Distant Metastatic Disease Research Articles

A retrospective study evaluating the efficacy of pembrolizumab for metastatic or locally recurrent head and neck cancer: A real-world experience.

e18018 Background: Metastatic and locally recurrent head and neck cancer is an unfortunate occurrence and is associated with a historically poor prognosis. The KEYNOTE 048 trial reported an overall response rate (ORR) of 17% in this patient population after treatment with pembrolizumab. The purpose of our study is to evaluate the real-world outcomes in patients with metastatic or recurrent head and neck cancers treated with pembrolizumab or pembrolizumab containing regimens at our NCI designated comprehensive cancer center. Methods: We reviewed the medical records of 39 patients with advanced head and neck cancers treated with pembrolizumab or pembrolizumab containing regimens between 9/1/2017 and 12/31/2021. Patients with a diagnosis of cutaneous squamous cell carcinoma in the head and neck region and nasopharyngeal cancers were excluded. Results: Thirty-seven patients were included in the final analysis with a median age of 67. The median time to last follow-up was 12 months with a median time on therapy of 3.2 months. The most common location was oropharynx (87%), and 59% of the study population had documented CPS scores greater than 1. Approximately 60% of patients had distant metastatic disease at the time of initiation of pembrolizumab including one patient with symptomatic brain metastases prior to initiation of therapy. The most common site of metastatic disease was the lungs (51%). The ORR was 11.7%, while the median OS and median PFS were 10 and 2.9 months, respectively. Three patients experienced a complete response (CR), including one patient with a lasting, durable response of 50.9 months. The six-month and one-year PFS were 100% in those who responded or had stable disease (five patients). Ten patients (27%) required hospitalization due to treatment related adverse effects. Conclusions: The role of pembrolizumab in the setting of advanced head and neck cancer is well-established based on findings from large clinical trials. We report an ORR of 11.7% and median PFS of 2.9 months in patients treated with pembrolizumab containing regimens. Although the findings of our small retrospective study suggest a lower response rate than previously reported, the progression free survival in responders at six and twelve months was 100%. Identification of potential responders to immunotherapy has been an active area of research and our study suggests that a subset of patients with metastatic and/or locally recurrent head and neck cancer may experience long and durable responses to pembrolizumab containing regimens. [Table: see text]

ALTER-UC-007: A prospective phase 2 study of anlotinib with gemcitabine and cisplatin or anlotinib with penpulimab as perioperative treatment for patients with muscle-invasive urothelial carcinoma (MIUC).

TPS4612 Background: Radical surgery involving cystectomy and nephroureterectomy is the standard of care for patients with localized muscle-invasive urothelial carcinoma (MIUC). In recent years, neoadjuvant- and adjuvant-containing multimodality therapies have gradually been adopted in attempt to eradicate micrometastatic disease and improve the outcomes achieved with radical surgery alone. This study aims to evaluate the efficacy and safety of anlotinib (a multi-target tyrosine kinase inhibitor of angiogenesis) with gemcitabine and cisplatin or anlotinib with penpulimab (a humanized anti-PD-1 IgG1 monoclonal antibody) as neoadjuvant and adjuvant therapy in patients with MIUC. Methods: In this open-label, prospective, phase 2 study, eligible patients include those with histologically confirmed clinical stage T1-T4N1-3M0, T3-4N0M0 MIUC (tumors of the bladder, renal pelvis, ureter and urethra) fit and planned for radical cystectomy, nephroureterectomy or ureterectomy. Main exclusion criteria are distant metastatic disease; prior chemotherapy, anti-angiogenic therapy, radiation therapy or immunotherapies; active autoimmune disease; uncontrolled hypertension or patients at high bleeding risk. Patients will be enrolled and receive treatment based on PD-L1 status in tumor tissue. The PD-L1 status of eligible patients will be centralized and assessed using an anti-PD-L1 antibody and an immunohistochemical (IHC) assay. PD-L1 positivity was defined as combined positive score (CPS) ≥1 (previously reported as and equivalent to CPS ≥1%). The study treatment is stratified into two cohorts based on PD-L1 expression levels. In cohort 1, the PD-L1 negative patients with MIUC will receive neoadjuvant anlotinib (12 mg orally QD D1-14 every 3 weeks) + gemcitabine (1000 mg/m2, intravenously [IV] on days 1 and 8) + cisplatin (35 mg/m2 IV on days 1 and 8) for a maximum of 4 cycles followed by radical surgery and 2 cycles of adjuvant treatment post-surgery. In cohort 2, PD-L1 positive patients will receive anlotinib (12 mg orally QD D1-14 every 3 weeks) + penpulimab (200 mg IV every 3 weeks) for a maximum of 4 cycles followed by radical surgery and 2 cycles of adjuvant treatment post-surgery. After the completion or discontinuation of the study treatment, safety follow-up and survival follow-up will be performed. Tumor imaging was performed by computed tomography (preferred) or magnetic resonance imaging at baseline, and every 6 weeks during treatment, then every 6 months through year 2. Objective response rate (ORR) is the primary endpoint. Secondary endpoints included pathological complete response rate (pCR), disease-free survival (DFS), overall survival (OS) and safety. Recruitment have begun in October 2022. Currently, the study is active with 1 participant has been enrolled. Clinical trial information: ChiCTR2200063085 .

Dose expansion results of the bifunctional EGFR/TGFβ inhibitor BCA101 with pembrolizumab in patients with recurrent, metastatic head and neck squamous cell carcinoma.

6005 Background: Pembrolizumab (P) is approved to treat patients (pts) with recurrent, metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). BCA101 is a first-in-class bifunctional EGFR antibody fused to a TGFβ immune modulating payload which is well tolerated and has clinical activity as monotherapy and in combination with pembrolizumab in advanced solid tumors (ESMO 2022 731MO). Here we report the results from the interim analysis of an expansion cohort combining BCA101+P as first line therapy in R/M HNSCC. Methods: This ongoing single-arm, open-label multicenter dose expansion cohort enrolled pts with R/M HNSCC with a tumor PD-L1 CPS≥1 with no prior systemic therapy for R/M disease, ECOG 0-1, and measurable disease (RECIST v1.1). Pts received BCA101 (1500 mg IV on days 1, 8, 15) with P (200 mg IV on day 1) every 21-days. Primary endpoint: safety; secondary endpoints: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS). Exploratory: molecular and immunologic predictors of response. A Simon optimal two-stage design was employed: among 18 evaluable pts in stage 1, >3 pts in response triggered continuation to stage 2 enrolling 21 additional pts targeting an ORR>35%. Results: From 2/2022 to 1/2023, 20 pts enrolled while 18 were evaluable (had first restaging scans) in stage 1. Pts were more often men (n=13, 65%) with a median age of 66 (range: 31-77). Oropharynx (10, 50%) [7/10 (70%) were HPV/p16-pos] and oral cavity (7, 35%) were the most common primary subsites (larynx/hypopharynx: 3). Fifteen (75%) had distant metastatic disease. The ORR in stage 1 was 44% (8 PRs, 4 SD) with a clinical benefit rate (CBR=PR+SD) of 67%; 7/12 (58%) HPV-neg pts achieved a response. Median DOR not reached, but median time on-treatment was 6.7 months (range: 2.7-11.0+) among responders. Ten pts discontinued therapy; all but 1 for PD (n=1 for toxicity). Grade 3+ treatment-related adverse events (TRAEs) were observed in 4 pts (20%, most common: anemia). No treatment-related deaths were observed. Acneiform rash was the most common TRAE of any grade (15, 75%). PFS and OS estimates are forthcoming. Eight (44%) had baseline PD-L1 CPS scores of 0-19, while ten (56%) were ≥20. Stage 2 is actively enrolling with completion of accrual expected by the meeting. Conclusions: Stage 1 of this dose expansion cohort of BCA101+P shows encouraging anti-tumor activity with additive potential, particularly among HPV-neg pts; and the combination is well tolerated among this R/M HNSCC population. Further investigation is warranted. Study funded by Bicara Therapeutics and conducted in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. USA (NCT04429542). Clinical trial information: NCT04429542 . [Table: see text]

Impact of neighborhood disadvantage on stage at diagnosis and outcomes in women diagnosed with breast cancer.

e18603 Background: Low socioeconomic status (SES) has been associated with higher incidence of high-risk breast cancer and poorer outcomes. However, previous studies have inconsistent definitions of SES. Using a more comprehensive definition of SES via the Neighborhood Atlas, which calculates one's relative level of Neighborhood Disadvantage (ND) using 17 variables from American Community Survey and US Census data, may address this problem. We aimed to determine if higher level of ND is associated with later stage breast cancer at diagnosis and/or higher five-year recurrence rates. Methods: We performed a retrospective chart review study of 418 women that were diagnosed with breast cancer in 2015 within the Froedtert Health System in WI. Data collected included: patient characteristics (age, race, BMI, menopausal status, genetic status), tumor characteristics (tumor size, nodal status, metastases, ER/PR/HER2 status, histology, grade, date of diagnosis, self- detected vs. abnormal mammogram), treatments received (surgery, radiation, chemotherapy, endocrine therapy), and outcomes (type of recurrence, date of recurrence, date of death if applicable, last follow-up, etc.). Patient home addresses at the time of diagnoses were geocoded and inputted into the Neighborhood Atlas Mapping Tool to obtain 2015 ND values. Spearman’s rank correlation was used to evaluate the association between ND and TNM stage at diagnosis. Cox regression was used to evaluate the effect of ND on cause-specific hazard of recurrence. Significance value of < 0.05 was utilized. Results: The average age at diagnosis was 60 years and most women were post-menopausal (74%). Most patients had ER and/or PR-positive cancer (82% and 72% respectively) and 15% had HER2-positive disease. The average tumor size was 1.3cm (range 0-10). Node positive disease was seen in 104 women (25%) and 20 women (4.8%) had distant metastatic disease at diagnosis. Only 24 (5.7%) patients experienced disease recurrence within five years of diagnosis. The average National ND value was 36 (range of 4 to 100). ND was not significantly associated with stage at breast cancer diagnosis (p = 0.37) or five-year recurrence rates (p = 0.19). Conclusions: The average National ND value was not significantly associated with stage at breast cancer diagnosis or five-year recurrence rates. It is important to consider our study population demographics in the context of these results. The average National ND value was low at 36 which suggests an unequal representation of those living in disadvantaged areas compared to those living in more advantaged areas. Additionally, we were unable to draw strong conclusions on effects of ND on patient outcomes due to low number of recurrences seen. Future studies with larger sample size are likely needed to capture the possible impact of ND on patient outcomes.

Association of patient and tumor characteristics with outcomes in young patients with head and neck squamous cell carcinoma (HNSCC).

e18054 Background: HNSCC is increasingly being diagnosed in a younger population, with a variable prognosis. While studies have evaluated outcomes in young compared to older patients, evaluation of prognostic factors specifically in younger patients, that may help guide treatment decisions, is needed. Therefore, we conducted a retrospective study to investigate the association of patient and tumor characteristics with disease specific survival (DSS) in HNSCC patients ≤45 years old (yo). Methods: Patients treated at the University of Pittsburgh Medical Center from January 1, 2007 to June 30, 2020, that were ≤45 yo at time of diagnosis with HNSCC without distant metastatic disease, were included. Those who received treatments at other institutions and who had no follow-up after index treatments were excluded. Patient demographics, social history, tumor pathology and treatment course were collected. The primary endpoint of DSS was defined as the interval between the time of pathologic diagnosis and the time of cancer-related death. Proportional hazards regression was applied separately for surgically and non-surgically treated patients. A multivariate analysis was conducted for surgically treated patients only. Results: 230 patients were included. Median age was 42, 73% male, 45% oral cavity primary, 35% oropharynx (89% Human papillomavirus positive), 14% larynx, 69% were smokers, and 73% received combined modality therapy. 35% of patients had a recurrence with the majority locoregional only (61%). Median DSS was not reached. The 5 year DSS was 73% (95% CI 67% to 80%). There was no difference in DSS between surgically treated (n = 169) and non-surgically treated (n = 61, p = 0.94) patients. For surgically treated patients, univariate analysis showed significantly worse DSS in those with higher pathologic T and N stages, positive margins, perineural invasion (PNI), extranodal extension (ENE), and negative HPV status. For non-surgically treated patients, only negative HPV status was associated with significantly worse DSS (p = 0.034). In the multivariate analysis for surgical treated patients, which included all significant characteristics from univariate analysis, pathologic T and N stage, positive margins, (HR 4.92, 95% CI 1.98-12.25, p = 0.006) and PNI (HR 2.66, 95% CI 1.17-6.08, p = 0.02) were significantly associated with worse DSS. Conclusions: Pathologic T and N stage, positive margins, and PNI are independently associated with significantly worse DSS in surgically treated HNSCC patients aged ≤45. Compared with classic prognostic factors seen in the overall population with HNSCC, PNI may be a uniquely strong prognostic factor in younger-aged HNSCC patients.

Intralesional therapy, limb infusion/perfusion, and immune checkpoint inhibitors as first-line therapy in surgically unresectable melanoma in-transit metastases.

9574 Background: Surgery remains the gold standard for resectable melanoma in-transit metastases (ITM). Unresectable ITM is a heterogenous disease with multiple treatment (tx) options including systemic therapies such as immune checkpoint inhibitors (ICI), regional therapies such as isolated limb infusion or perfusion (ILI/P), and intratumoral therapies such as talimogene laherparepvec (IT). Until now, there has been no direct comparison of these first-line tx for unresectable ITM. Methods: A retrospective chart review of patients (pts) with ITM treated first-line with IT, ILI/P, or ICI was performed at 11 institutions. Pts with unresectable ITM, synchronous nodal or distant metastatic disease were excluded. Results: 560 pts (54% women) were identified, 86 received IT, 353 received ILI/P, and 121 received ICI from 1990-2022. ICI pts were youngest, IT pts were oldest (p<0.001). Limb was the most common site of ITM. There was no difference in largest ITM size, but number of lesions (burden of disease (BOD)) was highest in ILI/P pts and lowest in IT pts (p=0.003). Toxicity (tox) requiring <90 days (p<0.001) or > 90 days (p=0.034) of pharmacologic tx as well as tox requiring hospitalization (p<0.001) was greatest in ICI pts. Lymphedema was more likely in ILI/P pts (p=0.016). Median follow-up was much longer for ILI/P pts at 8.0 yrs compared to 2.5 yrs for IT pts and 3.1 yrs for ICI pts. Overall response rate (ORR) was 82.2% in ILI/P pts, significantly higher than IT (72.1%, p=0.047) or ICI pts (63.6%, p<0.001). Overall survival was similar between modalities (p=0.167); however, ILI/P pts had worse progression-free survival (PFS) (p<0.0001) and melanoma-specific survival (MSS) (p=0.003). On multivariable analysis of MSS by number of ITM present, MSS remained worst if ILI/P was used for low BOD, ≤3 ITM (p=0.005), but no difference was seen between tx modalities for higher BOD, >3 ITM (p=0.211). Conclusions: ICI was used more often in younger pts with less BOD, IT in older pts with less BOD, and ILI/P in older pts with high BOD. Short and long-term tox was greater in ICI. ILI/P had the best ORR, but ICI and IT resulted in greater overall MSS. Multidisciplinary consideration of risks and benefits of each modality should guide ITM tx selection. [Table: see text]

Influence of adherence to adjuvant endocrine therapy in early breast cancer: Results from a large German real-world claims data analysis.

551 Background: In hormone-receptor positive (HR+) early breast cancer (EBC) adjuvant endocrine therapy (ET) significantly reduces recurrence and mortality. The most common way to estimate therapy adherence is the use of patient reported outcome measures. Yet, this method is inaccurate due to the social-desirability bias. We therefore aimed to analyze adherence to ET over the first 5 years of treatment by using claims data from a large German health insurance provider (AOK Baden-Wuerttemberg). Methods: Female patients diagnosed with HR+ EBC between July 1st 2010 and December 31st 2019 were included into the analysis. Adherence to ET was defined as the ratio of the summed number of pills of filled prescriptions for ET (either aromatase inhibitors or tamoxifen) and the duration of endocrine therapy in days (from the start of the first prescription after completion of surgery and chemotherapy, if applicable). ET administration was observed over 5 years. High/low adherence was defined as a ratio between 0.8 – 1 and 0 – 0.8, respectively. ET duration was divided into yearly intervals and adherence was calculated as above. Continuous high/low adherence was then defined as an adherence between 0.8 – 1 and 0 – 0.8 in each year. Distant recurrence-free survival (DRFS) was calculated from the day of the first diagnosis of EBC until onset of distant metastatic disease. Overall survival (OS) was defined as the period between first diagnosis of EBC until death. Results: In total, 20998 patients were included. 17006 patients (81%) were HR+. Regarding overall adherence during the first 5 years, average adherence was 0.81 ± 0.26, with 72% of all HR+ patients showing high adherence to ET. Of 17006 HR+ EBC patients, 8363 (49%) showed a continuous high adherence to ET and 1731 (10%) showed a continuous low adherence to ET over 5 consecutive years. Continuous adherence to endocrine therapy had a significant impact on DRFS (HR: 0.61; 95% CI: 0.52 - 0.71; p < 0.0001) and OS (HR: 0.52; 95% CI: 0.46 -0.59; p < 0.0001). The 10-year OS rate was 79% / 64% for patients with continuous high / low adherence to endocrine therapy. Conclusions: As measured by the number of prescribed pills, adherence during the first 5 years of endocrine therapy was higher than expected by literature. Continuous adherence to ET over 5 years has a significant impact on OS and DRFS. Future research should focus on identifying factors that influence therapy adherence in HR+ EBC patients.

A phase Ib study of endogenous T cell therapy using SLC45A2-specific CD8 T cells for patients with metastatic uveal melanoma.

9588 Background: Overall survival (OS) for patients (pts) with advanced uveal melanoma (UM) is poor compared with outcomes in cutaneous melanoma. Roughly half of all pts with UM will develop distant metastatic disease despite effective treatment of the primary tumor. Antigen-specific endogenous T cells (ETC) can be expanded and infused successfully in pts with many different types of cancer. Our group has identified epitopes of SLC45A2, a melanosomal transport protein, which are highly expressed in UM and are present at low levels in normal melanocytes. In vitro, we showed that cytotoxic T cells against SLC45A2 were able to kill HLA-matched UM cell lines. In vivo, we hypothesize that infused ETC can traffic to tumor sites. Methods: Between 6/2017 and 12/2022, we conducted a single-center, IRB-approved, first-in-human phase 1b dose escalation study of ETC targeting SLC45A2 in pts with metastatic UM (NCT03068624). Eligible pts with metastatic UM who express HLA-A*02:01 or A*24:02 underwent apheresis to collect peripheral T cells which were then selected and expanded (Turnstile 1). For Turnstile 2, conditioning with low-dose cyclophosphamide (300 mg/m2) occurred on Day -2. For pts in the radiation cohort, radiation occurred between Day -7 and Day -1. Infusion of ETC was done via hepatic arterial or central venous catheter on Day 0 followed by low dose subcutaneous interleukin-2 (IL-2) twice daily for 14 days +/- ipilimumab. The study utilized a 3+3 design with a starting dose level of 3.3 x 109 cells/m2 of ETC alone. The primary objective was to evaluate the safety and tolerability of infusing ETC targeting SLC45A2. Secondary objectives were to evaluate the in vivo persistence and anti-tumor efficacy of this regimen. Results: With a median age of 58 years (30-77), 34 pts were enrolled, 16 (47%) men and 18 (53%) women. 33 (97%) pts underwent apheresis and 11 (32%) received infusion of ETC. One dose limiting toxicity (DLT) thought to be unrelated to treatment or underlying cancer (cardiac disorder Grade 5) occurred at the starting dose level with no additional DLTs. The maximum tolerated dose was established as 1 x 1010 cells/m2. The most common treatment-related grade 3 and 4 toxicities were lymphocyte count decrease 9 (82%), hyponatremia 1 (9%), and hypophosphatemia 1 (9%). Per immune-related response criteria (irRC), 4 (36%) pts had stable disease (SD), 6 (55%) had progression of disease (PD), and 1 (9%) was not evaluable for best response. Median overall survival (OS) was 8.9 weeks (wks). OS was 91% at 4 wks, 55% at 8 wks and 46% at 13 wks. Median progression-free survival was 5.9 wks. In the 4 patients with stable disease, the median duration of SD was 5.7 months. Conclusions: ETC targeting SLC45A2 is safe and well-tolerated in pts with metastatic UM. Further analyses are underway to evaluate T cell trafficking and persistence. Clinical trial information: NCT03068624 .

Survival of patients with solid tumors and sepsis admitted to intensive care in a tertiary oncology center: A retrospective analysis.

6586 Background: Sepsis is a life threatening organ dysfunction caused by a dysregulated host response to infection. Patients with cancer are at high risk of developing sepsis and requiring admission to the intensive care unit (ICU). Patients with cancer and sepsis have been found to have worse survival than non-cancer patients, with 90 day survival for cancer patients ranging from 28% to 72%. Survival differs between studies due to multiple factors including variably mixed haemato-oncology and solid tumor cohorts and varying definitions of sepsis. Our objectives were to accurately assess short, medium and long term survival of patients admitted to ICU with a solid tumor and sepsis and to identify the best predictors of 90 day survival at admission. Methods: We conducted a retrospective cohort survival analysis. We identified adults (aged 18 years and over) admitted to ICU with sepsis and a solid tumor between 1st January 2011 and 31st December 2020 at a tertiary oncology center with hospitals at two sites (London and Surrey, United Kingdom). We defined sepsis using the Sepsis-3 definition. The primary outcome was 90 day survival, but we also calculated 30 day, 180 day, 1 year and 5 year survival. Survival was calculated excluding patients lost to follow up. Univariate and multivariate analyses were undertaken to identify factors that differed between survivors and non-survivors at day 90. We used the parametric accelerated failure time model for multivariate analysis to generate time ratios (TR). Results: 625 patients were identified, with 131 patients lost to follow up by 5 years. The median age was 64 years (Interquartile Range 54-71) and 56% were male. 84.8% (530/625) survived to ICU discharge. The 30, 90 and 180 day survival rates were 72% (439/610), 59.5% (353/593) and 51.7% (300/580) respectively. 1 year survival was 38.7% (221/571) and 5 year survival 8.1% (40/494). Multivariate analysis identified the presence of localized (TR 7.85, 95% CI 4.00 -15.41) or regionalized disease (TR 4.71, 95% CI 2.74-8.08) compared to distant metastatic disease, surgery on the day of admission (TR 6.78, 95% CI 3.24-14.19), lactate (TR 0.80, 95% CI 0.74-0.87), SOFA score (TR 0.84, 95% CI 0.79-0.89), previous radiotherapy (TR 0.53, 95% CI 0.32-0.88), previous medical cancer treatment (TR 0.67, 95% CI 0.42-1.07), bacteremia (TR 2.14, 95% CI 1.25-3.64) and albumin (TR 1.06, 95% CI 1.02-1.10) as independent predictors of 90 day survival. Conclusions: This study of solid tumor patients admitted to ICU is one of the largest to date with the longest follow up period, providing up to date survival data to inform clinicians and patients. Patients with solid tumors and sepsis admitted to ICU have short and medium term survival rates comparable to non-cancer populations and therefore the presence of cancer should not prevent ICU admission. Prior oncological therapies may affect survival in patients admitted to ICU with sepsis.

Diagnosis of high-grade prostate cancer in patients with unexpectedly low prostate specific antigen levels: a rare case series

Link of Video Abstract: https://youtu.be/PfhZ7H4kszQ Background: Prostate cancer is regarded as one of the most common leading causes of male cancer-related death worldwide. Clinicians agree that prostate specific antigen (PSA) is the best prostate cancer predictor. High PSA levels increase prostate cancer risk in most men. However, other research suggests that prostate cancer with low PSA levels is aggressive. In this uncommon case series, we present three high-grade prostate cancer patients with low PSA. Case Description: Between 2018 and 2019, three patients were referred for further therapeutic management after initial evaluation and treatment from secondary hospitals. All patients underwent complete diagnostic procedures including Laboratory examination, Pathological examination, and Radiologic imaging. PSA levels were 0.67 ng/mL, 4.0 ng/ml, and 4.93 ng/mL in the first, second, and third patients, respectively. The first two of three patients had a Gleason score (GS) of 9 (5+4), and one patient presented with GS of 8 (5+3). Distant metastatic disease was not found in our series. All of the patients underwent hormonal therapy, and none of them underwent radical prostatectomy. Follow-ups were completed in all patients, with the survival of 3 months, 4 months, and 12 months respectively. Conclusion: High-grade prostate cancer in patients with low PSA levels emphasizes the need for rigorous history taking and physical examination and quick investigation of new biomarkers and criteria for prostate cancer detection. These patients' prognosis and optimal therapy are unknown. These patients have a worse prognosis than those with high PSA values, according to multiple studies.

Approach to risk stratification for papillary thyroid carcinoma based on molecular profiling: institutional analysis

Currently, treatment recommendations for papillary thyroid carcinoma are not based on the genetic background causing tumourigenesis. The aim of the present study was to correlate the mutational profile of papillary thyroid carcinoma with clinical parameters of tumour aggressiveness, to establish recommendations for risk-stratified surgical treatment. Papillary thyroid carcinoma tumour tissue of patients undergoing thyroid surgery at the University Medical Centre Mainz underwent analysis of BRAF, TERT promoter and RAS mutational status as well as potential RET and NTRK rearrangements. Mutation status was correlated with clinical course of disease. One hundred and seventy-one patients operated for papillary thyroid carcinoma were included. The median age was 48 years (range 8-85) and 69 per cent (118/171) of patients were females. One hundred and nine papillary thyroid carcinomas were BRAF-V600E mutant, 16 TERT promotor mutant and 12 RAS mutant; 12 papillary thyroid carcinomas harboured RET rearrangements and two papillary thyroid carcinomas showed NTRK rearrangements. TERT promoter mutant papillary thyroid carcinomas had a higher risk of distant metastasis (OR 51.3, 7.0 to 1048.2, P < 0.001) and radioiodine-refractory disease (OR 37.8, 9.9 to 169.5, P < 0.001). Concomitant BRAF and TERT promoter mutations increased the risk of radioiodine-refractory disease in papillary thyroid carcinoma (OR 21.7, 5.6 to 88.9, P < 0.001). RET rearrangements were associated with a higher count of tumour-affected lymph nodes (OR 7950.9, 233.7 to 270495.7, P < 0.001) but did not influence distant metastasis or radioiodine-refractory disease. Papillary thyroid carcinoma with concomitant BRAF-V600E and TERT promoter mutations demonstrated an aggressive course of disease, suggesting the need for a more extensive surgical strategy. RET rearrangement-positive papillary thyroid carcinoma did not affect the clinical outcome, potentially obviating the need for prophylactic lymphadenectomy.

An Expanded Series of Pilomatrix-like High-grade Endometrioid Carcinoma (PiMHEC), Including Both MMR Deficient and MMR Proficient Cases.

An Expanded Series of Pilomatrix-like High-grade Endometrioid Carcinoma (PiMHEC), Including Both MMR Deficient and MMR Proficient Cases.

Omitting hemicolectomy for patients with appendiceal neuroendocrine tumours of 1–2 cm

Omitting hemicolectomy for patients with appendiceal neuroendocrine tumours of 1–2 cm

Abscopal responses in patients with metastatic melanoma involving skin and subcutaneous tissues treated with intralesional IL2 plus BCG.

Cutaneous melanoma is relatively common with increasing incidence and significant mortality. While the mainstay of therapy is surgical, patients with stage III and IV disease fare poorer than those with early-stage disease and often benefit from adjuvant therapies. While systemic immunotherapy has changed the landscape of melanoma treatment, for some patients systemic toxicities related to these treatments prohibit successful administration or completion of therapy. Moreover, it is becoming increasingly evident that nodal, regional, and in-transit disease appears to be resistant to systemic immunotherapy relative to responses observed in distant metastatic disease sites. In this scenario, intralesional immunotherapies may offer benefit. In this case series, we describe the use of intralesional IL-2 and BCG at our institution in ten patients with in-transit plus or minus distant cutaneous metastatic melanoma over the last twelve years. All patients received intralesional IL2 and BCG. Both treatments were very well tolerated with only grade 1/2 adverse events. In our cohort, complete clinical response was 60% (6/10), progressive disease in 20% (2/10), and no response in 20% (2/10) of patients. The overall response rate (ORR) was 70%. The median overall survival was 35.5 months and mean overall survival 43 months in this cohort. Herein we further highlight the clinical, histopathological, and radiological course of two complete responders, showing evidence of an abscopal effect with resolution of distant untreated metastasis. Together, this limited data supports the safe and effective use of intralesional IL2 and BCG for the treatment of metastatic or in-transit melanoma in this challenging patient cohort. To our knowledge, this is the first formal study to report on this combination therapy for the treatment of melanoma.

Health services costs for ovarian cancer in Australia: Estimates from the 45 and Up Study.

There have been significant advancements in risk identification and treatment for ovarian cancer over the last decade. However, their impact on health services costs is unclear. This study estimated the direct health system costs (government perspective) for women diagnosed with ovarian cancer in Australia during 2006-2013, as a benchmark prior to opportunities for precision-medicine approaches to treatment, and for health care planning. Using cancer registry data, we identified 176 incident ovarian cancers (including fallopian tube and primary peritoneal cancer) in the Australian 45 and Up Study cohort. Each case was matched with four cancer-free controls on sex, age, geography, and smoking history. Costs were derived from linked health records on hospitalisations, subsidised prescription medicines and medical services to 2016. Excess costs for cancer cases were estimated for different phases of care relative to cancer diagnosis. Overall costs for prevalent ovarian cancers in Australia in 2013 were estimated based on 5-year prevalence statistics. At diagnosis, 10% of women had localised disease, 15% regional spread and 70% distant metastasis (5% unknown). The mean excess cost per ovarian cancer case was $40,556 in the initial treatment phase (≤12 months post-diagnosis), $9,514 per annum in the continuing care phase and $49,208 in the terminal phase (up to 12 months before death). Hospital admissions accounted for the greatest proportion of costs during all phases (66%, 52% and 68% respectively). Excess costs were higher for patients diagnosed with distant metastatic disease, particularly during the continuing care phase ($13,814 versus $4,884 for localised/regional disease). The estimated overall direct health services cost of ovarian cancer in 2013 was AUD$99million (4,700 women nationally). The excess health system costs of ovarian cancer are substantial. Continued investment in ovarian cancer research, particularly prevention, early detection and more effective personalised treatments is necessary to reduce the burden of disease.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

Prognostic impact of increased lymph node yield in colorectal cancer patients with synchronous liver metastasis: a population-based retrospective study of the US database and a Chinese registry.

The National Quality Forum has endorsed at least 12 lymph node yield (LNY) as a surgical quality indicator in colorectal cancer (CRC), but the prognostic value of adequate lymphadenectomy has rarely been investigated for CRC patients with distant metastatic disease. A total of 4575 CRC patients with synchronous liver metastasis who underwent primary tumor resection were identified from a Chinese registry and the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The Kaplan-Meier methods and Cox regression models were performed to assess the correlations between LNY and 3-year cancer-specific survival (CSS). Propensity score matching were used to confirmed the survival comparison between patients with less than 12 and of at least 12 LNY. The retrieval of at least 12 LNY was identified in most CRC patients (SEER database, 3380/3899, 86.7%; Chinese cohort, 565/676, 83.6%). In both the SEER database and the Chinese cohort, the patients with LNY ≥12 was significantly associated with better CSS compared with patients with LNY <12 before and after propensity score matching, with all P -value less than 0.05. After controlling for the confounders, multivariate analysis demonstrated that LNY was also an independent prognostic factor for patients with distant metastasis in both cohorts. In subgroup analysis, the CSS benefit for patients with LNY ≥12 was observed across most of the subgroups. Clinical feasibility of the 12-node threshold as a guideline quality metric of cancer care for CRC patients is necessary, and an oncologically adequate lymphadenectomy is still a critical component of high-quality surgical standard in CRC patients with distant metastases.

Head and neck mucosal melanoma: radiological considerations and UK imaging guidelines.

Awareness of head and neck mucosal melanoma (HNMM) is important, as incorrect work-up can impact on the investigation and management of this rare and aggressive cancer. Following on from the 2020 HNMM UK guidelines, we set out the imaging recommendations and their rationale. To illustrate the key imaging characteristics, we also include a case series from our centre. All HNMM cases managed at our institution from January 2016 to January 2021 were identified, and the available imaging for each patient was reviewed. For each patient, the age, gender and location of primary tumour was recorded together with key staging and diagnostic imaging parameters. A total of 14 patients were identified. The median age was 65years with a female to male ratio of 1.33:1. Primary tumours were sinonasal in location in 93% of cases, with 7% of patients having metastatic neck nodes at presentation and 21% of cases having distant metastatic disease at presentation. This data set is in general concordance with other published series regarding the sinonasal origin of the vast majority of HNMM tumours along with the proportion of patients with metastatic neck nodes and distant metastases at presentation. We recommend dual-modality imaging with computed tomography (CT) and magnetic resonance imaging (MRI) of primary tumours whenever possible. In the systematic staging of HNMM, positron emission tomography (PET)-CT should be strongly considered, together with MRI of the brain. Pre-biopsy imaging of HNMM tumours is advisable whenever possible.

Incidental Meningioma With Altered PSMA Expression After Systemic Hormone Therapy and Local Radiotherapy Detected by 68Ga-PSMA PET/CT.

A 59-year-old man underwent radical prostatectomy for adenocarcinoma in 2009. Because of the progression of PSA levels, a 68Ga-PSMA PET/CT scan was performed in January 2020. A suspicious uptake was detected in the left cerebellar hemisphere, and there was no evidence of distant metastatic disease other than recurrent malignancy in the prostatectomy bed. MRI revealed a meningioma located in the left cerebellopontine angle. Although PSMA uptake of the lesion increased in the first imaging after hormone therapy, partial regression was noted after radiotherapy applied to this region.

MP33-11 P16 STATUS IS AN INDEPENDENT PREDICTOR OF OVERALL SURVIVAL IN METASTATIC PENILE CANCER IN A LARGE CONTEMPORARY COHORT

You have accessJournal of UrologyCME1 Apr 2023MP33-11 P16 STATUS IS AN INDEPENDENT PREDICTOR OF OVERALL SURVIVAL IN METASTATIC PENILE CANCER IN A LARGE CONTEMPORARY COHORT James Churchill, Ashwin Sachdeva, Craig Jones, Allaudin Issa, Christian Fankhauser, Andrew Hudson, Anna Tran, Pedro Oliveira, Helen Johnson, Maurice Lau, Arie Parnham, and Vijay Sangar James ChurchillJames Churchill More articles by this author , Ashwin SachdevaAshwin Sachdeva More articles by this author , Craig JonesCraig Jones More articles by this author , Allaudin IssaAllaudin Issa More articles by this author , Christian FankhauserChristian Fankhauser More articles by this author , Andrew HudsonAndrew Hudson More articles by this author , Anna TranAnna Tran More articles by this author , Pedro OliveiraPedro Oliveira More articles by this author , Helen JohnsonHelen Johnson More articles by this author , Maurice LauMaurice Lau More articles by this author , Arie ParnhamArie Parnham More articles by this author , and Vijay SangarVijay Sangar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Penile squamous cell carcinoma (PSCC) is rare and there is a need to refine selection of patients for optimal management. Human papilloma virus infection is a known PSCC risk factor, measured by the histopathological presence of the p16 protein. This study has examined effect of p16 status on overall survival (OS) of PSCC patients managed at a tertiary referral centre. METHODS: We analysed retrospective data from a prospectively maintained database for patients with PSCC treated between 2003 and 2022. We excluded patients without reported p16 status. TNM stage was defined by histopathology (AJCC v8) except where fixed inguinal nodes (cN3), pelvic lymphadenopathy (cN3) or distant metastatic disease (M1) were present without histopathological confirmation. The primary outcome was OS (time from definitive primary surgery to death, censored for last follow-up). Multivariate Cox regression analysis for age, p16 status, TNM-stage and grade was performed. Audit approval was obtained. RESULTS: We identified 470 eligible patients. Median follow-up was 28 months (range 0-265). 118 patients (25%) did not undergo invasive lymph node staging (pNX). For the whole cohort, p16+ patients demonstrated 10% greater 5-year OS compared to p16- (71% versus 61%; Figure 1). After multivariate analysis (Table 1), there remained a significant difference in OS with 40% reduction in the risk of death for p16+ patients compared to p16-. On exploratory analysis by stage, only the N1 group retained this difference, suggesting that this is the group where p16 status may be of most clinical impact. CONCLUSIONS: Our data demonstrate that p16+ predicts for improved OS compared to p16- status in PSCC patients. After adjusting for age, stage and grade, this difference was retained in patients with N1 disease, suggesting that p16 status could be further explored as a predictive biomarker in this group. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e454 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Churchill More articles by this author Ashwin Sachdeva More articles by this author Craig Jones More articles by this author Allaudin Issa More articles by this author Christian Fankhauser More articles by this author Andrew Hudson More articles by this author Anna Tran More articles by this author Pedro Oliveira More articles by this author Helen Johnson More articles by this author Maurice Lau More articles by this author Arie Parnham More articles by this author Vijay Sangar More articles by this author Expand All Advertisement PDF downloadLoading ...