5-year Progression-free Survival Research Articles

Long‐term outcomes of robot versus video-assisted thymectomy for thymic epithelial tumors: a propensity matched analysis

BackgroundRobot-assisted thoracoscopic surgery (RATS) thymectomy has been increasingly performed for treating thymic epithelial tumors in recent years. However, there are very limited reports on the long-term oncologic outcomes after RATS thymectomy, particularly in comparison to Video-assisted thoracoscopic surgery (VATS). This study aimed to compare the perioperative and long-term oncological outcomes between RATS and VATS.MethodsThe study was conducted on 180 consecutive patients undergoing RATS or VATS between July 2016 and December 2019, 85 of whom underwent RATS, and 95 of whom underwent VATS. A 1:1 matched propensity score-matched analysis was performed and the perioperative and long-term oncologic outcomes of the two groups compared.ResultRATS group experienced a shorter operation time (median: 100 min vs. 120 min; P = 0.039) and less blood loss (40.00 ml vs. 50.00 ml, P = 0.011). RATS demonstrated a significantly lower conversion rate to open surgery compared to VATS, with only two patients requiring conversion in the RATS group as opposed to ten patients in the VATS group (3.03% vs. 15.15%, P = 0.030). In the RATS group, the 5-year progression-free survival rate was 87.70%, and the 5-year tumor-related survival rate was 92.31%, demonstrating no statistically significant difference compared to those in the VATS group.ConclusionCompared with VATS, robotic thymectomy demonstrated excellent perioperative outcomes, and RATS achieved long-term oncologic outcomes comparable to those of VATS. RATS thymectomy could be considered as an effective alternative approach for treating thymic epithelial tumors.

Optimizing resources: low-dose nivolumab combinations in the management of relapsed/refractory Hodgkin lymphoma.

Up to one-third of patients with classical Hodgkin lymphoma (cHL) are not responsive to first-line therapy or eventually relapse. Immune checkpoint inhibitors (ICIs) have been successfully employed to treat relapsed/refractory cHL (r/r cHL) but place patients at risk of financial toxicity. Early-phase trials and observational data suggest that low doses of ICIs may achieve similar results to those obtained with high doses. In this study, we report a single-center experience using low-dose nivolumab (LD-Nivo) in different combinations for r/r cHL, including monotherapy, LD-Nivo plus brentuximab vedotin (BV), and LD-Nivo plus chemotherapy. The primary outcome was to assess the efficacy of LD-nivo in patients with r/r cHL. We included 23 consecutive patients (median age 27years; 57% female). LD-Nivo was prescribed in 40, 100, and 140mg fixed doses Q2W. Survival analysis was performed employing the Kaplan-Meier method. 73% of patients achieved an overall response, 43% complete response, and 30% partial response. One-year overall survival was 94.4% (95% CI, 0.84-1), and the 1-year progression-free survival was 89.4% (95% CI, 0.77-1). OS and PFS were similar accross combinations. The median dose of nivolumab was 0.78mg/kg (range, 0.62-1.11), and the median number of cycles until a response was documented was 6 (range, 2-9). During follow-up, 18 patients received transplantation (11 autologous, 6 allogeneic). No statistically significant differences in survival or response were detected between nivolumab combinations or doses. Adverse events were observed in 61% of the patients, with none grade 3-4. LD-Nivo demonstrated promising results in relapsed/refractory HL, highlighting its potential as a cost-effective treatment option. Further research is needed to validate these findings and guide clinical practice.

Hypofractionated accelerated radiation dose-painting (HARD) improves outcomes in unresected soft-tissue sarcoma

Soft tissue sarcomas (STS) are radioresistant with a low α/β, which may have a biologic benefit with hypofractionation. For unresectable STS, the dose escalation required to achieve durable control is often limited by long-term toxicity risk. We sought to compare an isotoxic approach utilizing hypofractionated accelerated radiation dose-painting (HARD) versus standard fractionated radiation therapy (SFT) in patients with unresected STS.We conducted a retrospective analysis of patients with unresected STS who received either HARD (n = 49) or SFT (n = 43) with photon-based therapy between 1990 and 2022. The 2 HARD regimens each use 3 dose levels based on risk of disease burden. The gross disease, intermediate risk, and low-risk clinical target volumes were treated with either 20–22 fractions of 3/2.5/2–2.2 Gy or 28 fractions of 2.5/2.2/1.8 Gy. SFT included patients treated with definitive intent, receiving ≥ 50 Gy in 1.8–2 Gy per fraction. Clinical endpoints included 3-year local control (LC), overall survival (OS), and progression-free survival (PFS), along with treatment-related toxicity.With a median age of 67 and tumor size of 7 cm, most patients were stage IV (37 %), grade 3 (67 %), had no concurrent systemic therapy (70 %), and were lower extremity tumors (24 %). HARD cohort consisted of higher age, stage, recurrent disease, and median BED4 (p < 0.05), when compared to SFT. With a median follow-up of 35.9 months, HARD demonstrated significant improvement in 3-year LC (96.4 % vs. 48.4 %, p < 0.001), compared to SFT overall, with a median PFS benefit (16 vs. 10 months, p = 0.037) for non-distantly metastatic patients at baseline. On multivariate analysis, HARD was significantly associated with improved LC (HR 0.058, 95 % CI 0.005–0.682, p = 0.024). The HARD regimen found no significant increase in toxicity, with limited acute grade 3 (24 %, all dermatitis) and late grade 3 toxicity (6 %) observed, with no grade 4 or 5 events.HARD regimen significantly improves LC for unresectable STS without a significant increase in toxicity, when compared to a standard fractionated approach, supporting further prospective investigation of this treatment approach.

Exploration of the value of concurrent chemotherapy for T2N1 nasopharyngeal carcinoma under intensity modulated radiotherapy mode.

In the era of intensity-modulated radiation therapy (IMRT), the status of concurrent chemoradiotherapy(CCRT) for stage II nasopharyngeal carcinoma(NPC), particularly for patients in T2N1 subtype, remains controversial nowadays. This study exclusively aims to explore the value of concurrent chemotherapy in the treatment of T2N1 NPC under IMRT mode. A retrospective analysis was conducted on 218 cases of T2N1 NPC patients treated at our hospital from January 2015 to December 2020, comprising 75 cases treated with IMRT and 143 cases treated with CCRT. The study compared therapeutic outcomes and side effects between the two groups. The 5-year progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS) and,distant metastasis-free survival (DMFS) estimated by the K-M method for the IMRT vs. CCRT groups were 86.1% vs. 85.1%,89.3% vs. 87.9%, 95.9% vs. 94.9%,and 90.2% vs. 89.1%, respectively, with no statistically significant differences (Log-rank P>0.05 for all comparisons). Cox regression analysis identified Epstein-Barr virus (EBV) DNA copy level (≥1000 vs. <1000 copies/ml)(the cutoff value was determined through the ROC curve), lymph node necrosis (yes vs. no) and extra-nodal extension (yes vs. no) as independent prognostic factors for PFS(P<0.05 for all comparisons). Subgroup analysis indicated an interaction effect between lymph node necrosis (yes vs. no) and treatment modality (IMRT vs. CCRT) regarding PFS (P for interaction<0.05). In the subgroup with lymph node necrosis, IMRT compared to CCRT had a poorer prognosis (HR: 1.85,95% CI: 1.02-3.50). CCRT was noted to increase acute hematological, gastrointestinal and other toxicities. This study provides a reference for clinical treatment decisions in T2N1 NPC. For the entire population of T2N1 NPC, the therapeutic effects of IMRT and CCRT are comparable, with increased acute toxicities in the latter. However, for patients with EBV-DNA copy level ≥1000 copies/ml, lymph node necrosis and extra-nodal extension, CCRT may be considered as appropriate. Particularly, patients with lymph node necrosis may be potential beneficiaries for CCRT.

Clinicopathologic features of primary central nervous system anaplastic large cell lymphoma: a multicenter study identifies age and ALK status as prognostic factors.

Anaplastic large cell lymphoma with primary presentation in, and disease limited to, the central nervous system (primary CNS ALCL) is a rare and aggressive lymphoma found in a sensitive anatomic site. We report the clinical and pathologic characteristics of 17 primary CNS ALCL cases that are newly reported from six academic medical centers. We are investigating the characteristics of these cases, alongside their commonalities and differences from systemic ALCL arising at conventional anatomic sites. Clinical, pathologic, and outcome data were extracted by medical record review. The median patient age was 32years with a male-to-female ratio of 2.4:1. Cases presented with either localized or multifocal central nervous system (CNS) disease without coinciding systemic disease. Histologically, the common pattern prevailed, and loss of pan-T-cell markers was frequent. There was a similar proportion of anaplastic lymphoma kinase (ALK) positivity in primary CNS ALCL (12/17, 71%) compared to that reported in systemic ALCL (70-80%). Our data indicate a 5-year overall survival (OS) rate of 65% and a 5-year progression-free survival (PFS) rate of 48%. Five patient deaths occurred in this study of which all were in the ALK-negative group, and all were patients over 40years old. ALK-positive patients were significantly younger than ALK-negative patients, and survival analyses showed that both ALK-positive and younger age (≤ 40years) were favorable prognostic factors. This is the largest series of primary CNS ALCL reported to date, which demonstrates a high proportion of ALK-positive cases and favorable outcomes for both younger and ALK-positive patients despite the involvement of a sensitive anatomic site.

Real-world outcomes of avelumab plus axitinib in patients with advanced renal cell carcinoma in Japan: long-term follow-up from the J-DART2 retrospective study.

Avelumab + axitinib was approved for advanced renal cell carcinoma (aRCC) in Japan in December 2019. We report long-term real-world outcomes with first-line avelumab + axitinib from the J-DART2 study in Japan. J-DART2 was a multicenter, noninterventional, retrospective study examining clinical data from patients with curatively unresectable locally advanced or metastatic RCC who started treatment with first-line avelumab + axitinib in Japan between December 2019 and October 2022. Endpoints included patient characteristics, treatment patterns, and outcomes. Data from 150 patients across 19 sites were analyzed; median follow-up was 18.7months (95% CI, 16.3-20.6months). Median age was 70.5years; 26.0% of patients wereaged ≤64years, 42.7% wereaged 65-74years, and 31.3% wereaged ≥75years. International Metastatic RCC Database Consortium risk was favorable in 26.0%, intermediate in 54.7% (1 risk factor in 30.7%; 2 risk factors in 24.0%), and poor in 19.3% of patients. Median progression-free survival (PFS) was 17.1months, with 1- and 2-year PFS rates of 57.7% and 37.5%, respectively. Median overall survival (OS) was not reached, with 1- and 2-year OS rates of 90.6% and 84.7%, respectively. Objective response rate was 53.3%; disease control rate was 88.9%. Outcomes were similar across age groups, including patients aged ≥75years. J-DART2 is the largest retrospective study to report long-term real-world outcomes in patients with aRCC treated with avelumab + axitinib in Japan. Findings were similar to those observed in previous studies and support the benefit of avelumab + axitinib in clinical practice in Japan.

Pretreatment neutrophil-lymphocyte ratio as a prognostic factor in recurrent/metastatic head and neck cancer treated with pembrolizumab.

Pembrolizumab-containing regimens are the standard first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) have been reported to be important prognostic factors in a variety of carcinomas, but none have been investigated in combination with pembrolizumab and chemotherapy or in first-line treatment. Seventy-four patients with R/M HNSCC received pembrolizumab-containing regimens at Tohoku University Hospital, Sendai, Japan, from April 2020 to March 2023. Patient characteristics, tumor response, overall survival (OS), progression-free survival (PFS), and laboratory findings were reviewed. Associations between NLR, CAR, and survival outcomes were analyzed. The 1-year OS and 1-year PFS rates were 60.4% and 18.1%, respectively. The disease control rate was 66.2%. In multivariate analysis, low NLR (< 5) was significantly associated with better OS and PFS. NLR may be a predictive factor for OS and PFS in patients with R/M HNSCC treated with a pembrolizumab-containing regimen.

Real-world outcomes of diffuse large B-cell lymphoma treated with frontline R-CHOP(-like) regimens in an Asian multi-ethnic population.

Recent breakthrough advances in the treatment of DLBCL, such as the antibody-drug conjugate polatuzumab vedotin, have yielded clinical survival benefit over rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for the first time in 20 years since the advent of the rituximab era. We thus examine the outcomes of standard immunochemotherapy for DLBCL in our multi-ethnic Asian population, so as to determine the real-world clinical need to adopt new therapeutics in this disease entity. We conducted a retrospective study involving patients (n = 1071) diagnosed with DLBCL at the National Cancer Centre Singapore from 2010 to 2022, and treated with first-line rituximab-based regimens. The median follow-up duration was 48 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. The cohort consisted of 590 male and 481 female patients with a median age of 63.8 years (range, 19.3-93.6). Most were stage III-IV at diagnosis (60.9%) and of non-germinal center B-cell like (non-GCB) subtype by Han's criteria (56.5%). The vast majority received R-CHOP(-like) regimens (n = 997, 93.1%), including rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-R) (n = 95), achieving a 5-year progression-free survival (PFS) and overall survival (OS) of 64.5% and 74.7% respectively. Male sex (p = 0.0294), age > 60 years (p < 0.0001), poor ECOG scores (2-4) (p < 0.0001), advanced stage (III-IV) (p < 0.0001), presence of B-symptoms (p = 0.0305), and raised LDH (p = 0.0161) were independent predictors of OS, 4 of which are risk factors in the International Prognostic Index (IPI). In the intermediate to high-risk subgroup (IPI scores 2-5; n = 752), the 5-year PFS and OS were only 59.0% and 69.8% respectively. EBV status, MYC and/or BCL2/BCL6 rearrangements, were not significantly associated with survival outcomes. EPOCH-R was used more frequently than R-CHOP in patients with MYC rearrangements (n = 82, p < 0.0001), including those with MYC/BCL2 double-hit genetics (n = 31, p < 0.0001). Notably, neither regimen significantly affected survival outcomes, both in MYC-rearranged (PFS: HR 0.60, p = 0.1704; OS: HR 0.49, p = 0.0852), and in MYC/BCL2 double-hit DLBCL (PFS: HR 1.30, p = 0.6433; OS: HR 1.02, p = 0.9803). Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial.

This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate. Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS. Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial

Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab. NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America. Eligible patients were aged 18 years or older with American Joint Committee on Cancer 8th edition stage III-IVB p16-negative HNSCC or unfavourable stage I-III p16-positive oropharyngeal or unknown primary carcinoma, who had a contraindication to cisplatin (Eastern Cooperative Oncology Group [ECOG] performance status 2, renal or hearing impairment, peripheral neuropathy, aged at least 70 years with moderate or severe comorbidity, or aged younger than 70 years with severe comorbidity). Patients were randomly assigned (2:1) by permuted block randomisation (multiples of 6) to intravenous durvalumab 1500 mg starting 2 weeks before radiotherapy then every 4 weeks starting week 2 of radiotherapy (seven cycles) or intravenous cetuximab 400 mg/m2 1 week before radiotherapy then 250 mg/m2 weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with ClinicalTrials.gov, NCT03258554, and is closed to enrolment. Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64-77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9-3·1) for the extended follow-up (data cutoff July 31, 2023; post-hoc analysis), 2-year progression-free survival was 50·6% (95% CI 41·5-59·8) in the durvalumab group versus 63·7% (51·3-76·1) in the cetuximab group (hazard ratio 1·33 [95% CI 0·84-2·12]; p=0·89). Adverse events were similar in both groups. The most common grade 3-4 adverse events were dysphagia (26 [22%] of 119 patients in the durvalumab group vs 18 [30%] of 61 patients in the cetuximab group), lymphopenia (33 [28%] vs 20 [33%]), and oral mucositis (13 [11%] vs 11 [18%]). Four (3%) patients in the durvalumab group and one (2%) in the cetuximab group died from treatment-related adverse events (death not otherwise specified, laryngeal oedema, lung infection, and respiratory failure in the durvalumab group and sudden death not otherwise specified in the cetuximab group). Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with HNSCC with contraindications to cisplatin. Further trials are needed to define the standard of care for this population. US National Cancer Institute and AstraZeneca.

The 5-factor modified frailty index as a prognostic factor for stereotactic radiosurgery in meningioma management.

Meningiomas are the most frequent primary intracranial malignancy. While surgical resection can confer long term tumor control, stereotactic radiosurgery (SRS) is often used for small, asymptomatic tumors in the adjuvant setting. Frailty has been associated with increased rates of peri-operative morbidity but has yet to be defined in the setting of SRS for meningiomas. We therefore sought to examine the relationship between frailty and clinical/radiographic outcomes of patients with meningiomas who have undergone SRS. A single-center, retrospective cohort study classified patients by their 5-factor modified frailty index (mFI-5) score into pre-frail (0-1) and frail (2-5) at the time of SRS treatment. Evaluations of overall survival (OS), progression free survival (PFS), local control (LC), and distant control (DC) were performed using Kaplan-Meier analysis. Cox proportional hazards regression analysis was used to further define factors associated with OS/PFS. 94 patients met inclusion criteria and underwent SRS for meningioma treatment from 2019 to 2023. Analyses compared prefrail (0-1) and frail (2-5) individuals. Kaplan-Meier analysis demonstrated a near significant association between frailty and OS (HR 3.66, 95% CI 0.49-26.8 p = 0.05) with 3-year OS rates of 75.4% in the pre-frail versus 36.6% in the frail group. However, a significant relationship was demonstrated between frailty and PFS (HR: 2.95 95% CI 1.12-7.81, p = 0.02) with 3-year PFS rates of 90.5% in the pre-frail group versus 49.2% in the frail group. Univariable regression analysis demonstrated that frailty, prior surgical excision, and cumulative tumor volume predicted PFS. Frailty, as assessed by the mFI-5, did not independently predict OS but did predict PFS in individuals with meningioma undergoing SRS.

Outcomes of adjuvant radiation treatment following subtotal resection of world health organization grade II meningiomas.

Existing literature on adjuvant radiation after subtotal resection (STR) of WHO II meningiomas is limited by heterogenous patient cohorts, combining adjuvant and salvage radiation, gross total resection (GTR) and STR, primary radiation treatment vs. re-treatment, or grade II and III meningiomas, all of which have different expected outcomes. Tumor control estimates in a large homogenous patient cohort are needed to accurately counsel patients. A retrospective review of patients that had immediate post-operative imaging-confirmed residual WHO grade II meningioma followed by either adjuvant intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS) between 1996 and 2020 was conducted. Kaplan-Meier survival analysis and log-rank test was used to assess progression-free survival (PFS). Thirty-nine patients met inclusion criteria (IMRT = 32; SRS = 7). Overall, the 3-, 5-, and 10-year PFS was 81.1%, 61.2%, and 44.6%, respectively. Median follow-up time was 37 months. When comparing IMRT and SRS cohorts, baseline characteristics did not differ significantly between groups, but significantly larger residual tumor volumes were treated with IMRT (22.2 cm3 vs. 6.3 cm3, p = 0.004). PFS was not significantly different between IMRT and SRS at 3 years (81.1% vs. 80.0%) or 5 years (65.5% vs. 40%) (p = 0.19). There was no significant difference in radiation necrosis between groups (IMRT = 3/32 patients vs. SRS = 0/7 patients, p = 0.32). Our homogenous patient cohort displayed acceptable control rates at 3 years using SRS or IMRT as adjuvant therapy. No significant difference in PFS or radiation necrosis was noted between patients treated with adjuvant IMRT versus SRS.

Abstract B023: Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer

Abstract Background: Cell-free HPV-DNA (cfHPV-DNA) in plasma represents a promising biomarker to grade treatment response and monitor for persistence/recurrence. We evaluated the dynamic changes of cfHPV-DNA during induction chemotherapy followed by response-stratified de-escalation in HPV associated (HPV+) oropharyngeal squamous cell cancer (OPSCC). Methods: A prospective biomarker clinical trial of response-stratified de-escalation therapy was conducted. Eligible patients had loco-regional HPV+ OPSCC and received induction chemotherapy with carboplatin and paclitaxel for three cycles followed by risk and response-stratified de-escalation with transoral robotic surgery (TORS), de-escalated radiation (RT) to 50Gy with or without cisplatin, or standard RT to 70Gy with cisplatin. Patients with deep response (&amp;gt;=50% tumor shrinkage per RECIST 1.1) qualified for de-escalated therapy. Cell-free HPV-DNA was measured using a CLIA-certified HPV-SEQ assay that utilizes NGS technology to detect and quantify HPV16 and HPV18 DNA in plasma at baseline, after each cycle of induction chemotherapy, during radiation, and post-treatment surveillance at 3, 6, 9, 12, 18, and 24 months following treatment. Results: Forty-six eligible patients were enrolled, with 464 cfHPV-DNA plasma samples analyzed (median 10 samples per patient). There were five recurrences (10.9%), all detected by HPV-SEQ. Baseline cfHPV-DNA was detected in 44/46 patients (96%). Patients with rapid early cfHPV-DNA clearance after one 3-week cycle of induction (&amp;gt;=95% clearance) predicted deep radiographic response following induction therapy (p=0.003). The detection of cfHPV-DNA at 3 months or later after treatment was associated with worse progression free survival (PFS), with 2-year PFS of 25% (95% CI 0.012-0.65) compared with patients without detectable cfHPV-DNA of 100% (95% CI 1.0-1.0); p&amp;lt;0.001). The longest lead-time from positive cfHPV-DNA to developing recurrent disease was 25 months. Conclusion: Rapid early clearance of cfHPV-DNA during induction has utility in predicting response to treatment. Detectable cfHPV-DNA following treatment is strongly associated with worse PFS. A subsequent trial using cfHPV-DNA to select patients for treatment de-escalation is ongoing. Clinicaltrials.gov ID: NCT04572100 Citation Format: Ari Rosenberg, Evgeny Izumchenko, John Cursio, Augustin Vannier, Aditya Juloori, Rohan Katipally, Rifat Hasina, Frederick Jones, Anna Starus, Elizabeth Blair, Daniel J. Haraf, Alexander T. Pearson, Everett E. Vokes, Nishant Agrawal. Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B023.

A prognostic nomogram for patients with III-IV nasopharyngeal carcinoma based on dynamic changes in the inflammatory and nutrition index.

The purpose of the study was to explore the value of dynamic changes in inflammatory and nutritional index after comprehensive treatment in patients with stage III-IVA nasopharyngeal carcinoma (NPC). A prognostic model was also established and validated for progression-free survival (PFS) of patients. We retrospectively selected 279 NPC patients with stage III-IVA. Their general clinical data and hematological index were collected and then calculated the changes during treatment. X-tile software was used to determine the optimal cut-off value. COX regression, Lasso method, and Boruta method were used to variable selection and model establishment. Using the bootstrap internal validation method, concordance index (C-index), calibration plot, and Kaplan-Meier curves were used to evaluate the model. To test the prognostic value of the model, we have also evaluated the performance of the nomogram against a conventional tumor metastasis staging system (TNM). Multivariable COX regression analysis demonstrated that clinical staging, delta lymphocyte, delta monocyte, delta albumin, delta platelet-to-lymphocyte ratio and delta systemic immune inflammation index were related to the PFS of NPC patients. The C-index of the model was 0.712, and the calibration curve indicated that the model had good consistency. The C-index of the TNM staging system was 0.597, which was considerably lower compared to our model (P = 0.015). We demonstrated the predictive value of dynamic changes in inflammatory and nutritional indices for the prognosis of NPC by successfully establishing and validating a prognostic model for predicting 1- and 3-year PFS after comprehensive treatment in patients with stage III-IVA NPC.

Phase II Trial of Induction Chemotherapy for Advanced Sinonasal Squamous Cell Carcinoma.

Outcomes after primary surgery for advanced sinonasal squamous cell carcinoma (SCC) are poor. We tested whether induction chemotherapy (IC) can improve disease control or organ preservation. A phase II trial evaluated previously untreated patients with stage II-IV, M0 sinonasal SCC. Patients received IC with docetaxel, cisplatin, and fluorouracil, followed by chemoradiotherapy (CRT) for responders and surgery with adjuvant radiotherapy or CRT for non-responders. The primary endpoints were overall response rate (ORR) and locoregional control (LRC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), organ preservation, and treatment toxicity. Of the 31 patients enrolled between 2008 and 2020, 28 were evaluated for efficacy. Disease was T4a, T4b, and N+ in 57%, 21%, and 36% of patients, respectively. The ORR was 82.1%; 17.9% of patients had stable disease, and 0% had progressive disease. Grade 3 and 4 adverse events (AE) occurred in 54% and 18% of patients, respectively; there were no Grade 5 AEs. The 2-year LRC and PFS rates were 64.3% (95% CI 40.4-77.6) and 52.4% (95% CI 32.3-69.0), respectively. The median PFS was 25.8 months. The median OS was 47.4 months, with a 2-year OS rate of 69.4% (95% CI 44.9-80.4). No survival difference was observed between surgery versus CRT (hazard ratio 1.07, 95% CI 0.9-3.84). Of patients alive at 2 years, 63% achieved organ preservation, avoiding maxillectomy (38%), craniotomy (13%), or orbital exenteration (38%). IC and response-directed treatment achieved promising disease control and added organ preservation for patients with advanced sinonasal SCC.

Ten-Year Outcome of a Randomized Trial: Cytoreduction and HIPEC with Mitomycin C Versus Oxaliplatin for Appendiceal Neoplasm with Peritoneal Dissemination.

Appendiceal cancer is a rare disease that has proven difficult to study in prospectively. Our initial reportof this trial showed minor hematologic toxicity with both mitomycin C and oxaliplatin and similar 3-year survival. We now report an update of the first prospective randomized trial for appendiceal cancer with 10-year follow up. Patients with mucinous appendiceal neoplasms and evidence of peritoneal dissemination were enrolled in the Multicenter Randomized Trial to evaluating HIPEC for 120min with oxaliplatin (200mg/M2) or mitomycin C (40mg). Overall survival and disease-free survival were calculated at 10 years and compared between the groups. A total of 121 patients were included in the study. The patients were 57% female, with a mean age of 55.3 years (range 22-82 years). The disease was low grade in 71% and high grade in 29%. The average peritoneal cancer index (PCI) score was 18 (SD 10) in the mitomycin C group and 17.9 (SD 9.4) in the oxaliplatin group (p = 0.94). The 10-year survival rate was 56.2% (SE 7.2) with mitomycin C and 47.5% (SE 8.4) with oxaliplatin, p = 0.83. The 10-year progression-free survival rate in the mitomycin C group was 45.2% (SE 8.4) compared with 50.4% (SE 6.7) in the oxaliplatin group, p = 0.95. Median survival was 9.1 years after HIPEC with oxaliplatin, and median not reached for the mitomycin C group (> 5.6years). Oxaliplatin and mitomycin C have similar long-term efficacy for hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal neoplasms and peritoneal dissemination. Long-term survival is experienced by most patients after cytoreduction surgery (CRS) and HIPEC for appendiceal neoplasms.

BIOM-51. MOLECULAR SUBTYPES, CLINICAL CHARACTERISTICS, AND THERAPEUTIC IMPLICATIONS FOR CNS TUMORS WITHBCOR/BCORL1 FUSION/INTERNAL TANDEM DUPLICATION

Abstract Central nervous system (CNS) tumors with either BCOR internal tandem duplication (BCOR ITD) or gene fusions involving BCOR/BCORL1 (BCOR FUS) are recognized as tumor types with characteristic molecular and clinical features but lacking clear therapeutic guidance. In an extensive international effort, we compiled a retrospective cohort of 229 (148 BCOR ITD, 81 BCOR FUS) unique cases via molecular profiling of CNS tumors. By analyzing DNA methylation patterns of 220 tumors we confirmed distinct epigenetic profiles of BCOR ITD versus BCOR FUS. The majority (91 percent) of BCOR FUS primary tumors was localized in the supratentorial region whereas BCOR ITD were localized across all anatomical CNS compartments. Median patient age at diagnosis was 20 years for BCOR FUS and 4 years for BCOR ITD. Metastatic disease was rare in BCOR FUS patients but more common in BCOR ITD tumors where 10 percent presented with metastatic disease and one third showed CNS or (rarely) extra-CNS metastasis in the course of disease. This was also reflected in clinical outcome as 5-year overall survival (OS) was 89 percent in BCOR FUS but 61 percent in BCOR ITD. In contrast, 5-year progression-free survival (PFS) was comparable reaching 27 percent in BCOR FUS and 30 percent in BCOR ITD. Integrating treatment details we found a trend towards benefit of gross-total resection on OS (BCOR FUS, n=18, p&amp;lt;0.08; BCOR ITD, n=67, p&amp;lt;0.12) but not for PFS (BCOR FUS, n=16, p&amp;lt;0.33; BCOR ITD, n=64, p&amp;lt;0.59). Radiotherapy was associated with improved PFS (BCOR FUS, n=18, p&amp;lt;0.01; BCOR ITD, n=70, p&amp;lt;0.001) and OS (BCOR FUS, n=20, p&amp;lt;0.01; BCOR ITD, n=73, p&amp;lt;0.001). Further in-depth analyses of clinical outcome parameters (primary metastatic disease, radiotherapy approach, chemotherapy type, patient age) are currently ongoing. In summary, we provide first robust annotation of CNS BCOR tumor types, clinical outcomes and therapy.

Screening high-risk individuals for primary gastric adenocarcinoma: evaluating progression-free survival probability score in the presence and absence of Rictor expression after gastrectomy.

Developing nomogram-based risk stratification model to determine 3-year and 5-year progression-free survival (PFS) and to identify high-risk patients with gastric adenocarcinoma based on different Rictor statuses. 1366 individuals who underwent radical gastric surgery to treat gastric adenocarcinoma at Shanxi Cancer Hospital from May 2002 to December 2020 were analyzed. Cox regression analysis was employed to create the nomograms. The nomograms' performance was assessed using C-index, time receiver operating characteristic (t-ROC) curves, calibration curves, and decision curve analysis (DCA) curves in training and validation cohorts. Subsequently, patients were categorized into high-risk and low-risk groups based on the nomogram's risk scores. The Rictor (-) nomogram for predicting PFS included variables such as age, number of positive lymph nodes, vascular invasion, maximum diameter of the tumor, omentum metastasis, and expression of MSH2. In the internal validation, the C-index of the Rictor (-) nomogram was 0.760 (95%CI: 0.720-0.799), which was superior to the C-index of the American Joint Committee on Cancer (AJCC) 8th edition TNM staging (0.683, 95%CI: 0.646-0.721). Similarly, the Rictor (+) nomogram for predicting PFS included variables such as gender, age, pT stage, number of positive lymph nodes, neural invasion, maximum diameter of the tumor, omentum metastasis, Clavien-Dindo classification for complications, and CGA expression. The C-index of the Rictor (+) nomogram was 0.795 (95%CI: 0.764-0.825), which outperformed the C-index of the AJCC 8th edition TNM staging (0.693, 95%CI: 0.662-0.723). The calibration curves, t-ROC curves, and decision curve analysis for both nomogram models demonstrated their excellent prediction ability. This study presents the first risk stratification for Rictor status in gastric adenocarcinoma. Our model identifies low-risk patients who may not require additional postoperative treatment, while high-risk patients should consider targeted therapies that specifically target Rictor-positive indicators.

Clinical features, treatment options and outcomes in primary cutaneous B-cell lymphomas: a real-world, multicenter, retrospective study.

Primary cutaneous B-cell lymphomas (PCBCLs) are rare cutaneous neoplasms with limited literature regarding treatment options and associated treatment outcomes. This study aimed to investigate and present real-world treatment outcomes in patients with PCBCLs. All patients with PCBCL who were treated in five major referral centers for cutaneous lymphoma in Greece over 10 years were retrospectively included with their baseline characteristics and treatment-associated outcomes collected and analyzed. In total, 235 PCBCL patients, of whom 125 (53.2%) were females, were included. The median age at diagnosis was 60 years (IQR 47-72), and the median follow-up duration was 3 years (IQR 1.3-6.4). The most common subtype was primary cutaneous marginal zone lymphoma (PCMZL) (52.3%), followed by primary cutaneous follicle center lymphoma (PCFCL) (40.9%), and primary cutaneous large B-cell lymphoma, leg type (PCDLBCL, LT) with 16 (6.8%) cases. Complete responses (CRs) were observed in 77.3% after first-line treatment. Both radiotherapy (RT) and surgical excision (SE) achieved superior outcomes, with 88.9% and 89% achieving CR, respectively. Relapses occurred in 22.6% of initial complete responders. The median time to the next treatment (TTNT) for the PCMZL and PCFCL was 349 days. RT and topical/intralesional steroids demonstrated longer TTNT compared to SE (445 and 359 vs. 154 days). For PCMZL and PCFCL, the 1-year progression-free survival (PFS) was 84.2% (75.7-89.9) and 85% (75.1-91.2), and the 5-year PFS was 66.5% (55.2-75.5) and 58.8% (44.4-70.7), respectively. PCBCLs have favorable outcomes. RT demonstrates significantly increased TTNT compared to SE, suggesting RT as the preferable option. After careful evaluation, "watch and wait" may be a reasonable option for asymptomatic patients.

DISP-20. SEX DIFFERENCES IN MENINGIOMA AGGRESSIVE BEHAVIOR IN RURAL POPULATIONS: A GEO-ECOLOGICAL RISK ASSESSMENT OF MENINGIOMAS IN A SINGLE RURAL HEALTH CARE SYSTEM

Abstract BACKGROUND Cause for health outcome disparities in rural populations is multifactorial. These populations are potentially more vulnerable due to rural area environmental policies and practices. Environmental justice populations (EJP) are designated by the Environmental Protection Agency as at risk for generational exposer to environmental contaminants. We assessed these population for an association between EJP density and aggressiveness of indolent brain tumors. Meningiomas are the most common benign intracranial tumor and have a female predominance. We evaluated meningioma patients in a large rural health system for oncogenic risk associated geo-ecological factors. METHODS A retrospective review of 415 pathology confirmed CNS WHO grades 1-3 meningiomas cases between 2007 – 2017 within the Geisinger Health system in Pennsylvania. Cases were mapped by county for meningioma incidence, tumor grade, and tumor recurrence. Counties were rated for EJP density. We mapped geographic areas with a higher meningioma incidence, grade, and rates of recurrence, and evaluated sex-predilections. RESULTS Seventy-three percent of tumors were WHO grade 1 (n=303), 23.4% (n=97) were grade 2, and 3.6% (n=15) were grade 3. The highest incidence of meningiomas were localized to higher density EJP counties that bordered riverbeds, Lackawanna and Luzerne. Females had a 3.5:1 predominance as compared to males. The grade 1 10-year progression free survival rate was 54.7% in Luzerne, Columbia, and Montour counties (moderate to high density EJP). Males in high EJP counties had a 12% increased risk for developing high grade meningiomas. Males aged 51-60 were more likely to develop a grade 2 or 3 meningioma as compared to males aged 61-70 in these counties. Females aged 50-60 more likely had grade 1 meningiomas but demonstrated consistently increasing risk for recurrence every decile. CONCLUSIONS Pennsylvania high density EJP counties (especially along the Lackawanna River supply) have a disproportionate risk for aggressive meningiomas and lower progression free survival as compared to national averages. A sex-discrepancy exists for males in these areas to have the most aggressive tumors.