Para-aortic Lymph Node Recurrence Research Articles

Comparative Analysis of Oncologic Outcomes in Patients with Squamous Cell Carcinoma of the Uterine Cervix with High-Risk Features for Para-Aortic Recurrence: Prophylactic Extended-Field versus Pelvic Chemoradiotherapy.

To compare the oncologic outcomes of prophylactic extended-field radiation therapy (EFRT) and whole pelvic radiation therapy (WPRT) in cervical patients at high risk of para-aortic lymph node (PALN) recurrence. From July 1999 to May 2022, a total of 115 patients with cervical cancer and high-risk features of PALN recurrence based on tumor markers, positive LNs and extensive parametrial invasion were retrospectively analyzed. All patients had received EFRT or WPRT at a dose of 39.6-45 Gy and concurrent chemotherapy. In EFRT, coverage was extended to include the para-aortic region below the level of the left renal vein or T12. Twenty-eight and 87 patients underwent EFRT and WPRT, respectively. For patients who survived, the median follow-up time was 60.8 months (range 9.2-131.6 months) in the EFRT group and 115.9 months (range 16.9-212.1 months) in the WPRT group. The 5-year overall survival (OS) and pelvic, extrapelvic and PALN recurrence rates were 87.7% vs 60.8% (p=0.019), 10.9% vs 25.3% (p=0.119), 18.1% vs 45.8% (p=0.011), and 0% vs 30.4% (p=0.005), respectively, between the EFRT and WPRT groups. Multivariate analysis revealed that EFRT and 2018 FIGO stage IV disease status were significant predictors ofOS and extrapelvic recurrence. Compared to WPRT, EFRT significantly improved OS and reduced extrapelvic and PALN recurrence in patients with cervical cancer with high-risk recurrence features.

Squamous cell carcinoma of the anus successfully treated with multidisciplinary therapy for metachronous metastatic and local recurrences after DCF chemotherapy: a case report

BackgroundDocetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy is reportedly an effective treatment strategy for squamous cell carcinoma of the anus (SCCA). However, studies regarding its use in Japanese patients remain scarce.Case presentationHere, we present the case of an 82-year-old woman with SCCA, cStage IIIB. Chemoradiotherapy was initiated after colostomy of the anorectal mass; however, para-aortic lymph node recurrence was observed 3 months after treatment completion. Five courses of DCF chemotherapy were subsequently administered, resulting in a complete response (CR). Two years and 1 month later, the aortic lymph node was enlarged again, and the patient achieved CR again after radiotherapy. Nine months later, local recurrence was detected in the anal canal, and laparoscopic perineal rectal amputation was performed. The patient remains progression-free 5 years and 10 months after the initial treatment and 1 year and 7 months after the final treatment.ConclusionsOur findings suggest that complementary treatment after DCF chemotherapy may be efficacious in Japanese patients with SCCA and help achieve CR. Despite occasional local recurrences, this approach may help achieve long-term progression-free survival.

The impact of different clinicopathologic factors and salvage therapies on cervical cancer patients with isolated para-aortic lymph node recurrence

BackgroundCervical cancer patients with isolated para-aortic lymph nodes (PALN) recurrence were mainly associated with treatment failure. For these patients, radiotherapy, chemotherapy, surgery ± adjuvant therapy or chemoradiotherapy may be advised, however, no specific therapy has been proposed yet. This study aimed to explore factors influencing the prognosis of cervical cancer cases with isolated PALN recurrence and to find out an effective salvage therapy.MethodsCervical cancer cases with isolated PALN recurrence who received therapies in Zhejiang Cancer Hospital between January 2013 and June 2021 were analyzed retrospectively.ResultsCarcinoembryonic antigen (CEA) level > 10 ng/mL and positron emission tomography/computed tomography (PET/CT) imaging method used to detect the recurrence were found to be associated with the local control rate. PALN (positive), squamous-cell carcinoma-antigen (SCC-Ag) level (> 10 ng/mL) upon initial diagnosis, and CEA level (> 10 ng/mL), number of metastatic lymph nodes (several) at recurrence were associated with worse survival. Compared with surgery ± adjuvant therapy, chemotherapy (CT) alone or sequential chemoradiotherapy (SCRT) was associated with worse PFS or OS. Concurrent chemoradiotherapy (CCRT) after PALN recurrence could reduce the risk of the second recurrence. 3-year OS of cases after surgery ± adjuvant therapy was the highest (65%), followed by CCRT (45.7%), SCRT (38.9%), radiotherapy (RT) (33.3%), and CT (20.6%).ConclusionIn cervical cancer patients with isolated PALN recurrence, chemoradiotherapy or surgery ± adjuvant therapy may be preferred as the salvage treatment.

Prognostic Importance of Uterine Body Invasion in Para-Aortic Lymph Node Recurrence in Patients with Cervical Carcinoma after Pelvic Radiotherapy

This study aimed to evaluate the correlation between the extent of uterine body invasion and para-aortic lymph node (PALN) recurrence in patients with cervical carcinoma who received pelvic radiotherapy. The data of 185 patients diagnosed with cervical carcinoma, initial stage IB to IVA without para-aortic lymph node metastasis, according to the FIGO 2009 Stage System, and treated between January 2011 and December 2016 were retrospectively analyzed. With using pelvic MRI with contrast, the extent of uterine body invasion was assessed and categorized into three types: non-uterine invasion, endocervical invasion, and invasion into the uterine body. Non-uterine invasion, by definition, referred to tumor located at the outer orifice of the cervix or ectocervix, while endocervical invasion referred to tumor invasion up to the endocervical canal, and the uterine body invasion referred to cervical carcinoma invading the uterine cavity from the squamocolumnar junction (SCJ) transformation zone. Definitive or adjuvant pelvic radiotherapy was given to the 185 patients, all of whom did not receive extended-field radiotherapy. The major result of PALN recurrence, defined as a short axial diameter of lymph node greater than 1cm, was diagnosed through computed tomography, pelvic MRI, or PET-CT. The actuarial rates of PALN recurrence were analyzed using Kaplan-Meier curves, and Cox regression models were used for multivariate analyses. There were 122 (65.9%), 37 (20.0%), and 26 (14.1%) patients with non-uterine invasion, endocervical invasion, and invasion into the uterine body, respectively. The 5-year PALN recurrence rates were 7.8% in the non-uterine invasion group, 13.1% in the endocervical invasion group, and 21.1% in the uterine body invasion group (p = 0.009), after a median follow-up of 65.5 months. The multivariate analysis revealed that uterine body invasion was the only independent factor of PALN recurrence (p = 0.004). Factors such as initial pelvic lymphadenopathy (p = 0.645), initial SCC-Ag level (p = 0.200), non-squamous cell carcinoma (p = 0.882), and FIGO stage III-IVA (p = 0.289) were not significant factors of PALN recurrence. This study demonstrates that cervical cancer patients with uterine body invasion have a higher risk of PALN recurrence following pelvic radiotherapy. Intensive follow-up schedules are recommended for these patients. Extended-field radiotherapy may be considered in cervical cancer patients with uterine body invasion to reduce PALN recurrence.

Chylous ascites following retroperitoneal lymphadenectomy in a patient with recurrent dysgerminoma of ovary: A case report

Chylous ascites is an uncommon condition of accumulation of milky fluid rich in lymph and chylomicrons in the peritoneal cavity. Post-surgical complications following dissection near the base of the mesentery, retroperitoneum, or near the cisterna chyli, malignancies (e.g., pancreatic adenocarcinomas, lymphoma, gastric carcinoma), cirrhosis, and trauma are the prime causes of chylous ascites. Here we report a rare case of chylous ascites following clearance of isolated paraaortic nodal recurrence in a 28-year-old female with dysgerminoma of ovary. The patient developed chylous ascites on the fifth day following surgery, which was confirmed by an increased drain fluid triglyceride level. She was managed conservatively with dietary modification including a high-protein and carbohydrate but low-fat-based diet mainly containing medium-chain fatty acids. Subsequently, she recovered from chylous ascites on the sixteenth day, completed second line chemotherapy, and is now doing well.

Isolated para-aortic nodal recurrence after treatment of early stage cervical carcinoma

ObjectiveSurgical evaluation of lymph node metastasis is paramount in the treatment of cervical cancer. We sought to explore the outcomes of patients with and without para-aortic lymphadenectomy undergoing curative-intent radical hysterectomy for stage IA-IIA cervical cancer. MethodsInstitutional data were retrospectively reviewed to identify women undergoing curative-intent radical hysterectomy with concurrent lymphadenectomy for stage IA-IIA cervical carcinoma from 2004 to 2021. Any carcinoma histology was allowed. Clinical risk stratification was performed according to GOG 92 and GOG 109 protocols. Disease outcomes, patterns of recurrence, and survival were analyzed with Chi square, t-test, Kaplan-Meier, and Cox proportional hazards multivariable statistics. Results300 patients were identified, 265 met inclusion criteria. Median follow up was 56 months. Pelvic lymphadenectomy (PLND) was performed in 71%, with the remainder undergoing combined para-aortic dissection (PPaLND). Baseline patient demographics and presence of clinical risk factors were well balanced between groups. PPaLND was more common in patients undergoing open surgery (OR 10.58, p <.0001), and tumors were larger in this group (2.96 vs 2.12 cm, p = .0002) and more likely non-squamous histology (OR 2.02, p = .017). Recurrence of disease was present in 13% of cases, with no difference between PLND and PPaLND regardless of histology. There were zero cases of isolated PaLN recurrence in either group. Neither progression free nor overall survival was different between groups. Prophylactic extended field radiation (EFRT) was not prescribed. ConclusionOmission of PaLN dissection, in the absence of suspicious nodes, did not decrease survival. There were no isolated PaLN recurrences after PLND alone.

The optimal extent of lymph node dissection for gastric cancer with para-aortic lymph node metastases.

413 Background: Gastric cancer (GC) with para-aortic lymph node (PAN) metastasis is diagnosed as stage IV and basically treated with chemotherapy. Recently, D2 and PAN dissection after neoadjuvant chemotherapy (NAC) was reportedly effective when PAN metastasis was limited within #16a2/b1 area. However, PAN dissection is highly invasive surgical procedure and it still remains unclear whether PAN dissection contributes to the survival for these tumors. This study aimed to determine the optimal extent of lymph node dissection for these tumors focusing on survival benefit of PAN dissection. Methods: The study examined patients who received radical gastrectomy with D2 and PAN dissection after NAC for gastric cancer with PAN metastasis (#16a2/b1) from 2004 to 2015. Survival benefit of lymph node dissection was estimated using therapeutic value index (TI). TI was calculated by multiplication of incidence of metastasis and 5-year survival rate of patients with metastasis for each lymph node area. TI of D2 dissection area (TI-D2) and PAN area (TI-PAN) was calculated separately. Overall survival (OS) was calculated in patients who had metastasis to PAN pathologically after surgery (pPAN+ group) and those who had not (pPAN- group). The recurrence site was also examined. Results: Thirty-two patients were analyzed. TI-D2 and TI-PAN were 15.6 and 0.0, respectively. 5y-OS was 81.0% in pPAN- group (21 cases) but was 0.0% in pPAN+ group (11 cases). The most frequent recurrence site was the lymph nodes (82.4% of all recurrences). Among lymph node recurrence, almost all recurrence patterns included the PANs (85.7% of lymph node recurrence). Conclusions: The prognosis was extremely poor when tumor cells remained on PAN after NAC. In these cases, PAN recurrence was seen most frequently even after PANs had been dissected. Patients with PAN could have the chance for the cure only when tumor cells on PAN was completely eliminated by NAC. It is unclear whether they actually needed PAN dissection for pathologically negative PAN. The optimal extent of lymph node dissection after NAC might be D2 for GC with PAN metastasis.

Thoracic para-aortic lymph node recurrence in patients with esophageal squamous cell carcinoma: A propensity score-matching analysis.

Thoracic para-aortic lymph node (TPLN) recurrence in esophageal squamous cell carcinoma (ESCC) is rare and its impact on survival is unknown. We studied survival in patients with ESCC who developed TPLN recurrence. To study the survival in patients with ESCC who developed TPLNs recurrence. Data were collected retrospectively for 219 patients who had undergone curative surgery for ESCC during January 2012 to November 2017 and who developed recurrences (36.29% of 604 patients who had undergone curative surgeries for ESCC). The patients were classified into positive (+) and negative (-) TPLN metastasis subgroups. We also investigated TPLN recurrence in 223 patients with ESCC following definitive chemoradiotherapy during 2012-2013. Following propensity score matching (PSM) and survival estimation, factors predictive of overall survival (OS) were explored using a Cox proportional hazards model. Among the patients with confirmed recurrence, 18 were TPLN (+) and 13 developed synchronous distant metastases. Before PSM, TPLN (+) was associated with worse recurrence-free (P = 0.00049) and OS [vs TPLN (-); P = 0.0027], whereas only the intergroup difference in recurrence-free survival remained significant after PSM (P = 0.013). The Cox analysis yielded similar results. Among the patients who had received definitive chemoradiotherapy, 3 (1.35%) had preoperative TPLN enlargement and none had developed recurrences. TPLN metastasis is rare but may be associated with poor survival.

Efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation for locally advanced cervical cancer: A systematic review and meta-analysis (307)

Objectives: For locally advanced cervical cancer (LACC) patients without para-aortic lymph node metastasis, the standard treatment is pelvic radiotherapy plus concurrent chemotherapy. After standard treatment, 7-15% of patients had a recurrence in para-aortic lymph nodes. The present study aimed to evaluate the efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation (EFI) for locally advanced cervical cancer (LACC). The present meta-analysis has been registered in PROSPERO (no. CRD42020167302). Methods: A systemic review and meta-analysis of recent studies retrieved from PubMed, EMBASE, and Cochrane databases from the establishment of the database to March 2021 was performed. All LACC patients with negative para-aortic lymph nodes received concurrent chemoradiotherapy. The experimental group consisted of patients undergoing pelvic irradiation plus prophylactic EFI, but the control group was undergoing pelvic irradiation. The primary outcomes were overall survival (OS) and para-aortic control. The secondary outcomes were: disease-free survival (DFS)/progression-free survival (PFS), distant metastasis, pelvic control, and toxicities. The quality of RCT was evaluated by the Cochrane bias risk tool. The quality of the retrospective study was evaluated by the Newcastle Ottawa scale (NOS). Revman5.3 software was used for statistical analysis. Results: A total of 180 studies were evaluated and six literatures met the inclusion criteria. Prophylactic EFI significantly improved 5-year OS (HR: 0.36 [0.22-0.59], p <0.0001) and DFS (3-year: HR: 0.53 [0.32-0.87], p=0.01; 5-year: HR: 0.45 [0.27-0.77], p=0.004). Prophylactic EFI reduced the rate of para-aortic failure (3-year: OR: 0.09 [0.01-0.70], p=0.02; 5-year: OR: 0.09 [0.03-0.30], p<0.0001) and distant metastasis (3-year: OR: 0.22 [0.11-0.45], p <0.0001; 5-year: OR: 0.53 [0.33-0.87], p=0.01). EFI did not increase the gastrointestinal toxicities (acute: OR: 1.94 [0.59-6.35], p=0.27; chronic: OR: 1.24 [0.65-2.40], p=0.51) and acute hematotoxicities (leukopenia: OR: 1.59 [0.98-2.59], p=0.06; thrombocytopenia: OR: 2.81 [0.87-9.03], p=0.08). Conclusions: The results of the present study suggested that prophylactic EFI using modern radiation techniques is beneficial for patients with LACC. Because five out of six pieces of literature included in our study are retrospective studies, prospective, large sample, and multicenter clinical trials are needed to further verify the impact of prophylactic EFI. Objectives: For locally advanced cervical cancer (LACC) patients without para-aortic lymph node metastasis, the standard treatment is pelvic radiotherapy plus concurrent chemotherapy. After standard treatment, 7-15% of patients had a recurrence in para-aortic lymph nodes. The present study aimed to evaluate the efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation (EFI) for locally advanced cervical cancer (LACC). The present meta-analysis has been registered in PROSPERO (no. CRD42020167302). Methods: A systemic review and meta-analysis of recent studies retrieved from PubMed, EMBASE, and Cochrane databases from the establishment of the database to March 2021 was performed. All LACC patients with negative para-aortic lymph nodes received concurrent chemoradiotherapy. The experimental group consisted of patients undergoing pelvic irradiation plus prophylactic EFI, but the control group was undergoing pelvic irradiation. The primary outcomes were overall survival (OS) and para-aortic control. The secondary outcomes were: disease-free survival (DFS)/progression-free survival (PFS), distant metastasis, pelvic control, and toxicities. The quality of RCT was evaluated by the Cochrane bias risk tool. The quality of the retrospective study was evaluated by the Newcastle Ottawa scale (NOS). Revman5.3 software was used for statistical analysis. Results: A total of 180 studies were evaluated and six literatures met the inclusion criteria. Prophylactic EFI significantly improved 5-year OS (HR: 0.36 [0.22-0.59], p <0.0001) and DFS (3-year: HR: 0.53 [0.32-0.87], p=0.01; 5-year: HR: 0.45 [0.27-0.77], p=0.004). Prophylactic EFI reduced the rate of para-aortic failure (3-year: OR: 0.09 [0.01-0.70], p=0.02; 5-year: OR: 0.09 [0.03-0.30], p<0.0001) and distant metastasis (3-year: OR: 0.22 [0.11-0.45], p <0.0001; 5-year: OR: 0.53 [0.33-0.87], p=0.01). EFI did not increase the gastrointestinal toxicities (acute: OR: 1.94 [0.59-6.35], p=0.27; chronic: OR: 1.24 [0.65-2.40], p=0.51) and acute hematotoxicities (leukopenia: OR: 1.59 [0.98-2.59], p=0.06; thrombocytopenia: OR: 2.81 [0.87-9.03], p=0.08). Conclusions: The results of the present study suggested that prophylactic EFI using modern radiation techniques is beneficial for patients with LACC. Because five out of six pieces of literature included in our study are retrospective studies, prospective, large sample, and multicenter clinical trials are needed to further verify the impact of prophylactic EFI.

Isolated para-aortic nodal metastasis or recurrence absent after radical hysterectomy for stage IA-IIA cervical carcinoma (401)

Objectives: Accumulating evidence suggests that due to the low risk of initially metastatic para-aortic lymph nodes (PaLNs), patients undergoing surgical management of early-stage cervical cancer could potentially be spared the operative and long-term morbidity of PaLN dissection. We sought to explore the upfront and downstream implications of this management philosophy in women undergoing radical hysterectomy for stage IA - IIA cervical cancer. Methods: A review of institutional data identified women undergoing curative-intent radical hysterectomy with concurrent lymphad- enectomy of any kind for FIGO stage IA - IIA cervical carcinoma from 2004 to 2021. Demographics and clinical-pathologic data were collected. Recurrence rates and locations were analyzed. Patients with no follow-up were excluded. Chi-square and Fisher’s exact test were used for statistical analysis. Results: Three hundred patients were identified, of whom 265 were included in the analysis. The Median follow-up was 56 months. Regarding tumor stages, 31 patients had stage IA, 195 stage IB1, 34 stage IB2, and five had stage IIA. Seventy-one percent of patients underwent pelvic lymphadenectomy only (PLND), with 29% undergoing both pelvic and para-aortic lymphadenectomy (PPaLND). Demographic distribution was similar between groups. LVSI was present in 37% of PLND compared to 32% of PPaLND groups (p = NS). High-risk features (GOG 109 criteria: positive nodes, parametria, or margins) were present in 13% and 15% of patients of each group, respectively (p = NS). Para-aortic nodal metastasis was not detected in any patient with early-stage cervical cancer. Disease recurrence was diagnosed in 13.8% of PLND compared to 10.3% of PPaLND patients (p =NS), of which 65% included distant or multisite recurrences. Among recurrences, median PFS was 15.5 months (IQR 8.2 - 29.7), and OS was 34 months (IQR 21.5 - 54.4). There were no isolated first disease recurrences involving the para-aortic nodal chain. Less than 3% of patients (n = 1) with multi-site recurrence had involvement of the PaLN chain, which was in the setting of receiving no adjuvant treatment with high-risk disease (positive pelvic LNs) on initial surgery. Most common distant and multi-site recurrences occurred in the liver, lungs, and brain. Conclusions: Isolated para-aortic nodal recurrence was absent in patients after surgical management of early-stage cervical cancer, irrespective of histologic type. PaLN involvement in multi-site recurrence was also very uncommon, less than 3%. These findings could potentially be utilized to further refine individualized treatment planning in the upfront setting to spare unnecessary surgical morbidity. Objectives: Accumulating evidence suggests that due to the low risk of initially metastatic para-aortic lymph nodes (PaLNs), patients undergoing surgical management of early-stage cervical cancer could potentially be spared the operative and long-term morbidity of PaLN dissection. We sought to explore the upfront and downstream implications of this management philosophy in women undergoing radical hysterectomy for stage IA - IIA cervical cancer. Methods: A review of institutional data identified women undergoing curative-intent radical hysterectomy with concurrent lymphad- enectomy of any kind for FIGO stage IA - IIA cervical carcinoma from 2004 to 2021. Demographics and clinical-pathologic data were collected. Recurrence rates and locations were analyzed. Patients with no follow-up were excluded. Chi-square and Fisher’s exact test were used for statistical analysis. Results: Three hundred patients were identified, of whom 265 were included in the analysis. The Median follow-up was 56 months. Regarding tumor stages, 31 patients had stage IA, 195 stage IB1, 34 stage IB2, and five had stage IIA. Seventy-one percent of patients underwent pelvic lymphadenectomy only (PLND), with 29% undergoing both pelvic and para-aortic lymphadenectomy (PPaLND). Demographic distribution was similar between groups. LVSI was present in 37% of PLND compared to 32% of PPaLND groups (p = NS). High-risk features (GOG 109 criteria: positive nodes, parametria, or margins) were present in 13% and 15% of patients of each group, respectively (p = NS). Para-aortic nodal metastasis was not detected in any patient with early-stage cervical cancer. Disease recurrence was diagnosed in 13.8% of PLND compared to 10.3% of PPaLND patients (p =NS), of which 65% included distant or multisite recurrences. Among recurrences, median PFS was 15.5 months (IQR 8.2 - 29.7), and OS was 34 months (IQR 21.5 - 54.4). There were no isolated first disease recurrences involving the para-aortic nodal chain. Less than 3% of patients (n = 1) with multi-site recurrence had involvement of the PaLN chain, which was in the setting of receiving no adjuvant treatment with high-risk disease (positive pelvic LNs) on initial surgery. Most common distant and multi-site recurrences occurred in the liver, lungs, and brain. Conclusions: Isolated para-aortic nodal recurrence was absent in patients after surgical management of early-stage cervical cancer, irrespective of histologic type. PaLN involvement in multi-site recurrence was also very uncommon, less than 3%. These findings could potentially be utilized to further refine individualized treatment planning in the upfront setting to spare unnecessary surgical morbidity.

Laparoscopic excision of isolated para-aortic lymph node recurrence in patient of hilar cholangiocarcinoma

Laparoscopic excision of isolated para-aortic lymph node recurrence in patient of hilar cholangiocarcinoma

Surgical Roles in the Management of Metachronus Para-aortic Lymph Node Recurrence and Synchronous Para-aortic Lymph Node Metastasis in Colorectal Cancer Patients

Abstract Background The relative rarity of synchronous para-aortic lymph node (PALN) metastasis (SPM) and metachronous PALN recurrence (MPR) in colorectal carcinoma (CRC) patients leads to a limited number of studies on patient management, and no treatment guidelines have been established to date. Objective To assess the prognostic, predictive roles, and long-term outcomes of different management strategies for isolated MPR and SPM in CRC patients to establish the best one. Materials and Methods We included 35 CRC patients with isolated MPR and 25 patients with isolated SPM who underwent curative R0 resection. We performed PALN dissection (PALND) in 15 cases in MPR group and in 10 cases in the SPM group; all remaining patients in both groups underwent chemoradiotherapy (CRT) without further surgical intervention. During the study period of about 5 years, we compared the patients who underwent PALND and those who underwent CRT. Results The overall survival and recurrence-free survival rates were significantly longer in patients who underwent PALND (p = 0.049 and 0.036 respectively). Conclusions We showed that PALND in cases of CRC patients with SPM and MPR previously submitted to R0 resection was associated with favorable outcomes and better patient survival.

Long-Term Outcomes of Surgical Resection of Pathologically Confirmed Isolated Para-Aortic Lymph Node Metastases in Colorectal Cancer: A Systematic Review.

Simple SummaryPara-aortic lymph node (PALN) metastases represent patterns of initial recurrence in only 2–6% CRC patients. Lack of consensus has impaired an unambiguous statement for PALN recurrence resection. Our systematic review identified 59.4–68% 3-year OS rate and 53.4–87.5% 5-year OS rate, with a 25–84 months median OS, 26.3–61% 3-year DFS rate and 0–60.5% 5-year DFS rate, with a 14–24 month median DFS, in patient undergoing isolated PALNM resection. Overall, 62.1% re-recurrence rate ranged from 43.8% to 100%. Although PALNMs resection in CRC patients may be considered a feasible and beneficial option, no conclusions or recommendations can be provided, taking into account the current evidence. Further randomized, possibly multicenter trials are strongly recommended and mandatory in order to confirm our results and clearly identify patient selection criteria.Background: Para-aortic lymph node (PALN) metastases represent patterns of initial recurrence in only 2–6% CRC patients, after an estimated 23–28 month time interval. An increasing trend towards curative surgery has been witnessed in patients presenting with controlled PALN recurrence. Nevertheless, lack of consensus has impaired an unambiguous statement for PALN recurrence resection. Methods: We performed a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, which led us to gain deeper insight into the prognostic factors and long-term outcomes after resection for synchronous or metachronous pathologically confirmed CRC isolated para-aortic lymph node metastases (PALNM). Pubmed/MEDLINE, Embase, Scopus, Cochrane Library and Web of Science databases were used to search all related literature. Results: The nine articles included covered a study period of 30 years (1988–2018), with a total of 161 patients. At presentation, most primary CRCs were located in the colon (74%) and 95.6%, 87.1% and 76.9% patients had T3–T4, N1–N2 and well/moderately differentiated CRC, respectively. We identified a 59.4–68% 3-year OS rate and 53.4–87.5% 5-year OS rate, with a 25–84 months median OS, 26.3–61% 3-year DFS rate and 0–60.5% 5-year DFS rate, with a 14–24 month median DFS. Overall, 62.1% re-recurrence rate ranged from 43.8% to 100%. Conclusions: Although PALNMs resection in CRC patients may be considered a feasible and beneficial option, no conclusions or recommendations can be made taking into account the current evidence. Therefore, further randomized, possibly multicenter trials are strongly recommended and mandatory if we want to have our results confirmed and patient selection criteria clearly identified.

Retrospective analysis of para-aortic lymph node recurrence in locally advanced cervix cancers treated with “pelvic-only field” radiotherapy

INTRODUCTION: Previous studies suggested that treating para-aortic lymph node micro-metastases with extended-field radiotherapy could result in higher rate of tumor control in high-risk locally advanced cervical cancers. Our study aimed to assess the patterns of recurrences following pelvic-only irradiation, with an emphasis on recurrence in para-aortic lymph node. MATERIALS AND METHODS: We retrospectively evaluated patterns of recurrences in patients with cervical cancers who were treated with definitive pelvic radiotherapy at our institution from 2013 to 2016. Univariate and multivariate analyses were performed to identify risk factors associated with para-aortic lymph node recurrence. RESULTS: We enrolled 463 patients in the study. The median of follow-up was 63.5 months. Five-years overall survival, recurrence-free survival, and para-aortic lymph node recurrence rates were respectively 78.9%, 76.2% and 6.5%. During follow-up, 23.33% experienced recurrences. Most often tumors recurred locally (42.60%). Para-aortic recurrences were found in 26 patients. Patients’ age (≤57 years) (HR=4.9, p=0.002), histological subtype (adenocarcinoma) (HR=2.7, p=0.035), presence of pelvic lymph node metastasis (HR=0.3, p=0.037) and absence of brachytherapy (HR=6.5, p&lt;0.0001) were significantly associated with para-aortic lymph node (PALN) recurrence in multivariate analysis. CONCLUSION: Recurrences following pelvic-only irradiation were frequently observed in the pelvis. Clinical characteristics associated with a high risk of PALN recurrence were young age, absence of brachytherapy, presence of pelvic lymph node metastases, and the adenocarcinoma subtype. However, further studies with a greater number of patients need to be undertaken.

Feasibility of Laparoscopic Para-Aortic Lymphadenectomy for Locally Advanced Cervical Cancer.

Background:Radiological evaluation of para-aortic lymph node metastasis in patients with locally advanced cervical cancer (LACC) possess the risk of missing microscopic metastasis. We commenced laparoscopic para-aortic lymphadenectomy (Lap-PAN) on patients with LACC for surgical staging in 2016. We assessed the feasibility of Lap-PAN in patients with LACC.Methods:We retrospectively reviewed the records of 31 patients with LACC who were staged at International Federation of Gynecology and Obstetrics (FIGO) 2009 IIB to IVA without enlargement of the para-aortic lymph nodes who underwent radiation therapy in our hospital between January 1, 2011 and December 31, 2018. The postoperative outcomes of Lap-PAN were analyzed, and distinct parameters for each patient, including sites of recurrence and disease-free survival, were compared between the Lap-PAN (n = 12) and no surgery (n = 19) groups.Results:The average operation time for Lap-PAN was 167 min, and the estimated blood loss was less than 50 ml in all patients. There were no perioperative complications. The average number of excised lymph nodes was 25, and no pathological metastases were observed. There was no difference in disease-free survival rates between the Lap-PAN and no surgery groups (p = 0.42). During the follow-up period, there were two cases of recurrence in the cervix in the Lap-PAN group, and three and four cases of lung and para-aortic lymph node recurrence, respectively in the no-surgery group.Conclusions:Lap-PAN was safely performed as a pretherapeutic staging method for LACC without worsening patient prognosis. Although Lap-PAN requires a high level of skill, it may be a method to avoid excessive radiation for LACC.

A Novel Risk Factor for Para-Aortic Lymph Node Recurrence After Definite Pelvic Radiotherapy in Stage IIIB Cervical Cancer.

Background: Studies determining which patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB disease benefit from prophylactic extended-field irradiation (EFRT), which can reduce para-aortic lymph node (PALN) failure rates, are limited. The study was designed to evaluate the value of the controlling nutritional status (CONUT) score as a risk factor for predicting PALN recurrence and identifying potential indications of prophylactic EFRT. Methods: From 2010 to 2015, a retrospective review was conducted among patients with FIGO stage IIIB cervical cancer who were treated with definitive pelvic radiotherapy or concurrent chemoradiotherapy. We analyzed para-aortic lymph node metastasis-free survival (PALNMFS) using Kaplan-Meier curves. Multivariate analyses were performed using Cox regression models. Results: A total of 116 patients with FIGO stage IIIB cervical cancer were included in the study and the median follow-up was 42.2 months (range: 3.5-104.2 months). Multivariate analysis revealed that the CONUT score (HR: 3.141; 95% CI: 2.321-5.436; P < .001) and ≥3 pelvic lymph node metastases (HR: 2.235; 95% CI: 1.428-11.242; P < .001) were independent risk predictors of PALNMFS. Compared with the low CONUT group (score<3), the high CONUT group (score≥3) was associated with a significantly worse 3-year disease-free survival rate (46.9 vs 69.5%, P = .001), a significantly lower 3-year overall survival rate (68.5 vs 79.7%, P = .016) and a significantly lower PALNMFS rate (74.8 vs 96.4%, P < .001). Conclusions: A high CONUT score (score≥3) and ≥3 pelvic metastatic lymph nodes were significant predictors of PALNMFS after pelvic radiation in FIGO stage IIIB cervical cancer patients. Patients with these risk factors might benefit from prophylactic EFRT.

Do Radiotherapy Planning Factors Influence Para-Aortic Recurrence in IIIC1 Cervical Cancer Patients?

Patients with locally advanced cervical cancer are at higher risk of para-aortic lymph node recurrence, however, the addition of prophylactic para-aortic irradiation is still controversial. The aim of this study was to evaluate prognostic factors related to para-aortic recurrence in patients with cervical cancer and pelvic lymph node metastasis (2018 FIGO Stage IIIC1).A retrospective cohort analysis was conducted with patients with cervical cancer and pelvic lymph node metastasis (2018 FIGO Stage IIIC1), that were treated with primary or adjuvant chemoradiotherapy from 2007 to 2018 at a single tertiary cancer center. Clinical and pathological variables were evaluated, as well as radiological and radiotherapy planning factors. Kaplan-Meier method was used to calculate survival and survival comparison between groups with log-rank method. Statistically significant was defined as P ≤ 0.05.Seventy-two patients were included: 56 (77.8%) had primary chemoradiotherapy and 16 (22.2%) adjuvant chemoradiotherapy after radical hysterectomy and lymph node staging. 58 (80.5%) underwent 3D-conformal, 14 (19.5%) intensity-modulated radiotherapy, and 67 (93%) also had high dose rate vaginal brachytherapy. Only 1 patient did not receive concomitant chemotherapy. Staging PET-CT was available in 23 (31.9%) cases and the remaining ones were staged with MRI or CT scans, Surgical para-aortic staging was not performed. The median follow-up was 42 months (range, 5 to 144 months). Overall, 27 (37.5 %) patients recurred during follow-up, and 7 (26 %) had isolated para-aortic lymph-node recurrence. Distant metastasis and pelvic recurrence were found in 12 (45 %) and 8 (29 %) cases, respectively. Median overall survival, disease free survival, distant metastasis free survival, loco-regional free survival and para-aortic free survival were 56, 52, 52, 51 and 42 months, respectively. In univariate analysis, PET SUV in pelvic lymph nodes higher than 10.2 (P = 0.02) and positive lymph nodes in the left common iliac station (P = 0.05) were identified as predictive factors for isolated para-aortic recurrence. We also identified positive lymph node in the common iliac station as a predictor for distant recurrence (P = 0.002). Tumor size larger than 66 mm (P = 0.046) and positive lymph node in the left common iliac lymph node station (P = 0.02) as predictors for pelvic recurrence. Lymph node > 24 mm was the only prognostic factor associated with overall survival (P = 0.012).In this retrospective cohort, radiological and radiotherapy planning factors as high lymph node's PET SUV and proximal location of positive pelvic lymph nodes were prognostic for para-aortic recurrence in IIIC1 cervical cancer patients. Further prospective and randomized studies are required to validate those risk factors as well as to determine if prophylactic para-aortic irradiation would improve outcomes in these patients.P.J. Pinto: None. S.L. Favareto: None. C.F. Souza: None. G. Baiocchi: None. A.A. da Costa: None. A.C. Pellizon: None. C. Abrahao: None. D.G. Castro: None. G.R. Gondim: None. H. Ramos: None. E. Santos Neto: None. R.C. Fogaroli: None. M.G. Silva: None. M.J. Chen: None.

Sentinel lymph node mapping detection and recurrence rates in clinical stage I endometrial cancer

Objectives: The literature suggests that sentinel lymph node biopsy (SLNB) is an acceptable alternative to pelvic and paraaortic lymph node dissection (PPALND) in patients with clinical stage I endometrial cancers. The referenced data is largely published from high-volume specialized institutions and a complete PPALND is still performed by many surgeons at smaller, non-specialized centers. Our aim is to demonstrate that SLNB is feasible, reproducible, and sensitive without affecting cancer-specific outcomes when implemented at a non-specialized center. Methods: A retrospective review of patients with clinical stage I endometrial cancer was performed from September 2016 through February 2020. All patients had undergone either a robot-assisted or laparoscopic hysterectomy with SLNB. Endometrioid, uterine papillary serous (UPSC), malignant mixed mesodermal tumor (MMMT), and clear cell (CC) histologies were included. Indocyanine green was injected into the cervix bilaterally as per a previously described protocol. Paraaortic LND was performed at the discretion of the surgeon. In addition to SLNB, complete PPALND was performed for patients with MMMT, UPSC or CC. Sentinel lymph nodes (SLN) were evaluated using ultra-staging protocols including serial sectioning and cytokeratin staining. The medical record was queried for clinical or radiographic evidence of recurrence. Results: A total of 92 patients were included: 69 stage IA, 12 stage IB, 3 stage II and 8 stage III (2 IIIA, 2 IIIC1, 4 IIIC2). The majority of patients were endometrioid (73%), followed by UPSC (15.0%), MMMT (5.0%) and CC (4%). At least one SLN was detected in 95.4% of cases. The rate of bilateral SLN detection was 74.3% and improved over time from 2017-2019: 70% (2017), 74.4% (2018), 80% (2019). Twenty patients underwent PPALND. Non-SLN were positive in 3 patients, all with high-risk histology. There were no other patients with false-negative SLNB. There have been 3 (3%) recurrences to date; one rectal recurrence, one pelvic side wall and one paraaortic lymph node recurrence. All three patients had detected bilateral SLN which were negative at the time of their initial surgery; all three recurrences were high grade histology. Conclusions: SLNB is a sensitive and specific method for assessing lymph node involvement in patients with clinical stage I endometrial cancers. Our detection and recurrence rates are comparable to the rates reported in the literature and demonstrate that when applied at non-specialized centers this approach is safe and reproducible without affecting cancer-specific 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.

Long-term survival achieved by repeated administration of ramucirumab after drug holidays due to proteinuria in recurrent gastric cancer

BackgroundThe prognosis of recurrent and unresectable gastric cancer remains poor despite the development of multidisciplinary treatments. Ramucirumab (RAM) has been proven effective against unresectable or recurrent gastric cancer. However, its administration is often discontinued because of adverse events, including hypertension and proteinuria. We report a patient with recurrent gastric cancer involving the paraaortic lymph node (PALN), who achieved long-term survival after repeated RAM administration following long-term drug holidays due to proteinuria.Case presentationA 79-year-old woman was diagnosed with advanced gastric cancer (cT4aN2) with PALN metastasis. Seven courses of S-1 plus cisplatin (SP) achieved downstaging. A distal gastrectomy with D2 lymphadenectomy was performed as a conversion surgery. The pathological diagnosis was ypT3N2M0. The dissected PALN did not contain viable cancer cells. CT and positron emission tomography/CT scans revealed PALN recurrence 1 year after the surgery. S-1 plus oxaliplatin (SOX) therapy was initiated. The recurrent PALN enlarged after seven courses of SOX therapy. Paclitaxel (PTX) plus ramucirumab (RAM) therapy was initiated as second-line chemotherapy. After three courses of PTX plus RAM therapy, a partial response was observed. PTX was discontinued because of a hematological adverse event 3.5 months after PALN recurrence. Disease progression was not observed after six courses of RAM monotherapy. However, RAM caused proteinuria and was withdrawn for 7 weeks. The recurrent PALN was enlarged on CT, and RAM monotherapy was resumed at a reduced dose of 6 mg/kg. The lesion subsequently shrank, but 4 + proteinuria occurred after three courses of RAM monotherapy. Thus, RAM was discontinued. The patient had chemotherapy-free days for 14 months until the PALN was re-enlarged to 13 mm in size. The three administrations of RAM successfully controlled PALN metastasis and proteinuria for 3 years.ConclusionIn conclusion, even if RAM withdrawal led to disease progression, re-administration of RAM monotherapy while considering its side effects reduced the tumor size and provided long-term survival benefits.