean (±SD) ADCmax values compared with lymph node negative patients (1.995 (0.3) vs 1.551 (0.5), p = 0.03).With a median follow-up of 32 months (range 5–43) 11 patients (17 %) have developed recurrent disease and 8 (12 %) have died because of cervical cancer. ROC curves based on DSS showed optimal cutoffs for ADCmin (0.488 × 10−3), ADCmean (0.827 × 10−3), ADCmax (1.838 × 10−3) and ADCdev (0.148 × 10−3). ADCmin higher than the cutoff was significantly associated with worse DFS (HR = 3.632–95 % CI: 1.094–12.054; p = 0.035) and DSS (HR = 4.401–95 % CI: 1.048–18.483; p = 0.043).ConclusionPre-treatment ADCmax measured in the primary tumor may be associated with FIGO stage and lymph node status. Pre-treatment ADCmin may be a prognostic factor associated with disease-free survival and disease-specific survival in cervical cancer patients treated with definitive chemoradiation. Prospective validation of these findings is currently ongoing.