Evidence Of Residual Disease Research Articles

Parotid Gland Metastasis of Conjunctival Squamous Cell Carcinoma: A Case Report of a Rare Phenomenon

Abstract Squamous cell carcinoma (SCC) of the conjunctiva is rare. It is commonly associated with ultraviolet ray exposure, viral infections, and conjunctivitis. Its management includes surgical excision with adjuvant treatment. Surgery alone leads to a high risk of recurrence even in early stages. Local recurrence is most common, and chemotherapy is preferred over resurgery in such cases. Lymphatic and distant metastases are seen in advanced cases. Here, we present an elderly female with early-stage SCC of the conjunctiva who underwent surgery alone, defaulted, and presented with parotid gland metastasis without any evidence of residual disease in the eye. The various lines of management have been discussed here.

NETOS: A personalized approach of neoadjuvant therapy, including INCB099280 monotherapy and bladder preservation, for muscle-invasive urothelial bladder carcinoma (MIBC) with ctDNA monitoring.

TPS4624 Background: MIBC is a systemic disease as >40% of patients (pts) ultimately develop recurrence after radical cystectomy (RC). For pts who cannot receive or refuse cisplatin-based chemotherapy there is no standard-of-care neoadjuvant therapy. Single-agent pembrolizumab, given neoadjuvantly in patients with T2-4N0M0 MIBC, was effective in PURE-01 trial. A proportion of these pts refused RC and were cured with pembro and redo transurethral resection of the bladder tumor (reTURBT; Bandini et al. PMID: 32979511). There are increasing concerns by the pts related to the need to undergo RC whenever they achieve a clinical complete response (cCR) with TURBT and systemic therapy. INCB099280 is a potent, orally bioavailable, selective, small molecule that targets PD-L1 that is being developed for the treatment of advanced malignant diseases. A phase 1, dose-escalation and expansion study is ongoing in pts with select advanced solid tumors (NCT04242199); safety and preliminary efficacy results have been reported (Prenen et al. ESMO-IO 2023). Our hypothesis is that INCB099280 can be offered in biomarker-selected pts as a maintenance therapy instead of any additional treatment, provided that a cCR after the induction phase is obtained. Methods: Pts should have a predominant urothelial carcinoma (UC) histology, have a clinical stage T2-T4N0M0 MIBC, be ineligible for or refuse to receive cisplatin-based chemotherapy. The study will also select pts with a circulating tumor DNA (ctDNA)-positive test (Signatera ctDNA assay) and will be staged with pelvic MRI. Pts will receive 12 weeks of INCB099280 at the dose of 400 mg twice daily (BID), continuously. Restaging will be planned with ctDNA, imaging and reTURBT. Pts who will achieve a cCR (i.e., no evidence of residual disease at the histological examination, clearance of ctDNA and the evidence of no residual detectable disease at cross-sectional imaging, evaluated locally) will receive additional INCB099280 400 mg BID for a maintenance period of 12 months. Pts with evidence of high grade or infiltrating residual disease will be discontinued from the study. Those with a Ta/T1-low grade disease will be managed according to physician’s preference: they may be eligible to continue within the study protocol and receive maintenance INCB099280 400 mg BID for a total period of 12 months. The primary endpoint is the proportion of cCR and the study is planned according to A'Hern one-stage binomial design, with H0 ≤5% and H1 ≥20%, 5% one-sided Alpha, 80% power and 10% drop-out rate. The overall sample size Will be of 30 pts. Secondary endpoints will include safety (CTCAE v.5.0), event-free survival, bladder-intact overall survival (OS) and OS (EUCT number: 2024-511029-73-00). Clinical trial information: 2024-511029-73-00.

The oncologic burden of residual disease in incidental gallbladder cancer: An elastic net regression model to profile high-risk features

IntroductionIncidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection's role as a modifying factor in the natural history of IGBC. MethodsAll patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD. ResultsAmong the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38–60) for IGBC patients with no evidence of RD, compared to 31 months (23–42) for those with RD (p < 0.001). ConclusionRe-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.

Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study

AimsWHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. Materials and methodsPatients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. Results84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection.Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27–1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27–0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy–60Gy), 45.8% of adjuvant RT was delivered using IMRT.At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. ConclusionSurgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

Yolk Sac Differentiation in Endometrial Carcinoma: Incidence and Clinicopathologic Features of Somatically Derived Yolk Sac Tumors Versus Carcinomas With Nonspecific Immunoexpression of Yolk Sac Markers.

Endometrial somatically derived yolk sac tumors are characterized by yolk sac morphology with AFP, SALL-4, and/or Glypican-3 immunoexpression. Yolk sac marker expression, however, is not limited to tumors with overt yolk sac histology. Three hundred consecutive endometrial malignancies were assessed for immunomarkers of yolk sac differentiation. Of these, 9% expressed ≥1 yolk sac marker, including 29% of high-grade tumors. Only 3 (1%) met morphologic criteria for yolk sac differentiation; these were originally diagnosed as serous, high-grade NOS, and dedifferentiated carcinoma. Two were MMR-intact and comprised exclusively of yolk sac elements, while the dedifferentiated case was MMR deficient and had a background low-grade endometrioid carcinoma; this case also showed BRG1 loss. All 3 were INI1 intact. Nonspecific yolk sac marker expression was seen in 14 carcinosarcomas, 4 endometrioid, 2 serous, 1 clear cell, 1 dedifferentiated, 1 mixed serous/clear cell, and 1 mesonephric-like carcinoma. INI1 was intact in all cases; one showed BRG1 loss. Twenty were MMR-intact, and 4 were MMR deficient. All MMR-deficient cases with yolk sac marker expression, both with and without true yolk sac morphology, had no evidence of residual disease on follow-up, whereas 82% of MMR-intact cases developed recurrent/metastatic disease. In summary, endometrial somatically derived yolk sac tumors were rare but under-recognized. While AFP immunostaining was specific for this diagnosis, Glypican-3 and SALL-4 expression was seen in a variety of other high-grade carcinomas. INI1 loss was not associated with yolk sac morphology or immunomarker expression in the endometrium, and BRG1 loss was rare. All patients with MMR-deficient carcinomas with yolk sac immunoexpression +/- morphology were disease-free on follow-up, whereas the majority of MMR-intact cancers showed aggressive disease.

Primary Well-Differentiated Neuroendocrine Tumor/Carcinoid of the Prostate: Case Report and Review of Literature.

Primary well-differentiated neuroendocrine tumor (WDNT)/carcinoid of the genitourinary tract is rare. Many WDNT reported in the prostate gland have been seen in close association with conventional prostatic adenocarcinoma and/or label for prostate-specific immunohistochemical markers and are best considered prostatic adenocarcinomas with "carcinoid-like" features. We present a case of primary WDNT/carcinoid incidentally detected in a 67-year-old man who underwent radical prostatectomy for Grade group 2 prostatic adenocarcinoma. Morphologically, the neuroendocrine (NE) lesion appeared distinct from the prostatic adenocarcinoma, labeled for NE markers, was negative for prostatic markers (NKX3.1, PSA, and ERG), and showed an overall low Ki-67 proliferation index (<1%). Follow-up was uneventful with no evidence of residual disease or metastasis.

A Rare Case of P63-Negative Sinonasal Nut Midline Carcinoma in the Elderly.

Molecular analysis of a NUT carcinoma and age at diagnosis may serve as a potential means for predicting patient prognosis in cases of midline NCC.Each patient should receive careful monitoring and a personalised treatment strategy based on their molecular studies. Surgical resection, along with a combination of radiotherapy and chemotherapy, has the potential to improve overall survival rates.In line with the commonly observed relationship between increased p63 mutation and poorer survival rates, a negative p63 expression in squamous cell carcinomas may indicate a more favorable prognosis. This hypothesis highlights the importance of further research to validate these findings.

Patterns of Care in Craniopharyngioma: Clinical Outcomes After Surgery and Radiation Therapy in a Real-World Setting

Craniopharyngioma (CP) is a benign neuroepithelial tumor generally treated with maximal safe resection and radiation therapy (RT) in incompletely resected CP or in recurrent tumors to achieve long-term control. We analyzed the clinical outcomes of patients with CPs treated with a multimodality approach. A retrospective clinical audit of histologically proven CPs registered between 2008 and 2019 at a specialized neuro-oncology center in India was performed. Time-to-event outcomes (overall survival [OS] and progression-free survival [PFS]) were analyzed. One hundred and twenty-two patients with CP were analyzed. The median age of the population was 14 years (interquartile range [IQR], 8-26) with a significant male preponderance. Gross total resection was achieved in only 25% of patients. At a median follow-up of 57.1 months (IQR, 27.8-87.8), 5-year estimates of PFS and OS were 52% (95% confidence interval, 46%-63.4%) and 85.8% (95% confidence interval, 78.6%-93%), respectively. Recurrence or progression was observed in 48 of 122 patients (39.3%) at a median time of 84.4 months (IQR, 24.7-174.8). On multivariate analysis, the absence of residual disease (P= 0.004), near-total resection (P= 0.035), and use of up-front adjuvant RT (P < 0.001) significantly improved the 5-year PFS, whereas the absence of extracavernous extension (P= 0.058) and any use of postoperative RT (P= 0.026) significantly improved the 5-year OS. This study represents one of the largest single-institutional series of CPs, showing improved PFS with up-front adjuvant RT in most cases of CP. Deferring adjuvant RT should be considered only in patients with no evidence of residual disease (as shown on dedicated sellar imaging) after primary surgery.

MRD Directed Treatment Intensification with Either FLAG-Ida or DA-Cladribine Improves Survival in Older AML Patients: Results from the NCRI AML18 Randomised Trial

Background Following intensive chemotherapy in acute myeloid leukemia (AML), residual disease, assessed by failure to achieve a remission (CR/CRi) or the presence of measurable residual disease (MRD) in remission identifies a poor risk group of patients. In the NCRI AML16 trial for older adults (&amp;gt;60yrs), patients who were MRD+ve by flow cytometry in their remission bone marrow after course 1 had significantly poorer survival (26% at 3yrs vs 42% if MRD-ve) due to a higher risk of relapse (Freeman et al JCO 2016). These results suggested that flow cytometric MRD after course 1, by identifying patients who have a poor outcome with standard therapy, could be used to risk stratify for further treatment. However, although not infrequently used, it is uncertain whether chemotherapy intensification is of benefit to older adults with residual disease. In the AML18 trial we therefore conducted a course 2 randomization to evaluate MRD directed chemotherapy intensification in older adults. Methods AML18 patients who did not achieve MRD negativity after their first course (either not in CR/CRi or MRD+ve or MRD unknown) were randomized to either continue treatment with up to two courses of standard DA (Daunorubicin, AraC) (DA3+8 followed by DA2+5) or to receive up to 2 courses of intensified chemotherapy:- either FLAG-Ida or DA with Cladribine (DAC) (DA3+8, followed by DA2+5 both including Cladribine 5 mg/m 2 x 5 days). Course 1 had comprised DA (3+10) with 0, 1 or 2 doses of gemtuzumab ozogamicin. FLAG-Ida was dose reduced for patients over 70yrs and in course 3 for all patients (Fludarabine from 30mg/m 2 days 1-5 to 25mg/m 2 days 1-4, Idarubicin from 8mg/m 2 days 3-5 to 5mg/m 2 days 2-4). The DAC randomization was closed May 2019 due to drug supply issues. The primary endpoint was overall survival (OS). Rate ratios (RR) were used when appropriate to account for non-proportional hazards effect. Secondary endpoints included conversion to MRD negativity (defined as undetectable MFC-MRD) following course 2. Results Between Nov 2014 and Jan 2023, 523 patients (median age 67yrs) entered this randomization (193 DA, 191 FLAG-Ida, 139 DAC) following course 1 response assessment. Of these patients 164 (31%) were not in CR/CRi, 260 (50%) were in CR/CRi MRD+ve and the remaining 99 (19%) were in CR/CRi but with MRD unknown (due to an absence of a leukaemia-associated-immunophenotype at diagnosis or inadequate/missing samples). 99/477 (21%) of patients had adverse risk cytogenetics. All characteristics were balanced between arms. Median follow-up was 51 months. Following course 2, 47% (78/164) of those not in CR/CRi after course 1 converted to CR/CRi within 50 days: 55%, 57%, 34% for DA, DAC and FLAG-Ida respectively (DA vs DAC P=0.63, DA vs FLAG P=0.015). Of 282 patients providing MRD results after both course 1 and 2, 51% (60/117), 63% (50/79) and 58% (50/86) converted to MRD negativity after DA, DAC and FLAG-Ida respectively (DA vs DAC P=0.16, DA vs FLAG P=0.33). Greater hematological toxicity was seen with DAC or FLAG-Ida compared to DA (P&amp;lt;.001 for both platelet and neutrophil recovery). Day 60 mortality was increased in patients randomized to FLAG-Ida (9% vs 4% with DA and 4% with DAC, P=0.032). In total, 213 (41%) patients underwent allogeneic SCT (DA 42%, DAC 47%, Flag-Ida 35%). OS at 5yrs was 27%, 32% and 32% for DA, DAC and Flag-Ida respectively (DAC vs DA HR=0.82 95%CI 0.62-1.09, P=0.174; FLAG-Ida vs DA HR=0.90 95%CI 0.70-1.16, P=0.407). In subgroup analyses, comparing patients with known and unknown MRD status, there was no detectable survival benefit from intensification for MRD unknown patients (FLAG-Ida vs DA RR 1.52 95%CI 0.92-2.50, P value = 0.105; DAC vs DA RR 1.10, 95%CI 0.81-1.45, P value = 0.549). In a sensitivity analysis, excluding patients with unknown MRD, there was a significant OS benefit for both DAC (OS at 5yrs, 32% vs 22% for DA; RR 0.84, 95%CI 0.77-0.98, P=0.029, Figure A) and FLAG-Ida (OS at 5yrs, 34% vs 23% for DA; RR 0.71, 95%CI 0.54-0.96, P=0.026, Figure B). Conclusion In older AML patients with evidence of residual disease following first induction, we saw a significant long-term survival benefit for intensified therapy with both DAC and FLAG-Ida in a randomized comparison with DA. This was despite early toxicity, observed particularly after FLAG-Ida. DAC intensification appeared better tolerated, delivered more patients to transplant and was associated with a greater conversion to MRD negativity.

Percutaneous CT-Guided Cryoablation for Locally Recurrent Prostate Cancer: Technical Feasibility, Safety, and Effectiveness

PurposeTo assess the feasibility and safety of using computed tomography (CT) guidance for ablation of prostate cancer in the salvage setting. Materials and MethodsThis institutional review board–approved retrospective study of consecutive patients who presented with prostate cancer recurrence and underwent percutaneous CT-guided cryoablation was conducted between July 2020 and September 2022. A total of 18 patients met the inclusion criteria, and a total of 19 procedures were performed. Demographic details; preablation and postablation urinary, rectal, and erectile function assessment; procedure details; and preoperative and postoperative imaging findings and prostate-specific antigen (PSA) values were recorded. ResultsThe mean treated tumor size was 15.7 mm ± 6.2. Technical success was achieved in 18 of the 19 procedures (94.7%), with 1 procedure aborted due to inability to obtain a safe plane. The mean follow-up time was 10.0 months (range, 2.3–26.7 months) at the time of manuscript preparation. The mean PSA before ablation was 8.1 ng/mL ± 9.3, and postablation PSA nadir was 2.6 ng/mL ± 4.0 (P = .002). Of the 18 patients who had postoperative imaging, 16 (88.9%) had a complete response (ie, no evidence of residual disease), and 2 (11.1%) patients had residual disease. Overall, 16 (88.9%) of the 18 treated patients demonstrated a PSA and/or imaging response to ablation. Mild adverse events occurred in 4 (22%) of the 18 cases. ConclusionsCT-guided cryoablation appears to be a technically feasible, safe option for treating locally recurrent prostate cancer.

Abstract PO-050: Preliminary results from an early-phase, open-label study of tolinapant and radiation in cisplatin-ineligible patients with previously untreated, locally advanced head and neck cancer

Abstract Background: Genomic alterations in NF-kB and inhibitor of apoptosis protein (IAP) pathways are common in head and neck cancer (HNC). IAP antagonists have shown activity in HNC, especially when paired with radiation therapy (RT), in both preclinical and early clinical studies. Our preclinical studies suggest that the combination of tolinapant and RT works in part by enhancing T cell activation, dendritic cell maturation, immunogenic cell death, and other aspects of the anti-tumor immune response. However, the safety and efficacy of IAPi combined with definitive RT, without platinum chemotherapy, has not been explored clinically. Methods: This is an open-label, early-phase study to determine the safety of the IAPi tolinapant combined with definitive or adjuvant RT. Eligible patients have previously untreated, locally advanced HNC, ECOG ≤1, with plan for definitive or adjuvant RT but are ineligible for treatment with cisplatin. Patients are treated with intensity-modulated radiation therapy (IMRT) or proton therapy (IMPT) to 60-70 Gy with tolinapant 180 mg (the single-agent recommended phase 2 dose) daily by mouth or feeding tube for 7 days during weeks 1, 3, 5, and 7 of RT, with the option of tolinapant dose reduction to 90 mg daily for toxicity. In the adjuvant setting, patients are treated for 6 weeks with 3 cycles of tolinapant. Blood is collected for research at baseline and during weeks 2 and 7. Tissue biopsies at baseline and during week 2 are optional. Results: Eight patients have been consented, including 3 screen failures and 5 enrolled (accrual target = 10 enrolled). All enrolled patients to date received definitive RT; four patients were treated with IMPT. Tumor sites included nasopharynx (1), oropharynx (one HPV+, one HPV-), and larynx (2). The most common reason for cisplatin ineligibility was hearing loss. The median age was 70 (range, 64-81). One patient had a grade 2 rash with pruritis that persisted for several weeks after treatment; other AEs included one treatment interruption during week 1, attributed to RT. Dose reduction of tolinapant was not required for any patients. Three patients have been evaluated by imaging and clinical exam 3 months after treatment, with no evidence of residual disease. Flow cytometry of peripheral blood samples showed a decrease in the proportion of CD4+CD25+ T cells (3/5 patients) and increase of differentiation markers on CD8+ T cells (4/5 patients) from baseline to week 2; these trends were more pronounced at week 7. The one patient who experienced a persistent grade 2 rash with pruritis had a &amp;gt;10-fold increase in activated (HLA-DR+CD38+) CD8+ T cells by week 7. Conclusions: Based on preliminary safety and tolerability data reviewed at this interim analysis, tolinapant at 180 mg appears to be a safe dose for combination with definitive RT. Additional studies will further characterize the dynamics of the peripheral immune response and provide longer follow up on a larger cohort of patients. This study was supported by Astex Pharmaceuticals, Inc. with a research grant to NCS and NFS. Citation Format: Nicole C. Schmitt, William A. Stokes, James E. Bates, Madison Stallings, Brendan L. C. Kinney, Mark W. McDonald, Soumon Rudra, Jill Remick, Zachary S. Buchwald, Dong M. Shin, Azeem S. Kaka, Mihir R. Patel, Nabil F. Saba. Preliminary results from an early-phase, open-label study of tolinapant and radiation in cisplatin-ineligible patients with previously untreated, locally advanced head and neck 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-050.

An extremely rare case of recurrent pleomorphic myxoidliposarcoma with response to eribulin chemotherapy – A case report

Pleomorphic myxoid liposarcoma (PML) is a newly recognized entity with aggressive clinical behavior and a tendency to recur. It has histological features of both myxoid and pleomorphic liposarcoma and lacks the molecular and structural chromosomal abnormalities associated with myxoid and pleomorphic liposarcoma. The data about their response to chemotherapy is quite sparse. We report a case of incidentally detected pleomorphic myxoid liposarcoma of the mediastinum in a 32-year-old gentleman. After resection and adjuvant chemotherapy with doxorubicin and ifosfamide, there was no evidence of residual disease at the end of treatment. During a routine follow-up 5 months later, he was found to have a recurrence of the disease with histological confirmation. He received a trabectedin given its activity in myxoid liposarcoma. However, he had toxicities and progression leading to its discontinuation. Subsequently, eribulin was started as the next line of therapy. After 4 cycles of chemotherapy, response assessment was suggestive of partial response, which is still maintained after 7 cycles of eribulin. This is the first report of this entity responding to a newer chemotherapy regimen.

Equivocal end-of-therapy imaging findings do not predict a higher risk of local relapse after definitive radiotherapy in pediatric Ewing sarcoma and rhabdomyosarcoma.

Posttherapy imaging studies can provide reassurance or induce anxiety regarding risk of recurrence for patients and their families. In some cases, it is difficult to determine if imaging findings represent posttreatment changes or residual disease. Equivocal radiographic findings can occur due to therapy-related inflammation or residual, inactive soft tissue masses, but it is unknown if such findings indicate an increased likelihood of local recurrence. The aim of this study was to assess the value of initial posttherapy scans for predicting local relapse in patients with Ewing sarcoma (EWS) or rhabdomyosarcoma (RMS) who received radiotherapy (RT) for local control. These findings are critical to inform clinicians' surveillance recommendations and ability to accurately counsel patients and their families. The primary endpoint was time to local progression (LP). Patients were classified as having posttherapy scans that were "positive" (residual disease within the RT field), "negative" (no evidence of residual disease within the RT field), or "equivocal" (no determination could be made). The value of initial posttreatment scans for predicting LP was assessed using positive predictive value (PPV) and negative predictive value (NPV). Negative imaging findings (n=51) had an NPV of 88%, and positive imaging findings (n=1) had a PPV of 100%. When equivocal findings (n=16) were categorized with negative results (i.e., positive vs. equivocal/negative), the NPV was 90%. When equivocal findings were categorized with positive results (equivocal/positive vs. negative), the PPV was 12%. Equivocal findings within the RT field on end-of-therapy imaging studies indicate no higher risk of local recurrence than negative findings. These results may contribute to appropriate surveillance schedules and accurate counseling of patients with RMS and EWS who have received RT for local control.

Accuracy of FDG-PET/CT for Response Evaluation of Muscle-Invasive Bladder Cancer following Neoadjuvant or Induction Chemotherapy

Introduction: The aim of the study was to confirm the diagnostic accuracy of a second FDG-PET/CT following neoadjuvant or induction chemotherapy (NAIC) prior to radical cystectomy for patients with localized muscle-invasive bladder cancer (MIBC). Methods: Retrospective review of 62 consecutive patients with MIBC, that had a first FDG-PET/CT between April 2016 and September 2021. Patients then underwent NAIC, followed by a second FDG-PET/CT and radical cystectomy. Patients with no hypermetabolism in the bladder and lymph nodes on the second FDG-PET/CT were considered metabolic complete responders, while patients with no evidence of residual disease on histopathology were considered pathologic complete responders. The accuracy of the second FDG-PET/CT to distinguish complete responders from patients with residual disease was calculated, with histopathology as gold standard. Results: Of 62 patients, 1 was lost to follow-up, 5 died before radical cystectomy, 5 had delay >2 months between the second FDG-PET/CT and radical cystectomy, and 6 did not undergo radical cystectomy and instead underwent alternative treatment. The study cohort comprised 45 patients, 39 males and 6 females, with an age of 66 ± 6 years. In comparison to histopathology, FDG-PET/CT provided (i) sensitivity of 95% and specificity of 42%, for the overall disease; (ii) sensitivity of 100% and specificity of 36%, for the primary tumor only; and (iii) sensitivity of 97% and specificity of 30%, for the lymph nodes only. Conclusion: FDG-PET/CT has over 95% sensitivity for distinguishing complete responders from patients with residual disease. Thus, FDG-PET/CT can be used for early response evaluation following NAIC to identify patients that did not completely respond to chemotherapy and may require alternative treatment pathways.

An unusual pseudolymphoma in the context of necrotizing fasciitis: A case report.

The diagnosis of lymphoma in routine diagnostics can be challenging due to clinical, morphological and immunphenotypical overlap with unusual reactive processes termed "pseudolymphomas." 45-year-old male that underwent surgical debridement for a necrotizing fasciitis of the thigh with concomitant excision of a regional lymph node. The lymph node demonstrated an architecture-effacing activation and proliferation of lymphoblasts and was initially misdiagnosed as an aggressive lymphoma. Only in consideration of the clinical context and with the help of additional immunohistochemical and molecular analyses the final diagnosis of a reactive lymphadenopathy could be made. No further therapy was required after the final diagnosis of a reactive lymphadenopathy was made. The clinical follow-up was unremarkable, with no evidence of residual disease after 6 months. This case report adds the parafollicular activation and proliferation of blasts and plasmablasts in the drainage area of an active infection to the spectrum of "pseudolymphomas" and reiterizes the importance of placing histopathological findings in the proper context.

FDG-PET/MRI for Nonoperative Management of Rectal Cancer: A Prospective Pilot Study.

Nonoperative management (NOM) is increasingly utilized for rectal cancer patients with a clinical complete response (cCR) following total neoadjuvant therapy (TNT). The objective of this pilot study was to determine whether FDG-PET/MRI alters clinical response assessments among stage I-III rectal cancer patients undergoing TNT followed by NOM, relative to MRI alone. This prospective study included 14 subjects with new rectal cancer diagnoses. Imaging consisted of FDG-PET/MRI for initial staging, post-TNT restaging, and surveillance during NOM. Two independent readers assessed treatment response on MRI followed by FDG-PET/MRI. Inter-reader differences were resolved by consensus review. The reference standard for post-TNT restaging consisted of surgical pathology or clinical follow-up. 7/14 subjects completed post-TNT restaging FDG-PET/MRIs. 5/7 subjects had evidence of residual disease and underwent total mesorectal excision; 2/7 subjects had initial cCR with no evidence of disease after 12 months of NOM. FDG-PET/MRI assessments of cCR status at post-TNT restaging had an accuracy of 100%, compared with 71% for MRI alone, as FDG-PET detected residual tumor in 2 more subjects. Inter-reader agreement for cCR status on FDG-PET/MRI was moderate (kappa, 0.56). FDG-PET provided added value in 82% (9/11) of restaging/surveillance scans. Our preliminary data indicate that FDG-PET/MRI can detect more residual disease after TNT than MRI alone, with the FDG-PET component providing added value in most restaging/surveillance scans.

PSAT016 Deoxycorticosterone-Producing Adrenocortical Carcinoma: A Rare Cause of Resistant Hypertension

Abstract Background Rare causes of secondary hypertension should be considered after negative initial evaluation for more common conditions. 11-Deoxycorticosterone-secreting tumors are one such rare cause. Clinical Case A 38-year-old male with two-year history of resistant hypertension on four antihypertensive medications (amlodipine, hydrochlorothiazide, lisinopril, spironolactone) presented to the emergency room with one-day history of headaches and hypertension. Initial vitals were blood pressure of 179/117, heart rate 68, respiratory rate 18, and SpO2 of 100% on room air. Labs were notable for hypokalemia of 2.2, normal creatinine of 1.03, and troponin elevation of 0.08. EKG showed no ischemic changes. During the hospital admission, spironolactone dose was increased, amiloride was added, hydrochlorothiazide was discontinued, and potassium was supplemented. The patient's blood pressure stabilized, and troponin normalized. Evaluation for secondary causes was also initiated, including plasma renin, aldosterone, and metanephrines, with results pending on discharge. Outpatient CT abdomen and pelvis was also ordered. The patient was discharged on the third day of admission on an increased dose of spironolactone 100mg daily, amiloride 5mg daily, amlodipine 10mg daily, lisinopril 40mg daily, and potassium 20meq twice daily. Laboratory studies and outpatient endocrinology evaluation revealed suppressed plasma renin activity 0.1 ng/mL/hr, low aldosterone &amp;lt;3.0 ng/dL, elevated 11-deoxycorticosterone (DOC) 869 ng/dL (reference range ≤19 ng/dL), and elevated 11-deoxycortisol 719 ng/dL (reference range ≤49 ng/dL). Plasma and urine metanephrines, 24-hour urinary free cortisol, and plasma DHEAS were normal. CT revealed a large 9.7×10.0×10.7cm heterogeneously enhancing right adrenal mass and several subcentimeter bilateral pulmonary nodules. FDG PET-CT showed mild heterogeneous uptake of the adrenal mass with SUVmax of 5.1 and hepatic SUVmean of 2.5, without convincing metabolic evidence of metastasis. Mild uptake was noted in the mediastinal, hilar and left axillary lymph nodes, which were not suspiciously hypermetabolic and favored to be reactive, perhaps related to recent COVID-19 vaccination administered to the left upper extremity. The subcentimeter pulmonary nodules did not have increased avidity. The patient underwent open right adrenalectomy without complications. Pathology revealed 11.5cm low-grade adrenocortical carcinoma with clear margins and angioinvasion, Ki67 proliferation index of 1-2%, and without necrosis, lymphovascular invasion, or extra-adrenal extension. 11-deoxycortisol normalized and DOC was undetectable at one and three months postoperatively. Blood pressure improved significantly, and all antihypertensives were discontinued except amlodipine 10mg daily. On surveillance CT scan six months after surgery, there was no evidence of residual disease in the adrenalectomy bed and pulmonary nodules appeared stable. Conclusions Adrenocortical carcinomas rarely produce aldosterone and even less commonly produce DOC as the major steroid product. DOC should be evaluated in the setting of hypertension with hypokalemia, suppressed renin and aldosterone. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Re-excision After Unplanned Excision of Soft Tissue Sarcoma is Associated with High Morbidity and Limited Pathologic Identification of Residual Disease.

Patients with unplanned excision (UPE) of trunk and extremity soft tissue sarcoma (STS) present a significant management challenge for sarcoma specialists. Oncologic re-resection has been considered standard practice after UPE with positive or uncertain margins. A strategy of active surveillance or "watch and wait" has been suggested as a safe alternative to routine re-excision. In this context, the current study sought to evaluate short-term outcomes and morbidity after re-resection to better understand the risks and benefits of this treatment strategy. A retrospective, single-institution study reviewed patients undergoing oncologic re-resection after UPE of an STS during a 5-year period (2015-2020), excluding those with evidence of gross residual disease. Short-term clinical outcomes were evaluated together with final pathologic findings. The review identified 67 patients undergoing re-resection after UPE of an STS. Of these 67 patients, 45 (67%) were treated with a combination of external beam radiation therapy (EBRT) and surgery. Plastic surgery was involved for reconstruction in 49 cases (73%). The rate of wound complications after re-resection was 45 % (n = 30), with 15 % (n = 10) of the patients experiencing a major wound complication. Radiation therapy and plastic surgery involvement were independently associated with wound complications. Notably, 45 patients (67%) had no evidence of residual disease in the re-resection specimen, whereas 13 patients (19 %) had microscopic disease, and 9 patients (13%) had indeterminate pathology. Given the morbidity of re-resection and limited identification of residual disease, treatment plans and discussions with patients should outline the expected pathologic findings and morbidity of surgery.

LBA4 Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: Results from the randomized, phase III CheckMate 914 trial

CheckMate 914 (NCT03138512) is a phase III, randomized, double-blind, multicenter, 2-part trial evaluating NIVO+IPI vs PBO (part A) or NIVO monotherapy vs NIVO+IPI vs PBO (part B) in mutually exclusive patients (pts) with localized RCC at high risk of post-nephrectomy relapse. We report the primary analysis for part A of this trial. CheckMate 914 key inclusion criteria: radical or partial nephrectomy with negative surgical margins > 4 and ≤ 12 weeks before randomization; predominant clear cell histology; pathological TNM stage T2a (grade [G] 3 or 4) N0M0, T2b (any G) N0M0, T3 (any G) N0M0, T4 (any G) N0M0, or any T (any G) N1M0; and no clinical/radiological evidence of residual disease or distant metastases. Pts were randomized 1:1 to NIVO 240 mg Q2W (× 12 doses) + IPI 1 mg/kg Q6W (× 4 doses) or equivalent PBO for 24 weeks or until disease recurrence/unacceptable toxicity. Stratification factors: TNM stage and type of nephrectomy. Primary endpoint: disease-free survival (DFS) per blinded independent central review; secondary endpoints include overall survival and safety. 816 pts were randomized to NIVO+IPI (n = 405) vs PBO (n = 411). With 37.0 months of median follow-up (range, 15.4–58.0), the primary efficacy endpoint of DFS was not met (HR, 0.92; 95% CI, 0.71–1.19; P = 0.5347). Median DFS was not reached with NIVO+IPI and 50.7 months with PBO; DFS probabilities at 24 months were 76.4% and 74.0%, respectively. Median (Q1, Q3) treatment duration was 5.1 (2.8, 5.3) months and 5.1 (5.1, 5.3) months, respectively. Any-grade treatment-related adverse events (AEs) were reported in 88.9% vs 56.8% of pts treated with NIVO+IPI vs PBO; grade ≥ 3 treatment-related AEs were reported in 28.5% vs 2.0%, respectively. Treatment-related AEs led to discontinuation of NIVO+IPI in 29.0% of pts and of PBO in 1.0% of pts. The CheckMate 914 trial of NIVO+IPI vs PBO in pts with localized RCC at high risk of relapse after nephrectomy did not meet the primary endpoint of DFS. Safety of NIVO+IPI was consistent with its known profile in advanced RCC, although the rate of discontinuation due to treatment-related AEs was higher with adjuvant NIVO+IPI vs PBO in this trial.

Abstract CT562: PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of Olaparib to Platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients

Abstract Background: Triple Negative Breast Cancers (TNBC) are a biologically diverse and aggressive subgroup lacking targeted therapy. TNBC and Germline BRCA (gBRCA) breast cancer share certain phenotypic and molecular similarities, with gBRCA mutations seen in 10% to 20% of TNBC patients. Homologous recombination deficient tumours, especially those caused by germline or somatic BRCA mutations, are thought to be particularly sensitive to PARP inhibitors. Aim: To establish if the addition of Olaparib to neoadjuvant Platinum-based chemotherapy in the treatment of basal TNBC and/or gBRCA breast cancer is safe and increases efficacy. Trial design: 3-stage open label randomised phase II/III trial of neoadjuvant Paclitaxel and Carboplatin +/- Olaparib, followed by clinicians' choice of Anthracycline regimen. Stages 1 and 2: Randomisation (1:1:1) to control (3-weekly carboplatin AUC5/weekly with paclitaxel 80mg/m2 for 4 cycles), or to one of two research arms. These use an identical chemotherapy regimen and also include different treatment schedules of Olaparib 150mg BD for 12 days. Stage 3: Randomisation (1:1) to either the control or research arm chosen following stage 2. End-points: Stage 1: Safety; Stage 2: Schedule selection based on pCR rate and Olaparib completion rate using a “pick-the-winner” design. Stage 3: pCR rate. This trial includes an optional pathway (PARTNERING) for patients with evidence of residual disease after six chemotherapy cycles. This aims to establish if the addition of new agents (ATR inhibitor and PD-L1 inhibitor) improves treatment response. Eligibility criteria: Aged 16-70; histologically confirmed invasive breast cancer; ER-negative, HER2-negative with TNBC basal phenotype or gBRCA positive, HER2-negative irrespective of hormone status; stage T1-4 N0-2; performance status 0-1; treatment within 6 weeks of diagnostic biopsy; biomarker scores: TILs, CK 5/6, EGFR +/- AR. Statistical methods: The recruitment of TNBC non-gBRCA and gBRCA patients is independent. Enrichment design is applied with an overall significance level 0.05(α) and 80% power. A minimum of 780 patients will be included to detect an absolute improvement of 15% (all patients and TNBC non-gBRCA cohort) and 20% (gBRCA patients) by combining Olaparib with Platinum based chemotherapy. A minimum of 478 TNBC non-gBRCA and 188 gBRCA patients will be recruited. Each PARTNERING cohort will consist of 15 patients. Current Enrollment: Since May 2016, 756 patients from 30 sites have been enrolled. Stages 1 and 2 are completed. An IDSMC review identified no safety concerns and Research Arm 2 was selected. This arm involves Olaparib administration on days 3-14. Stage 3 Phase I (recruitment of non-gBRCA and gBRCA patients) completed in December 2021. Stage 3 Phase II (recruitment of gBRCA patients only) remains open to patients to UK and internationally. 5 patients have been enrolled in PARTNERING. ClinicalTrials.gov Identifier: NCT03150576 Citation Format: Lynsey Drewett, Karen A. Pinilla, Louise Grybowicz, Jerome Wulff, Alimu Dayimu, Nikolaos Demiris, Rebecca Lucey, Anne-Laure Vallier, Wendi Qian, Andrea Machin, PARTNER Research Team, Karen McAdam, Rebecca Roylance, Ellen R. Copson, Anne Armstrong, Nicola Levitt, Elena Provenzano, Marc Tischkowitz, Emma McMurtry, Helena Earl, Jean E. Abraham. PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of Olaparib to Platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT562.