Para-aortic Lymph Node Metastasis Research Articles

Machine Learning to Predict Local Recurrence and Distant Metastasis of Cervical Cancer after Definitive Radiotherapy

Radiotherapy is a widely recommended treatment for cervical cancer. The main cause of treatment failure is known to be local recurrence and distant metastasis. This study aimed to develop a predictive model for local recurrence and distance metastasis after radiotherapy, including concurrent chemoradiotherapy and radiotherapy alone, which could play a significant role in treatment plan making. Using clinical characteristics of 1421 cervical cancer patients, among whom all received intensity-modulated radiation therapy, 99.5 % received high-dose-rate brachytherapy and 92.5 % received concurrent sensitization chemotherapy during radiotherapy with an average of 5 cycles, models were generated using machine learning methods of random forest, adaboost and logistic regression. Finally, a combined (stacking) model of the above was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. All the models show good discrimination in predicting OS, DFS, LC and DMFS. Out of the four predictive models, the accuracies for all metrics were similar, with the stacking model performing the best (86.0% for OS, 83.7% for DFS, 87.3% for LC and 86.9% for DMFS). Performance was also similar when evaluated under the receiver operating characteristic (ROC) curve (AUCs) (AUC 0.77 for OS, 0.73 for DFS, 0.73 for LC and 0.71 for DMFS). In the final model, the most important variables for OS, DFS and LC were 2018 FIGO stage (14.2%, 17.9% and 16.4%), para-aortic lymph node metastasis (15.6%, 15.8% and 15.8%) and chemotherapy times (13.0%, 16.3% and 22.0%). For DMFS, the most important variables were iliac lymph node metastasis (13.7%) and total EQD2 (13.4%). The machine learning models trained with a handcraft cervical cancer dataset provide excellent performance in quantifying OS, DFS, LC and DMFS and could further help with the clinical prognostic factor’s analysis.

Breath Hold Upper Abdominal Stereotactic Body Radiotherapy (SBRT) with Surface Guidance: Single Center Experience

Surface tracking systems which is integrated to SBRT treatments enables motion tracking with 3D camera technology. We aim to evaluate treatment related outcomes in breath hold upper abdominal SBRT with surface guidance. Patients with upper abdominal lesions treated with breath hold and SGRT were evaluated retrospectively. Half an hour coaching was given to each patient prior to simulation. The CT scans were performed with IV contrast mostly in end insprium or end exprium phases whichever more comfortable and reproducible. The planning CTs were fused with magnetic resonance images (MRI) and positron emission CTs (PET-CT). Target and critical structures were contoured. All treatments were done in Varian EDGE (Varian, Palo Alto, CA, USA). Patients were navigated both with verbal guidance and tracking screen. Cone beam CTs (CBCT) were acquired with breath hold before treatment and 6D couch corrections were done. Optical Surface Management System (OSMS; Varian, Palo Alto, CA, USA) was used both in setup and motion tracking. Automated beam hold control was used during the treatment when patients moved outside of pre-defined range. Treatment duration varied depending on patient’s breath hold performance, prescribed dose, field number and modulation. Local recurrence is defined as size increase in MRI or increase in uptake in PET-CT. Fifty lesions were treated between May 2017 and July 2019. There are 33 liver metastases, 10 pancreatic tumors, 4 primary liver tumors and 3 paraaortic lymph node metastases. Thirty-eight patients have regular follow ups. Median follow up is 9 months. The doses are 25-60 Gy in 3-5 fractions. Ten patients experienced local failure. Local control rates for liver metastases, pancreatic tumors and hepatocellular carcinoma 85%, 60% and 66% respectively. Gastric bleeding is observed in one patient who has a pancreatic tail tumor after 1 year of treatment. It is possible to reduce respiratory organ motion with breath hold in SBRT treatments. SGRT is a noninvasive, real time method without using ionized radiation and allow us to make a correct setup and intra fractional monitoring.

Prognostic Impact of Paraaortic Lymph Node Metastasis in Extrahepatic Cholangiocarcinoma.

Surgical resection in patients with extrahepatic cholangiocarcinoma (EHCC) with paraaortic lymph node metastasis (PALNM) remains controversial. The objective of this study was to investigate the prognostic impact of PALNM in resected EHCC. The present retrospective study included 410 patients, including 16 patients with PALNM, who underwent surgical resection of EHCC between September 2002 and December 2018. These were compared to 9 patients in whom EHCC was not resected due to PALNM. The clinicopathological features and survival outcomes were investigated to identify the prognostic factors in resected EHCC. The overall survival in the resected patients with PALNM was significantly better than that in unresected patients (median survival time [MST] 33.7 vs. 16.7months, p=0.009) and was not significantly worse than that of patients with regional lymph node metastasis (LNM) (MST 33.7 vs 36.0months, p=0.278). The multivariate analysis identified age > 70years, male sex, tumor location (perihilar), residual tumor status, histological grade, microscopic venous invasion, and regional LNM as independent prognostic factors. There was no significant difference in survival between the resected patients with PALNM and patients with regional LNM, and PALNM was not a significant prognostic factor in the multivariate analysis. Surgical resection may be considered an acceptable approach for EHCC with PALNM in selected patients.

Prognostic Nomograms Predicting Survival in Patients With Locally Advanced Cervical Squamous Cell Carcinoma: The First Nomogram Compared With Revised FIGO 2018 Staging System.

ObjectivesTo develop nomograms to assess prognostic factors for 5-year overall survival (OS) and 5-year progression-free survival (PFS) in locally advanced cervical squamous cell carcinoma (LACSC).MethodsOverall, 618 patients with LACSC were included in this retrospective analysis. Nomograms for 5-year OS and PFS were developed based on Cox proportional hazards regression models. Concordance index (C-index) and calibration curves were used to define the predictive and discriminatory capacity of the nomogram. A comparison between the nomogram and the International Federation of Gynecology and Obstetrics (FIGO) staging system was conducted using time-dependent receiver operating characteristic (tROC) and area under the curve (tAUC).ResultsMultivariate analysis identified several prognostic factors for OS including squamous cell carcinoma antigen (SCC-Ag), body mass index (BMI), tumor size, pelvic wall involvement, and para-aortic lymph node metastasis (PALNM). Prognostic factors for PFS included BMI, hemoglobin (HGB), tumor size, pelvic wall involvement, pelvic lymph node metastasis (PLNM) and PALNM. Following bootstrap correction, the C-index of OS and PFS was 0.713 and 0.686, respectively. These nomograms showed superior performance compared with the FIGO 2009 and 2018 staging schema.ConclusionsNomograms were developed to identify prognostic factors for 5-year OS and PFS in patients with LACSC. These nomograms showed good prognostication and are more comprehensive in predicting survival outcomes than existing staging criteria.

Laparoscopic liver resection after laparoscopic pancreatoduodenectomy for liver metastases of ampulla of Vater adenocarcinoma

BackgroundRepeat laparoscopic surgery has become increasingly common. However, reports of liver resection after pancreatoduodenectomy are scarce, and we report the first successful case of a patient who underwent laparoscopic liver resection after laparoscopic pancreatoduodenectomy.Case presentationA 65-year-old man underwent laparoscopic pancreatoduodenectomy for ampulla of Vater adenocarcinoma. According to the American Joint Committee on Cancer (8th edition) staging guidelines, the tumour was labelled as stage IIIB (fT2N2M0). Twelve months later, a computed tomography (CT) scan revealed liver masses (in segments 3 and 5) and swollen para-aortic lymph nodes. After six chemotherapy courses of gemcitabine with cisplatin, the CT scan showed the disappearance of the para-aortic lymph nodes and progression of liver metastases. Nineteen months after the initial surgery, the patient underwent laparoscopic partial liver resection of segment 5 and left lateral sectionectomy. First, we performed the operation in the left half lateral decubitus position. In this position, the portal vein was isolated safely without hindering the hepato-jejunal anastomosis, although the adhesions around the hepato-jejunal anastomosis were dense. Therefore, we were able to perform liver transection safely with vascular inflow control. The operation duration was 235 min, and the volume of blood loss was 100 g. Macroscopically, the resected margins were negative. The patient was uneventfully discharged 12 days after the second operation. Afterwards, drainage was needed because of an intra-abdominal abscess. Currently, he has been alive for 8 months postoperatively, receives chemotherapy to suppress para-aortic lymph node metastases, and has not had another recurrence.ConclusionsLiver resection after pancreatoduodenectomy can be performed safely with an innovative body position to isolate the portal vein, which is a key point of the surgery. A laparoscopic approach for liver resection after pancreatoduodenectomy is a feasible option.

Prophylactic Extended-Field Irradiation in Patients With Cervical Cancer: A Literature Review.

Currently, the standard radiation field for locally advanced cervical cancer patients without evidence of para-aortic lymph node (PALN) metastasis is the pelvis. Due to the low accuracy of imaging in the diagnosis of PALN metastasis and the high incidence of PALN failure after pelvic radiotherapy, prophylactic pelvic and para-aortic irradiation, also called extended-field irradiation (EFI), is performed for patients with cervical cancer. In the era of concurrent chemoradiotherapy, randomized controlled trials are limited, and whether patients with cervical cancer can benefit from prophylactic EFI is still controversial. With conformal or intensity-modulated radiation therapy, patients tolerate prophylactic EFI very well. The severe toxicities of prophylactic EFI are not significantly higher than those of pelvic radiotherapy. We recommend delivering prophylactic EFI to cervical cancer patients with common iliac lymph nodes metastasis. Clinical trials are needed to investigate whether patients with ≥3 positive pelvic lymph nodes and FIGO stage IIIB disease can benefit from prophylactic EFI. According to the distribution of PALNs, it is reasonable to use the renal vein as the upper border of the radiation therapy field for patients treated with prophylactic EFI. The clinical target volume expansion of the node from the vessel should be smaller in the right para-caval region than in the left lateral para-aortic region. The right para-caval region above L2 or L3 may be omitted from the PALN target volume to reduce the dose to the duodenum. More clinical trials on prophylactic EFI in cervical cancer are needed.

Inferior Vena Caval Syndrom in Paraaortic Metastastic Lession of Ovarian Dysgerminoma in Pregnancy Manage with Chemotherapy : a Case Report

Background : Inferior caval syndrom is a rare case. It can caused by compresssion of the tumor mass and paraaortic metastastasis lession of ovarian dysgerminoma. Dysgerminoma is one of the most common germ cell tumor, approximately 3-5% of all ovarian cancers.1 Rate of dysgerminoma metastasis to lymph node is around 28%. In all type of germ cell, dysgerminoma has higher insidens to lymph node metastasis compare to the others. The first level of lymph node metastsis is paraaortic lymph node. However, the insidens is unknown because there is no research about it yet.2,3 Dysgerminoma frequently in young age, less then 30 years. The exact etiology of dysgerminomas has not been determined, although recent molecular studies have implicated loss function of potential tumor suppressor gene TRC8/RNF139, abnormality of Y chromosome and gonadal dysgenesis.4 The problem arises when dysgerminoma is diagnosed in pregnancy woman as clinically has inferior vena cava syndrom sign and symptoms which acquired efective and fast management.Objective : Discuss inferior caval syndrom as effect of compression by tumor mass, metastasis tumor lesion and chemotherapy management in dysgerminoma with pregnancyCase Report : Patient 32 years old admitted to M. Djamil central general hospital referred from Batusangkar hospital with diagnosis G3P2A0L2 25-26 weeks of preterm pregnancy + dysgerminoma + obs. Dyspnue. Patient has symptoms dispnue, exercise intolerance, oedem extremity. Physical examination : blood pressure was 100/70 mmHg, HR 120 dpm, RR 35 bpm, T 37 C. Abdomen : uterus fundal was palpated 2 fingers above umbilical, ballotement (+), FHR 150-158 bpm. Genitalia : I V/U normal, vaginal bleeding (-), oedem extremity +/+. From ultrasonography found dysgerminoma ovary with compression to inferior vena cava and paraaortic metastatic. Patient was diagnosed with dispnue ec. inferior vena cava syndrom caused by compression of tumor mass + paraaortic lymph node metastasis lession of ovarian dysgerminoma on G3P2A0L2 25-26 weeks of preterm pregnancy. Patient was managed by BEP chemotherapy and symptom was dissapeared. Patient was admitted to M. Djamil again with 34-35 weeks of preterm pregnancy in active phase of first stage. Because obtructed of labor patient was decide to performed LSCS. Female baby was born 1800 gram, baby’s length was 45 cm, A/S 7/8, there is no congenital anomaly. Patient was followed up 1 month after surgery, there is no symptoms, but fromUltrasonograhy found corpus metastasis and CT scan impressed paraaortic lymph node metastasis + copus metastasis. Chemotherapy was continue one month after caesarean section. She was completed 4 cycles chemothrapy and the disease was cureable.Conclusion : Caval syndrom is a rare case and fatal, caused by direct compression of dysgerminoma mass and paraaortic lymph node metastasis. Diagnosis of dysgerminoma is anatomy pathology diagnose. Management of dysgerminoma is surgical staging and 3-4 cycle of chemoterapy with BEP regimen. Chemoterapy with BEP (Bleomisin-Etopuside-Cisplatin) is safe to performed at second trimester with inferior vena cava syndrom ec paraaorta lymph nodes metastasis. Dysgerminoma has a good response to chemotherapy with survival rate 96%Keywords: Caval syndrom, lymph node paraaortic metastatic

The treatment strategy of R0 resection in colorectal cancer with synchronous para-aortic lymph node metastasis

BackgroundSynchronous metastatic para-aortic lymph node (mPALN) dissectionin colorectal cancer has relatively good oncological outcomes, though many patients develop recurrence. Universal prognostic factor remain unclear and no definitive perioperative chemotherapy is available, making the treatment of mPALN controversial. In the present study, we aimed to establish a treatment strategy for synchronous mPALN.MethodsThis retrospective study involved 20 patients with pathological mPALN below the renal vein who underwent R0 resection. Long-term outcomes, recurrence type, and prognostic factors for survival were investigated.ResultsThe 5-year overall survival and recurrence-free survival rates were 39% and 25%, respectively. Seventeen patients (85%) developed recurrence, including 13 (76%) within 1 year after surgery, and ~ 70% of all recurrences were multiple recurrences. Four patients (20%) survived > 5 years. Pathological T stage (p= 0.011), time to recurrence (p = 0.007), and recurrence resection (p = 0.009) were identified as prognostic factors for long-term survival.ConclusionsR0 resection of synchronous mPALN in colorectal cancer resulted in acceptable oncological outcomes, though we found a high rate of early unresectable recurrence. If the recurrence occurs late or isolated, surgical resection should be considered for longer survival.

Predictors of Survival in Women with High-Risk Endometrial Cancer and Comparisons of Sandwich versus Concurrent Adjuvant Chemotherapy and Radiotherapy.

Background: to elucidate the predictors of progression-free survival (PFS) and overall survival (OS) in high-risk endometrial cancer patients. Methods: the medical records of all consecutivewomen with high-risk endometrial cancer were reviewed. Results: among 92 high-risk endometrial cancer patients, 30 women experienced recurrence, and 21 women died. The 5-year PFS and OS probabilities were 65.3% and 75.9%, respectively. Multivariable Cox regression revealed that body mass index (hazard ratio (HR) = 1.11), paraaortic lymph node metastasis (HR = 11.11), lymphovascular space invasion (HR = 5.61), and sandwich chemoradiotherapy (HR = 0.15) were independently predictors of PFS. Body mass index (HR = 1.31), paraaortic lymph node metastasis (HR = 32.74), non-endometrioid cell type (HR = 11.31), and sandwich chemoradiotherapy (HR = 0.07) were independently predictors of OS. Among 51 women who underwent sandwich (n = 35) or concurrent (n = 16) chemoradiotherapy, the use of sandwich chemoradiotherapy were associated with better PFS (adjusted HR = 0.26, 95% CI = 0.08–0.87, p = 0.03) and OS (adjusted HR = 0.11, 95% CI = 0.02–0.71, p = 0.02) compared with concurrent chemoradiotherapy. Conclusion: compared with concurrent chemoradiotherapy, sandwich chemoradiotherapy was associated with better PFS and OS in high-risk endometrial cancer patients. In addition, high body mass index, paraaortic lymph node metastasis, and non-endometrioid cell type were also predictors of poor OS in high-risk endometrial cancer patients.

Decreased secretoglobin family 2A member 1expression is associated with poor outcomes in endometrial cancer.

Endometrial cancer is the most common malignancies in developed countries. The present study aimed to identify the role of secretoglobin family 2A member 1 (SCGB2A1) expression in uteri corpus endometrial carcinoma (UCEC) from The Cancer Genome Atlas (TCGA) database, and determine the SCGB2A1-associated downstream signaling pathways. The clinicopathological characteristics and gene expression data were downloaded from TCGA database. The Kaplan-Meier method and Cox multivariate model were used for survival analysis. Logistic regression was used to analyze the association between the clinicopathological features and SCGB2A1 expression. For validation, data of SCGB2A1 mRNA expression and protein expression were obtained and then survival analysis was performed for 47 patients with endometrial cancer from the Fudan University Shanghai Cancer Center (FUSCC). In TCGA dataset, SCGB2A1 expression was significantly higher in tumor tissues (n=528) compared with normal tissues (n=23, P<0.001). The decrease in SCGB2A1 expression in UCEC was significantly associated with age at diagnosis, high tumor grade, residual tumor, positive peritoneal cytology, pelvic lymph node metastasis, para-aortic lymph node metastasis and advanced clinical stage with P<0.05. In the multivariate analysis, SCGB2A1 expression was identified as an independent prognostic factor. In the FUSCC validation set, low SCGB2A1 expression was also associated with worse survival compared with high expression in endometrial cancer (P<0.001). Gene Set Enrichment Analysis revealed that SCGB2A1 may be involved in tumor proliferation and cell cycle regulation. In conclusion, SCGB2A1 may have an important role in the prognosis of UCEC, and has value as a new target for novel therapeutic strategies.

Role of adjuvant therapy in stage IIIC2 endometrial cancer

ObjectiveThe role of the different types of adjuvant treatments in endometrial cancer with para-aortic node metastases is unclear. The aim of this study was to report oncologic outcomes after adjuvant...

Advances in para-aortic nodal dissection in gastric cancer surgery: A review of research progress over the last decade.

Approximately 17%-40% of para-aortic lymph node (PAN) metastasis occurs in patients with advanced gastric cancer. As the third tier of lymphatic drainage of the stomach and the final station in front of the systemic circulation, PAN infiltration is defined as distant metastasis and plays a key role in the evaluation of the prognosis of advanced gastric cancer. Many clinical factors including tumor size ≥ 5 cm, pT3 or pT4 depth of tumor invasion, pN2 and pN3 stages, the macroscopic type of Borrmann III/IV, and the diffuse/mixed Lauren classification are indicators of PAN metastasis. Whether PAN dissection (PAND) should be performed on patients with or without the macroscopic PAN invasion remains unascertained, regardless of the numerous retrospective comparative studies reported on the improved prognosis over D2 alone. Another paradoxical result from many other studies showed no significant difference in the overall survival between these two lymphadenectomies. A phase II trial launched by the Japan Clinical Oncology Group indicated that two or three courses of S-1 and cisplatin preoperatively followed by radical surgery with D2 + PAND and postoperative S-1 is the current standard strategy for the treatment of patients with extensive lymph node metastasis, and this regimen could be substituted by a promising strategy with effective combination chemotherapy or suitable chemotherapy duration. This review focuses on the advances in radical gastrectomy plus PAND with or without chemotherapy for patients with advanced gastric cancer.

Extended lymphadenectomy in hilar cholangiocarcinoma: What it will bring?

Lymph node dissection is always a hot issue in radical resection of hilar cholangiocarcinoma (HCCA). There are still controversies regarding whether some lymph nodes should be dissected, of which the para-aortic lymph nodes are the most controversial. This review synthesized findings in the literature using the PubMed database of articles in the English language published between 1990 and 2019 on the effectiveness of extended lymphadenectomy including para-aortic lymph nodes dissection in radical resection of HCCA. Hepatobiliary surgeons have basically achieved a consensus that enough lymph nodes should be obtained to accurately stage HCCA. Only a very small number of studies have focused on the effectiveness of extended lymphadenectomy including para-aortic nodes dissection on HCCA. They reported that extended lymphadenectomy can bring some survival benefits for patients with potential para-aortic lymph node metastasis and more lymph nodes can be obtained to make the patient's tumor staging more accurate without increasing the related complications. Extended lymphadenectomy should not be adopted for HCCA patients with intraoperatively confirmed distant lymph node metastases. For these patients, radical resection combined with postoperative adjuvant chemotherapy seems to be a better choice. A prospective, multicenter, randomized, controlled clinical study of regional lymphotomy and extended lymphadenectomy in HCCA should be conducted to guide clinical practice. A standardized extended lymphadenectomy may help to more accurately stage HCCA. Future studies are required to further assess whether extended lymphadenectomy can improve long-term survival in negative celiac, superior mesenteric, and para-aortic lymph node diseases.

Significance of para-aortic lymph node evaluation in patients with FIGO IIIC1 cervical cancer.

This study investigated the effect of para-aortic lymph node sampling or dissection in recently revised International Federation of Gynecology and Obstetrics IIIC1p cervical cancer treated with primary surgery and adjuvant radiation therapy with concurrent chemotherapy. We retrospectively reviewed the records of 343 patients with early-stage cervical cancer and pathologically proven pelvic lymph node metastasis following curative surgery from 2001 to 2014. No patient had imaging evidence of para-aortic lymph node involvement, and all patients received adjuvant concurrent chemotherapy with or without concurrent chemotherapy. We investigated the significance of para-aortic lymph node sampling or dissection on disease-free survival and overall survival. After median follow-up of 58.3months, 5-year disease-free survival and overall survival in all patients were 69.9 and 80.2%, respectively. Disease-free survival and overall survival did not differ between the para-aortic lymph node dissection group and the No para-aortic lymph node dissection group (P=0.700 and P=0.605). However, patients with para-aortic lymph node-positive disease had poorer disease-free survival and overall survival compared with those with para-aortic lymph node-negative disease (P<0.001 and P<0.001). This study found no survival benefit of para-aortic lymph node evaluation among patients with International Federation of Gynecology and Obstetrics IIIC1p cervical cancer who were clinically para-aortic lymph node-negative. Although para-aortic lymph node metastasis is a poor prognosticator, the benefit of para-aortic lymph node dissection in terms of survival needs further investigation.

Adjuvant chemotherapy after radiotherapy or concurrent chemoradiotherapy for pelvic lymph node-positive patients with locally advanced cervical cancer: a propensity score matching analysis

ObjectiveThe benefit of adjuvant chemotherapy after definitive chemoradiotherapy in patients with pelvic lymph node-positive cervical cancer has been poorly studied. This study aimed to test the hypothesis that the addition...

Prognostic factors in women with cervical cancer stage IIIC1r treated with concurrent chemoradiotherapy.

The purpose of this study was to evaluate the prognostic factors of patients with stage IIIC1r cervical cancer who underwent concurrent chemoradiotherapy. A total of 134 patients treated with chemoradiotherapy for cervical cancer with pelvic and/or paraaortic lymph node metastasis (PALNM) were enrolled in this study. Clinical variables were investigated through review of the patients' medical records. The 5-year overall survival (OS) rate in patients with stage IIICr cervical cancer was 70.5%. Age, PALNM, parametrial invasion, T stage, pelvic side wall invasion, differentiation, lymphovascular space involvement and high squamous cell carcinoma antigen level (>8 ng/mL) were prognostic factors for survival. The 5-year OS rate of patients with stage IIIC1r was 74.5%, and that of stage IIIC2r was 38.1% (P-value = 0.012). The 5-year OS rate of patients with stage IIIC1r with the presence of pelvic side wall invasion was 48.3% and that in its absence was 83.0% (P-value < 0.001). The 5-year OS rate of patients with stage IIIC1r with the presence of parametrial invasion was 68.9% and that in its absence was 82.4% (P-value = 0.031). In multivariable analysis via backward conditional modeling, age, PALNM and pelvic side wall invasion were independent prognostic factors for survival of stage IIICr. Age and pelvic side wall invasion were independent prognostic factors for survival of stage IIIC1r cervical cancer. In stage IIICr cervical cancer, patients with PALNM, and/or pelvic side wall invasion can expect to have a poor prognosis. Particularly, pelvic side wall invasion in stage IIIC1r is an independent prognosis factor.

Long-term follow-up of volumetric modulated arc therapy in definitive radiotherapy for cervical cancer: A single-center retrospective experience

ObjectiveTo evaluate the treatment outcomes and toxicity of volumetric modulated arc therapy (VMAT) in definitive radiotherapy for patients with cervical cancer. MethodsMedical records of 440 patients with cervical cancer treated with VMAT in definitive radiotherapy with or without concurrent chemotherapy between January 2010 and June 2015 in our institution were retrospectively reviewed. A dose of 45 ​Gy was prescribed to the planning target volume with VMAT in 25 fractions, followed by high-dose rate intracavitary brachytherapy with 28–36 ​Gy in 4–6 fractions. Survival time was estimated using Kaplan-Meier method. Risk factors for treatment failure were identified using Cox proportional hazards regression model. ResultsThe median follow-up periods were 58.3 months (range: 2.7–112.9 months). The 3- and 5-year survival rates were overall survival (OS) 79.4% and 74.4%, cancer-specific survival (CSS) 81.4% and 77.1%, progression-free survival (PFS) 73.3% and 71.1%, locoregional control (LC) 83.3% and 82% and distant metastasis-free survival (DMFS) 80.8% and 77.7%, respectively. The 5-year OS for patients with different stages was IB1 91.6%, IB2 100%, IIA 82.5%, IIB 74.4%, IIIA 57.1%, IIIB 61.7% and IVB 17.6%, respectively. Of the 124 patients with recurrence, 93 patients (75.0%) experienced distant failure. Multivariate analysis showed that non-squamous cell carcinoma of the cervix (P ​< ​0.001), more advanced stage (P ​= ​0.004), pelvic lymph node metastasis (P ​< ​0.001) and para-aortic lymph node metastasis (P ​= ​0.019) were all independent risk factors of PFS. The incidence of grades 3–4 late bowel toxicities was 2.7%. No grades 3–4 bladder toxicity was observed. ConclusionThis study demonstrated that the use of VMAT in definitive radiotherapy resulted in satisfactory outcomes with acceptable toxicities for patients with cervical cancer. Distant metastasis predominated as the pattern of disease relapse. Further studies are needed to investigate the intensified systemic therapies.

Para-aortic lymph node metastasis detected intraoperatively by systematic frozen section examination in pancreatic head adenocarcinoma: is resection improving the prognosis?

BackgroundThis study aimed to evaluate the controversial benefit of a pancreaticoduodenectomy (PD) in patients with PALN metastasis intraoperatively detected by systematic frozen section examination in pancreatic adenocarcinoma. MethodsPALN intraoperative examination by frozen section was systematically performed from January 2006 to February 2018 prior to performing PD for pancreatic adenocarcinoma. Until June 2012, PALN + patients still underwent PD (PALN+/PD group) in the framework of a prospective study. Since July 2012, PALN+ was considered as contraindicating the planned PD (PALN+/No-PD group). Post-operative morbidity and survival were compared between these two groups. ResultsOf the 32 PALN + patients intraoperatively detected, the first 13 underwent a PD, while the last 19 did not undergo resection. Seven patients (54%) among 13 PALN+/PD patients developed a post-operative complication against 3 (16%) among 19 PALN+/No-PD patients (p = 0.049). The median length of stay was 5 days longer for PALN+/PD patients (p = 0.001). The median survival did not differ between PALN+/No-PD and PALN+/PD groups (respectively 13.4 months (95%CI:7.6–19.3) and 11.5 months (95%CI:5.9–17.1), p = 0.471). No patient was alive 4 years after surgery in both the PALN+/No-PD or PALN+/PD groups. ConclusionIn case of PALN detected intraoperatively in pancreatic adenocarcinoma, PD does not improve survival compared to current palliative treatment.

Enlarged cardiophrenic lymph nodes predict disease involvement of the upper abdomen and the outcome of primary surgical debulking in advanced ovarian cancer.

IntroductionThe outcome of ovarian cancer patients is highly dependent on the success of primary debulking surgery in terms of postoperative residual disease. This study critically evaluates the clinical impact of preoperative radiologic assessment of the cardiophrenic lymph node (CPLN) status in advanced ovarian cancer.Material and methodsBaseline CT scans of 178 stage III and IV ovarian cancer patients were retrospectively reviewed by two independent radiologists. CPLN enlargement defined at a short‐axis ≥5 mm was evaluated for its prognostic value and predictive power of upper abdominal tumor involvement and the chance of complete intra‐abdominal tumor resection at primary debulking surgery. Only patients without surgically removed CPLN were eligible for this study.ResultsEnlarged CPLNs were detected in 50% of patients and correlated with radiologically suspicious (P = .028) and histologically confirmed (P = .001) paraaortic lymph node metastases. CPLNs ≥ 5 mm were associated with high CA‐125 levels at baseline and revealed independent prognostic relevance for progression‐free survival (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.33‐3.42) and overall survival (HR 2.18, 95% CI 1.16‐4.08). Noteworthy, patients with enlarged CPLNs nonetheless benefit from complete intra‐abdominal tumor debulking in terms of an improvement in progression‐free survival (HR 0.60, 95% CI 0.38‐0.94) and overall survival (HR 0.59, 95% CI 0.35‐0.82). Enlarged CPLNs correctly predicted carcinomatosis of the upper abdomen in 94.6%. A predictive score of complete tumor debulking, termed CD‐score, which integrates, beside a CPLN short axis <5 mm, an ascites volume <500 mL, and CA‐125 levels <500 U/mL at baseline, correctly predicted complete intra‐abdominal debulking in 100% of patients.ConclusionsCPLNs ≥5 mm predict upper abdominal tumor involvement. The application of the CD‐score predicted complete macroscopic tumor resection at primary surgery in all of the patients. Although, CPLN pathology suggests extra‐abdominal disease, we consistently demonstrated that patients nonetheless benefit from complete intra‐abdominal tumor resection.

Pretreatment tumor-related leukocytosis misleads positron emission tomography-computed tomography during lymph node staging in gynecological malignancies

The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Here, using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. We demonstrate that pretreatment TRL misleads 18F-FDG-PET/CT during lymph node staging in gynecological malignancies. In the mechanistic investigations, we show that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis can be reproduced in animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also show that increased 18F-FDG uptake in non-metastatic nodes can be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed. Together, our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.