Para-aortic Node Involvement Research Articles

ATOMICC trial: a randomized, open-label, phase II trial of anti-PD1, dostarlimab, as maintenance therapy for patients with high-risk locally advanced cervical cancer after chemoradiation

BackgroundCurrently, women diagnosed with high-risk locally advanced cervical cancer are at high risk of recurrence after treatment with concurrent chemoradiation and represent a population with high unmet need.Primary ObjectiveThe primary...

Interest of para-aortic lymphadenectomy for locally advanced cervical cancer in the era of PET scanning

Background and objectivesTreatment of locally advanced cervical cancer (LACC) involves pelvic chemoradiotherapy, using an extended field in the case of para-aortic involvement. 18-Fluoro-D-glucose positron emission tomography combined with computer tomography (PET-CT) is an accurate method for the detection of metastatic nodes. The objective of this study was to evaluate the performance of PET-CT for lymph node staging of LACC. MethodsThis bicentric retrospective study included patients with LACC who had a PET-CT scan followed by para-aortic lymphadenectomy between January 2015 and December 2019. Based on pathological findings, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and false-negative (FN) rates of PET-CT for para-aortic node involvement were evaluated. ResultsSeventy-one patients who had undergone laparoscopic lymphadenectomy were included in this study. The intraoperative complication rate was 2.8%. Sensitivity, specificity, NPV and PPV for PET-CT were 55% [95% confidence interval (CI) 44.6–67.1], 84% (95% CI 75–92), 93% (95% CI 87–99) and 33% (95% CI 22–44), respectively. FN rates in the case of negative or positive pelvic PET-CT were 5.7% and 9.5%, respectively. ConclusionsPara-aortic lymphadenectomy is recommended for lymph node staging in the case of negative para-aortic PET-CT. In view of the low FN rate of PET-CT, surgical staging should be discussed regardless of pelvic status if the patient presents high surgical risk, or if this delays the commencement of chemoradiotherapy.

262 FDG-PET/CT and para-aortic staging in endometrial cancer. a french multicentric study

Introduction and aims of the study: FDG-PET/CT is a noninvasive examination that could be helpful for the management of endometrial cancer. The aim of this study was to evaluate the performance of FDG-PET/CT in assessing para-aortic lymph-node involvement in high-risk endometrial cancer. Methods: We performed a retrospective multicenter study including all patients who had a high-risk endometrial cancer with a preoperative FDG-PET/CT and a para-aortic lymphadenectomy (PAL) between 2009 and 2019.

Long term outcomes of patients who underwent radical hsyterectomy for cervical cancer

Introduction: We aimed to examine the parameters affecting long-term prognosis and survival in patients diagnosed with early stage cervical cancer and undergoing radical hysterectomy in our Gynecology and Obstetrics Clinic.
 Material and Method: The files of 86 cervical cancer patients who underwent radical hysterectomy and pelvic paraaortic lymph node dissection for cervical cancer between 2010 and 2021 were retrospectively reviewed. Tumor size, FIGO stage, vagina, endometrium, ovary, parametrium, pelvic lymph node, paraaortic lymph node and deep stromal involvement were examined by examining the files and pathology reports of the patients. Then, the effects of these parameters on pelvic and paraaortic lymph node involvement, postoperative prognosis and survival of the patients were tried to be revealed.
 Results: The 86 patients included in the analysis had a mean age of 55.2 (range: 38-72) and a median tumor size of 35 mm (range: 2-74). Cell type was squamous cell carcinoma in 81.4% and adenocarcinoma in 18.6% of the patient group. During the follow-ups, recurrence was detected in 22 (25.6%) patients. During the follow-up period, it was found that 18 (20.9%) patients died. In univariate analysis, the presence of metastases in any lymph node was found to reduce DFS and OS. The mean follow-up period of the cases examined was 66 (min:12-max:132) months; The mean OS and DFS of the patients were 111.84 (95% CI:103.26-120.43) and 105.72 (95% CI:95.87-115.57) months, respectively.
 Conclusion: Pelvic and paraaortic lymph node involvement was found to be the most important prognostic factor regardless of histological type in cervical cancers. Survival was found to be significantly lower in patients with any lymph node involvement.

Neoadjuvant Chemotherapy in Locally Advanced Cervical Carcinoma – a Role in Patients with Para-aortic Lymph Node Involvement? A 10-year Institutional Experience

AimsOverall survival and progression-free survival with concomitant chemoradiotherapy for locally advanced cervical carcinoma have been described as 66% and 58%, respectively, at 5 years. Para-aortic lymph node involvement significantly increases the risk of relapse and death. The role of additional chemotherapy in these patients is as yet undefined. This aim of the present study was to determine the outcome of a cohort of para-aortic lymph node-positive patients treated with neoadjuvant chemotherapy followed by extended-field chemoradiation compared with patients treated with extended-field chemoradiation without neoadjuvant chemotherapy. Materials and methodsWe reviewed patients with International Federation of Gynaecology and Obstetrics (FIGO) 2014 stage IB1–IVA cervical carcinoma who received extended-field radiotherapy in addition to standard pelvic chemoradiotherapy with or without neoadjuvant chemotherapy, at University College London Hospital (January 2007 to January 2018). Patients in open clinical trials were excluded. ResultsOverall, 47 patients (15.8% of 298 eligible patients) with pelvic and/or para-aortic lymph node-positive cervical carcinoma received extended-field radiotherapy. Nineteen patients (40.4%) had both neoadjuvant chemotherapy (all received six cycles) and extended-field radiotherapy (median 44 days); 28 (59.6%) patients received extended-field radiotherapy alone (median 43 days). All patients completed radical radiotherapy within 49 days. We observed evidence that patients receiving neoadjuvant chemotherapy and extended-field radiotherapy had a lower risk of death (median follow-up 4.8 years, three deaths) compared with extended-field radiotherapy alone (median follow-up 3.0 years, 11 deaths; hazard ratio = 0.27, 95% confidence interval 0.08–1.00; P = 0.05). Three-year overall survival rates were 83.3% (95% confidence interval 66.1–100) and 64.6% (95% confidence interval 44.6–84.6), respectively. A PFS benefit was seen (hazard ratio 0.25, 95% confidence interval 0.08–0.77; P = 0.02), with 3-year PFS rates of 77.8% (95% confidence interval 58.6–97.0) and 35.0% (95% confidence interval 14.0–56.0), respectively. ConclusionsOur institutional experience suggests that the use of additional systemic therapy before chemoradiotherapy benefits patients with locoregionally advanced (FIGO 2018 IIIC2) cervical cancer. Neoadjuvant chemotherapy was associated with longer overall survival and PFS, without compromising definitive extended-field chemoradiation.

An International Survey of the Operative Management of Gallbladder Cancer (OMEGA-S) – Global Consistency or Widespread Heterogeny?

Introduction: The rarity of gallbladder cancer (GBC) means that definitive evidence for optimal management is lacking. The extent of variability in diagnostic workup and management of GBC across HPB units globally has not been hitherto assessed. Method: A survey on the management of GBC was designed by the EAHPBA Scientific and Research committee and OMEGA study collaborators and disseminated to EAHPBA, A-PHPBA and AHPBA members. Results: Over 110 surgeons responded from more than 35 countries. Pre-operative staging was mainly via CT, while PET was predominantly performed for suspected metastases. Factors considered contraindications to resection varied between centres. Solitary right-sided liver metastasis or main portal vein involvement were only considered contraindications to resection by around 50% of centres. Half the centres would abort planned surgery if coeliac, SMA or para-aortic nodal involvement was suspected preoperatively for any stage of disease. However, for T3/4 tumours, regardless of pre-operative imaging appearances, a quarter of centres always resected this group of lymph nodes and 50% of centres always sampled para-aortic nodes for frozen section. SIVb/V resections were more commonly performed for T2b compared to T2a tumours, and extent of liver resection increased with stage of disease. Hepaticojejunostomy was always performed for T3/4 disease in 20% of units regardless of cystic duct margin histology. Conclusions: This is the first survey of GBC management across HPB units internationally, highlighting areas of consistency but also surprising areas of heterogeneity. More robust evidence and clinical trials are required to help guide the management and improve outcomes from GBC.

High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy

PurposeTumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer.Materials and methodsTMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel.ResultsThe study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy.ConclusionThese data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy.Secondary abstractThis retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.

Pathologic Primary Tumor Factors Associated With Risk of Lymph Node Involvement in Patients With High-Risk Endometrial Cancer

National Comprehensive Cancer Network guidelines recommend adjuvant systemic therapy with or without external beam radiation and/or intravaginal brachytherapy for high-risk endometrial cancer histologies. Being able to estimate the risk of pelvic/para-aortic lymph node (LN) involvement could assist in making clinical decisions regarding whether to treat with external beam versus brachytherapy alone. The National Cancer Data Base was queried to develop predictive nomograms based on primary uterine factors to estimate the risk of pathologic LN involvement.Patients diagnosed with pathologic T1-T2 clear cell, uterine papillary serous (UPS), carcinosarcoma, or mixed endometrial cancer between 2004-2016 undergoing primary surgery with at least 10 LNs sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Pathologic variables assessed included primary tumor histology, pathologic tumor stage, tumor size, and presence/absence of lymphovascular invasion (LVI). Nomograms were created to predict overall, pelvic only, and paraaortic and/or pelvic LN involvement.Among 7,918 patients included, 1,407 (18%) were node positive. On multivariable analysis, relative to carcinosarcoma, both clear cell (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.34-2.32, P < 0.001) and UPS (OR 1.76, 95% CI 1.46-2.13, P < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.14, 95% CI 0.95-1.37, P = 0.16). Furthermore, increasing pathologic tumor stage (pT2 versus pT1a, OR 3.62, 95% CI 3.04-4.28, P < 0.001), increase in tumor size per centimeter (OR 1.09, 95% CI 1.06-1.11, P < 0.001), and presence of LVI (OR 5.23, 95% CI 4.58-6.02, P < 0.001) were predictive of overall LN positivity. Nomograms demonstrated that the impact of primary tumor pathologic variables was comparable for predicting any LN involvement, pelvic only, and paraaortic with or without pelvic LN involvement.Among endometrial cancer patients with high-risk histologies, predictors of LN positivity are similar to those with endometrial adenocarcinoma. Patients with carcinosarcoma are the least likely to be diagnosed with node positive disease relative to other high-risk histologies. Predictive nomograms can help to individualize the risk of pelvic and paraaortic LN involvement and may assist in adjuvant treatment decisions.E. Anderson: None. M. Luu: None. D.J. Lu: None. E.M. Chung: None. M. Kamrava: American Board of Radiology, Brachytherapy Journal, American Brachytherapy Society Board of Directors. Co-Editor; Journal of Contemporary Brachytherapy.

Para-aortic lymph node involvement in cervical cancer: Implications for staging, outcome and treatment.

Locally advanced cervical cancer with the involvement of para-aortic lymph nodes (PALN) is a common occurrence in low-income and low-middle-income countries. With the incorporation of PALN in the recent FIGO staging, therapeutic management becomes crucial. There are varied presentations of this group which may range from microscopic involvement to extensive lymphadenopathy. Various imaging modalities have been studied to accurately diagnose PALN metastases without surgical intervention, while some investigators have studied the survival benefit of para-aortic lymph node dissection for accurate staging and guiding extent of radiation. With recent advances in radiation therapy, its application to treat bulky nodal metastases and the role of prophylactic irradiation have been reported. In this review, the available evidence and the scope of further interventions is presented.

What is the impact of corpus uterine invasion on oncologic outcomes in surgically treated cervical cancer?

To investigate the clinical significance of uterine corpus involvement in patients with surgically treated cervical cancer. Patients (n=354) with clinical early-stage (stage IB1-IIA2) cervical cancer who underwent radical hysterectomy and pelvic ± paraaortic lymphadenectomy were evaluated. Uterine invasion was detected in 60 (16.9%) patients. Patients with uterine invasion had a higher rate of pelvic lymph node metastasis than those without uterine invasion (35% vs 22.8%, p=0.046). In multivariate analysis, no statistically significant difference was identified between patients with and without uterine invasion for pelvic lymph node metastasis (p=0.953). Uterine invasion was identified as an independent risk factor for paraaortic lymph node metastasis in multivariate analysis (p=0.012). The presence of pelvic lymph node metastasis was found to be another significant predictor of paraaortic lymph node involvement (p=0.022). In addition, uterine invasion and lymph node metastasis were identified as an independent risk factors regarding poor prognosis in cancer-specific survival (hazard ratio [HR]: 4.537; 95% confidence interval [CI], 1.304-15.782; p=0.017 and HR: 5.598; 95% CI, 1.581-19.823; p=0.008, respectively). Uterine invasion is an independent predictor of decreased survival and the presence of paraaortic lymph node metastasis in cervical cancer. The presence of the uterine invasion in cervical cancer should be considered as a poor prognostic factor in the decision of treatment.

Impact of nodal boost irradiation and MR-based brachytherapy on oncologic outcomes in node-positive cervical cancer

This study aimed to prospectively evaluate the impact of dose-escalated irradiation of nodal metastases on clinical outcomes compared to no boost in patients with node-positive, bulky, locally advanced cervical cancer (LACC) undergoing standard chemoradiation and MRI-based brachytherapy. MethodsThis comparative study included 161 patients with node-positive LACC treated with definitive chemoradiation and MRI-based brachytherapy. The prospective Boost arm accrued 71 patients to receive nodal boost either sequentially or simultaneously to an equivalent dose of 60 Gy. The control arm comprised 90 patients treated before this protocol period with no additional nodal boost. ResultBaseline patient and tumor characteristics were similar in both groups. All patients had at least one tumor dimension >5 cm at presentation, and 31% had para-aortic node involvement. With a median follow-up of 36 months (IQR:19–50.5), the overall 3-year Local control rate was 88.8%. The 3-year Regional control (93% vs. 80%, p = 0.035) was statistically better in the Boost arm. No nodal failure was observed in nodes <3 cc and < 2 cm, even in the No-boost arm. There was no significant difference in Disease-free survival (67.6% vs. 58.9%,p = 0.454) and Overall Survival (78.9% vs. 74.4%,p = 0.87) between the two arms. Incidence of acute or late toxicities did not differ significantly with nodal boost or the boost delivery technique. ConclusionThe addition of external radiation nodal boost to standard treatment of high-volume cervical cancer has improved pelvic control with an acceptable rate of toxicities. However, high systemic failures continue to pose a challenge in improving survival outcomes.

Mapping patterns of para-aortic lymph node recurrence in cervical cancer: a retrospective cohort analysis

BackgroundTo map anatomic patterns of para-aortic lymph node (PALN) recurrence in cervical cancer patients and validate currently available guidelines on PA clinical target volumes (CTV).MethodsCervical cancer patients who developed PALN recurrence were included. The PALNs were classified as left-lateral para-aortic (LPA), aorto-caval (AC), and right para-caval (RPC). Four PA CTVs were contoured for each patient to validate PALN coverage. CTVRTOG was contoured based on the Radiation Therapy Oncology Group guideline. CTVK was contoured as proposed by Keenan et al. CTVM was contoured by expanding symmetrical margins around the aorta and inferior vena cava of 7 mm up to the T12–L1 interspace. CTVnew was created by modifying CTVRTOG to obtain better coverage.ResultsWe identified 92 PALNs in 35 cervical cancer patients. 46.8% of the PALNs were at LPA, 38.0% were at AC, and 15.2% were at RPC areas. CTVRTOG, CTVK, and CTVM covered 87.0%, 88.0%, and 62.0% of all PALNs, respectively. PALN recurrence above the left renal vein was associated with PALN involvement at diagnosis (p = 0.043). Extending upper border to the superior mesenteric artery allowed the CTVnew to cover 96.7% of all PALNs and all nodes in 91.4% of patients.ConclusionCTVRTOG and CTVK encompassed most PALN recurrences. For high-risk patients, such as those having PALN involvement at diagnosis, extending the superior border of CTV from the left renal vein to superior mesenteric artery could be considered.

How to predict para-aortic node involvement in advanced cervical cancer? Development of a predictive score. A FRANCOGYN study

IntroductionNode involvement is one of the main prognostic factors for cervical cancer. Para-aortic lymph node (PALN) assessment is crucial for treating advanced cervical cancer, to define irradiation fields. Objective of this study was to develop a score predicting para-aortic lymph node involvement in patients with advanced cervical cancer. Patients and methodWe performed a multicenter, retrospective, study on 9 French centers from 2000 to 2015, including patients with advanced squamous cell cervix carcinoma who had PALN status assessed by imaging and/or by surgery. Factors associated with a risk of PALN involvement were determined by univariate and multivariate analysis using a logistic regression model. A score was then developed and validated. ResultsA total of 1446 patients treated for cervical cancer were included. Of these, 498 had an advanced squamous cell cervical cancer. Ninety-one patients (18.3%) had positive PALN. After univariate and multivariate analysis, tumor size on pelvic MRI, initial SCC, and suspected pelvic node involvement on PET-CT were included in our score. This model allowed the population to be divided into 3 risk groups. Area under the ROC curve of the score was 0.81 (95%CI = 0.72–0.90). In the low-risk group, 9% (28/287) had PALN involvement, whereas in the high-risk group, 43% (22/51) had PALN involvement. ConclusionWe developed a simple score predicting PALN involvement in advanced cervical cancers. Three risk groups can be defined, and patients considered to be at low risk may avoid para-aortic staging as well as extensive field irradiation.

Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer.

Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period. We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease compared to HPV integration site and PIK3CA mutations. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse. HPV E7 gene was the most sensitive tumor marker, superior to both HPV integration sites and PIK3CA mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (P = 0.02) and para-aortic lymph node involvement (P = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R = 0.39, P < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (P < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2-15) from HPV ctDNA detection. HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.See related commentary by Wentzensen and Clarke, p. 5733.

Postreatment squamous cell carcinoma antigen as a survival prognostic factor in patients with locally advanced cervical cancer. A Spanish multicenter study. The SEGO Spain-GOG group

ObjectiveTo evaluate the clinical value of postreatment plasmatic levels of the squamous cell carcinoma antigen (SCC-Ag) as a survival independent prognostic factor in patients with LACC. MethodsRetrospective, multicenter study including LACC patients (FIGO 2009 stages IB2, IIA2-IVA) managed at the Gynecology Oncological Units corresponding to eight reference hospitals in Spain between 2000 and 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values of postreatment SCC-Ag levels in prediction of survival. Survival curves were calculated by using the Kaplan-Meier method and were compared with the log-rank test. Cox models were used to analyze different factors in terms of their prognosis predictive value. ResultsThe study included 447 patients with a median follow-up time of 53 months (IQR 26–101) and median pre- and postreatment SCC-Ag levels of 3.4 ng/ml (IQR 1.2–11) and 0.8 ng/ml (IQR 0.5–1.2), respectively. The cut-off level of pretreatment SCC-Ag was 11.75 ng/ml (sensibility 37.5%; specificity 80.5%) and that of postreatment SCC-Ag was 1.24 ng/ml (sensibility 34.6%; specificity 83.1%). In a multivariate Cox regression analysis, factors that were independent predictors of OS were: FIGO stage (HR 2.12; 95%CI 1.18–3.8; p = 0.011), paraaortic lymph node involvement (HR 3.56; 95%CI 2.04–6.2; p < 0.0001), postreatment SCC-Ag level ≥ 1.2 ng/ml (HR 1.95; 95%CI 1.11–3.44; p = 0.02) and incomplete response to treatment (HR 4.5; 95%CI 2.5–8.11; p < 0.0001). ConclusionPostreatment plasmatic SCC-Ag level ≥ 1.2 ng/ml was an independent risk factor for the survival of patients with LACC. Further factors influencing survival included: paraaortic lymph node involvement, advanced disease and poor response to concomitant chemoradiotherapy.

FDG-PET/CT and Para-Aortic Staging in Endometrial Cancer. A French Multicentric Study.

Background: FDG-PET/CT is a noninvasive examination that could be helpful for the management of endometrial cancer. The aim of this study was to evaluate the performance of FDG-PET/CT in assessing para-aortic lymph-node involvement in high-risk endometrial cancer. Methods: We performed a retrospective multicenter study including all patients who had a high-risk endometrial cancer with a preoperative FDG-PET/CT and a para-aortic lymphadenectomy (PAL) between 2009 and 2019. The main objective was to evaluate the overall performance of FDG-PET/CT. The secondary objectives were to evaluate its performances according to the histological type and according to FDG-PET/CT date (before or after hysterectomy), and to compare its overall performance with that of the MRI scan. Results: We included 200 patients from six different centers. After the false positive FDG-PET/CT was reread by nuclear physicians, FDG-PET/CT had a sensitivity of 61.8%, a specificity of 89.7%, a positive predictive value of 69.4%, a negative predictive value of 86.1%, and an AUC of 0.76. There were no statistically significant differences in the performances according to either histological type and or FDG-PET/CT date. The sensitivity of FDG-PET/CT was better than that of MRI (p < 0.01), but the specificity was not (p = 0.82). Conclusion: Currently, FDG-PET/CT alone cannot replace PAL for the lymph node evaluation of high-risk endometrial cancers. It seems essential to reread it in multidisciplinary meetings before validating the therapeutic management of patients, particularly in the case of isolated para-aortic involvement.

Long-Term Outcomes of Cervical Cancer Patients Treated With Definitive Chemoradiation Following a Complete Metabolic Response

AimsA complete metabolic response (CMR) on early post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a positive prognostic factor for cervical cancer patients treated with definitive chemoradiation, but long-term outcomes of this group of patients are unknown. Patterns of failure and risk subgroups are identified. Materials and methodsPatients who received curative-intent chemoradiation from 1998 to 2018 for International Federation of Gynecology and Obstetrics (FIGO) stage IB1–IVA cervical cancer and had a CMR on post-treatment FDG-PET within 5 months of treatment completion were included. Cox proportional hazards models determined factors associated with locoregional and distant failure. Kaplan–Meier estimates of freedom from any recurrence (FFR) of patient subgroups were compared with Log-rank tests. ResultsThere were 402 patients with a CMR after chemoradiation on FDG-PET. Initial T stage was T1 (38%)/T2 (40%)/T3 (20%)/T4 (2%); initial FDG-avid nodal status was no nodes (50%)/pelvic lymph nodes (40%)/pelvic and para-aortic lymph nodes (10%). After a median follow-up of 6 years, 109 (27%) recurred. The pattern of recurrence was locoregional (27%), distant (61%) or both (12%). No factors were associated with locoregional failure. Distant recurrence was more likely in patients with T3–4 lesions (hazard ratio = 2.4, 95% confidence interval 1.5–3.8) and involvement of pelvic (hazard ratio = 1.6, 95% confidence interval 1.0–2.7) or para-aortic lymph nodes (hazard ratio = 2.7, 95% confidence interval 1.4–5.0) at diagnosis. The 5-year FFR rates for T1–2 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 85, 76 and 62%, respectively (P = 0.04, none versus para-aortic nodes). The 5-year FFR for T3–4 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 68, 56 and 25%, respectively (P = 0.09, none versus para-aortic nodes). ConclusionsT3–4 tumours and para-aortic nodal involvement at diagnosis are poor prognostic factors, even after a CMR following chemoradiation.

False negative rate at 18F-FDG PET/CT in para-aortic lymphnode involvement in patients with locally advanced cervical cancer: impact of PET technology

BackgroundThe identification of factors responsible for false negative (FN) rate at 18F- Fluorodeoxyglucose (FDG) Positron Emission Tomography /Computed Tomography (PET/CT) in para-aortic (PA) lymph nodes in the presurgical staging of patients with locally advanced cervical cancer (LACC) is challenging. The aim of this study was to evaluate the impact of PET/CT technology.MethodsA total of 240 consecutive patients with LACC (International Federation of Gynecology and Obstetrics, FIGO, stage IB2-IVA) and negative Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and negative 18F-FDG PET/CT in the PA region, undergoing laparoscopic PA lymphadenectomy before chemoradiotherapy were included. The FN rate in patients studied with Time of flight (TOF) PET/CT (TOF PET) or non-Time of flight PET/CT (no-TOF PET) technology was retrospectively compared.ResultsPatients presented with FIGO stage IB (n = 78), stage IIA-B (n = 134), stage III (n = 18) and stage IVa (n = 10), squamous cell carcinoma (n = 191) and adenocarcinoma (n = 49). 141/240 patients were evaluated with no-TOF PET/CT and 99/240 with TOF PET/CT. Twenty-two patients (9%) had PA nodal involvement at histological analysis and considered PET/CT FN findings. The FN rate was 8.5% for no-TOF PET and 10% for TOF PET subgroup respectively (p = 0.98). Ninety patients (38%) presented with pelvic node uptakes at PET/CT. The FN rate in the PA region was 18% (16/90) and 4% (6/150) in patients with and without pelvic node involvement at PET/CT respectively (19 vs 3% for no-TOF PET and 17 vs 5% for TOF PET subgroup).ConclusionsIn LACC, FN rate in PA lymph nodes detection is a clinical issue even for modern PET/CT, especially in patients with pelvic uptake. Surgical lymphadenectomy should be performed in case of negative PET/CT at PA level in these patients, while it could be discussed in the absence of pelvic uptake.

Prospective Non-randomized Control Trial on Role of Systematic High Para-Aortic Lymphadenectomy in Endometrial Cancer: Indian Study

Endometrial cancer (EC) accounts for approximately 10% of all cancers in females and is the second most common gynecologic cancer. The primary goal of surgical staging in EC is to identify extrauterine disease. Pelvic and para-aortic lymph node dissection (PLND and PaLND) is the gold standard in the detection of lymph node metastases in EC. However, there is still no uniformity worldwide regarding the scope and extent of lymph node dissection in EC. The present prospective non-randomized study was conducted to establish the importance of systematic lymphadenectomy (LND), especially PaLND above the inferior mesenteric artery (IMA), and to identify the risk factors associated with lymph node metastasis. A total of 210 patients with EC were included. All patients underwent comprehensive surgical staging which included simultaneous PLND and PaLND. In addition for non-endometrioid, additional omental and peritoneal biopsies were also performed. PLND consisted of complete removal of common iliac, external iliac, internal iliac and obturator lymph nodes as per standard techniques. The extent of PaLND was up to the renal veins. Pelvic lymph nodes (PLN), para-aortic lymph nodes (PaLN) harvested below the IMA and PaLN dissected above the IMA were labeled separately and submitted for histopathological examination (HPE). Patient’s demographic factors, surgical outcomes and tumor histological findings were tabulated for analysis. Patients diagnosed with EC were most commonly in their seventh decade (59.5%). The mean time for LND was 35 min. In 66% of the cases with positive PLN, the PaLN was also positive. Twenty-nine (13.8%) patients had both PLN and PaLN involvement. In all cases of positive PaLN, the nodes between IMA and renal veins were the only positive nodes. In 15 (7.1%) patients, PaLN were the only positive nodes. The mean PaLN yield was 9.1. Predictors of PaLN positivity were pelvic node positivity, Grade III tumors and lymphovascular space invasion (LVSI). Major complications observed were wound infection, paralytic ileus and subacute intestinal obstruction. In oncology, a good loco-regional control has the greatest impact on survival. Systematic para-aortic lymphadenectomy done with good surgical technique results in minimal morbidity and mortality without any additional blood transfusion requirement. The trend toward greater use of complete surgical staging has been accompanied by a judicious use of adjuvant therapy. This has led to marked decrease in the use of pelvic radiation therapy and its complications and has a significant impact on the cost of treatment.

Para-aortic lymph node involvement is not an independent predictor of overall survival after resection of pancreatic ductal adenocarcinoma

Para-aortic lymph node involvement is not an independent predictor of overall survival after resection of pancreatic ductal adenocarcinoma