Clinical Evidence Of Recurrence Research Articles

Sensitive Detection of Gynecological Cancer Recurrence Using Circulating Tumor DNA and Digital PCR: A Comparative Study with Serum Biochemical Markers

Early detection of recurrences in gynecological cancers is crucial for women’s health. Circulating tumor DNA (ctDNA) analysis through liquid biopsy offers a promising approach for monitoring disease progression and identifying relapses. This study investigated the utility of digital Polymerase Chain Reaction (dPCR) for ctDNA detection in three gynecological cancer patients with clinically confirmed relapses during a two-year post-surgical follow-up. Patient-specific tumor mutations were identified through whole-exome sequencing (WES) and confirmed via Sanger sequencing. dPCR probes targeting these mutations were used to quantify the ctDNA levels in plasma samples collected throughout the follow-up period, and the findings were compared with standard serum biochemical markers. In two patients, persistent positive dPCR signals for the selected mutations were detected after tumor removal, with ctDNA levels progressively increasing even after post-surgical chemotherapy. Notably, dPCR identified elevated ctDNA levels before an increase in the cancer antigen 125 (CA125) biochemical marker was observed. In the third patient, no ctDNA signals from the two selected mutations were detected despite clinical evidence of recurrence, suggesting the emergence of new mutations. While this study highlights the promise of dPCR for early recurrence detection in gynecological cancers, it also underscores the critical need for comprehensive mutation panels to overcome the inherent challenges posed by tumor heterogeneity and the emergence of new mutations during disease progression.

Osteochondroma of the Distal Tibia in an Adolescent: A Case Report

A 17-year-old male presented with a painful left ankle that had been worsening over the preceding 1 year. Clinical and radiographic inspection revealed marked bowing with a deformation of the fibula secondary to the laterally outgrowing bone lesion from the distal tibia proximal to the growth plate. MRI appearance suggestive of an osteochondroma of the lower extremity of the left tibia with signs of degeneration, It is surrounded by a cartilaginous cap, thickened in places, measuring 22 mm in maximum thickness. Although the radiographic characteristics of the lesion were indicative of osteochondroma, a typically asymptomatic and benign tumor that is usually identified as an incidental finding, the large size and symptoms associated with the lesion described in this article make it rather unusual. In this particular case, excessive bony outgrowth, pain, joint malposition, necessitated surgical intervention. The patient was successfully treated with resection of the tumor, after which gradual restoration of the alignment of the distal leg ensued without the need for fibular osteotomy. After more than 1 year of postoperative follow-up, neither radiographic nor clinical evidence of recurrence had been observed and the patient displayed a pain-free range of ankle motion without any physical limitations.

Laryngeal Sarcoma: A Case Report

Laryngeal sarcoma is a rare malignant tumour and the diagnosis requires comprehensive histopathological and immunohistochemical examinations. Due to its rarity, there is paucity of information on its behaviour and management. We report a case of an elderly male presented with one month history of hoarseness. Laryngoscopic examination showed a large exophytic mass at anterior commissure causing partial airway obstruction. Tracheostomy, direct laryngoscopy and excision of tumour with adequate margin were performed. The histopathological examination revealed myofibroblastic sarcoma. Computed tomography of the neck showed no regional or distant metastasis. Post-operatively, he was decannulated and there was no clinical evidence of recurrence. Management of LS is highly individualised. Complete tumour excision with clear margins is the primary treatment. Neck dissection is not required if there is no nodal metastasis. Radiotherapy is advocated in selected cases to achieve loco-regional control.

Simultaneous stoma closure and type IV parastomal hernia repair after botulinum toxin and progressive pneumoperitoneum

Abstract Surgery is the only treatment for parastomal hernia (PH). When possible, stoma closure is the best way to manage this type of hernia, however, whether to perform it in a single approach with abdominal wall reconstruction (AWR) is still debatable. A 58-year-old woman with a type IV PH with loss of domain was submitted to preoperative optimization [botulinum toxin type A and progressive pneumoperitoneum (PPP)], followed by simultaneous stoma closure and AWR. Hospital discharge was on the eighth day with no complications. Six months later, no clinical evidence of recurrence or other complication was observed. Large PHs are technically challenging. Stoma closure and simultaneous AWR increase surgical risk. Preoperative optimization with a combination of adjuvants (including PPP) is feasible in PH and may overcome technical complexity, even though patient selection remains the key when choosing a PH repair with synchronous stoma closure.

Respiratory Epithelial Adenomatoid Hamartoma: An Uncommon Differential of Nasopharyngeal Tumor

Respiratory epithelial adenomatoid hamartoma (REAH) is an uncommon tumor-like lesion that has been reported within the nose, paranasal sinuses, and less frequently in the nasopharynx. While it is believed to be benign, its clinical presentation, radiological characteristics, and microscopic features may closely mimic more aggressive tumors of the upper respiratory tract, potentially leading to needless life-altering treatment. Prior to now, there had been no reported cases of this lesion in West Africa. We present a 35-year-old male with persistent bilateral nasal obstruction, difficulty with swallowing, and bilateral reduction in hearing, whose CT findings were highly suggestive of a nasopharyngeal tumor, but upon biopsy and histology showed features most consistent with REAH. Surgery completely alleviated his symptoms with no clinical evidence of recurrence after a 1-year follow-up period.

Using (1,3)-β-D-glucan concentrations in serum to monitor the response of azole therapy in patients with eumycetoma caused by Madurella mycetomatis.

(1,3)-β-D-glucan is a panfungal biomarker secreted by many fungi, including Madurella mycetomatis, the main causative agent of eumycetoma. Previously we demonstrated that (1,3)-β-D-glucan was present in serum of patients with eumycetoma. However, the use of (1,3)-β-D-glucan to monitor treatment responses in patients with eumycetoma has not been evaluated. In this study, we measured (1,3)-β-D-glucan concentrations in serum with the WAKO (1,3)-β-D-glucan assay in 104 patients with eumycetoma treated with either 400 mg itraconazole daily, or 200 mg or 300 mg fosravuconazole weekly. Serial serum (1,3)-β-D-glucan concentrations were measured at seven different timepoints. Any correlation between initial and final (1,3)-β-D-glucan concentrations and clinical outcome was evaluated. The concentration of (1,3)-β-D-glucan was obtained in a total of 654 serum samples. Before treatment, the average (1,3)-β-D-glucan concentration was 22.86 pg/mL. During the first 6 months of treatment, this concentration remained stable. (1,3)-β-D-glucan concentrations significantly dropped after surgery to 8.56 pg/mL. After treatment was stopped, there was clinical evidence of recurrence in 18 patients. Seven of these 18 patients had a (1,3)-β-D-glucan concentration above the 5.5 pg/mL cut-off value for positivity, while in the remaining 11 patients, (1,3)-β-D-glucan concentrations were below the cut-off value. This resulted in a sensitivity of 38.9% and specificity of 75.0%. A correlation between lesion size and (1,3)-β-D-glucan concentration was noted. Although in general (1,3)-β-D-glucan concentrations can be measured in the serum of patients with eumycetoma during treatment, a sharp decrease in β-glucan concentration was only noted after surgery and not during or after antimicrobial treatment. (1,3)-β-D-glucan concentrations were not predictive for recurrence and seem to have no value in determining treatment response to azoles in patients with eumycetoma.

Abstract PO-045: Utility of circulating tumor tissue modified viral (TTMV)-HPV DNA to resolve clinically indeterminate findings in patients following definitive treatment for HPV-driven oropharyngeal cancer

Abstract Introduction: Indeterminate results of clinical or imaging examinations are common across the care continuum, and decisions made can lead to overtreatment and psychological and financial harms for the patient. Additionally, due to the emergence of highly sensitive circulating tumor DNA assays, an indeterminate clinical status can also arise when molecular detection precedes clinical or radiological evidence of recurrence for a period of time. We recently reported >99% negative and >95% positive predictive value of circulating tumor tissue modified viral (TTMV)-HPV DNA for recurrence detection in a large, real-world cohort of patients with HPV-driven oropharyngeal cancer. Here we quantified the frequency of clinically indeterminate findings (CIF) in this patient cohort and assessed the prognostic value of TTMV-HPV DNA to resolve these CIF. Methods: This IRB-approved, retrospective observational cohort study included 543 patients across eight U.S. centers who were ≥3 months post-treatment for HPV-driven OPSCC. Patients had one or more TTMV-HPV DNA results (NavDx®, Naveris Laboratories) obtained during surveillance between February 2020 and January 2022 (n=1372 total tests), with mean follow-up time of 24 months (range: 4.9-185). Test results were correlated with physician-reported exam and imaging findings to assess disease status in follow-up. Results: Of the 543 patients, 245 patients (45.1%) had 797 CIF by imaging and/or clinical examination during their surveillance period. Of these 245 patients, 71 patients had 93 CIF that had a coincident TTMV-HPV DNA result (either negative or positive) available within 3 months of the CIF. The TTMV-HPV DNA result was able to correctly predict the presence or absence of recurrence across 91 of the 93 (97.8%) individual CIF. Both incorrectly predicted CIF were in the setting of an undetectable TTMV-HPV DNA result. One patient had their recurrence detected by chest CT 63 days later and had a positive TTMV-HPV DNA test the same day. The second patient had a positive TTMV-HPV DNA test during their subsequent immunotherapy. In contrast to the 45% of patients with CIF as a result of imaging and/or clinical examination, only 18 patients (3.3%) had CIF due to a positive TTMV-HPV DNA result that was not accompanied by clinical evidence of recurrence within 3 months. Importantly, of these 18 patients, 15 patients had confirmed recurrence at a subsequent time point (median time to recurrence: 232 days), leaving only 3 of 543 (0.6%) patients with an ongoing indeterminate recurrence status. Conclusion: Clinical indeterminate findings as a result of imaging and/or clinical examination are common, whereas clinically indeterminate status due to circulating TTMV-HPV DNA testing is rare. Our findings strongly support the clinical utility and value of monitoring circulating TTMV-HPV DNA during post-treatment surveillance to inform interpretation of indeterminate clinical findings. Citation Format: Scott Roof, Glenn Hanna, James Jabalee, Eleni Rettig, Rocco Ferrandino, Sida Chen, Marshall R. Posner, Krzysztof J. Misiukiewicz, Eric M. Genden, Raymond L. Chai, John Sims, Elaine Thrash, Scott Stern, Noah S. Kalman, Sreenija Yarlagadda, Adam Raben, Lydia Clements, Abie Mendelsohn, John M. Kaczmar, Yadav Pandey, Mihir Bhayani, Piyush Gupta, Charlotte Kuperwasser, Catherine Del Vecchio Fitz, Barry M. Berger. Utility of circulating tumor tissue modified viral (TTMV)-HPV DNA to resolve clinically indeterminate findings in patients following definitive treatment for HPV-driven oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-045.

Abstract P2-11-06: Plasma assay of methylated DNA markers (MDM) detects patients with metastatic breast cancer (MBC) compared to healthy controls and treated breast cancer patients with no evidence of disease

Abstract Objective: Aberrantly methylated DNA may be used to detect minimal residual disease or early recurrence in breast cancer. As a 1st step, we aimed to develop an MDM panel to delineate between healthy women, stage I-III breast cancer in remission with no evidence of disease (NED), and metastatic breast cancer (MBC). Methods: We prospectively enrolled patients into 3 groups: healthy controls (adult females with a normal mammogram in past 12 months with no history of breast cancer), NED [stage I-III breast cancer with no clinical evidence of recurrence 6 months - 3 years post-treatment (adjuvant endocrine therapy allowed)], and MBC (collected either at initial diagnosis of untreated metastatic disease or radiographic progression). DNA was extracted from 6 mL of plasma derived from blood collected in LBgard tubes (Exact Sciences Corp., San Diego CA), and was bisulfite-treated and assayed by target enrichment long-probe quantitative amplified signal (TELQASTM) method for a panel of 15 previously identified MDMs [Table], normalized by the control gene, B3GALT6. Areas under the receiver operating characteristic curve (AUC) were calculated for each MDM to assess discrimination of MBC from other groups. With 60 patients per group, we had greater than 80% power to detect a difference of 0.20 from the null AUC of 0.7. Results: We tested samples from 60 MBC (10 untreated, 50 recurrent), 60 NED, and 60 healthy women. The median age was 63 (IQR, 55-72) and was not different between groups. The NED group was all hormone-receptor (HR) positive, with 47 (78%) being human epidermal growth factor receptor 2 negative (HER2-) and 13 (22%) HER2+; 48 (80%) were stage I and 9 (15%) were N+. The MBC group had 35 (58%) patients with HR+/HER2- tumors, 11 (18%) HR+/HER2+, and 6 (10%) HR-/HER2-, 4 (7%) HR-/HER2+, with 4 (7%) unknown. Of the 41 MBC whose original stage and nodal status were known 9 (22%) were stage I and 22 (54%) were N+. The markers were able to discriminate between MBC and NED patient samples with AUCs from 0.97 to 0.72. AUCs for 10/15 MDMs (ITPRIPL1, EMX1, C17orf64, OSR2, TRIM67, CHST2, IFFO1, TRH, FAM59B, and MPZ) were >0.90. No difference in MDMs was observed between the healthy and NED groups. Conclusions: MDMs, assayed from plasma, appear highly discriminant for metastatic breast cancer cases in comparison to control patients with NED or healthy controls. Further clinical validation of this MDM panel in a larger cohort is warranted. Table 1. Plasma MDM discrimination of metastatic breast cancer (MBC) from healthy controls and previously treated breast cancer patients with no evidence of disease (NED) Citation Format: Karthik V. Giridhar, Fergus J. Couch, Jason P. Sinnwell, Seth W. Slettedahl, William R. Taylor, Douglas W. Mahoney, Patrick H. Foote, Maria C. O’Connell, Mariah J. Robran, Mary E. Devens, Anna M. Gonser, Nicole Larson, Karen A. Doering, Kelli N. Burger, Michael Kaiser, Hatim Allawi, Kathryn Ruddy, Janet Olson, John B. Kisiel. Plasma assay of methylated DNA markers (MDM) detects patients with metastatic breast cancer (MBC) compared to healthy controls and treated breast cancer patients with no evidence of disease [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-06.

Genome-Wide Methylation Profiling in 229 Patients With Crohn’s Disease Requiring Intestinal Resection: Epigenetic Analysis of the Trial of Prevention of Post-operative Crohn’s Disease (TOPPIC)

DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn's disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts. TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n= 123; Control, n= 198). CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P < .05), including probes mapping to WHSC1 (P= 4.1× 10-9, Holm P= .002) and EFNA3 (P= 4.9× 10-8, Holm P= .02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P= 6.4× 10-5). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge+ 2 years; 95% confidence interval, 1.2-2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge+1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P= 1.2× 10-19, SBNO2= 1.2× 10-11) and regions (TXK [false discovery rate, P= 3.6× 10-14], WRAP73 [false discovery rate, P= 1.9× 10-9], VMP1 [false discovery rate, P= 1.7× 10-7], and ITGB2 [false discovery rate, P= 1.4× 10-7]). We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery.

Giant gluteal-pelvic lipoblastoma in a four-year-old girl. Report of a rare case

Lipoblastoma is a rare benign tumor, accounting for less than 1% of childhood neoplasms. It begins from embryonic fat cells, with approximately 80% of cases occurring before the age of 3 and 40% occurring before the age of 1. Herein, we present an extremely rare case of gluteal-pelvic lipoblastoma in a 3.6-year-old girl successfully treated by excision of the tumour, with no evidence of clinical recurrence 3 months postoperatively.

Surgical management of subependymoma in a cat

AbstractA 10‐year‐old, domestic shorthair cat was presented with a 7‐month history of anorexia and 2‐month history of severe obtundation. Neurological examination revealed proprioceptive ataxia and decreased postural reactions in the four limbs. On magnetic resonance imaging, a contrast‐enhanced mass lesion dorsal to the obex region was found, causing cerebellar and brainstem compression. The mass was aspirated by an ultrasonic aspirator and complete removal was achieved. After surgery, the mental status and appetite of the cat was markedly improved. On histopathological examination, the mass was diagnosed as subependymoma. The cat was neurologically normal, and no recurrence was observed on magnetic resonance imaging 3 months postoperatively. There was no evidence of clinical recurrence at 8 month postoperative follow‐up by telephone interview. This is the first description of surgical management of subependymoma in a cat. Subependymoma is a benign tumour in cats, and the prognosis is expected to be good after surgical management as reported in humans.

Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

To examine the prevalence and dynamics of circulating tumor DNA (ctDNA) and its association with metastatic recurrence in patients with high-risk early-stage hormone receptor-positive breast cancer (HR+ BC) more than 5 years from diagnosis. We enrolled 103 patients with high-risk stage II-III HR+ BC diagnosed more than 5 years prior without clinical evidence of recurrence. We performed whole-exome sequencing (WES) on primary tumor tissue to identify somatic mutations tracked via a personalized, tumor-informed ctDNA test to detect minimal residual disease (MRD). We collected plasma at the time of consent and at routine visits every 6-12 months. Patients were followed for clinical recurrence. In total, 85 of 103 patients had sufficient tumor tissue; of them, 83 of 85 (97.6%) patients had successful whole-exome sequencing. Personalized ctDNA assays were designed targeting a median of 36 variants to test 219 plasma samples. The median time from diagnosis to first sample was 8.4 years. The median follow-up was 10.4 years from diagnosis and 2.0 years from first sample. The median number of plasma samples per patient was two. Eight patients (10%) had positive MRD testing at any time point. Six patients (7.2%) developed distant metastatic recurrence, all of whom were MRD-positive before overt clinical recurrence, with median ctDNA lead time of 12.4 months. MRD was not identified in one patient (1.2%) with local recurrence. Two of eight MRD-positive patients had not had clinical recurrence at last follow-up. In this prospective study, in patients with high-risk HR+ BC in the late adjuvant setting, ctDNA was identified a median of 1 year before all cases of distant metastasis. Future studies will determine if ctDNA-guided intervention in patients with HR+ BC can alter clinical outcomes.

Correlation of circulating tumor DNA (ctDNA) with clinical outcomes in appendiceal cancers (AC).

29 Background: Appendiceal Cancers are a heterogenous group of rare tumors with distinct histopathologic and genomic alterations. These often have peritoneal spread that might not be easily detected on current imaging modalities, and conventional tumor markers may not lend diagnostic support. Hence, novel diagnostic techniques are needed. Measurement of ctDNA for recurrence risk prediction, response to therapy and and early diagnosis is a promising technique. However, limited published data exist in AC to validate the role and utility of ctDNA in clinical practice. Here we present a single institution experience of ctDNA analysis in patients with AC. Methods: ctDNA measurements of 37 pts with stage II-IV AC treated between 1/1/2019 and 9/15/2021 were reviewed retrospectively. ctDNA analysis was done using Signatera bespoke mPCR NGS assay. ctDNA results were compared to crossectional imaging, CEA levels, and clinical evaluation. Results: 19/37 patients (51%) had at least one positive ctDNA test result. Of those, 8 had testing done during the surveillance setting (two with grade 3, one with grade 2, two with grade 1, and three with unknown grade). Of those, 5 pts (62.5%) had positive ctDNA detected, while 33.33% had elevated CEA level, 25% had radiographic and 42.9% had clinical evidence of recurrence (Table). 7/14 (50%) pts had high-grade pathology and positive ct-DNA, 3/6 (50%) patients had low-grade (grade 1) pathology and positive ct-DNA findings. 4 patients had longitudinal ct-DNA measurements available which correlated well with their disease course. Median duration to recurrence (radiographic or laparoscopic) was 376 days. Median duration to the first positive ctDNA test was 370 days. Median duration to positive CEA after initial treatment was 475 days. Conclusions: Measurement of ctDNA can be a useful tool to follow disease course and to guide management decision-making in patients with AC. Prospective studies with serial measurements of ctDNA are planned. [Table: see text]

Capillary Hemangioma of the Testis: A Case Report and Literature Review

Abstract Introduction/Objective Testicular capillary hemangioma is a rare benign vascular tumor and typically occurs in patients younger than 20 years. Study suggests that the mean age of these patients is usually 25.1 ± 22.7 years. We report a case of a 63-year-old man who underwent an uncomplicated radical orchiectomy for scrotal irritation and testicular fullness. Methods/Case Report Clinically he was found to have a large testicular mass. Ultrasound showed cystocele and an intratesticular tumor. Increased LDH was also found. Gross examination showed a single large cystic cavity containing yellow-colored fluid and a well-circumscribed tan-brown nodule measuring 2.5 × 1.8 × 1.0 cm within the testicular parenchyma. There was no extension into the tunica albuginea. Microscopic examination showed groups of capillaries of varying sizes in a lobular arrangement with bland spindle-like endothelial cells lining these capillary structures. The circumscribed vascular lesion was well-demarcated from the testicular parenchyma by a fibrous 0.1-cm pseudocapsule. The benign nature of this lesion was suggested by the lack of any mitotic activity, anaplasia, or dysplasia. Immunohistochemical staining was strongly positive for endothelial markers (CD31 and CD 34), and negative for mesothelial (WT1) and lymphatic markers (D2-40), excluding an adenomatoid tumor. Based on these characteristic morphological and immunohistochemical findings, the diagnosis of testicular capillary hemangioma was made. After 6 months of follow-up, the patient was well without any clinical evidence of recurrence. Results (if a Case Study enter NA) NA Conclusion While rarity of testicular capillary hemangioma impedes significant changes in how we approach adult testicular masses, the possibility of a benign tumor should always be in mind to consider. This is especially pertinent when patients fall outside the typical age range for germ-cell tumors, and for patients with a solitary testicular mass.

Gynaecomastia-like hyperplasia of axillary ectopic breast tissue – a case report

Aim: To highlight the incidental finding of gynaecomastia-like hyperplasia of axillary ectopic breast tissue in a female patient, with review of the literature. Case report: A 36 year old multiparous female presented for surgical management of right axillary ectopic breast tissue on a background history of a previously excised right lower quadrant breast lesion one year prior that showed a 29mm grade 3 invasive breast carcinoma of no special type with triple negative immunophenotype. The sentinel nodes were uninvolved and excision margins were clear. She underwent neoadjuvant chemotherapy and local radiotherapy. There was no radiological or clinical evidence of recurrence at the one year mark. Excised axillary fibroadipose tissue histologically showed benign breast ducts without lobules demonstrating occasional micropapillary hyperplasia, as well as stromal pseudoangiomatous stromal hyperplasia (PASH). There was no evidence of in-situ or invasive malignancy. The overall appearance was that of gynaecomastia-like hyperplasia. Discussion: Gynaecomastia-like hyperplasia is a rare finding in breast specimens in female patients. It is exceedingly rare in ectopic breast tissue, with only a single case report in the literature to date. The spectrum of histologic changes are characteristic, although the pathogenesis is poorly understood due to the rare nature of this process.

82 A Case of Recurrent Calcifying Aponeurotic Fibroma of the Hand: Managing a Rare Hand Tumour in an Evolving Healthcare Landscape

Abstract Introduction Calcifying Aponeurotic Fibroma (CAF) is a rare benign tumour originating from the aponeuroses of tendons and their bony insertions. Our case illustrates the technical challenges and considerations of removing a large, recurrent CAF of the hand. Case Report A 15-year-old student presented to his GP with a one-year history of a progressively enlarging painless swelling on the dorsum of the middle phalanx of the left middle finger. Plain radiographs identified a calcified soft tissue swelling with no bony involvement. The lesion was excised by the local paediatric orthopaedic service and recurred rapidly. Histology confirmed the diagnosis. He was referred to our specialist hand surgery service and the lesion was excised with the overlying skin (which demonstrated histological but not clinical disease). At six months, there was no clinical evidence of recurrence. Conclusions CAF may present atypically, and a high index of suspicion is warranted with calcified soft tissue hand lesions. Excision with conservative margins, and we newly suggest, the overlying skin, is recommended to preserve hand function but minimise recurrence (very common). Hand surgery provision in the UK is changing with adoption of the hub and spoke model and hand tumours may be more appropriately managed at specialist centres.

P.829Clinical characteristics of schizophrenia offspring, children diagnosed with attention deficit hiperactivity disorder and healthy controls

The relevance of human papillomavirus (HPV)-related features in cutaneous, non-anogenital SCC is not known and not incorporated into current diagnostic categories and treatment algorithms. Here, we describe the case of a 78-year-old male with bilateral inguinal warty-basaloid carcinoma, which is an HPV-related SCC that, in men, has been described only in a penile location. The patient underwent surgical excision without lymphadenectomy and declined radiation therapy due to concerns of poor wound healing. Adjuvant chemotherapy was not offered given the patient's Stage IV chronic kidney disease and undefined degree of benefit in the absence of concurrent radiotherapy. We therefore opted for close follow up and surveillance with PET/CT imaging and full body skin exams. The patient also received HPV vaccination. No clinical evidence of recurrence or metastasis was apparent at 6 months following initial excision. The identification of HPV-associated cutaneous SCC and correlation with patient outcomes is necessary to evaluate the prognostic significance of these features and to clarify the role of different treatment strategies in this setting.

Plasma Cell-Free Human Papillomavirus Oncogene E6 and E7 DNA Predicts Outcome in Oropharyngeal Squamous Cell Carcinoma

Persistent human papillomavirus (HPV) infection is associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), and increasing incidences of OPSCC are reported. The generally favorable treatment outcome in patients with HPV-driven OPSCC has brought de-escalation of treatment into discussion. Nevertheless, 13% to 25% develop a relapse within two years after current standard treatment. New biomarkers are urgently required to monitor therapy response, tumor burden, and minimal residual disease during follow-up. This observational study examined 50 patients with OPSCC to investigate plasma cell-free (cf) HPV-DNA derived from tumor cells before therapy and during follow-up. Real-time quantitative PCR was applied to quantify the DNA concentration of HPV oncogenes E6 and E7. A total of 85.7% of pretreatment samples from patients with HPV-driven OPSCC (n=28) were positive for at least one marker, and cfHPV-DNA concentration increased with tumor size. Virtually no signals were detected in HPV-negative OPSCC patients (n=20; P≤0.001). Patients without clinical evidence of recurrence had significantly reduced cfHPV-DNA concentrations after therapy (P≤0.001). Conversely, cfHPV-DNA levels increased or remained above threshold in five patients who had residual disease or developed recurrence. In conclusion, plasma cfHPV-DNA detection correlates with the clinical course of disease in patients with HPV-driven OPSCC. Consequently, extensive clinical investigation should be considered if cfHPV-DNA is detected during follow-up of patients with HPV-driven OPSCC.

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.

Abstract A46: Next-generation sequencing of circulating tumor DNA for detecting minimal residual disease and predicting recurrence in colorectal cancer patients

Abstract Background: Although the prognosis of colorectal cancer (CRC) has improved in the past decade, a subset of CRC patients may still suffer from relapse due to the progression from minimal residual disease (MRD) after surgical resection. A sensitive and noninvasive method to efficiently detect MRD is essential to further improve clinical prognosis. In this study, we have evaluated the feasibility of circulating tumor DNA (ctDNA) analysis in detecting MRD in CRC patients. Methods: Plasma samples were prospectively collected from 38 CRC patients, ranging from stage I to IV, who underwent surgical resection. A preoperative blood sample was taken just before surgery and postoperative samples were collected on multiple time-points to monitor the changes of mutation profiles. The extracted nucleic acid from matched surgically resected tumor tissues, peripheral blood cells (PBCs), and plasma were subjected to ultradeep targeted next-generation sequencing (NGS) using Oncomine Pan-Cancer Panel. Results: Cell-free DNA/RNA (cfDNA/RNA) was extracted from 208 preoperative and postoperative plasma samples with a median input of 20 ng for targeted-NGS (ranged from 8-20 ng). The median of sequencing depth, molecular coverage, and barcode tagging efficiency of the sequencing were 54,000x, 4,642x and 84%, respectively. 74 nonsynonymous mutations were identified from tumor tissues and 64 mutations from the preoperative plasma samples. 41 (64.1%) of the 64 mutations detected in plasma samples were concordantly identified from the tumor tissue DNA. Paired PBCs sequencing identified 11 of the mutations detected from plasma and 4 mutations detected from tumor tissues to be clonal hematopoiesis-related mutations. After the exclusion of clonal hematopoiesis-related mutations, 34 (89.5%) of the 38 patients harbor at least one preoperative mutation either from tumor tissue or plasma to be monitored postoperatively. Fourteen patients were detected with ctDNA mutations from postoperative plasma samples and to date, two of them have developed clinical recurrence. One patient was detected to carry TP53-G245D and KRAS-A146T from both the preoperative plasma and resected-tumor tissue. Both mutations were not detected from plasma during adjuvant chemotherapy. At 4.5 months after the completion of chemotherapy, both mutations were positively detected from plasma with no signs of radiologic or clinical evidence of recurrence. Clinical recurrence was confirmed by PET scan 3 months after the detection of molecular recurrence from ctDNA. Similarly, positive ctDNA mutations also preceded radiologic and clinical evidence of recurrence by 3.5 months in another patient who has developed recurrence. Conclusions: Our current results indicate that ctDNA analysis allows the detection of MRD in CRC patients. The integration of ctDNA analysis with current standard monitoring guidelines holds great promise in early detection of recurrence to allow clinical intervention to be applied promptly. Citation Format: Hiu Ting Chan, Satoshi Nagayama, Yoon Ming Chin, Masumi Otaki, Rie Hayashi, Kazuma Kiyotani, Yosuke Fukunaga, Masashi Ueno, Yusuke Nakamura, Siew-Kee Low. Next-generation sequencing of circulating tumor DNA for detecting minimal residual disease and predicting recurrence in colorectal cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A46.