Occult Disease Research Articles

Circulating hybrid cells predict presence of occult nodal metastases in oral cavity carcinoma.

Levels of circulating hybrid cells (CHCs), a newly identified circulating tumor cell (CTC), correlate with disease stage and progression in cancer. We investigated their utility to risk-stratify patients with clinically N0 (cN0) oral cavity squamous cell carcinoma (OCSCC), and to identify patients with occult cervical lymph node metastases (pN+). We analyzed peripheral blood samples for CHCs with co-expression of cytokeratin (tumor) and CD45 (leukocyte) from 22 patients with cN0 OCSCC using immunofluorescence microscopy, then correlated levels with pathologic lymph node status. CHC levels exceeded CTCs and correlated with the presence of both clinically overt (p= 0.002) and occult nodal metastases (p= 0.006). For evaluated cN0 OCSCC patients, those with cN0 → pN+ status harbored elevated CHC levels compared to patients without occult disease. Our findings highlight a promising blood-based biologic assay with potential utility to determine the necessity of surgical neck dissection for staging and treatment.

Usefulness of Routine Preoperative Investigations in Patients Undergoing Uncomplicated Elective General Surgical Procedures

Background: Investigations are classified as routine and specific. Specific investigations are done to confirm or exclude a strongly suspected diagnosis, and routine investigations are done to find occult disease not detected during clinical evaluation. Mostly, these are done as an institutional policy or custom and for medicolegal reasons in the event of any complications. The value of these routine investigations in all patients is controversial. Data suggest that these have little influence on patient management and perioperative complications. Aims and Objectives: The objective of this study was to evaluate the usefulness of routine preoperative investigations in patients undergoing elective surgical procedures and their influence on perioperative management. Materials and Methods: We included various laboratory, radiological, and hematological investigations which were performed routinely in all patients irrespective of diagnosis. Results: A total of 1671 investigations were performed in 170 patients. Only 153 (9.2%) investigations were found to be abnormal. Complete blood picture was performed in 168 (98.2%) patients; random blood sugar estimation was done in 147 (86.4%) patients. Chest X-rays were performed in 166 (97.6%) patients. Electrocardiography was performed in 160 (94.2%) patients. The percentage of overall abnormal results was very low. None of these abnormal investigations influenced surgical management and had adverse perioperative complications. Conclusion: Preoperative investigations should be done based on clinical examination and comorbid conditions. Routine preoperative investigations do not influence patient management and predict complications and should not be done in all patients.

Imaging in Cutaneous Melanoma: Which Test to Order and When?

Imaging in Cutaneous Melanoma: Which Test to Order and When?

Gastric mucosal pathology in Belgian Shepherd dogs with and without clinical signs of gastric disease

BackgroundGastric carcinoma (GC) is uncommon in dogs, except in predisposed breeds such as Belgian Shepherd dogs (BSD) of the Tervuren and Groenendael varieties. When GC is diagnosed in dogs it is often late in the disease, resulting in a poorer prognosis. The aim of this prospective clinical study was to investigate possible associations of gastric mucosal pathologies with clinical signs, laboratory test results and GC in BSD. An online survey gathered epidemiological data to generate potential risk factors for vomiting as the predominant gastric clinical sign, and supported patient recruitment for endoscopy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) score and signs of gastroesophageal reflux (GER) were used to allocate BSD older than five years to either Group A, with signs of gastric disease, or Group B, without signs. Findings in the clinical history, laboratory tests and gastric histopathology of endoscopic biopsies were statistically analysed in search of associations.ResultsThe online survey included 232 responses. Logistic regression analysis recognized an association of vomiting with gagging, poor appetite and change in attitude. Recruitment for endoscopy included 16 BSD in Group A (mean age 9.1 ± 1.8 years, mean CCECAI = 3.1 ± 2.2 and signs of GER); and 11 in Group B (mean age 9.8 ± 1.4 years, CCECAI = 0, no signs of GER). Seven (25.9%) of the 27 BSD (Group A 4/16, Group B 3/11) had leukopenia. Serum C-reactive protein tended to be increased with more advanced GC (P = 0.063). Frequency of GC, mucosal atrophy, mucous metaplasia, or glandular dysplasia did not differ between groups. GC was frequently diagnosed (6/27), even without clinical signs (2/11). The odds ratio for vomiting (OR = 9.9; P = 0.016) was increased only when glandular dysplasia was present. GC was associated with mucous metaplasia (P = 0.024) and glandular dysplasia (P = 0.006), but not with mucosal atrophy (P = 1).ConclusionsGC can develop as an occult disease, associated with metaplasia and dysplasia of the gastric mucosa. Suggestive clinical signs, notably vomiting, should warrant timely endoscopy in BSD. Extensive endoscopic screening of asymptomatic dogs remains, however, unrealistic. Therefore, biomarkers of mucosal pathology preceding clinical illness are needed to support an indication for endoscopy and enable early diagnosis of GC.

Factors that Minimize Curative Resection for Gallbladder Adenocarcinoma: an Analysis of Clinical Decision-Making and Survival

BackgroundGallbladder adenocarcinoma has a poor prognosis as it is often diagnosed incidentally, and patients have a high risk for residual and occult metastatic disease. Expert guidelines recommend definitive surgery for ≥T1b tumors; however, surgical management is inconsistent. This study evaluates the factors that affect the completion of radical resection with portal lymphadenectomy and its impact on survival. MethodsA retrospective review of patients who underwent surgery for gallbladder cancer from 2008 to 2017 at an academic institution was performed. Patients were analyzed based on whether they underwent definitive surgical resection. Patient factors and clinical decision-making were analyzed; overall survival was compared using Kaplan-Meier analysis. ResultsSeventy-five patients with ≥T1b tumors were identified, of who 32 (42.7%) underwent definitive resection. Fifty-four (72%) patients had gallbladder cancer identified as an incidental diagnosis following laparoscopic cholecystectomy. Among patients who did not undergo definitive resection, the underlying factors were varied. Only 24 (55.8%) patients in the non-definitive resection group were seen by surgical oncology. Among patients who underwent re-operation for definitive resection, 12 (38.7%) were upstaged on final pathology. Of the 43 patients who did not undergo definitive resection, 4 (9.3%) had metastatic disease identified during attempted re-resection. Patients who underwent definitive resection had a significantly longer median overall survival compared to those who did not (4.3 v. 1.9 years, p = 0.02). ConclusionsPatients undergoing definitive resection have a significantly improved survival, including as part of a re-operative strategy. Universal referral to a surgical specialist is a modifiable factor resulting in increased definitive resection rates.

Nipple-sparing mastectomy: A review of outcomes at a single institution.

Nipple-sparing mastectomy (NSM) offers patients who are not candidates for breast-conserving treatment an aesthetically pleasing alternative to traditional mastectomy. Some studies have demonstrated its oncologic safety while others have demonstrated residual occult tumor cells at the nipple-areolar complex (NAC). These data prompt further review of oncologic outcomes after NSM.A single institution retrospective chart review was performed of all NSMs performed by 4 breast surgeons at Thomas Jefferson University Hospital over a span of 2012-2019. In this cohort, we review the reconstruction performed, axillary lymph node status, surgical margins, final pathology, loss of the NAC, recurrence rates, and follow-up. In our cohort, we reviewed 170 NSMs performed on 105 patients. All patients were female, and the average age was 46.9years. Prophylactic procedures were performed on 43% of patients with 17.1% of patients being BRCA positive. Of those undergoing NSM for cancer (n=94), the associated pathology was 28.8% DCIS, 32.9% IDC, and 3.5% ILC (this accounts for some patients with multiple diagnoses on final pathology). Sentinel lymph node biopsy (SLNB) was performed in 52.9% of cases with 10.6% of cases being positive for axillary disease. Margins were positive in 10.6% (n=10) of cases performed for cancer with 8.5% (n=8) of cases having positive margin at the NAC and the remainder being at the deep margin. Based on margin positivity, 2.4% (n=4) of patients underwent redo surgery with 1 patient requiring re-resection at the NAC margin and 3 patients having total NAC resection. Total loss of NAC occurred in 5.9% (n=10) of cases due to positive margins (n=3) and necrosis (n=7). Recurrence occurred in 7.2% (n=7) of cases who underwent NSM for cancer. Locoregional recurrence in breast tissue, skin, or axilla occurred in 4.1% (n=4) of cases with 0 recurrences at the NAC. Distant recurrence occurred in 4.1% (n=4) of cases at both liver and bone. Average time to recurrence was 27.3months. Of the 170 NSM performed, 98% had immediate tissue expander placement with 60% converting to permanent subpectoral implant reconstruction, 14% latissimus dorsi flap reconstruction, 0.6% delayed deep inferior epigastric artery perforator free-flap reconstruction, and 5.2% undergoing delayed free transversus abdominus muscle flap reconstruction. Of all the cases reviewed, there was only 1 death. Our average follow-up was 26.7months. We demonstrate similar numbers in our analysis as other studies that have looked at oncologic outcomes after NSM. Although we demonstrate evidence of occult disease at the NAC margin when performing NSM, there was no evidence of recurrence at the NAC demonstrating its efficacy and safety. With proper patient selection, this procedure can be safely offered as an esthetically appealing alternative to traditional mastectomy.

Abstract PO-27: Clonotypic cell-free DNA (cfDNA) in the cerebrospinal fluid (CSF) of patients with aggressive lymphomas

Abstract Current methods for detection of CNS involvement in lymphoma (CSF cytology, flow cytometry) have very limited sensitivity, particularly in cases of parenchymal brain involvement. Early detection is critical to institute CNS-directed therapy and avert dismal outcomes of overt CNS recurrence. Clonotype-specific cfDNA can be detected in the plasma of patients with lymphoma using next-generation sequencing (NGS), and cfDNA-based minimal residual disease (MRD) assay can predict impending recurrence (Roschewski, Lancet Oncol 2015). cfDNA has not been systematically evaluated in the CSF, yet it may hold promise as a sensitive and specific method to detect CNS invasion. To evaluate the ability of an NGS-MRD assay in CSF to detect CNS invasion, we examined CSF and plasma samples from patients with aggressive lymphomas who either had overt CNS disease or who were without known CNS invasion, but at high clinical risk. Genomic DNA from primary tumors was analyzed for tumor-specific clonotype using NGS of rearranged IGK, IGH (VJ or DJ), or IGL loci (Adaptive Biotechnologies; Carlson, Nat Commun 2013). Tumor-specific clonotypes from each case were selected for subsequent tracking by NGS-MRD in CSF and plasma samples. Clonotype copy numbers are expressed per mL for acellular CSF, and clonotype frequency per all B cells. NGS identified median 3 (range, 2-7) dominant immunoglobulin sequences in each primary lymphoma (N=16), with median dominant clonotype frequency 50.3% (range, 26.8-9.28%). In the CSF, the NGS-MRD assay detected the dominant clonotype in 9 out of 16 samples, including all (N=4) with overt CNS invasion (sensitivity=100%), of which 2 had parenchymal disease only with negative CSF cytology, flow cytometry, or IGH PCR. Median detectable cfDNA clonotype in the CSF was 1,077 copies per mL (range, 2-5,620), with median clonotype frequency of 28.4% (range, 0.1-98.5%). cfDNA copy counts were significantly higher in cases with positive CSF cytology than those with parenchymal or clinically occult disease (P=.0016). We observed no significant correlation between the red blood cell count in the CSF and the cfDNA clonotype concentration (P=0.73) or frequency (P=0.62), suggesting that the presence of cfDNA in the CSF was not due to contamination by blood plasma. There was also no evident correlation between cfDNA in plasma and CSF. Within median 11 months of follow-up, 1 of 4 patients (25%) with a positive CSF NGS-MRD assay and no CNS disease developed a fatal CNS recurrence. Our results suggest that NGS-MRD assay for cfDNA in the CSF can identify intraparenchymal or leptomeningeal CNS invasion with high sensitivity, including cases not identifiable by traditional methods. Prognostic significance of detecting lymphoma-specific cfDNA in the CSF of high-risk patients without overt CNS disease will be explored in a larger sample. Pretreatment NGS-MRD assay could be prospectively tested to predict the risk of CNS recurrence and potentially enable more accurate selection of patients for CNS prophylaxis therapy. Citation Format: Adam J. Olszewski, Anna Chorzalska, Habibe Kurt, Thomas A. Ollila, Diana O. Treaba, Andrew Hsu, Adam Zayac, John L. Reagan, Ilyas Sahin, William Rafelson, Pamela C. Egan, Jordan Robison, John Vatkevich, Chelsea D. Mullins, Max Petersen, Patrycja M. Dubielecka. Clonotypic cell-free DNA (cfDNA) in the cerebrospinal fluid (CSF) of patients with aggressive lymphomas [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-27.

Preserving Neurocognition Without Compromising Tumor Control During Whole-Brain Radiotherapy Therapy In Patients With Numerous Brain Metastases Via A Novel Superoxide Dismutase Mimetic: Initial Safety Lead-In And Design Of A Clinical Trial

Patients with a large number of brain metastases (BM) present a clinical challenge. While stereotactic radiosurgery (SRS) has extended the number of BM that can be effectively treated, SRS does not treat occult disease and distant brain failure (DBF) post-SRS remains high. In contrast, whole-brain radiotherapy (WBRT) provides high rates of local control and, compared to SRS, reduces the risk of distant brain failure. Unfortunately, WBRT is also associated with substantial neurocognitive deficits, even with hippocampal avoidance, altered fractionation and neuroprotectants. BMX-001, a novel Mn-porphyrin superoxide dismutase mimetic, has been shown to protect normal tissues from ionizing radiation in preclinical trials, reducing neurocognitive adverse effects, as well as enhancing tumor response. We hypothesized that this agent would reduce neurocognitive decline while possibly improving tumor control in patients with numerous brain metastases undergoing WBRT. This protocol is composed of a lead-in safety study of 5 patients followed by a randomized Phase 2 clinical trial of BMX-001, in 64 patients with multiple brain metastases (MBM) undergoing WBRT. Eligible patients are adults with more than 10 brain metastases, a KPS of >60 and a life expectancy >3 months. All patients will undergo WBRT to a total dose of 30 Gy in 3 Gy daily fractions. Patients in the safety lead-in study and the BMX-001 cohort of the randomized trial will receive a loading dose of this agent immediately prior to starting WBRT, then a maintenance dose twice weekly during WBRT and once within 4 days of completing WBRT. Primary endpoint is change in neurocognition, as measured by Trailmaking, Hopkins Verbal Learning and Controlled Oral Word Association tests pre and post WBRT. Secondary endpoints include overall survival, quality of life, toxicity, local recurrence, distant brain failure, neurologic death and radionecrosis. The safety lead-in portion of this trial was completed in August 2019. All 5 patients completed WBRT and BMX-001 per protocol. The majority of subjects experienced Grade 1 non-hematologic AEs, primarily injection site reactions (including erythema, itching, welts, bruising around injection sites); 1 patient experienced a Grade 2 QT prolongation. No severe toxicities (Grade 3), life-threatening toxicities (Grade 4), or treatment related deaths (Grade 5) were reported. Initial post-WBRT brain MR imaging showed at least a partial tumor response. The randomized clinical trial is now open at multiple institutions. It appears reasonable to proceed with the randomized clinical trial of WBRT +/- BMX-001 in patients with numerous brain metastases. Enrollment on this trial is essential to test the hypothesis that this agent is an effective neuroprotectant.

Diagnosis and management of pediatric epithelial salivary gland malignancy

Salivary tumors are uncommon among children but are more likely to be malignant compared with adults. A lack of experience makes consensus in treatment elusive. Amidst recent publication of large institutional and national series, this review aims to discuss the epidemiology, diagnosis, investigation, and treatment for pediatric epithelial salivary malignancies. Pediatric salivary malignancies are often low grade and carry a favorable prognosis. High-grade tumors portend an increased risk of recurrence and a decreased survival. Surgeons should strive for oncologic resection with clear margins and avoid enucleation and excisional biopsies. Overt nodal metastases require concurrent neck dissection, whereas elective neck dissections may be reserved for cases with high risk of occult disease, such as advanced stage and high-grade neoplasms. Adjuvant radiation should be considered in high-grade tumors. The paucity of high-level evidence clouds treatment decisions and further encourages pediatric salivary malignancies to be treated in an experienced center with a multidisciplinary approach.

Distribution of residual disease in the peritoneum following neoadjuvant chemotherapy in advanced epithelial ovarian cancer and its potential therapeutic implications

IntroductionResidual disease in ‘normal appearing’ peritoneum is seen in nearly 30% of the patients following neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. The goal was to study the sequence of response in different regions, the commonest sites of occult residual disease, its incidence in different peritoneal regions and the potential therapeutic implications of these. MethodsThis was a prospective multi-centre study (July 2018–June 2019). Pathological evaluation of cytoreductive surgery specimens was performed according to a fixed protocol. Prevalence of residual disease in different regions was used to study patterns of response and distribution of residual disease. ResultIn 85 patients treated between July 2018 to June 2019, microscopic disease in ‘normal appearing’ peritoneal regions was seen in 22 (25.2%) and in normal peritoneum around tumor nodules in 30 (35.2%) patients. Regions 4 and 8 of Sugarbaker’s PCI had the highest incidence of occult disease and regions 9 and 10 the lowest. The response to chemotherapy occurred in a similar manner in over 95%- the least common site of residual disease was the small bowel mesentery, followed by upper regions (regions 1–3), omentum and middle regions (regions 0, 4, 8), lower regions (regions 5–7) and lastly the ovaries. ConclusionsDuring interval CRS, based on the disease mapping provided in this manuscript, regions that have a high probability of residual disease should be explored and dissected. Complete resection of involved the peritoneal region can completely address the occult disease. The role of resection of the entire region as well as ‘normal appearing’ parietal peritoneal regions should be prospectively evaluated.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

Determining the significance of psammoma bodies in pelvic washings: A 10-year retrospective review.

Pelvic washing specimens are relatively common and are submitted for patients undergoing gynecologic surgery to evaluate them for metastatic or occult disease. Psammoma bodies are a relatively uncommon finding in these specimens. To date, large-scale studies of their cytologic-histologic correlates and thus clinical significance have been limited. A 10-year retrospective search for all pelvic washing specimens was performed, and all cases were reviewed for the presence of psammoma bodies. The findings for the corresponding surgical pathology specimens were then catalogued. Psammoma bodies were present in 138 cases (3.6% of 3840 total pelvic washings). More than half of the cases (n=73 [53%]) were associated with benign processes, including mesothelial hyperplasia (n=44), endosalpingiosis (n=11), endometriosis (n=11), and ovarian cystadenoma/cystadenofibroma (n=7). Nineteen cases (14%) were associated with serous borderline tumors. Malignancies were noted in a third of the cases (n=46 [33%]) and were most frequently low-grade serous adenocarcinomas (n=15), high-grade serous adenocarcinomas (n=11), or endometrioid endometrial carcinomas (n=8). Patients found to have benign processes (median age, 50 years) or borderline disease (median age, 56 years) were significantly younger than patients with malignancies (median age, 65 years; P<.0001). In addition, the correlation of cytologic interpretation categories with concurrent histopathologic findings showed that cytologic analysis was highly sensitive and specific in determining the nature of underlying processes. The majority of psammoma bodies noted in pelvic washings were associated with benign processes or borderline tumors, with approximately a third of the cases associated with malignancies. Psammoma bodies in pelvic washings from younger patients were significantly more likely to be associated with benign processes or borderline tumors.

Patterns of Nodal Metastases and Predictors of Occult Disease in HPV-Associated Oropharynx Cancer.

For human papilloma virus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC), we evaluated the distribution of neck-level lymph node (LN) metastasis, based on postsurgical histopathology, and the incidence of and risk factors for occult LN metastases, as these patterns need clarification for this newer cancer subset. Retrospective cohort study. National Cancer Database (NCDB). We analyzed 2358 patients in the NCDB with HPV+ OPSCC who underwent neck dissection (ND) from 2010 to 2015. Incidence and distribution of LN metastases were calculated for neck levels I to V. Variables associated with occult LN metastasis were assessed by multivariate logistic regression. In therapeutic NDs (n = 1935), the following proportions of positive LNs were found: level I, 9.0% (n = 175); level II, 81.0% (n = 1568); level III, 29.6% (n = 573); level IV, 11.9% (n = 230); and level V, 4.9% (n = 95). In elective NDs (n = 423), occult-positive LNs were found in 35.8% (n = 152), with the following proportions by level: level I, 3.3% (n = 14); level II, 26.9% (n = 114); level III, 8.7% (n = 37); level IV, 4.0% (n = 17); and level V, 0.2% (n = 1). The presence of occult LNs was independently associated with a Charlson-Deyo score of 1 (odds ratio, 2.26; 95% CI, 1.18-4.31; P = .014) and lymphovascular invasion (odds ratio, 5.91; 95% CI, 3.21-11.18; P < .001). Occult LN metastases were not significantly associated with pT classification, primary site, or number of LNs resected. For HPV+ OPSCC, occult nodal disease is common. Therapeutic NDs should encompass at least levels II, III, and IV and possibly I, whereas elective NDs could possibly encompass levels II and III. 4.

Abstract 733: Clonotypic cell-free DNA(cfDNA) in the cerebrospinal fluid (CSF) of patients with aggressive lymphomas

Abstract Current methods for detection of CNS involvement in lymphoma (CSF cytology, flow cytometry) have very limited sensitivity, particularly in cases of parenchymal brain involvement. Early detection is however critical to institute CNS-directed therapy that can avert dismal outcomes of overt CNS recurrence. Clonotype-specific cfDNA can be detected in the plasma of patients with lymphoma using next-generation sequencing (NGS), and residual cfDNA-based minimal residual disease (MRD) assay can predict impending recurrence (Roschewski et al., Lancet Oncol. 2015). cfDNA has not been systematically evaluated in the CSF, yet it may hold promise as a sensitive and specific method to detect CNS invasion. To evaluate the ability of an NGS-MRD assay in the CSF to detect CNS invasion, we examined CSF and plasma samples from patients with aggressive lymphomas who either had overt CNS disease, or who were without evident CNS invasion, but at high clinical risk. Genomic DNA from primary tumors was analyzed for tumor-specific clonotype using NGS of rearranged IGK, IGH (VJ or DJ), or IGL loci (Adaptive Biotechnologies; Carlson CS et al., Nat Commun. 2013). Tumor-specific clonotypes from each case were selected for subsequent tracking by NGS-MRD in CSF and plasma samples. Clonotype copy numbers are expressed per mL for acellular CSF, and clonotype frequency per all B-cells. NGS identified median 3 (range, 2-7) dominant immunoglobulin sequences in each primary lymphoma (N=16), with median dominant clonotype frequency 50.3% (range, 26.8-9.28%). In the CSF, the NGS-MRD assay detected the dominant clonotype in 9 out of 16 samples, including all (N=4) with overt CNS invasion (sensitivity=100%), of which 2 had parenchymal disease only with negative standard CSF cytology, flow cytometry, or IGH PCR. Median detectable cfDNA clonotype in the CSF was 1,077 copies per mL (range, 2-5,620), with median clonotype frequency of 28.4% (range, 0.1-98.5%). cfDNA copy counts were significantly higher in cases with positive CSF cytology than those with parenchymal or clinically occult disease (P=.0016). We observed no significant correlation between the red cell count in the CSF and the clonotype cfDNA concentration (P=0.73) or frequency (P=0.62) suggesting that the CSF cfDNA was not due to contamination by blood. There was also no evident correlation between cfDNA in plasma and CSF. Our results suggest that NGS-MRD assay for cfDNA in the CSF can identify intraparenchymal or leptomeningeal CNS invasion with high sensitivity, including cases not identifiable by traditional methods. Prognostic significance of detecting lymphoma-specific cfDNA in the CSF of some high-risk patients without overt CNS disease will be further explored in a larger sample. Pre-treatment NGS-MRD assay could be prospectively tested to predict the risk of CNS recurrence, with a future potential to enable more accurate selection of patients for CNS prophylaxis therapy. Citation Format: Adam J. Olszewski, Anna Chorzalska, Diana O. Treaba, John L. Reagan, Andrew Hsu, Pamela C. Egan, Habibe Kurt, James Butera, William Rafelson, Thomas Ollila, Rabin Niroula, Jordan Robison, Chelsea D. Mullins, Patrycja M. Dubielecka. Clonotypic cell-free DNA(cfDNA) in the cerebrospinal fluid (CSF) of patients with aggressive lymphomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 733.

Screening Sarcoidosis Patients for Occult Disease.

As sarcoidosis may involve any organ, sarcoidosis patients should be evaluated for occult disease. Screening for some organ involvement may not be warranted if it is unlikely to cause symptoms, organ dysfunction, or affect clinical outcome. Even organ involvement that affects clinical outcome does not necessarily require screening if early detection fails to change the patient's quality of life or prognosis. On the other hand, early detection of some forms of sarcoidosis may improve outcomes and survival. This manuscript describes the approach to screening sarcoidosis patients for previously undetected disease. Screening for sarcoidosis should commence with a meticulous medical history and physical examination. Many sarcoidosis patients present with physical signs or symptoms of sarcoidosis that have not been recognized as manifestations of the disease. Detection of sarcoidosis in these instances depends on the clinician's familiarity with the varied clinical presentations of sarcoidosis. In addition, sarcoidosis patients may present with symptoms or signs that are not related to specific organ involvement that have been described as parasarcoidosis syndromes. It is conjectured that parasarcoidosis syndromes result from systemic release of inflammatory mediators from the sarcoidosis granuloma. Certain forms of sarcoidosis may cause permanent and serious problems that can be prevented if they are detected early in the course of their disease. These include (1) ocular involvement that may lead to permanent vision impairment; (2) vitamin D dysregulation that may lead to hypercalcemia, nephrolithiasis, and permanent kidney injury; and (3) cardiac sarcoidosis that may lead to a cardiomyopathy, ventricular arrhythmias, heart block, and sudden death. Screening for these forms of organ involvement requires detailed screening approaches.

Pre-operative surgical algorithm: sentinel lymph node biopsy as predictor of parametrial involvement in early-stage cervical cancer

IntroductionRadical hysterectomy is the gold standard in the management of early-stage cervical cancer. Parametrectomy aims to remove occult disease but is associated with significant surgical morbidity. Avoiding unnecessary parametrectomy in...

Total Parietal Peritonectomy Can Be Performed with Acceptable Morbidity for Patients with Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: Results From a Prospective Multi-centric Study.

Total parietal peritonectomy (TPP) removes areas of "normal-appearing" parietal peritoneum bearing microscopic residual disease and has the potential to improve survival of patients undergoing interval cytoreductive surgery (CRS) for advanced serous epithelial ovarian cancer. This report presents the morbidity outcomes for the first 50 patients enrolled in TORPEDO (CTRI/2018/12/016789), a prospective study. All the patients underwent a TPP during interval CRS. A surgicalprotocol that includes a description ofthe boundaries for each of the five peritonectomies was followed. The common toxicology criteria for adverse events (CTCAE) classification was used to record 90-day morbidity and mortality. The median Peritoneal Cancer Index (PCI) for 50 patients was 15 (range, 5-37). A complete cytoreduction (CC-0 resection) was obtained in 80%, a CC-1 resection in 16%. Abowel resection was performedin 70% of the patients. Grade 3 or 4 complications were seen in 11 patients (22%), and one patient died within 90days after surgery due to intraperitoneal hemorrhage. The most common complications were postoperative fluid collection requiring aspiration (n = 5), intraperitoneal hemorrhage (n = 2), abdominal wound dehiscence (n = 2), pseudo-obstruction (n = 1), urinary sepsis (n = 2), and ileostomy-related complications (n = 2). No bowel fistulas or anastomotic leaks occurred. Microscopic disease in 'normal appearing'peritoneum adjacent to tumor nodules was observed in 46% of the patients, and in regions given a lesion score of 0 in 34%. The parietal peritoneal regions (0-8) had a higher incidence of residual disease (p < 0.001) and occult disease (p < 0.001). During interval CRS, TPP can be performed with acceptable morbidity and mortality. The pathologic findings further support this therapeutic rationale. Survival outcomes should determine the future role of such a procedure in routine clinical practice.

90 YEARS OF PROGESTERONE: Progesterone and progesterone receptors in breast cancer: past, present, future.

Progesterone and progesterone receptors (PR) have a storied albeit controversial history in breast cancers. As endocrine therapies for breast cancer progressed through the twentieth century from oophorectomy to antiestrogens, it was recognized in the 1970s that the presence of estrogen receptors (ER) alone could not efficiently predict treatment responses. PR, an estrogen regulated protein, became the first prognostic and predictive marker of response to endocrine therapies. It remains today as the gold standard for predicting the existence of functional, targetable ER in breast malignancies. PRs were subsequently identified as highly structured transcription factors that regulate diverse physiological processes in breast cancer cells. In the early 2000s, the somewhat surprising finding that prolonged use of synthetic progestin-containing menopausal hormone therapies was associated with increased breast cancer incidence raised new questions about the role of PR in 'tumorigenesis'. Most recently, PR have been linked to expansion of cancer stem cells that are postulated to be the principal cells reactivated in occult or dormant disease. Other studies establish PR as dominant modulators of ER activity. Together, these findings mark PR as bona fide targets for progestin or antiprogestin therapies, yet their diverse actions have confounded that use. Here we summarize the early history of PR in breast cancer; debunk the theory that progesterone causes cancer; discuss recent discoveries that PR regulate cell heterogeneity; attempt to unify theories describing PR as either good or bad actors in tumors; and discuss emerging areas of research that may help explain this enigmatic hormone and receptor.

Extent and distribution of peritoneal disease in patients undergoing cytoreductive surgery for first platinum sensitive recurrence in ovarian cancer and its potential therapeutic implications

BackgroundSelected patients with platinum sensitive recurrent ovarian cancer may benefit from cytoreductive surgery (CRS). The aim was to study the pattern of peritoneal involvement in these patients that has not been done before. MethodsA comparison was made between the surgical and pathological findings in 60 patients undergoing salvage CRS from July 2018 to December 2019. The sites of residual disease, correlation with surgical and pathological peritoneal cancer index (PCI), small bowel involvement and regional lymph node involvement were studied. ResultsFifty-eight (96.6%) had serous carcinoma and 2 (3.4%) clear cell carcinoma. The median surgical PCI (sPCI) was 7 [range 0–27] and median pathological PCI (pPCI) 4 [range 0–21]. CC-0 resection was performed in 81.6%. The upper regions (region 1,2,3) were the commonest sites of residual disease (63.3%) followed by lower regions (region 5,6,7) in 55.0%, middle regions (regions 0,4,8) in 53.3% and small bowel regions (regions 9–12) in 26.6%. Small bowel involvement was associated with a higher sPCI and pPCI (p < 0.001 for both). Regional nodes were involved in 46.6%. A pathological complete response was seen in 8 (13.3%) patients of which 2 had residual disease in regional nodes. Microscopic disease in ‘normal appearing’ peritoneum was seen in 21%. ConclusionsThe parietal peritoneum was the commonest site of recurrence. Small bowel involvement occurred late and was associated with more extensive disease. Regional lymph node involvement was seen nearly 50% and was a common site for occult disease. The role of more extensive parietal peritoneal resection for recurrent disease should be evaluated prospectively.

Posttreatment Imaging in Patients with Head and Neck Cancer without Clinical Evidence of Recurrence: Should Surveillance Imaging Extend Beyond 6 Months?

Early detection of residual or recurrent disease is important for effective salvage treatment in patients with head and neck cancer. Current National Comprehensive Cancer Network guidelines do not recommend standard surveillance imaging beyond 6 months unless there are worrisome signs or symptoms on clinical examination and offer vague guidelines for imaging of high-risk patients beyond that timeframe. Our goal was to evaluate the frequency of clinically occult recurrence in patients with head and neck squamous cell carcinoma with positive imaging findings (Neck Imaging Reporting and Data Systems scores of 2-4), especially after 6 months. This institutional review board-approved, retrospective data base search queried neck CT reports with Neck Imaging Reporting and Data Systems scores of 2-4 from June 2014 to March 2018. The electronic medical records were reviewed to determine outcomes of clinical and radiologic follow-up, including symptoms, physical examination findings, pathologic correlation, and clinical notes within 3 months of imaging. A total of 255 cases, all with Neck Imaging Reporting and Data Systems scores of 2 or 3, met the inclusion criteria. Fifty-nine patients (23%) demonstrated recurrence (45 biopsy-proven, 14 based on clinical and imaging progression), and 21 patients (36%) had clinically occult recurrence (ie, no clinical evidence of disease at the time of the imaging examination). The median overall time to radiologically detected, clinically occult recurrence was 11.4 months from treatment completion. Imaging surveillance beyond the first posttreatment baseline study was critical for detecting clinically occult recurrent disease in patients with head and neck squamous cell carcinoma. More than one-third of all recurrences were seen in patients without clinical evidence of disease; and 81% of clinically occult recurrences occurred beyond 6 months.