Positive Para-aortic Nodes Research Articles

Assessing para-aortic nodal status in high-grade endometrial cancer patients with negative pelvic sentinel lymph node biopsy.

To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs. This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis. Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%. The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification.

Sentinel node mapping decreases the risk of failed detection of isolated positive para-aortic lymph node in endometrial cancer

BackgroundIsolated positive para-aortic lymph node metastasis in endometrial cancer is an uncommon event, ranging from 1% to 3%.ObjectiveOur aim was to evaluate the impact of sentinel lymph node (SLN) mapping...

Survival associated with the use of sentinel lymph node in addition to lymphadenectomy in early-stage cervical cancer treated with surgery alone: A sub-analysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

AimThe aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer. MethodsInternational, multicenter, retrospective study. Inclusion criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy (‘SLN’ group) or pelvic lymphadenectomy alone (‘non-SLN’ group). Results1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5–98.5 versus 92.0 %,95 %CI:90.0–94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8–99.9 versus 96.8 %,95 %CI:95.4–98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266–0.959, p = 0.037 and HR:2.703,95 %CI:1.389–5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039). ConclusionAdding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer.

Para-aortic Lymph Node Dissection for Colorectal Cancer: Predicting Pathologic Lymph Node Positivity and Optimizing Outcomes.

In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.

Adjuvant chemotherapy following concurrent chemoradiation (CRT) in patients with high-risk early-stage cervical carcinoma following radical hysterectomy: Results of NRG oncology/RTOG 0724/GOG-0724.

5504 Background: To assess the efficacy of adjuvant systemic chemotherapy following CRT for patients (pts) with high-risk early-stage cervical carcinoma. Methods: Pts with clinical stage IA2, IB, or IIA cervical carcinoma with at least one of the following high-risk features after radical hysterectomy: positive pelvic nodes, positive parametrium, and/or positive para-aortic nodes were stratified by intention to use brachy (yes v no), RT (Standard v IMRT); and RT dose (45 v 50.4 Gy) then randomized 1:1 to CRT or CRT and 4 cycles of adjuvant chemotherapy with paclitaxel and carboplatin (CRT + chemo). Primary endpoint was disease-free survival (DFS: death, local or regional failure, or distant mets). Reported secondary endpoints are OS (death due to any cause) and AEs (CTCAEv4). Sample size was 235 pts (50 DFS events, HR=0.47, corresponding to an increase in 4-year DFS from 80% to 90% for the CRT + chemo arm, 80% power, 1-sided log-rank α=0.05). Multivariable analysis (MVA) used Cox regression models. Results: From 9/16/2009 to 3/2/2022, this phase III international trial enrolled 236 pts, with 212 eligible/analyzed (109 CRT and 103 CRT + chemo). Median age was 46 yrs (min-max: 25-77) and median follow-up for all pts was 4.5 yrs (min-max: 0.02-12.8). Fifty-one percent of pts identified as white, 39% as Asian, and 6% Black. Most pts had squamous cell carcinoma (76%), with 18% adenocarcinoma and 5% adenosquamous. 56% of pts had open radical hysterectomy, 23% laparoscopic, and 22% robotic. Most pts had stage IB (87%) and 74% had positive pelvic nodes. Four (4%) pts on the CRT arm and 1 (1%) patient on CRT + chemo did not receive RT. The median (min-max) RT dose delivered was 50.4 Gy (7.2-60.4). Four pts (2 on each arm) did not receive concurrent cisplatin and 27 (26%) pts did not receive adjuvant carboplatin and paclitaxel on the CRT + chemo arm. Grade 3 and 4 events occurred in 36% and 7% of CRT pts; 44% and 21% in the CRT + chemo arm. There were 50 failures, 26 and 24 on the CRT and CRT + chemo arms, respectively, with 4-yr DFS estimates of 76% (90% CI: 69%, 83%) and 77% (90% CI: 70%, 84%) for the CRT and CRT + chemo arms, respectively (HR=1.05 [90% CI: 0.65, 1.68], p=0.56). Thirty-seven of 50 first failures were distant [74%], 20 (40%) and 17 (34%) in CRT and CRT + chemo arms, respectively. On MVA, factors that were statistically significant for worse DFS were receiving vaginal brachy (p<0.0001), RT dose ≥50 Gy (p=0.0021), and adenocarcinoma histology (p=0.03). Pts receiving brachy had close or positive margins. The estimated 4-yrs OS is 87% (90% CI: 82%, 93%) and 89% (90% CI: 84%, 94%) for the CRT and CRT +chemo arms, respectively (HR=0.91 [90% CI: 0.49 to 1.69]; 1-sided log-rank p=0.40). Conclusions: The addition of systemic chemotherapy following CRT didn't improve DFS or OS in cervical cancer patients with high-risk factors after radical hysterectomy. Clinical trial information: NRG Oncology/RTOG 0724/GOG-0724.

Prognostic factors and the role of primary debulking in operable stage IVB ovarian cancer with supraclavicular lymph node metastasis: a retrospective study in Chinese patients

BackgroundRecent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis.MethodsWe retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT).ResultsIn 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as “continuous-metastasis type”, while the other 7 (13.7%) defined as “skip-metastasis type”. Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3–63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that “continuous-metastasis type” had longer OS and PFS than “skip-metastasis type” (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among “continuous-metastasis type” patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors.ConclusionsIn stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as “continuous-metastasis type” with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected.

The impact of positive para-aortic lymph nodes on survival in resected pancreatic ductal adenocarcinoma: a retrospective single-center study

The impact of positive para-aortic lymph nodes on survival in resected pancreatic ductal adenocarcinoma: a retrospective single-center study

Poor Survival Outcomes in Patients with Stage IIIC2 Cervical Cancer Receiving Concurrent Chemoradiotherapy

Patients with cervical cancer who have para-aortic lymph nodes metastasis are staged as IIIC2 according to the 2018 FIGO staging system. In this study, we evaluated the survival and toxicity outcomes of patients with stage IIIC2 cervical cancer who received concurrent chemoradiotherapy. We included patients with stage IIIC2 cervical cancer who received definitive concurrent chemoradiotherapy at our institute between 2007 and 2015. The treatment consisted of intensity modulated radiation therapy (IMRT) delivering a dose of 50.4 Gy in 28 fractions to the pelvic and para-aortic lymph node regions, with escalated doses of 60-70 Gy for positive lymph nodes. A dose of 30 Gy in 5 fractions was delivered with intracavitary brachytherapy. The first-line chemotherapy regimen was weekly cisplatin. A total of 88 patients were included in the study. The median follow-up periods for all patients and surviving patients were 20 months (range: 5-114 months) and 62 months (range: 5-114 months), respectively. The median survival was 20.9 months. The 1-year, 3-year, 5-year, and 8-year overall survival rates were 73.4%, 41.3%, 34.5%, and 25.3%, respectively, while the progression-free survival rates were 50.8%, 29.7%, 28.4%, and 21.2%. The local control rates were 58.6%, 52.2%, 52.2%, and 42.8%, respectively. Multivariate analysis showed that the number of positive para-aortic lymph nodes and histology type were independent factors affecting progression-free survival. The 5-year progression-free survival rates were 40.2% and 0% for patients with one and two or more positive para-aortic lymph nodes, respectively, and 30.1% and 21.4% for patients with squamous cell carcinoma and adenocarcinoma, respectively. Grade 3 or higher toxicities were observed in 8 patients (9.1%), including 4 patients (4.5%) with gastrointestinal toxicities and 4 patients (4.5%) with genitourinary toxicities. The results of this study suggest that the survival outcomes of patients with stage IIIC2 cervical cancer receiving concurrent chemoradiotherapy were poor. Further treatment options, such as consolidation chemotherapy or immunotherapy, should be considered for these patients.

Impact of Lymphopenia on Definitive Treatment of Locally Advanced Cervical Cancer

Pre-treatment lymphopenia prior to initiating treatment has been correlated with reduced survival in a number of different cancers. The purpose of this study is to evaluate the association between lymphopenia and survival in women with locally advanced cervical cancer (LACC) treated with primary chemoradiation (CRT). We retrospectively reviewed patients with LACC treated at a single institution from 2005 - 2021 with available lymphocyte information. Patient and treatment characteristics were recorded including age, tumor size and stage, EBRT dose/fractionation, and brachytherapy dosimetry data. Absolute lymphocyte counts (ALC) were collected prior to initiating CRT and at 3-month intervals following CRT and graded based on severity of lymphopenia using CTCAE v 5.0. Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated from the start of treatment to date of last follow-up. Kaplan-Meier survival analysis was performed to evaluate whether lymphocyte changes were associated with OS, PFS, or LC. A total of 124 patients met study inclusion criteria with stage IB - IV disease (41 stage I, 41 stage II, 36 stage III, 6 stage IV) and a median follow up of 3.6 years (range 0.2-16.5 years). The median age was 49 years (range 26-77). The median EBRT dose was 45 Gy (range: 26-57.5 Gy) and 44.2% of patients received para-aortic (PA) nodal EBRT (28.8% elective and 15.4% with positive PA nodes). 5-year OS, PFS, and LC were 60.3% (95% CI 51.5-70.7), 47.5% (95% CI 39-58), and 75.5% (95% CI 67.3-82.9), respectively. Pre-treatment lymphopenia (ALC <1000 cells/mm3) was present in 11 (9%) patients. When the total cohort was divided into patients with and without pre-treatment lymphopenia, OS was statistically improved in the patients without baseline lymphopenia, with a 5-year OS of 63.2% (95% CI 53.9-73.9) versus 35.3% (95% CI 14.5-86.3) in the lymphopenia group (p = 0.034). LC also trended to being improved in the patients without lymphopenia, though this did not reach statistical significance in our small sample size of lymphopenic patients, with 5-year LC of 76.8% (95% CI 68.4-84.3) versus 67.5% (05% CI 36.6-93.8), p = 0.45. In this single institution experience of LACC treated with definitive CRT, we found that baseline lymphopenia is associated with inferior OS. Patients with higher pre-CRT ALC may represent a population with more robust immune systems, producing more favorable tumor responses to treatment. Additional studies are warranted to investigate the evolving role of combined EBRT and systemic therapy in LACC.

A Cost-Effective, Machine Learning-Based New Unified Risk-Classification Score (NU-CATS) for Patients with Endometrial Cancer

Treatment for endometrial cancer (EC) with radiotherapy is increasingly guided by molecular risk classifications. Derived from genomic profiling of The Cancer Genome Atlas (TCGA) project, several EC risk classification systems, including ProMisE and Leiden/TransPORTEC, have been developed. However, the current systems were developed on a relatively homogeneous population. Black or African American (BOAA) patients have consistently been demonstrated to have worse stage-adjusted prognosis than Caucasians. Given this, we intended to develop a new unified risk classification system (NU-CATS) for EC patients using machine learning (ML) utilizing datasets with demographically diverse populations. TCGA-Uterine Corpus Endometrial Carcinoma (n = 596), Memorial Sloan Kettering-Metastatic Events and Tropisms (MSK-MET, n = 1,315) and the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR-GENIE, n = 4,561) were used to identify genetic alterations and clinicopathological features, including age, race, stage, histologic grade and features, and distribution of metastatic disease. Software packages including Keras, Pytorch, and Scikit Learn were tested to build artificial neural networks (ANNs) with a binary output as either intra-abdominal metastatic lesions vs. non-metastatic. A 5-layered ANN (5-6-4-2-1) using 5 inputs ('age at surgery', 'histology', 'race', 'mismatch repair status' and 'TP53'). The optimal performing ANN was selected and cross validated. The weights and biases of the trained ANN were used to reconstruct the algorithm. BOAA patients with EC have worse prognosis than Caucasians, adjusting for TP53 or POLE mutation status. TP53 is the most common gene differentially altered by race in EC. Over 75% of BOAA patients carry TP53 mutations as compared to approximately 40% of Caucasians. Older age is associated with an increasing likelihood of TP53 mutations, high risk histology, and distant metastasis. For patients above age 70, 91% of BOAA and 60% of Caucasian EC patients carry TP53 mutations. The NU-CATS that incorporates age, race, histology, mismatch repair (MMR) status, and TP53 mutation status showed 75% accuracy in prognosticating intra-abdominal metastasis. A higher NU-CATS (>50) is associated with about 2-fold increased risk of having positive pelvic or para-aortic lymph nodes (LNs) and distant. NU-CATS was shown to outperformed TransPORTEC model for estimating risk of FIGO Stage I/II disease progression and survival in BOAA EC patients. Despite adjusting for molecular classification, race and age retain prognostic importance in EC. NU-CATS, a ML-based, cost-effective algorithm, incorporates diverse clinicopathologic and molecular variables of EC, and yields superior prognostication of the risk of nodal involvement, distant metastasis, disease progression, and overall survival as compared to other classification systems.

Predicting Lymph Node Metastasis From Primary Cervical Squamous Cell Carcinoma Based on Deep Learning in Histopathologic Images

We developed a deep learning framework to accurately predict the lymph node status of patients with cervical cancer based on hematoxylin and eosin–stained pathological sections of the primary tumor. In total, 1524 hematoxylin and eosin–stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes). We constructed and trained a multi-instance deep convolutional neural network based on a multiscale attention mechanism, in which an internal independent test set (100 patients, 228 WSIs) from the FUSCC cohort and an external independent test set (159 patients, 363 WSIs) from the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program database were used to evaluate the predictive performance of the network. In predicting the occurrence of lymph node metastasis, our network achieved areas under the receiver operating characteristic curve of 0.87 in the cross-validation set, 0.84 in the internal independent test set of the FUSCC cohort, and 0.75 in the external test set of the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program. For patients with positive pelvic lymph node metastases, we retrained the network to predict whether they also had para-aortic lymph node metastases. Our network achieved areas under the receiver operating characteristic curve of 0.91 in the cross-validation set and 0.88 in the test set of the FUSCC cohort. Deep learning analysis based on pathological images of primary foci is very likely to provide new ideas for preoperatively assessing cervical cancer lymph node status; its true value must be validated with cervical biopsy specimens and large multicenter datasets.

Curative treatment for stage IIIC2 cervical cancer: what to expect?

Since the GOG125 study, treating radically patients with positive para-aortic lymph nodes has been a valid approach. Nevertheless, literature lacks data on how to better treat these patients since they are usually excluded from trials. In this study, we aimed to report the outcomes of patients with advanced cervical cancer and positive para-aortic lymph nodes (PAN) treated in a single tertiary/academic institution and try to identify variables that may impact survival. We retrospectively reviewed patients with positive para-aortic lymph nodes treated in our institution. Demographic variables and treatment options were assessed and their impact on overall survival (OS), locorregional control, distant metastasis free survival, and para-aortic lymph node progression was analyzed. We assessed 65 patients treated from April 2010 to May 2017. Median OS was 38.7 months. Median locorregional and para-aortic progression free survivals were not reached. Median distant metastasis progression-free survival was 64.3 months. Better ECOG performance status (p > 0.001), concurrent chemotherapy (p = 0.031), and brachytherapy (p = 0.02) were independently related to better overall survival. Patients with current stage IIIC2 cervix cancer may present long term survival. Treating positive PAN cervical cancer patients with concurrent chemoradiation including brachytherapy with curative intent should be standard. Poor PS and more advanced pelvic disease may represent a higher risk for worse outcomes. Distant metastases are still a challenge for disease control.

A cost-effective, machine learning-based new unified risk-classification score (NU-CATS) for patients with endometrial cancer

IntroductionTreatment for endometrial cancer (EC) is increasingly guided by molecular risk classifications. Here, we aimed at using machine learning (ML) to incorporate clinical and molecular risk factors to optimize risk assessment. MethodsThe Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma (n = 596), Memorial Sloan Kettering-Metastatic Events and Tropisms (n = 1315) and the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (n = 4561) datasets were used to identify genetic alterations and clinicopathological features. Software packages including Keras, Pytorch, and Scikit Learn were tested to build artificial neural networks (ANNs) with a binary output as either intra-abdominal metastatic progression (‘1’) vs. non-metastatic (‘0’). ResultsBlack patients with EC have worse prognosis than White patients, adjusting for TP53 or POLE mutation status. Over 75% of Black patients carry TP53 mutations as compared to approximately 40% of White patients. Older age is associated with an increasing likelihood of TP53 mutation, high risk histology, and distant metastasis. For patients above age 70, 91% of Black and 60% of White EC patients carry TP53 mutations. A ML-based New Unified classifiCATion Score (NU-CATS) that incorporates age, race, histology, mismatch repair status, and TP53 mutation status showed 75% accuracy in prognosticating intra-abdominal progression. A higher NU-CATS is associated with an increasing risk of having positive pelvic or para-aortic lymph nodes and distant metastasis. NU-CATS was shown to outperform Leiden/TransPORTEC model for estimating risk of FIGO Stage I/II disease progression and survival in Black EC patients. ConclusionThe NU-CATS, a ML-based, cost-effective algorithm, incorporates diverse clinicopathologic and molecular variables of EC and yields superior prognostication of the risk of nodal involvement, distant metastasis, disease progression, and overall survival.

The prognostic value of the presence of pelvic and/or para-aortic lymph node metastases in cervical cancer patients; the influence of the new FIGO classification (stage IIIC)

IntroductionOne of the major changes in the revised (2018) FIGO-staging system is the addition of stage IIIC to the previously used 2009 system. We evaluated the prognostic value of positive pelvic and/or para-aortic lymph nodes in patients with cervical cancer. MethodsA nationwide retrospective cohort study was performed by analyzing data from the Netherlands Cancer Registry. All patients newly diagnosed with stage IB-IVA between 2005 and 2018 were identified. Three-year, 5-year and 15-year overall survival (OS) rates were estimated with the Kaplan-Meier method. ResultsOf the included 6082 patients, 1740 patients (29%) had pelvic and/or para-aortic lymph node metastases. For patients with FIGO 2009 stage IB-IB1-IIA-IIA1 and stage IB2-IIA2-IIB with pelvic and/or para-aortic lymph node metastases the OS was significantly different (p < 0.001 and p = 0.009), with a 5-year OS of 77% and 67%, compared with 92% and 74% for women without lymph node metastases. For FIGO 2009 stage IIIA-IIIB-IVA with and without lymph node metastases, survival rates are not significantly different (p = 0.064). For FIGO 2018 stage IIIC the 3y-OS, 5y-OS and 15-year OS are 72%, 65% and 59% respectively. Survival rates of IIIC diagnosed based on imaging (IIICr) are significantly impaired compared to stage IIIC diagnosed based on pathology (IIICp) (p < 0.001). ConclusionPatients with FIGO 2009 stage IB–IIB cervical cancer with pelvic and/or para-aortic lymph node metastases have significantly impaired survival compared to patients without metastases. Survival rates of patients with FIGO 2009 stage IIIA–IVA are not affected by lymph node metastases.

Safety and efficacy of conversion therapy for esophageal squamous cell carcinoma.

362 Background: The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable esophageal squamous cell carcinoma (ESCC) after initial treatment. Conversion therapy has been commonly defined as treatment aiming at a curable intention after tumors initially deemed technically or oncologically unresectable or only marginally resectable respond to chemotherapy. In our institute, conversion therapy is considered for patients with para-aortic lymph node-positive advanced ESCC who have no other distant metastasis, if the para-aortic lymph node metastases have disappeared after systemic chemotherapy. Methods: There were 33 patients of unresectable esophageal cancer with positive para-aortic lymph node metastases from 2011 to 2021. Nine of these patients showed disappearance of para-aortic lymph node metastases and underwent conversion therapy, seven patients underwent esophagectomy and two patients underwent chemoradiation therapy (CRT). Characteristics, short-term and long-term results of these nine cases are studied. Results: All of the nine patients who had para-aortic lymph node metastases were treated with induction DCF (Docetaxel + Cisplatin + 5-FU) therapy as initial treatment. After disappearance of para-aortic lymph node metastasis, minimally invasive or open esophagectomy was performed in seven patients and CRT was performed in two patients. In operation group, four patients (57%) had Clavien-Dindo grade 2 or 3 complications, but no perioperative death was observed. In CRT group, there was no toxicity over CTCAE grade 3. Four of nine patients (44%) had recurrence, within mediastinum lymph node, abdominal lymph node or adrenal gland. 3-year DFS was 56% and 3-year OS was 67%. Conclusions: Conversion therapy is safe and feasible in cases that responded to systemic chemotherapy. Some cases showed good prognosis. Long-term survival is expected with conversion therapy. In our study, there was few cases that could led to conversion therapy. It is expected that more aggressive initial chemotherapy will be used in the future for patients with positive para-aortic lymph node metastases with a view to conversion therapy.

PARa-aOrtic LymphAdenectomy in locally advanced cervical cancer (PAROLA trial): a GINECO, ENGOT, and GCIG study

BackgroundPositron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification...

The Impact of Racial Disparities on Outcome in Patients With Stage IIIC Endometrial Carcinoma: A Pooled Data Analysis.

To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma. A retrospective multi-institutional study included 90 black and 568 non-black patients with stage IIIC endometrial carcinoma who received adjuvant chemotherapy and radiation treatments. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method. Propensity score matching (PSM) was conducted. Statistical analyses were conducted using SPSS version 27. The Median follow-up was 45.3 months. black patients were significantly older, had more nonendometrioid histology, grade 3 tumors, and were more likely to have >1 positive paraaortic lymph nodes compared with non-black patients (all P <0.0001). The 5-year estimated OS and RFS rates were 45% and 47% compared with 77% and 68% for black patients versus non-black patients, respectively ( P <0.001). After PSM, the 2 groups were well-balanced for all prognostic covariates. The estimated hazard ratios of black versus non-black patients were 1.613 ( P value=0.045) for OS and 1.487 ( P value=0.116) for RFS. After PSM, black patients were more likely to receive the "Sandwich" approach and concurrent chemoradiotherapy compared with non-black ( P =0.013) patients. Black patients have higher rates of nonendometrioid histology, grade 3 tumors, and number of involved paraaortic lymph nodes, worse OS, and RFS, and were more likely to receive the "Sandwich" approach compared with non-black patients. After PSM, black patients had worse OS with a nonsignificant trend in RFS. Access to care, equitable inclusion on randomized trials, and identification of genomic differences are warranted to help mitigate disparities.

Pattern of Care of Recurrent Cervical Cancer in Low-resource Settings: Challenges and Patient-initiated Follow-up as a Novel Opportunity.

The availability of optimum diagnostic strategies remains a major problem in resource-constraint countries. This technique of patient-initiated follow-up (PIFU) has been recently adopted in the UK for gynecological cancers and has proven cost benefits. However, no study from the Indian subcontinent has ever been reported. The primary objective was to study the pattern of care of recurrent cervical cancer in low-resource settings. The secondary objective was to compare the reliability of symptomatology/clinical evaluation and imaging methods on follow-up to detect recurrence and thus explore the feasibility of symptom-based PIFU. This was a single-institutional retrospective analysis of recurrent cervical cancer cases for a period of 3 years from January 2019 to January 2022. Patients who followed up for minimum of 6 months were included in the study. In 57 of the total 69 patients, symptoms alone were the index diagnostic method. Interestingly, neither of the methods of recurrence detection had impact on overall survival (OS). Cox regression analysis revealed adverse impact of erratic/lost to follow-up (hazard ratio [HR] = 3.8) and pelvic side wall disease (HR = 1.33) on survival. Patients with positive para-aortic nodes had significantly shorter disease-free interval of 11 months, so adding systemic therapy to adjuvant treatment in this cohort needs to be further investigated. Our analysis showed that patients with recurrence who were diagnosed with clinical manifestations alone vis-à-vis the ones who were diagnosed primarily on routine follow-up visit by some imaging or diagnostic test had comparable oncologic outcomes. PIFU can be a "practice changing modality" in patient management system, especially in low-resource settings. It will prove to be a simple cost-effective method to detect recurrence and prevent fallouts. Our study points to the feasibility of PIFU in Indian scenario.

Prognostic value of paraaortic lymph node metastases in patients with ductal adenocarcinoma of the pancreatic head

IntroductionThe role of paraaortic lymphadenectomy for cancer of the pancreatic head is controversial. The aim of this study is to analyze the prognostic role of paraaortic lymph node (PALN) metastases after resection for ductal adenocarcinoma of the pancreatic head. Materials and methodsA retrospective analysis of all patients, who underwent upfront resection for ductal adenocarcinoma of the pancreatic head at the Frankfurt University Hospital from 2011 to 2020 was performed. The primary endpoint was survival, according to the presence of PALN metastases. ResultsOut of 468 patients with pancreatic resection, 148 had an upfront resection for ductal adenocarcinoma. Of those, in 125 (85%) a paraaortic lymphadenectomy was performed. In 19 (15.2%) PALN metastases were detected. The estimated overall median survival after resection was 21.7 months (95% CI 18.8 to 26.4), the disease free survival 16 months (95% CI 12 to 18). Among the patients with lymph node metastases, PALN metastases had no significant influence on overall (18.9 versus 19 months, HR = 1.3, 95% CI 0.7 to 2.6, p = 0.392) or disease free survival (14 versus 10.7 months, HR = 1.7, 95% CI 0.9 to 3.2, p = 0.076). After adjusting for T-stage, N-stage, grade, resection margin, PALN metastases, and adjuvant therapy, only adjuvant therapy had a prognostic significance for overall survival (HR = 0.47, 95% CI 0.26 to 0.85, p = 0.013). ConclusionPatients with ductal adenocarcinoma of the pancreatic head and PALN metastases do not have inferior outcomes than those with regional lymph node metastases. Thus, positive PALN should not be considered a contraindication for resection.

Management of Radiographically Positive Pelvic and/or Para-aortic Lymph Nodes During Primary Chemoradiation Therapy for Cervix Cancer

Advanced imaging in the initial workup of cervix cancer has become standard of care and has led to the need for complex decision making regarding optimal management of locoregional nodal metastases. 1 National Comprehensive Cancer Network. Cervical cancer. National Comprehensive Cancer Network guidelines. 2021;1:1-90. Google Scholar When treating a patient with cervix cancer using primary radiation therapy (RT) or chemoradiation therapy (CRT), radiation oncologists must decide on the total radiation therapy dose and fractionation for radiographically positive pelvic and/or para-aortic lymph nodes. It is evident that nodal involvement negatively affects disease-free survival and risk of developing distant metastases; thus, the updated International Federation of Gynecology and Obstetrics (FIGO) 2018 cervix cancer staging system includes lymph node status. 2 MacDonald KO Chen J Dodson M et al. Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix. Am J Clin Oncol. 2009; 32: 411-416 Crossref PubMed Scopus (77) Google Scholar , 3 Kidd EA Siegel BA Dehdashti F et al. Lymph node staging by positron emission tomography in cervical cancer: Relationship to prognosis. J Clin Oncol. 2010; 28: 2108-2113 Crossref PubMed Scopus (241) Google Scholar , 4 Bhatla N Berek JS Fredes MC et al. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet. 2019; 145: 129-135 Crossref PubMed Scopus (413) Google Scholar This article will first summarize the available data regarding RT dose for positive nodes and then discuss the treatment typically used at our institutions.