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Correlation Between Pelvic Peritoneal Disease and Nodal Metastasis in Advanced Ovarian Cancer: Can Intraoperative Findings Define the Need for Systematic Nodal Dissection?

ABSTRACT: To explore the relationship of peritoneal, and rectal involvement with lymph nodal metastases to identify clinical parameters to guide systematic nodal dissection in advanced ovarian cancer (stage 3c). It is a retrospective study of stage III C epithelial ovarian cancers undergoing cytoreductive surgery with systematic nodal dissection, from January 2011 to December 2016. LS3 score is a cumulative score given for the presence of size 3 lesion (peritoneal disease measuring more than 5 cm) in regions 5, 6, and 7. The depth of rectal involvement was assigned progressive numerical values from 1 (for serosa) to maximum 4 (for mucosa) to generate rectal involvement score. There were 91 patients. 48.35% patients had LS3 lesions in regions 5, 6, 7. Of these, 36% (27/44) had positive nodes. Of the 41 node-positive cases, 43.9% had single and 34.14% had two station involvements. Rectum was involved in 47 patients (51.64%), serosal involvement being the most common type (50.57%). Twenty patients had positive mesorectal nodes (42.55%). The presence of rectal involvement was influenced by the Peritoneal Carcinomatosis Index (PCI) score, the presence of LS3 in lower quadrants (p?=?0.008), and LSE score of lower quadrants (p?=?0.003). With the increasing depth of rectal infiltration, mesorectal positivity increased significantly (p?=?0.000). In multivariate analysis, lower quadrant (regions 5, 6, 7) PCI, LS3 in lower quadrants, LS3 score, rectal involvement score, and the total number of lines of chemotherapy significantly affected different nodal disease parameters. In advanced ovarian cancer, LS3 disease in regions 5, 6, and 7 and rectal involvement directly impact the nodal metastasis and hence mandates a systematic nodal dissection. Mesorectal nodal involvement significantly increases with the increasing depth of rectal involvement necessitating systematic mesorectal nodal clearance for all rectal resections.

SUBMITTER: Kammar P

PROVIDER: S-EPMC6397118 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Correlation Between Pelvic Peritoneal Disease and Nodal Metastasis in Advanced Ovarian Cancer: Can Intraoperative Findings Define the Need for Systematic Nodal Dissection?

Kammar Praveen P Bhatt Aditi A Anam Jay J Waghoo Shazia S Pandey Jageshwar J Mehta Sanket S

Indian journal of surgical oncology 20190207 Suppl 1

To explore the relationship of peritoneal, and rectal involvement with lymph nodal metastases to identify clinical parameters to guide systematic nodal dissection in advanced ovarian cancer (stage 3c). It is a retrospective study of stage III C epithelial ovarian cancers undergoing cytoreductive surgery with systematic nodal dissection, from January 2011 to December 2016. LS3 score is a cumulative score given for the presence of size 3 lesion (peritoneal disease measuring more than 5 cm) in regi ...[more]

PMID: 30886499

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Project description:ImportanceThe presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy.ObjectiveTo assess the accuracy of prostate-specific membrane antigen (PSMA) 68Ga-PSMA-11 positron emission tomographic (PET) imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection.Design, setting, and participantsThis investigator-initiated prospective multicenter single-arm open-label phase 3 imaging trial of diagnostic efficacy enrolled 764 patients with intermediate- to high-risk prostate cancer considered for prostatectomy at University of California, San Francisco and University of California, Los Angeles from December 2015 to December 2019. Data analysis took place from October 2018 to July 2021.InterventionsImaging scan with 3 to 7 mCi of 68Ga-PSMA-11 PET.Main outcomes and measuresThe primary end point was the sensitivity and specificity for the detection pelvic lymph nodes compared with histopathology on a per-patient basis using nodal region correlation. Each scan was read centrally by 3 blinded independent central readers, and a majority rule was used for analysis.ResultsA total of 764 men (median [interquartile range] age, 69 [63-73] years) underwent 1 68Ga-PSMA-11 PET imaging scan for primary staging, and 277 of 764 (36%) subsequently underwent prostatectomy with lymph node dissection (efficacy analysis cohort). Based on pathology reports, 75 of 277 patients (27%) had pelvic nodal metastasis. Results of 68Ga-PSMA-11 PET were positive in 40 of 277 (14%), 2 of 277 (1%), and 7 of 277 (3%) of patients for pelvic nodal, extrapelvic nodal, and bone metastatic disease. Sensitivity, specificity, positive predictive value, and negative predictive value for pelvic nodal metastases were 0.40 (95% CI, 0.34-0.46), 0.95 (95% CI, 0.92-0.97), 0.75 (95% CI, 0.70-0.80), and 0.81 (95% CI, 0.76-0.85), respectively. Of the 764 patients, 487 (64%) did not undergo prostatectomy, of which 108 were lost to follow-up. Patients with follow-up instead underwent radiotherapy (262 of 379 [69%]), systemic therapy (82 of 379 [22%]), surveillance (16 of 379 [4%]), or other treatments (19 of 379 [5%]).Conclusions and relevanceThis phase 3 diagnostic efficacy trial found that in men with intermediate- to high-risk prostate cancer who underwent radical prostatectomy and lymph node dissection, the sensitivity and specificity of 68Ga-PSMA-11 PET were 0.40 and 0.95, respectively. This academic collaboration is the largest known to date and formed the foundation of a New Drug Application for 68Ga-PSMA-11.Trial registrationClinicalTrials.gov Identifiers: NCT03368547, NCT02611882, and NCT02919111.

Project description:BackgroundPelvic nodal metastasis in prostate cancer impacts patient outcome negatively.ObjectiveTo explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis.Design setting and participantsWe applied multiplex immunofluorescence and targeted transcriptomic analysis on 94 radical prostatectomy specimens in patients with (LN+) or without (LN-) pelvic nodal metastases. Both intraepithelial and stromal infiltrations of immune cells and differentially expressed genes (mRNA and protein levels) were correlated with the nodal status.Outcome measurements and statistical analysisThe identified CD4 effector cell signature of nodal metastasis was validated in a comparable independent patient cohort of 184 informative cases. Patient outcome analysis and decision curve analysis were performed with the CD4 effector cell density-based signature.Results and limitationsIn the discovery cohort, both tumor epithelium and stroma from patients with nodal metastasis had significantly lower infiltration of multiple immune cell types, with stromal CD4 effector cells highlighted as the top candidate marker. Targeted gene expression analysis and confirmatory protein analysis revealed key alteration of extracellular matrix components in tumors with nodal metastasis. Of note, stromal CD4 immune cell density was a significant independent predictor of LN metastasis (odds ratio [OR] = 0.15, p = 0.004), and was further validated as a significant predictor of nodal metastasis in the validation cohort (OR = 0.26, p < 0.001).ConclusionsDecreased T-cell infiltrates in the primary tumor (particularly CD4 effector cells) are associated with a higher risk of LN metastasis. Future evaluation of CD4-based assays on prostate cancer diagnostic biopsy materials may improve selection of at-risk patients for the treatment of LN metastasis.Patient summaryIn this report, we found that cancer showing evidence of cancer metastasis to the lymph nodes tends to have less immune cells present within the tumor. We conclude that the extent of immune cells present within a prostate tumor can help doctors determine the most appropriate treatment plan for individual patients.

Project description:ObjectivesPelvic lymph nodal regions receive an incidental dose from conformal treatment of the prostate. This study was conducted to investigate the doses received by the different pelvic nodal regions with varying techniques used for prostate radiotherapy.Methods and materialsTwenty patients of high-risk node-negative prostate cancer treated with intensity-modulated radiotherapy to the prostate alone were studied. Replanning was done for intensity-modulated radiotherapy, 3-dimensional conformal treatment, and 2-dimensional conventional radiotherapy with additional delineation of the pelvic nodal regions, namely, common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose-volume parameters such as Dmean, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients.ResultsThe obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator nodal region was 44, 29, and 22 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The mean dose was significantly higher when compared between 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment ( P < .001), 2-dimensional conventional radiotherapy and intensity-modulated radiotherapy ( P < .001), and 3-dimensional conformal treatment and intensity-modulated radiotherapy ( P < .001). The D33% of the obturator region was 64, 39, and 37 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant.ConclusionThe incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques as used in the trials studying elective pelvic nodal irradiation. However, with intensity-modulated radiotherapy, this dose is lower, making elective pelvic irradiation more relevant. Advances in Knowledge: This study highlights that incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques.

Project description:BackgroundTraditional clinical target volume (CTV) definition for pelvic radiotherapy in prostate cancer consists of large volumes being treated with homogeneous doses without fully utilizing information on the probability of microscopic involvement to guide target volume design and prescription dose distribution.MethodsWe analyzed patterns of nodal involvement in 75 patients that received RT for pelvic and paraaortic lymph node metastases (LNs) from prostate cancer in regard to the new NRG-CTV recommendation. Non-rigid registration-based LN mapping and weighted three-dimensional kernel density estimation were used to visualize the average probability distribution for nodal metastases. As independent approach, the mean relative proportion of LNs observed for each level was determined manually and NRG and non-NRG levels were evaluated for frequency of involvement. Computer-automated distance measurements were used to compare LN distances in individual patients to the spatial proximity of nodal metastases at a cohort level.Results34.7% of patients had pelvic LNs outside NRG-consensus, of which perirectal was most common (25.3% of all patients) followed by left common iliac nodes near the left psoas major (6.7%). A substantial portion of patients (13.3%) had nodes at the posterior edge of the NRG obturator level. Observer-independent mapping consistently visualized high-probability hotspots outside NRG-consensus in the perirectal and left common iliac regions. Affected nodes in individual patients occurred in highly significantly closer proximity than at cohort-level (mean distance, 6.6 cm vs. 8.7 cm, p < 0.001).ConclusionsBased on this analysis, the common iliac level should extend to the left psoas major and obturator levels should extend posteriorly 5 mm beyond the obturator internus. Incomplete coverage by the NRG-consensus was mostly because of perirectal involvement. We introduce three-dimensional kernel density estimation after non-rigid registration-based mapping for the analysis of recurrence data in radiotherapy. This technique provides an estimate of the underlying probability distribution of nodal involvement and may help in addressing institution- or subgroup-specific differences. Nodal metastases in individual patients occurred in highly significantly closer proximity than at a cohort-level, which supports that personalized target volumes could be reduced in size compared to a "one-size-fits-all" approach and is an important basis for further investigation into individualized field designs.

Dataset Information

Correlation Between Pelvic Peritoneal Disease and Nodal Metastasis in Advanced Ovarian Cancer: Can Intraoperative Findings Define the Need for Systematic Nodal Dissection?

Publications

Correlation Between Pelvic Peritoneal Disease and Nodal Metastasis in Advanced Ovarian Cancer: Can Intraoperative Findings Define the Need for Systematic Nodal Dissection?

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