Systemic complement protein levels as biomarkers of chemoradiotherapy response in anal squamous cell carcinoma.

Long-term outcome of patient choice of surgery or active surveillance following a clinical complete response to neoadjuvant chemoradiotherapy for oesophageal cancer.

Health-related Quality of Life Outcomes of Salvage Metastasis-directed Treatment Versus Elective Nodal Treatment for Oligorecurrent Nodal Prostate Cancer: A Secondary Analysis of the Phase 2, Open-label PEACE V-STORM Randomized Trial.

Abstract Background: The incidence of metastatic gastric cancer among young adults is rising and has a dismal prognosis with 5-year survival of only 4%. Little is known about the clinicopathologic features associated with metastatic vs locoregional disease in young adults compared to older adults. Methods: This retrospective case control study evaluated patients treated for gastric cancer at USC Norris Comprehensive Cancer Center and LA General Hospital from 2000-2022. Sociodemographic characteristics, clinical presentation and tumor features were compared for early-onset (EO; age <50 years) cases and typical onset (TO; >50 years) controls in a 1:2 ratio matched by diagnosis year and facility. All analyses were performed within matched sets, with three samples per set. Using conditional logistic regression to estimate odds ratios, the pooled analysis tested whether there is an association between sociodemographic, clinical and tumor characteristics and metastatic vs locoregional presentation in aggregate. The early versus older onset analysis examined whether these associations differ by onset type, in terms of either the direction or the magnitude of the association. Results: 795 patients were evaluable (265 EO, 530 TO). Hispanic patients are more likely to present with metastatic disease compared to Asian (OR=2.22, 95%CI 1.34-3.70, p=0.002). Non-Hispanic White are more likely to present with metastatic disease compared to Asian (OR=2.97, 95%CI 1.61-55.48, p<0.001). This association did not differ by EO vs TO. There was no difference in stage at presentation by sex, BMI, primary location of tumor or H. pylori status of the tumor. Overall, patients with intestinal histologic compared to diffuse histologic characteristics are less likely to present with metastatic disease (OR=0.30, 95%CI 0.11-0.85, p=0.023). This association does not differ between EO and TO (p=0.48). There was no difference in the association between MSI status and metastatic disease by EO vs TO (p=0.54). Patients with HER2 amplified status are more likely to present with metastatic disease compared to patients with non-amplified HER2 (OR=2.97, 95%CI 1.25-7.09, p=0.014); however, there was no difference in risk between EO vs TO (p=0.87). Patients with a negative endoscopy prior to diagnosis (16% EO, 18% TO) were equally likely to present with locoregional or metastatic disease (p=0.91). There was no difference in association between metastatic disease and smoking or alcohol use (p=0.069, p=0.64 respectively). Conclusions: Early detection of gastric cancer, especially in non-Asian communities, is crucial as they are more likely to present with metastatic disease. The similarities in disease presentation and characteristics between early vs older onset patients suggests unmeasured environmental exposures may be associated with adverse biological features driving the rising incidence of metastatic disease in young adults. Deeper molecular characterization of metastatic vs locoregional patients may identify other factors contributing to poor outcomes. Citation Format: Jessica Sheth Bhutada, Fox Bravo, Maureen Cairns, Qi Nie4, Ruopei Wu, Danielle Estell, Arthur Bookstein, Justine Po, Myles Cockburn, Chanita Hughes Halbert, Syma Iqbal, David Freyer. Clinicopathologic features associated with metastatic early-onset gastric cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B031.

Dermal metastasis from head and neck squamous cell carcinoma (HNSCC) is a rare and poorly understood manifestation of advanced disease, historically linked to poor prognosis. This systematic review aims to better characterize the clinical associations, treatment paradigms, and survival outcomes associated with this entity. PubMed, Embase, and Scopus databases were systematically searched through May 1, 2025. The protocol was registered on PROSPERO, and the systematic review was reported in accordance with PRISMA guidelines. Patient-level data on demographics, disease characteristics, treatments, and survival outcomes were extracted from cases, and pooled analyses were conducted using logistic regression, Kaplan-Meier survival estimates, and Cox proportional hazards regression. Seventy-eight studies comprising 279 cases were included. Most patients were male (83%). The majority had advanced-stage primary disease (87%) originating in the oral cavity (42%), larynx (21%), and oropharynx (18%). Dermal metastases most often affected the neck (57%) or trunk (23%). Median survival following diagnosis was 3.5 months. The receipt of treatment was independently associated with a 45% lower hazard of death compared with no treatment (HR: 0.55; 95% CI: 0.32-0.96; p = 0.036), although no individual modality conferred a significant survival advantage. Primary tumor characteristics, anatomical location of dermal lesions, and the presence of locoregional or distant metastatic disease were not predictive of survival. Dermal metastasis from HNSCC signifies aggressive disease with limited survival. These findings underscore the importance of individualized patient counseling and the need for further research into effective therapeutic strategies.

Prognostic Differences in Melanoma Between Patients With Locoregional Disease at Initial Diagnosis and Those Who Develop Locoregional Disease After Progression During Follow-Up.

Talimogene laherparepvec (T-VEC) is an oncolytic virus that is hypothesized to enhance responses to systemic therapy. This Phase 1b trial evaluated the safety and efficacy of intratumoral T-VEC plus chemotherapy (CT) or endocrine therapy (ET) for patients with hormone receptor positive (HR + )/HER2- and triple negative (TN) advanced breast cancer (ABC) with injectable locoregional/chest wall disease. The primary endpoint was safety/tolerability. Secondary endpoints were objective response rate by irRECIST 1.1 and clinical assessment of local response. 19 patients enrolled (9 HR + /HER2-; 10 TN; median two lines of prior CT). Intratumoral T-VEC was administered with the following partners: gemcitabine/carboplatin (n = 8), nab-paclitaxel (n = 7), paclitaxel (n = 2), or ET (n = 2). Eight patients in the T-VEC + gemcitabine/carboplatin arm were formally evaluated for dose limiting toxicities (DLTs) based on pre-specified protocol criteria, and one DLT (grade 3 neutropenia leading to carboplatin dose reduction) was identified. Response per irRECIST 1.1 was evaluated in 16 patients: partial response (n = 2, 12.5%), stable disease (n = 7, 43.8%), progressive disease (n = 7, 43.8%). Patients with higher pre-treatment tumor infiltrating lymphocytes (TILs) were more likely to respond, and clinical responders had induction of Ki-67 in multiple peripheral myeloid populations. In conclusion, the addition of intratumoral T-VEC to CT or ET was safe in patients with ABC and injectable locoregional disease, supporting the continued investigation of direct intratumoral immunomodulatory strategies that can enhance local and systemic immune responses. NCT03554044.

Radiation Therapy for Gastric Cancer: An ASTRO Clinical Practice Guideline.

ACR Appropriateness Criteria® Screening, Locoregional Assessment, and Surveillance of Pancreatic Ductal Adenocarcinoma: 2025 Update.

Background: Treatment of oral cavity cancer includes surgery, radiotherapy (RT), chemotherapy, and immunotherapy. Surgery followed by adjuvant RT plays an important role in patients with intermediate risk factors but many studies showed locoregional failure following adjuvant RT alone. Elevated epidermal growth factor receptor (EGFR) expression is detected in 90% of patients with head and neck squamous cell carcinoma (SCC). Aims and Objectives: The objective of this study was locoregional disease control, toxicities, disease-free survival (DFS), and OS between post-operative only RT and concurrent cetuximab (CP) with RT in oral cavity SCC with intermediate risk factors. Materials and Methods: Arm A received adjuvant RT at a dose of 60 Gy by 30 fractions, total 6 weeks duration. In study arm B received the same dose of adjuvant RT as study arm A along with concomitant injection of cetuximab at a dose of 400 mg/m2 prior to start of RT and then 250 mg/m2 weekly. Results: In arm A, 14 (56.0%) and arm B, 14 (56.0%) patients had anterior 2/3rd of tongue and buccal mucosa cancer, respectively. In arm A, 15 (60.0%) and arm B, 12 (48.0%) patients had pT2 status, respectively. There was no rash in arm A but 9 (36%) patients developed rash in arm B. DFS at 12 months was higher in CP arm B compared to arm A but not statistically significant. Conclusion: This study showed addition of CP to RT improved LRC with increased and manageable adverse effects.

Background: Patients with locally advanced head and neck cancer, specifically those with high-risk features like margin-positive resection or extracapsular nodal extension, have high recurrence rate following surgery alone. There are limited data available in the literature on adjuvant chemoradiation with weekly cisplatin versus docetaxel and cetuximab in patients with post-operative high-risk head and neck squamous cell carcinoma (HNSCC) in Eastern India. Aims and Objectives: The Objectives of this study were to compare loco-regional disease control, toxicities, progression-free survival, and distant metastasis-free survival (DMFS) between adjuvant chemoradiation with weekly cisplatin versus docetaxel and cetuximab in post-operative-high-risk HNSCC. Materials and Methods: About 30 patients in ARM-1 received weekly cisplatin with concurrent radiotherapy, and 30 patients in ARM-2 received weekly docetaxel and cetuximab with concurrent radiotherapy. Radiation dose was 66 Gy in 33 fractions in each arm. Results: In ARM-1, 19 (63.3%) patients had grade 2, and 6 (20.0%) patients had grade 3 mucositis. In ARM-2, 10 (33.3%) patients had grade 2, and 19 (63.3%) patients had grade 3 mucositis. In ARM-1, 3 (10.0%) and ARM-2, 18 (60.0%) patients had a rash. In ARM-1, 2 (16.7%) and ARM-2, 1 (5.3%) patients had metastasis, and in ARM-1, 10 (83.3%) and ARM-2, 18 (94.7%) patients had achieved DMFS of 15 months. Conclusion: Loco-regional failure-free survival at 12th months shows statistical significance in favor of ARM-2. Cetuximab plus docetaxel may be established as a treatment option as concurrent chemotherapy with radiation at the adjuvant setting in head and neck carcinoma, especially in situations where cisplatin is contraindicated or difficult to administer.

Abstract Introduction/Objective Adenoid cystic carcinoma (ACC) of the Bartholin gland is an exceptionally rare malignancy, comprising of approximately 0.1% to 5% of vulvar cancers. Its indolent and unpredictable behavior presents unique management challenges. Methods/Case Report We report a case of a 63-year-old female diagnosed with ACC of the Bartholin gland resected 11 years earlier. The patient experienced two local recurrences, each managed with surgical re-resection. During a routine follow up surveillance computed tomography (CT), multiple bilateral pulmonary nodules were identified; positron emission tomography (PET) imaging showed low metabolic activity in the nodules with no evidence of additional disease. Electromagnetic navigation (EMN) guidance fine needle aspiration of a left upper lobe nodule showed basaloid cells consistent with ACC; the concurrent biopsy confirmed metastatic ACC. Results NA Conclusion This case highlights the potential for delayed hematogenous spread of Bartholin gland ACC, even in the absence of ongoing locoregional disease. Given its propensity for late distant metastasis, particularly to the lungs, prolonged surveillance is essential.

BackgroundA significant minority of patients in high income countries with symptomatic mucosal head and neck squamous cell carcinomas (HNSCC) warrant treatment of their locoregional disease but are not suitable for standard high dose radiation therapy (RT) with or without concurrent chemotherapy. This study aimed to determine the factors associated with locoregional control (LRC) and survival for patients undergoing high dose palliative-intent RT, to help improve patient selection for this treatment approach.Materials and methodsThis retrospective cohort study included all patients with HNSCC who received high dose RT (50–55 Gy in 20 fractions over 4 weeks) with palliative-intent from 2007–2024 at an academic Australian cancer centre.Results53 patients comprised the study cohort, of which 92% completed the prescribed RT in full. Median overall survival was 21.6 months and in-field LRC at 12-months was 80%. Acute toxicities were low [Common Terminology Criteria for Adverse Events (CTCAE) grade 3 mucositis 17%, local pain 6.5%, and dysphagia 4.4%, with no grade 4–5 toxicities], with resolution of majority by six months post RT (7% grade 2, no grade 3 or higher toxicities). Larger primary tumours (T3 or T4) and more advanced stage disease [American Joint Committee on Cancer (AJCC) stage III–IV, 8th edition] were associated with worse in-field LRC.ConclusionsHigh dose palliative-RT in patients with mucosal HNSCC not suitable for definitive chemoradiotherapy provided durable local control with low toxicities after 12 months. In-field locoregional failures were more likely for more advanced disease.

Disclosure: H. Ali: None. S. Bajwa: None. B. Agrawal: None. U. Bajwa: None. A. Imran: None. F. Cavdar: None. K. Pereira: None. K. Desai: None. S. Durugu: None. R. Thirumaran: None.Background: Paragangliomas (PGL) are rare neuroendocrine tumors of autonomic ganglia. Sporadic cases are common in women while hereditary cases are commonly seen with MEN2 A&B, neurofibromatosis type 1 and VHL disease. Metastasis, rather than histology, affirms the diagnosis of malignant paraganglioma. Surgery is the first line of treatment, while metastatic or extensive disease may require radiation or chemotherapy. The purpose of this study is to determine epidemiological trends and factors affecting survival in PGL. Methods: Data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2023 Sub (2000-2021), using the ICD Code 8680/3 for malignant paraganglioma. The analysis was stratified based on age, sex, race, stage, laterality, primary site labelled, median household income inflation adjusted to 2022, various treatment modalities, and analyzed using the Log-Rank test (GraphPad Prism). Results: Total 550 cases of PGL were identified, of which 47.27% were males and 52.73% were females. The median age of diagnosis was 50 years. Racial distribution was observed as: 60.73% Caucasians, 17.09% Blacks, 13.09% Hispanics, 8.18% Asian or Pacific Islanders, and <1% were American Indians/Alaskan natives and unknown race. Overall median of survival (MoS) was 180 months, with 1-year OS of 0.93 (CI 95%, 0.90-0.95), 3-year OS of 0.84 (CI 95%, 0.80-0.87), and 5-year OS of 0.74 (CI 95%, 0.69-0.78). MoS were significant for Age: 0-30 years (undefined), 31-60 years (196), and 60+ years (81) (p <0.0001); Gender: males (129) vs females (188) (p 0.0224); Laterality: right (220), left (174), unknown origin (129) (p 0.0018). Stage based survival analysis showed higher survival for locoregional disease, while lower for distant disease with unknown stage in between (p <0.0001). Comparing survival based on treatment types showed: surgery 215 vs no-surgery 88 (p value <0.0001), chemotherapy 49 vs no chemo 200 (p value <0.0001), and radiotherapy (XRT) 113 vs no XRT 200 (p value 0.0025). Survival analysis was insignificant on the basis of race, primary site, and income. Undefined MoS was likely observed due to insignificant numbers of death in that age category (0-30 yrs) to calculate 50% survival probability. Conclusion: Only 550 cases were noted in a period of 22 years, rendering it one of the rarest encountered malignancies. Malignant paraganglioma had a predilection for female gender, and Caucasians. Better survival outcomes were associated with younger age, female sex, right-sided origin, locoregional disease, and surgical management. Survival was independent of race, primary site, and median household income. Arguably, lower survival observed with chemotherapy/radiotherapy could be secondary to their use in higher tumor burden states w/wo systemic metastasis, leading to lower overall survival in that cohort.Presentation: Sunday, July 13, 2025

Recurrence of head and neck squamous cell carcinoma (HNSCC) affects nearly half of patients and greatly reduces survival. There are currently no well-established mechanisms to predict which HNSCC patients will experience disease recurrence. We have previously shown that an elevated proportion of highly differentiated, CD57+ effector memory T (HD TEMRA) cells in circulation is associated with early recurrence and poor locoregional disease control in HNSCC patients. Here, we present refined flow cytometry panels utilizing fewer fluorescent antibodies that retain the prognostic value of HD TEMRA cells in predicting HNSCC recurrence. In our cohort of surgically treated HNSCC patients, identifying HD TEMRA cells via flow cytometry as live CD8+ CD28- CD57+ cells effectively predicted disease recurrence. When assessing this cohort by disease subsite, we found that for patients with oral squamous cell carcinoma, identifying HD TEMRA cells by CD8+ CD57+ alone was sufficient for predicting locoregional disease recurrence. These refined panels enhance the clinical utility of HD TEMRA proportion as a biomarker due to their technical and analytic ease. Implementation of HD TEMRA cell proportion as a clinical biomarker could aid in personalized HNSCC treatment planning.

In nasopharyngeal carcinoma (NPC), the 12-week period following radiotherapy (RT) represents a critical surveillance window for detecting residual disease and distant metastasis. We aim to assess the role of PET/CT And cfEBV DNA levels at 12weeks post-RT in the surveillance of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Patients with stage III-IVa LA-NPC were included. PET/CT scans were conducted both pre-treatment And at 12weeks post-RT. cfEBV DNA was assessed pre-treatment, at 4, 12, And 24weeks post-RT, And subsequently at 3- to 6-month intervals. The primary endpoint was the negative predictive value (NPV) of 12-week PET/CT for identifying locoregional residual disease (RD) and/or distant metastasis (DM). Between 2018 And 2021, 506 eligible patients were prospectively enrolled (median follow-up: 45.2months). At 12weeks post-RT, RD was identified in 22 patients (4.3%), DM in 30 patients (5.9%), And both RD And DM in 6 patients (1.2%). For overall RD and/or DM, 12-week PET/CT demonstrated An NPV of 96.3%, sensitivity of 72.4%, specificity of 93.3%, positive predictive value (PPV) of 58.3%, And accuracy of 90.9%. The corresponding values for 12-week cfEBV DNA were An NPV of 91.7%, sensitivity of 41.7%, specificity of 34.5%, PPV of 93.8%, And accuracy of 87.0%. Among subgroups defined by 12-week cfEBV DNA levels, patients with undetectable cfEBV DNA showed a 96.8% NPV for PET/CT, whereas those with detectable cfEBV DNA demonstrated an 85.0% sensitivity for PET/CT. PET/CT performed at 12weeks post-RT is a reliable tool for surveillance in LA-NPC, facilitating the optimization of follow-up strategies and enabling timely therapeutic interventions. The combined use of PET/CT and cfEBV DNA provides valuable risk-stratified insights for managing patients effectively.

Contemporary Advances, Evidence, and Considerations in Preoperative Therapy for Pancreatic Ductal Adenocarcinoma.

Use of staging in intermediate-risk prostate cancer: A real-world data analysis.

Melanoma is a lethal skin cancer and accounts for the highest mortality rate caused by cutaneous malignancies. Prognosis is dependent on stage. Patients with "thick" melanomas of 4-mm Breslow depth or greater are at increased risk for nodal metastases. Positron emission tomography/computed tomography (PET/CT) may be an underutilized imaging study for preoperative clinical staging in those with T4 melanoma. This was a single-institution retrospective analysis of adult patients with biopsy-proven T4 predominantly cutaneous melanoma (> 4 mm tumor thickness) who underwent preoperative PET/CT at a single National Cancer Institute (NCI)-designated cancer center between 1 January 2010 and 30 December 2022. Patients were excluded if there was clinical evidence of locoregional or distant metastatic disease at time of preoperative PET/CT. A total of 94 patients met inclusion criteria. They were predominantly male (n = 56, 59.6%) and Caucasian (n = 83, 94.3%) with an average body mass index (BMI) of 27.97 and median age of 69.5 years. A total of 69.7% of patients had tumor ulceration on biopsy and 2% had microsatellitosis. Positive PET/CT scans were found in eight patients (8.5%), which changed clinical management in seven of the eight patients. When comparing PET/CT results to sentinel lymph node biopsy (SLNB) results, sensitivity was 15.4%, specificity was 94.1%, positive predictive value was 50%, and negative predictive value was 74.4%. Patients with T4 melanoma without clinical suspicion of nodal disease do not have a high rate of occult metastases on preoperative PET/CT. We argue that clinical exam remains the most important tool for preoperative workup in these patients, but that PET/CT may be considered on the basis of patient-specific factors.

Merkel cell carcinoma (MCC) is typically caused by the Merkel cell polyomavirus (MCPyV) and recurs in 40% of patients. Half of patients with MCC produce antibodies to MCPyV oncoproteins, the titers of which rise with disease recurrence and fall after successful treatment. To assess the utility of MCPyV oncoprotein antibodies for early detection of first recurrence of MCC in a real-world clinical setting. This prospective cohort study used a data and specimen repository from 2008 to 2020 in Seattle, Washington. Patients with MCC with locoregional disease underwent serum antibody testing at diagnosis. Statistical analysis was conducted between 2020 and 2025. The first posttreatment titer was necessary to establish a trend and was not used to assess risk (deferred). Subsequent titers were defined as (1) falling or negative, (2) rising, or (3) stable compared with the preceding titer. Among the 503 patients in the cohort (median [IQR] age at diagnosis, 70 [62-77] years; 40% female), 1402 tests were performed; 247 (49%) were seropositive. A total of 877 were falling or negative, 62 were rising, 317 were stable, and 146 were deferred. Median (IQR) follow-up was 4.2 (1.8-7.4) years. On average, antibody titers fell by half every 3 months among patients not experiencing a recurrence. After a falling or negative titer, the likelihood that a given patient would remain recurrence-free for 3 months was 99.3% (95% CI, 98.6%-99.8%). In contrast, after a single rising titer, the risk of recurrence over the next 3 months was 36% (95% CI, 22%-52%), increasing to 58% (95% CI, 40%-78%) by 12 months and 68% (95% CI, 48%-86%) by 24 months. A rising titer preceded clinical or radiographic evidence of recurrence in 57% of cases (20/35). The median (IQR) interval between a rising titer and clinical disease detection was 3.7 (1.1-7.5) months, with 90% of recurrences (18/20) occurring within 14 months of the rising titer. Recurrences and antibody titers were analyzed in 196 patients with multiple blood draws. In this prospective cohort study, given a negative predictive value of 99.3%, a falling or negative titer may obviate the need for imaging, reducing radiation and contrast dye exposure. Conversely, a rising antibody titer should trigger closer follow-up, as it may lead to earlier detection of clinical recurrence and initiation of therapy.