Metastatic Para-aortic Nodes Research Articles

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

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

The prognostic value of FIGO staging defined by combining MRI and [18F]FDG PET/CT in patients with locally advanced cervical cancer

The last version of the FIGO classification recommended imaging tools to complete the clinical assessment of patients with cervical cancer. However, the preferable imaging approach is still unclear. We aimed to explore the prognostic power of Magnetic Resonance Imaging (MRI), contrast-enhanced Computed Tomography (ceCT), and [18F]-Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET)/CT in patients staged for locally advanced cervical cancer (LACC, FIGO stages IB3-IVA). Thirty-six LACC patients (mean age 55.47 ± 14.01, range 31-82) were retrospectively enrolled. All of them underwent MRI, ceCT and [18F]FDG-PET/CT before receiving concurrent chemoradiotherapy. A median dose of 45 Gy (range 42-50.4; 25-28 fractions, 5 fractions per week, 1 per day) was delivered through the external-beam radiation therapy (EBRT) on the pelvic area, while a median dose of 57.5 Gy (range 16-61.1; 25-28 fractions, 5 fractions per week, 1 per day) was administered on metastatic nodes. The median doses for brachytherapy treatment were 28 Gy (range 28-30; 4-5 fractions, 1 every other day). Six cycles of cisplatin or carboplatin were administered weekly. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Metastatic pelvic lymph nodes at MRI independently predicted RFS (HR 13.271, 95% CI 1.730-101.805; P = 0.027), while metastatic paraaortic lymph nodes at [18F]FDG-PET/CT independently predicted both RFS (HR 11.734, 95% CI 3.200-43.026; P = .005) and OS (HR 13.799, 95% CI 3.378-56.361; P < 0.001). MRI and [18F]FDG-PET/CT findings were incorporated with clinical evidences into the FIGO classification. With respect to the combination of clinical, MRI and ceCT data, the use of next-generation imaging (NGI) determined a stage migration in 10/36 (27.7%) of patients. Different NGI-based FIGO classes showed remarkably different median RFS (stage IIB: not reached; stage IIIC1: 44 months; stage IIIC2: 3 months; P < 0.001) and OS (stage IIB: not reached; stage IIIC1: not reached; stage IIIC2: 14 months; P < 0.001). A FIGO classification based on the combination of MRI and [18F]FDG-PET/CT might predict RFS and OS of LACC patients treated with concurrent chemoradiotherapy.

Effective radiotherapy in rarely observed para-aortic lymph node metastases of sinonasal schwannoma-clinical case from our practice

Schwannoma is benign neurogenic tumor, that arise from Schwann cells of the peripheral nerve sheath. Malignant schwannomas transformation is extremely rare. Histopathological and immunohistochemical analysis confirmed the final pathohistological diagnosis, which is extremely important for the assessment of the therapeutic approach. Schwannomas lymph node metastases are extremely rare and poorly characterized. We present an extremely rare sinonasal schwannoma with metastases in the para-aortic lymph nodes. More interesting is that metastatic para-aortic lymph nodes were affected by radiotherapy . In this article, we share the surprising fact, that the proved through FDG-PET/CT para -aortic lymph node metastases in sinonasal schwannoma with a limitation of more than 3 years, is effectively responded after radiotherapy with total dose over 45 Gy.

Multicenter study of prognostic factors in paraaortic lymph node dissection for metastatic colorectal cancer.

The role of paraaortic lymph node dissection (PALND) in colorectal cancer (CRC) has been less evaluated than surgical treatments for other distant metastases. We evaluated surgical outcomes after PALND and identified prognostic factors. The medical records of patients who underwent PALND for paraaortic lymph node metastasis (PALNM) were reviewed retrospectively. All patients were categorized into the M1a group (isolated PALNM, n = 27), and the M1bc group (distant metastases other than PALNM, n = 26). Three severity factors (PALNM-SF: number of harvested paraaortic lymph nodes [hLN], ≥14; number of metastatic paraaortic lymph nodes [mLN], ≥5; and lymph nodes ratio [mLN/hLN], ≥0.5) were defined to determine their effects on survival. The 5-year overall survival (OS) of the M1a and M1bc groups were 61.1% and 6.4%, respectively (P = 0.0013). The 5-year disease-free survival (DFS) of the M1a group was 47.4%, and the 3-year DFS of the M1bc group was 9.1% (P < 0.001). Patients with 2 or more PALNM-SFs showed worse OS than those with 1 PALNM-SF (P = 0.017). In multivariate analysis, M1bc (non-isolated PALNM) was the only significant factor for survival. In the M1a group, patients with 2 or more PALNM-SFs showed significantly worse survival than those with a single PALNM-SF. In multivariate analysis, 2 or more PALNM-SF was a significant factor for survival. PALND for CRC provided favorable outcomes in the survival of an isolated PALNM, although this was uncertain for non-isolated PALNMs. The PALNM-SFs helped assess the prognosis after PALND.

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.

An Artificial Intelligence Approach for Automatic Delineation of Para-Aortic Clinical Target Volume

Treatment of metastatic para-aortic lymph nodes (PAN) is critical for locally advanced cervical cancer (LACC) control. However, the clinical target volume (CTV) delineation for the para-aortic region is tedious and time-consuming even for a well-trained radiation oncologist. In this study, we trained a deep learning (DL) segmentation network that led to automatic and accurate PAN-CTV delineation.We retrospectively collected 47 radiotherapy planning CTs of LACC patients. For each planning CT, the Aorta, Inferior Vena Cava (IVC) and PAN-CTV were manually delineated for radiotherapy treatment planning for the elective para-aortic region from the left renal vein to the aortic bifurcation. The PAN-CTV was prophylactically contoured (ignoring gross para-aortic nodes) according to the recent Small et al. (2020) consensus guidelines. For each CT set, the spine structures were automatically delineated using threshold- and morphology-based segmentation. Then, all CTs were registered to a common reference frame based on the delineated spine structures and cropped to dimensions of 15 cm x 15 cm x 20 cm centered along the spine. A U-Net-based DL segmentation network was developed and trained to automatically segment Spine, Aorta, IVC, and PAN-CTV in the registered and cropped region. The segmented structures were converted into DICOM RTStruct with the original CT association.We used 32 CTs for training, 8 for validation, and 7 for testing. The Dice coefficient (DC) and Hausdorff distance (HD95) were used as the evaluation metrics. The mean (std) DC of PAN-CTV for training, validation and test sets were 0.911 (0.027), 0.757 (0.046) and 0.755 (0.073), respectively. The mean (std) HD95 of PAN-CTV for training, validation and test sets were 2.39 (2.77) mm, 10.12 (6.83) mm and 8.42 (4.52) mm, respectively. All testing PAN-CTVs were visually checked by an attending radiation oncologist specializing in gynecologic malignancies and deemed clinically acceptable.An Artificial Intelligence approach comprised of registration and DL network was developed and validated for automatic segmentation of Spine, Aorta, IVC, and PAN-CTV in LACC. Registration was used to improve the boundary definition of the virtual structure, PAN-CTV, for DL segmentation without human intervention. This approach could facilitate efficient workflow and allow for optimal dose delivery to the involved nodal basins in LACC.W. Chi: None. P. D'Cunha: None. M. Chen: None. L. Ma: None. M. Kazemimoghadam: None. Z. Yang: None. X. Gu: None. K.V. Albuquerque: Research Grant; Astra Zeneca. Honoraria; ACR, ARRT. Travel Expenses; ACR, ARRT, ASCO.W. Lu: None.

Intensity modulated radiotherapy in carcinoma cervix with metastatic para-aortic nodes: an institutional experience from a Regional Cancer Centre of Eastern India.

BackgroundCervical cancer is a major health problem, especially in developing countries like India. Extended field radiotherapy (EFRT) for cancer cervix treatment remains a challenging task for radiation oncologists. In the last decade studies have shown that EFRT using intensity modulated radiotherapy (IMRT) is feasible in treating gynaecological malignancies but there is a dearth of literature on this specific topic from this part of the world where patient profile differs greatly in several aspects from that of the western world. The aim of the study was evaluation of treatment response and toxicity profile in cases of carcinoma cervix with metastatic para-aortic nodes treated with intensity modulated radiotherapy technique.Materials and methodsIn this retrospective study the treatment records of 45 para-aortic node positive cervical cancer patients treated with EFRT (IMRT) and concurrent cisplatin were analysed for evaluation of loco-regional control and toxicities.ResultsForty-four patients received full course of treatment. Among those 44 patients, 93.2% achieved complete response. Overall, the treatment was tolerated well and toxicities were within acceptable limits. Acute grade 3–4 toxicities were observed mostly in the form of anaemia and leucopenia. Most common late toxicities were those of small and large intestine.ConclusionEFRT with concurrent chemotherapy was successfully delivered for para-aortic nodes positive cervical cancer patients in Indian scenario where under-nutrition, infection, anaemia and several other factors adversely influence treatment outcome. Pelvic and para-aortic control rates were satisfactory. The technique was associated with an acceptable acute and late toxicity profile.

Patterns of Treatment Failure after Concurrent Chemoradiotherapy or Adjuvant Radiotherapy in Patients with Locally Advanced Cervical Cancer

Objective: To identify patterns of therapy failure after radiotherapy in Chinese patients with locally advanced cervical cancer (LACC). Methods: A retrospective study was conducted at a Chinese hospital from June 2012 to July 2018. All analyses were done using SPSS 26. Results: 105 patients with treatment failure were included. After a median follow-up of 27 months (range 10–82), the 3-year survival rate after therapy failure was 19.4%. In multivariate analysis, squamous cell carcinoma antigen (SCC-Ag) <4 ng/mL (p < 0.001) and disease-free interval >12 months (p = 0.013) showed significant survival benefits. We identified 3 types of failure: distant lymph node metastasis (n = 50), hematogenous metastasis (n = 53) and pelvic failure (n = 48). Most metastatic para-aortic lymph nodes (PALN) were inferior to the level of left renal hilum (84.8%, n = 28). A total of 80% of patients with supraclavicular lymph nodes (SCLN) metastasis ignored imaging on supraclavicular region. For solitary SCLN or lung metastasis, the prognosis was better than that combined with other sites failure, respectively (p = 0.005; p = 0.001). Many patients with central sites recurrence received insufficient doses of intracavitary brachytherapy (IBT) for low tolerance to pain. Conclusion: The distribution of metastatic PALN is asymmetrical and optimizing clinical target volume to minimize toxicity of para-aortic radiation is necessary. The effect of ultrasonography as preliminary screening and follow-up means on SCLN metastasis can be expected. Pain management and psychological interventions are essential for patients receiving IBT.

Prognostic impact of para-aortic lymph node involvement in solid pancreatic ductal adenocarcinoma and malignant intraductal papillary mucinous neoplasm

Purpose: Para-aortic lymph nodes (PALN) metastases in solid pancreatic ductal adenocarcinoma (sPDAC) indicates short survival. In malignant intraductal papillary mucinous neoplasms (mIPMN) the role of PALN has not been well explored. The present study investigated the rate of metastatic PALN, N status, and lymph node (LN) ratio as prognostic factors in sPDAC and mIPMN. Method: This consecutive single-center series included patients with sPDAC and mIPMN in the pancreatic head who underwent pancreatoduodenectomy or total pancreatectomy including PALN resection during a ten-year period, 2009-2018. Median overall survival (mOS) and impact of clinicopathological factors including PALN status on survival were evaluated. Results: There were 403 patients, of which 89 had mIPMN and 314 sPDAC. PALN were metastatic in 16% of sPDAC and 17% of mIPMN (p=0.962). N0 status was present in 6% and 16%, respectively (p=0.007). A LN ratio>15% was more common in sPDAC (52%) than in mIPMN (34%) (p=0.004). The mOS was 12.7 months in the presence of PALN metastases and 22.7 months without (p<0.0001)(Figure). Age>70 years, CA19-9>200, sPDAC and N2 status were significant in multivariable analysis but PALN status and LN ratio were not independent prognostic factors. There was no difference in mOS in N2 status regardless the presence of PALN metastases. Conclusion: The frequency of PALN metastases was similar in sPDAC and mIPMN. Although mOS was shorter in PALN positive status it was not an independent risk factor and in N2 disease PALN metastases did not influence survival.

Adjuvant Chemotherapy After Concurrent Chemoradiotherapy for Pelvic Lymph Node-Positive Cervical Squamous Cell Carcinoma

Distant metastasis predominates the failure pattern of patients with pelvic lymph node (PLN)-positive cervical cancer. This study evaluated whether adjuvant chemotherapy (ACT) yields better treatment outcomes than observation after concurrent chemoradiotherapy (CCRT) for patients with (PLN)-positive cervical squamous cell carcinoma (SCC). The records of 159 patients with PLN-positive cervical SCC treated with CCRT between March 2007 and February 2018 were retrospectively reviewed. Patients with metastatic para-aortic lymph nodes and/or distant metastasis were excluded. The ACT regimens consisted of 5-Fluorouracil plus cisplatin and paclitaxel plus cisplatin. Treatment outcomes were compared according to the use of ACT before and after propensity score matching. Among the 159 eligible patients, 141 patients (88.7%) underwent CCRT and 42 patients underwent a median of 2 ACT cycles (range: 1-6 cycles) using cisplatin-based doublet chemotherapy. The median follow-up period was 33.8 months (range: 2.9-113.0 months). In multivariate analysis, poor overall survival was independently predicted by larger PLN size (≥15mm) and common iliac lymph node involvement. After propensity score matching, none of the patients was over 65 years old. The ACT group had non-significantly better estimated 3-year rates of overall survival (83.0% and 63.7%, p = 0.173), progression-free survival (80.2% and 60.4%, p = 0.071), local control (94.0% and 81.9%, p = 0.123), as well as a significantly better estimated 3-year rate of distant metastasis-free survival (DMFS) (85.9% and 60.1%, p = 0.040). Grades 3-4 neutropenia were significantly more common in the ACT group (38.1% versus 17.9%, p = 0.008). ACT significantly improved DMFS and tended to improve progression-free survival with tolerable toxicities in patients with PLN-positive cervical SCC. Further studies are needed to verify these findings and clarify the relationship between PLN involvement and prognosis in patients with cervical cancer.

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.

Implications of extraperitoneal paraaortic lymphadenectomy to the left renal vein in locally advanced cervical cancer. A Spanish multicenter study

ObjectiveParaaortic lymph node involvement is an important prognostic factor in locally advanced cervical cancer (LACC), but the anatomic limit of aortic lymphadenectomy is controversial. We assessed the impact of extraperitoneal paraaortic lymphadenectomy up to the left renal vein in patients with LACC undergoing pretherapeutic staging. MethodsA retrospective, multicenter study of patients with LACC stages FIGO 2009 IB2 and IIA2-IVA treated in 10 Spanish reference hospitals in gynecological oncology between 2000 and 2016. Sites of metastatic paraaortic lymph nodes above or below the inferior mesenteric artery were evaluated. Procedural-related intraoperative and early and late complications were assessed. ResultsWe included 634 patients undergoing paraaortic lymphadenectomy, in 616 (97.2%) of which the left renal vein was the upper limit of dissection (laparoscopy 592, robotic-assisted 24). The median surgical time was 150 min (interquartile range (IQR) 120–180), blood loss was 50 mL (range 20–80), and the length of stay was 2 days (range 2–3).Metastatic paraaortic involvement was found in 114 patients (18.5%), with infrarenal metastases in 73 (64%) of them. There were 11 patients (9.6%) with infrarenal metastases only, whereas in the remaining 62 (54.4%) patients concomitant infrarenal and inframesenteric metastases were observed. Intraoperative, early, and late postoperative complications occurred in 3.6%, 7.0%, and 4.5% of patients, respectively. ConclusionsIn this study of patients with LACC undergoing surgical staging, paraaortic lymphadenectomy up to the left renal vein detected skip or isolated infrarenal metastasis in 9.6% of patients, with an acceptable surgical morbidity.

Prognostic impact of para-aortic lymph node metastases in non-pancreatic periampullary cancer

BackgroundResection of the para-aortic lymph node (PALN) group Ln16b1 during pancreatoduodenectomy remains controversial because PALN metastases are associated with a worse prognosis in pancreatic cancer patients. The present study aimed to analyze the impact of PALN metastases on outcome after non-pancreatic periampullary cancer resection.MethodsOne hundred sixty-four patients with non-pancreatic periampullary cancer who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005 and 2016 were retrospectively investigated. The data were supplemented with a systematic literature review on this topic.ResultsIn 67 cases, the PALNs were clearly assigned and could be histopathologically analyzed. In 10.4% of cases (7/67), tumor-infiltrated PALNs (PALN+) were found. Metastatic PALN+ stage was associated with increased tumor size (P = 0.03) and a positive nodal stage (P < 0.001). The median overall survival (OS) of patients with metastatic PALN and non-metastatic PALN (PALN–) was 24.8 and 29.5 months, respectively. There was no significant difference in the OS of PALN+ and pN1 PALN patients (P = 0.834). Patients who underwent palliative surgical treatment (n = 20) had a lower median OS of 13.6 (95% confidence interval 2.7–24.5) months. Including the systematic literature review, only 23 cases with PALN+ status and associated OS could be identified; the average survival was 19.8 months.ConclusionPALN metastasis reflects advanced tumor growth and lymph node spread; however, it did not limit overall survival in single-center series. The available evidence of the prognostic impact of PALN metastasis is scarce and a recommendation against resection in these cases cannot be given.

Unexpected Para-aortic Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma: a Contraindication to Resection?

BackgroundMargin-negative resection is the only cure for pancreatic cancer. However, para-aortic lymph node metastasis is considered a contraindication to curative resection in pancreatic cancer. To determine if there are long-term survival differences according to the presence or absence of para-aortic lymph node metastasis in patients undergoing pancreatectomy, we evaluated oncologic outcomes in resected pancreatic cancer with unexpected para-aortic lymph node metastasis confirmed on intraoperative frozen section biopsy. MethodsWe retrospectively investigated 362 patients with pathologically confirmed pancreatic ductal adenocarcinoma who underwent pancreatectomy between 1996 and 2016. ResultsPatients with a metastatic para-aortic lymph node had the poorest median disease-specific survival [hazard ratio 14, 95% confidence interval 10–19]. However, after chemotherapy, patients with a metastatic para-aortic lymph node had a much higher disease-specific survival rate (para-aortic lymph node+/postoperative chemotherapy− versus para-aortic lymph node+/postoperative chemotherapy+, P = 0.0003, adjusted P = 0.0015). Patients with a metastatic para-aortic lymph node who underwent postoperative chemotherapy had a similar survival benefit to patients with metastatic regional lymph node without para-aortic lymph node metastasis, regardless of postoperative chemotherapy (para-aortic lymph node+/postoperative chemotherapy+ versus regional lymph node+/postoperative chemotherapy−, P = 0.3047, adjusted P > 0.9999; para-aortic lymph node+/postoperative chemotherapy+ versus regional lymph node+/postoperative chemotherapy+, P = 0.0905, adjusted P = 0.4525). ConclusionsUnexpected para-aortic lymph node metastasis on frozen section biopsy may no longer be a contraindication to curative resection in “resectable” pancreatic ductal adenocarcinoma, as long as postoperative adjuvant chemotherapy can be administered.

Therapeutic value of surgical paraaortic staging in locally advanced cervical cancer: a multicenter cohort analysis from the FRANCOGYN study group

BackgroundThe prognostic impact of surgical paraaortic staging remains unclear in patients with locally advanced cervical cancer (LACC). The objective of our study was to evaluate the survival impact of surgical staging in patients with LACC and no evidence of paraaortic lymph node (PALN) metastasis on pre-operative imaging work-up.MethodsData of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with locally advanced disease (IB2 or more) treated by concurrent chemoradiation therapy (CRT) and no evidence of paraaortic metastasis on pre-operative imaging work-up were selected for further analysis. The Kaplan–Meier method was used to estimate the survival distribution. A Cox proportional hazards model was used to account for the influence of multiple variables.ResultsSix hundred and forty-seven patients were included, 377 (58.3%) with surgical staging and 270 (41.7%) without, with a mean follow up of 38.1 months (QI 13.0–56.0). Pathologic analysis revealed positive lymph nodes in 47 patients (12.5%). In multivariate model analysis, surgical staging remained an independent prognostic factor for DFS (OR 0.64, CI 95% 0.46–0.89, p = 0.008) and OS (OR 0.43, CI 95% 0.27–0.68, p < 0.001). The other significant parameter in multivariate analysis for both DFS and OS was treatment by intracavitary brachytherapy (OR respectively of 0.7 (0.5–1.0) and 0.6 (0.4–0.9), p < 0.05).ConclusionNodal surgical staging had an independent positive impact on survival in patients with LACC treated with CRT with no evidence of metastatic PALN on imaging.

Improving Selection for Resection of Synchronous Para-Aortic Lymph Node Metastases in Colorectal Cancer

Introduction: The clinical benefit of extended lymphadenectomy for synchronous extraregional lymph node metastasis, such as para-aortic lymph node (PALN) metastasis in colorectal cancer, remains highly controversial. Aim: To evaluate the clinical benefit of PALN dissection in colorectal cancer patients with synchronous PALN metastasis with or without multiorgan metastases. Methods: Thirty-six patients with pathologically positive PALN metastasis below the renal veins who underwent concurrent PALN dissection and primary colorectal cancer resection from January 1984 through September 2011 at the National Cancer Center Hospital in Tokyo, Japan, were included in this retrospective cohort study. We examined 5-year recurrence-free survival (RFS) rates in patient groups depending on the number of nodes involved (≤2 and ≥3 nodes) and on the presence or absence of other organ involvement (M1a and M1b,c categories in TNM staging). Results: The 5-year RFS rate was significantly different depending on the number of metastatic PALNs (42.1 and 0.6% for PALN ≤2 and ≥3, respectively, p = 0.01). The 5-year RFS rate was significantly better in patients in the M1a category than in patients in the M1b and M1c categories (27.6 and 0.0%, respectively, p < 0.01). Twenty-nine patients (80.6%) experienced recurrence after PALN dissection. Postoperative complications were seen in 14 (38.9%) patients. Conclusion: PALN dissection below the renal veins for patients with isolated PALN metastasis with 2 or fewer involved PALNs may be effective in improving prognosis in colorectal cancer.

Influence of Prognostic Factors on Lymph Node Involvement in Endometrial Cancer: A Single-Center Experience.

The requirement for and extent of lymphadenectomy in endometrial cancer is still controversial. Clinicopathological prognostic factors could be helpful to predict lymph node involvement and avoid therefore unnecessary lymphadenectomy. The aim of this study was to investigate which factors can predict lymph node involvement and how lymph node metastases are distributed in the pelvic and para-aortic regions. This retrospective analysis was performed by analyzing data from patients with endometrial cancer treated with standard surgery and lymphadenectomy at the Department of Gynecology and Obstetrics of the University Hospital Ulm in 2000 to 2013. One hundred twenty-five patients received pelvic lymphadenectomy with a median of 25 removed nodes, and 111 patients additionally received para-aortic lymphadenectomy with a median of 12 removed nodes. Metastatic lymph nodes were found in 24.8% of the patients, and a multivariate logistic regression showed that lymphovascular space invasion, histological type, and tumor stage significantly and independently predicted lymph node involvement. Of the 111 patients with both pelvic and para-aortic lymphadenectomy, 18 (16.2%) patients had metastatic para-aortic nodes, and 3 (2.7%) patients had isolated positive para-aortic lymph nodes without involvement of pelvic lymph nodes. Lymphovascular space invasion, histological type, and tumor stage are significant predictors of lymph node involvement in endometrial cancer. In patients at high risk of nodal involvement, lymphadenectomy should be performed systematically up to the renal vein. Large and carefully designed prospective studies are needed to evaluate patient cohorts for which a complete lymphadenectomy provides a survival benefit. In the future, the increasing use of sentinel node biopsy may facilitate a more personalized treatment of patients with endometrial cancer.

Prognostic effect of isolated paraaortic nodal spread in endometrial cancer

Objective:To evaluate the prognostic effect of isolated paraaortic lymph node metastasis in endometrial cancer (EC).Material and Methods:This retrospective study included patients with FIGO 2009 stage IIIC2 disease due to isolated paraaortic lymph node metastasis (LNM). Patients with sarcomatous histology, synchronous gynecologic cancers and patients with concurrent pelvic lymph node metastases or patients that have intraabdominal tumor spread were excluded. Kaplan-Meier method was used for calculation of progression free survival (PFS) and overall survival.Results:One thousand six hundred and fourteen patients were operated for EC during study period. Nine hundred and sixty-one patients underwent lymph node dissection and 25 (2.6%) were found to have isolated LNM in paraaortic region and these constituted the study cohort. Twenty (80%) patients had endometrioid EC. Median number of retrieved lymph nodes from pelvic region and paraaortic region was 21.5 (range: 5-41) and 34.5 (range: 1-65), respectively. Median number of metastatic paraaortic nodes was 1 (range: 1-32). The median follow-up time was 15 months (range 5-94). Seven (28%) patients recurred after a median of 20 months (range, 3-99) from initial surgery. Three patients recurred only in pelvis, one patient had upper abdominal spread and 3 had isolated extraabdominal recurrence. Involvement of uterine serosa, positive peritoneal cytology and presence of adnexal metastasis were significantly associated with diminished PFS (p<0.05).Conclusion:The presence of serosal involvement or adnexal involvement is as important as gross peritoneal spread and is related with poor survival in patients with isolated paraaortic nodal spread in EC. Chemotherapy should be the mainstay of treatment in this patient cohort which may eradicate systemic tumor spread.

Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report

BackgroundRegorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years.Case presentationA 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression.ConclusionsTo the best of our knowledge, this is the longest treatment with regorafenib without tumor progression ever reported. A reduced dosage of regorafenib at induction may ameliorate the cutaneous and hepatic toxicity associated with its use.

Para-aortic lymph node metastases in pancreatic cancer should not be considered a watershed for curative resection

No international consensus regarding the resection of the para-aortic lymph node (PALN) station Ln16b1 during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) has been reached. The present retrospectively investigated 264 patients with PDAC who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005–2015. In 95 cases, the PALN were separately labelled and histopathologically analysed. Metastatic PALN (PALN+) were found in 14.7% (14/95). PALN+ stage was associated with increased regional lymph node metastasis. The median overall survival (OS) of patients with metastatic PALN and with non-metastatic PALN (PALN−) was 14.1 and 20.2 months, respectively. Five of the PALN+ patients (36%) survived >19 months. The OS of PALN+ and those staged pN1 PALN− was not significantly different (P = 0.743). Patients who underwent surgical exploration or palliative surgery (n = 194) had a lower median survival of 8.8 (95% confidence interval: 7.3–10.1) months. PALN status could not be reliably predicted by preoperative computed tomography. We concluded that the survival data of PALN+ cases is comparable with advanced pN+ stages; one-third of the patients may expect longer survival after radical resection. Therefore, routine refusal of curative resection in the case of PALN metastasis is not indicated.