Local Disease Control Research Articles

O10 Guiding metastasis-directed therapy with different PET/CT radiotracers affects distant but not local disease control in oligorecurrent hormone-sensitive prostate cancer patients: a secondary analysis of the PRECISE-MDT Study

O10 Guiding metastasis-directed therapy with different PET/CT radiotracers affects distant but not local disease control in oligorecurrent hormone-sensitive prostate cancer patients: a secondary analysis of the PRECISE-MDT Study

[Translated article] Can 3D-printed patient-specific instruments improve local control and overall survival in pelvic sarcoma? A clinical validation study

Background and objectives 3D-printed patient-specific instruments (PSIs), also known as 3D guides, have been shown to improve accuracy in resection of pelvic tumors in cadaver studies and achieve better surgical margins in vivo. This study evaluates the clinical impact of 3D-printed guides on medium-term local and distant disease control, as well as disease-free and overall survival in patients.Material and methods A cohort study included 25 patients with primary pelvic or sacral sarcomas: 10 in the 3D group and 15 in the control group, with a median follow-up of 47 months. Demographic and clinical data, including tumor histology, stage, resection technique, associated reconstruction, adjuvant therapies, and complications, were evaluated. Surgical margins (free, marginal, and contaminated) and relapse-free and overall survival curves were analyzed.Results The 3D group achieved a higher rate of free margins (80% vs 66.7%, p = 0.345). Local recurrence (50% vs 60%, P=.244) and distant disease relapse (20% vs 47%, p = 0.132) rates were lower in the 3D group. At the end of the follow-up, the 3D group had a higher overall survival rate (60% vs 40%, p = 0.327). The complication rate was similar in both groups, with a deep infection rate of 40%.Conclusions The use of 3D guides in resecting primary pelvic tumors not only achieves a higher rate of free margins compared to conventional techniques but also shows a trend towards higher local, distant, and overall disease-free survival. Further studies with larger sample sizes and higher levels of evidence are necessary to validate these clinical trends.

Juvenile idiopathic arthritis management: insights into the utilization of intra-articular corticosteroid injections

ABSTRACT Background Juvenile idiopathic arthritis (JIA) is a common chronic rheumatic disease in children, requiring careful management to reduce both short- and long-term morbidity. In this study, our objective was to assess the clinical features of patients diagnosed with JIA who received intra-articular corticosteroid injections (IACI). Methods In this retrospective study, we evaluated the clinical and laboratory characteristics of 225 JIA patients monitored from January 2012 to October 2023 at a tertiary care center. We focused on patients who underwent intra-articular corticosteroid injections (IACI) as part of their treatment. Triamcinolone hexacetonide (TH) was used due to its demonstrated safety and efficacy. Results Our analysis revealed that IACI, particularly utilizing TH, was a widely employed and effective adjunct therapy, contributing to rapid symptom relief and local disease control. Patients receiving IACI exhibited earlier symptom onset, younger age at diagnosis, longer follow-up durations, and higher cumulative treatment burden (p < 0.001, p < 0.001, p < 0.01, p < 0.001 respectively). Despite inconclusive acute-phase reactants, a higher frequency of ANA positivity and elevated initial lymphocyte counts were associated with increased IACI use (p < 0.001, p < 0.001 respectively). Importantly, on a joint basis, a high percentage of arthritis remission following IACI underscores its efficacy and favorable safety profile. Conclusions Notably, the high percentage of arthritis remission achieved with intra-articular corticosteroid injections (IACI) on a joint-specific basis highlights its efficacy and favorable safety profile. A lymphocyte count exceeding 5000/mm3 at the time of diagnosis may serve as an early indicator for considering intra-articular steroid administration. These findings emphasize the need for nuanced and individualized treatment strategies in JIA management to optimize outcomes for affected children.

Tailored management of advanced thyroid cancer patients treated with lenvatinib or vandetanib: the role of a multimodal approach.

In differentiated/poorly differentiated (DTC/PDTC) or medullary thyroid cancer (MTC) treated with kinase inhibitors (KIs), additional treatments (ATs) can be performed in selected cases. We retrospectively analysed all the ATs performed in our center in KI-treated TC patients, evaluating the subsequent KI modulation, the local PD in case of loco-regional procedure (LRP) and the AT-related complications. DTC/PDTC patients with or without progressive disease before the first AT (PD and NO PD GROUP, respectively) were analysed separately. In our center, 32 ATs (30 LRPs and 2 radioactive iodine treatments) were performed in 14 DTC/PDTC patients and 4 MTC subjects after the start of systemic therapy with lenvatinib or vandetanib (27 and 5 ATs, respectively). Brain was the most treated site (11/30 LRPs) and external beam radiation was the most employed LRP (18/30 LRPs). KIs dose reduction or discontinuation of KI therapy (at least transient) was performed after 50% of ATs in DTC/PDTC NO PD GROUP. The KI was maintained at the same dosage after 75% and 50% of the ATs performed in DTC/PDTC PD GROUP and MTC, respectively. During the follow-up, local PD was detected after 14 LRPs. Local progression-free survival (LPFS) was significantly shorter in DTC/PDTC PD GROUP in comparison to NO PD GROUP (12 month-LPFS 91.7% versus 15.2%); in patients with MTC, 12 month-LPFS was 50%. AT-related AEs were mostly G1-G2. In selected DTC/PDTC without previous PD and treated with a multimodal strategy, local disease control is generally maintained regardless the KI dose modulation. In DTC/PDTC patients with previous limited PD and in MTC subjects, the choice of performing a LRP and continue the ongoing KI therapy must consider the risk of early local progression. AT-related AEs in KI treated patients were mild in most cases.

La radiothérapie des CBNPC de stade III : nouvelles techniques, nouvelles combinaisons

Defining the optimal treatment approach for patients with stage III non-small cell lung cancer, where the loco-regional disease extension renders a surgical approach obsolete, represents an important clinical challenge. In addition, many of these patients present with several comorbidities, compromising their tolerance to treatment. This article describes how innovative radiotherapy approaches try to enhance loco-regional tumour control as a first step towards improved survival, often by exploring novel avenues to dose-escalation, while at the same time focus on limiting early and long-term radiation-induced toxicity by applying the most advanced radiotherapy techniques. Moreover, the path towards new combinations with systemic agents, particularly immunotherapy building on the actual standard of combined chemo-radiotherapy with durvalumab in consolidation, is reported. This article wants to give a balanced view on the importance to investigate how we can obtain better local and metastatic disease control by intensifying our combined treatment strategies, while bearing in mind that many of our patients in daily clinical practice may not be able tolerate this. This urges us to also explore less disruptive treatment approaches for our more frail and aged patient population and define in a multidisciplinary manner the most optimal treatment strategy for each individual patient in our daily clinical practice.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The role of wide local excision of a primary lesion in cutaneous malignant melanoma: a retrospective analysis of its usefulness in local and general control of disease.

Currently, wide local excision is recommended after the primary excision of cutaneous melanomas. The definition of margins for wide local excision indicated by the guidelines has remained unchanged over the years, although the reported indications are derived from fairly dated studies in which melanomas tended to be thicker or in advanced stages at diagnosis. This study aimed to retrospectively evaluate the usefulness of wide local excision for local and general control of the disease and to identify patients who had benefited from the wide local excision procedure in terms of prognosis improvement. This retrospective observational study was conducted on patients who had undergone surgery for melanoma at a single institution. The primary endpoint was progression-free survival after wide local excision in patients with or without residual melanoma. The secondary endpoint was to evaluate which patients' demographic features and melanoma histological data were associated with residual melanoma after wide local excision. In the univariate model, melanoma-positive wide local excision resulted in the worst progression-free survival; however, this association was not confirmed in the multivariate model. The results also showed that Breslow thickness was the only factor associated with an increased risk of metastasis to the wide local excision area. According to the receiver operating characteristic analysis, the optimum cutoff value of Breslow's thickness to predict a tumor-positive wide local excision was 2.31 mm for males and 2.4 mm for females.

The impact of preoperative treatments on the immune environment of rectal cancer.

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell-T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.

A new surgical strategy for T4 stage posterior buccal carcinoma: anatomical unit resection

Objective: To investigate the effect of anatomical unit resection on the overall survival rate of patients with T4 stage posterior buccal carcinoma. Methods: We conducted a retrospective study on 79 patients with T4 stage posterior buccal squamous cell carcinoma underwent radical surgery for buccal mucosa cancer and reconstruction with free anterolateral thigh flap in the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University from March 2014 to December 2019. The 74 patients were males and the 5 patients were females, aged from 28 to 72 years old. The 40 patients in control group underwent traditional extended resection (1.5-2.0 cm safe margin), and 39 patients in the experimental group underwent anatomical unit resection. The clinicopathological parameters of patients were collected and followed up regularly. The overall survival rate was assessed by Log-rank and Cox proportional risk regression model. Multivariate analysis was performed by linear regression model. Results: There were significant differences between experimental group and control group in overall survival rates (61.53% vs 27.50%, χ2=6.624, P=0.010) and local disease control rates (74.36% vs 27.50%, χ2=17.350, P<0.001). Multiple linear regression analysis showed that local disease control rate was significantly correlated with anatomical unit resection (t=3.880, P<0.001) and lymph node metastasis (t=2.619, P=0.011), and also Cox proportional hazards regression model analysis identified that overall survival rate was significantly correlated with anatomical unit resection (Z=2.421, P=0.016) and lymph node metastasis (Z=2.793, P=0.005). Conclusion: For posterior buccal carcinoma with multiple anatomical units involved, anatomical unit resection can significantly reduce local recurrence and improve overall survival rate of patients.

Therapeutic Treatment Options for In-Transit Metastases from Melanoma.

In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM. Methods include a comprehensive review of clinical studies examining the impact of treatments like immune checkpoint inhibitors, targeted therapies, Isolated Limb Perfusion, and electrochemotherapy. The results indicate that combining systemic therapies with locoregional treatments enhances both local disease control and overall survival rates. The introduction of modern immunotherapies has not diminished the effectiveness of locoregional therapies but rather improved patient outcomes when used in conjunction. The conclusions emphasize that a multidisciplinary approach integrating systemic and locoregional therapies offers a promising strategy for optimizing the management of ITM in melanoma patients. This integrated treatment model not only improves survival rates but also enhances the quality of life for patients, suggesting a shift in standard care practices toward more comprehensive therapeutic regimens.

Early circulating tumor DNA changes predict outcomes in head and neck cancer patients under re-radiotherapy.

Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription.

Perioperative chemotherapy with nivolumab for HER2-negative locally advanced gastric cancer: a case series

BackgroundNivolumab with chemotherapy has been transformative for metastatic gastric cancer (GC). The potential of this regimen for local tumor control could be utilized for perioperative chemotherapy in locally advanced GC with bulky tumors or lymph node metastasis involving other organs.Case presentationFive patients with HER2-negative advanced GC were treated with nivolumab and oxaliplatin-based chemotherapy. All patients presented with clinical stage III or IVA GC with tumors in contact with either the pancreas or liver. Following chemotherapy, all tumors demonstrated shrinkage, allowing successful radical gastrectomies including four minimally invasive approach without postoperative complications. Four patients avoided combined resection of other organs.ConclusionsPerioperative chemotherapy with nivolumab was effective for local disease control in this case series. This regimen could be a promising treatment approach for locally advanced GC; however, its survival benefits should be evaluated in clinical trials.

Intra-Abdominal Metastasis After Pelvic Primary Synovial Sarcoma Resection: Case Report

Introduction: Synovial sarcoma is a malignant soft tissue sarcoma. It occurs predominantly in young adults. 90% of synovial sarcomas occur in the extremities, they have been reported in other sites, including the abdomen and pelvis. Up to 40% of all patients with soft tissue sarcomas develop distant metastasis, despite adequate local disease control. Aim of the article: To provide an update on one of the rarest and most aggressive tumors, to affirm the importance of early management and especially surveillance, and to encourage the codification and the management of these tumors. Presentation of cases: Here, we discuss a case of a 78-year-old female patient, operated 10 years earlier for a pelvic Synovial sarcoma, who presented with intra-abdominal mass to our hospital that eventually turned out to be a metastatic intra-abdominal synovial sarcoma following biopsy. Conclusion: It is important to be aware that primary intraabdominal tumors can occur and delayed metastasis is more typical of synovial sarcoma than of many other sarcomas and should be considered in determining the appropriate frequency and duration of follow-up imaging.

Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial

The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P= 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P= 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P= 0.033). The safety profile remained unchanged since the previous analysis. Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.

Recurrent choroid plexus carcinoma treated with CyberKnife radiosurgery: illustrative case.

Choroid plexus carcinomas (CPCs) are rare malignant brain tumors primarily affecting children younger than 2 years old. These tumors originate from the choroid plexus epithelium and are a subtype of choroid plexus tumors, which account for 1%-4% of pediatric brain tumors. Although CPCs often show a notably high recurrence rate after surgery, the standard treatment approach remains gross-total resection (GTR) of the tumor, given the lack of clinical data supporting the effectiveness of adjunct treatment options such as radiotherapy or chemotherapy. A 16-year-old female with a history of a recurrent cranial CPC resistant to surgery and radiotherapy was treated with CyberKnife stereotactic radiosurgery (SRS), following resection. The procedures successfully maintained local disease control for 41 months; however, there was a subsequent recurrence, ultimately leading to the death of the patient. CPC treatment remains challenging. SRS can be used as a viable adjunct to surgery, which remains the gold standard, although it can also be considered for nonsurgical candidates or when GTR cannot be achieved. Nevertheless, it is crucial to conduct additional research to explore diverse approaches for radiosurgery, including its role as the primary treatment modality versus its combination with surgery, radiotherapy, or chemotherapy. https://thejns.org/doi/10.3171/CASE23748.

Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases

Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report final PFS and OS results. TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period. T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of ADCs as systemic therapy for active BM.

Guías impresas en 3D: ¿mejoran el control local y la supervivencia global en el tratamiento de los sarcomas pélvicos? Estudio de validación clínica

Background and objectives3D-printed patient-specific instruments (PSIs), also known as 3D guides, have been shown to improve accuracy in resection of pelvic tumors in cadaver studies and achieve better surgical margins in vivo. This study evaluates the clinical impact of 3D-printed guides on medium-term local and distant disease control, as well as disease-free and overall survival in patients. Material and methodsA cohort study included 25 patients with primary pelvic or sacral sarcomas: 10 in the 3D group and 15 in the control group, with a median follow-up of 47 months. Demographic and clinical data, including tumor histology, stage, resection technique, associated reconstruction, adjuvant therapies, and complications, were evaluated. Surgical margins (free, marginal, and contaminated) and relapse-free and overall survival curves were analyzed. ResultsThe 3D group achieved a higher rate of free margins (80% vs 66.7%, p = 0.345). Local recurrence (50% vs 60%, P=.244) and distant disease relapse (20% vs 47%, p = 0.132) rates were lower in the 3D group. At the end of the follow-up, the 3D group had a higher overall survival rate (60% vs 40%, p = 0.327). The complication rate was similar in both groups, with a deep infection rate of 40%. ConclusionsThe use of 3D guides in resecting primary pelvic tumors not only achieves a higher rate of free margins compared to conventional techniques but also shows a trend towards higher local, distant, and overall disease-free survival. Further studies with larger sample sizes and higher levels of evidence are necessary to validate these clinical trends.

Predictive capacity for local disease control of neogenin-1 (NEO1) transcriptional expression in patients with head and neck squamous cell carcinoma.

To analyze the predictive capacity for local disease control of the transcriptional expression of neogenin-1 (NEO1) gene in patients with head and neck squamous cell carcinoma (HNSCC). A retrospective study was performed on tumor biopsies from 107 patients with HNSCC treated surgically. The transcriptional expression of NEO1 was determined by RT-PCR. NEO1 transcriptional expression value was categorized according to local disease control by recursive partitioning analysis. Lower NEO1 transcriptional expression was associated with worse local control after surgical treatment. Patients with lower NEO1 expression (n = 25, 23.4%) had a 5-year local recurrence-free survival of 61.8% (95% CI: 42.1-81.5%), while patients with higher NEO1 expression (n = 82, 76.6%) had a 5-year local recurrence-free survival of 85.6% (95% CI: 77.6-93.6%), (P = 0.003). According to the result of multivariable analysis, patients with lower NEO1 expression had a 2.7-fold increased risk of local tumor recurrence (95% CI: 1.0-7.0, P = 0.043) compared to patients with higher NEO1 expression. HNSCC patients with a lower transcriptional expression of NEO1 have a significantly higher risk of local recurrence after surgical treatment.

Better Local Disease Control With Mastectomy in Metaplastic Breast Carcinoma: Findings of a Retrospective Cohort.

Metaplastic breast cancer (MBC) is a rare type of breast carcinoma with clinicopathological differences. The prognosis and treatment strategies for MBC are usually conflicting. In this study, we aim to present the clinicopathologic features, treatment strategies, and prognosis of our MBC patients. In our retrospective study, 18 metaplastic breast cancer patients treated in our institution between January 2005 and December 2022 were evaluated. Demographic and clinicopathological characteristics, surgical and systemic treatment options, locoregional recurrences, distant metastases, and overall survival (OS) of the MBC patients were retrieved from the patient files. All patients were female; the median age was 54.42 ± 12.37 years. Most of the patients (n = 15, 83.33%) presented with palpable masses. Tumors were mostly triple-negative, with a high grade and a high Ki‑67 proliferation index. Spindle cell carcinoma and MBC with mesenchymal differentiation were the most common subtypes. Most of the patients underwent mastectomy (n = 11, 61.11%); breast-conserving surgery (BCS) was performed on seven (38,88%) patients. Lymph node positivity was detected in six of 18 patients (33.33%). Fewer patients (n = 4, 22.22%) received neoadjuvant chemotherapy. While local recurrence developed in two out of seven patients (28.57%) who underwent BCS, there was no local recurrence in patients who had mastectomy. The OS time varied according to tumor size and the presence of lymph node metastases (p <0.001; p = 0.005). Metaplastic breast cancer is genetically heterogeneous and resistant to conventional treatment strategies. Mastectomy is still the surgical treatment method that is performed more frequently and provides better local control for patients with metaplastic breast cancer.

The impact of adjuvant radiation therapy on disease-specific survival in stage I and II Merkel cell carcinoma: A SEER database analysis.

9593 Background: Merkel Cell Carcinoma (MCC) is a rare, cutaneous neuroendocrine tumor associated with poor prognosis. Adjuvant radiation therapy (RT) is commonly used for the treatment of locoregional disease, but the impact on survival remains controversial. Previous studies from the Survival, Epidemiology, and End Results (SEER) database have shown an overall survival benefit to adjuvant RT without controlling for important prognostic differences in comparison groups such as age. To better control for these variables, we examined the impact of postoperative adjuvant radiation therapy on stage I and II disease-specific survival using the SEER database. Methods: SEERStat was used to obtain and analyze the outcomes of 2423 histologically confirmed MCC patients treated with surgery monotherapy or surgery with postoperative radiation therapy between 2004 and 2020 in the 17-registry (November 2021) SEER database. We compared the 5-year disease-specific survival (DSS) between the surgery monotherapy and adjuvant RT groups for stage I (n=1697) and stage II (n=726) MCC patients. Results: Patients treated with surgery and adjuvant RT were younger than those who received surgery monotherapy (median age 72 versus 77, respectively). Adjuvant RT was not associated with an increase in disease-specific survival. In contrast, adjuvant RT was associated with a statistically significant decrease in 5-year DSS among stage I patients (82.8% for those treated with RT versus 87.5% for those treated with surgery monotherapy, p = 0.023). Additionally, RT was not associated with a significant increase in DSS among stage II patients (77.0% versus 74.4% for patients treated with surgery monotherapy, p=0.490). Conclusions: This study demonstrates that there is no statistically significant disease-specific survival benefit from adjuvant radiation therapy for stage I and II MCC in the SEER database. Interestingly, in stage I patients we find a significant negative association between adjuvant RT and DSS. Younger patients are more likely to receive adjuvant RT, which likely contributes to higher overall survival previously reported from the SEER database, but the explanation for decreased DSS in patients who received RT remains unclear. Further studies regarding the effect of radiation therapy on local disease control and tumor microenvironment are needed to establish the appropriate role of RT in stage I-II MCC patients. [Table: see text]

Molecular analysis of surgical margins with NGS to assess microscopic residual disease in early oral squamous cell carcinomas.

6063 Background: The prognosis of early oral squamous cell carcinomas (OSCC) is strongly correlated with local disease control. However, patients with T1-T2 OSCC operated with clear margins have a 5-year local relapse rate of 10 to 15%. An accurate evaluation of the microscopic residual disease (MRD) is therefore essential. Interestingly, innovative techniques have recently been developed to detect circulating tumor DNA. Methods: A prospective multicenter trial based on patients with T1-T2 OSCC treated surgically with clear margins, was designed to assess the feasibility of a molecular analysis (tetranucleotide instability) of these margins to evaluate a potential MRD while adapting the postoperative strategy (NCT00232960). We, then, evaluate the feasibility of detecting MRD in the margins by identifying specific molecular abnormalities in the primary tumor with Whole Exome Sequencing (WES) and explore them in margins with deep target NGS panel (TGS) and digital PCR (dPCR) for hotspot mutations. Results: 310 patients were included initially with 216 tumor/margins samples available for molecular analysis. After a standard pathologic analysis, all surgical margins were negative.Median follow-up was 58 months [30;83]. Tumor was informative for tetranucleotide instability analysis in 63% of cases. Positive molecular margins were observed in 17.3% of cases, leading to a postoperative treatment (surgery or radiotherapy). In informative tumors, molecularly driven treatment seemed to lower the 5-year local recurrence rate from 14.1% to 6.4% (p=0.15). Among this initial cohort, 108 primary tumors were secondarily screened by WES to find mutations of interest, with an informativity rate of 75%. Positive molecular results (TGS or dPCR), with at least one positive margin, were observed in 19.4% of patients. Then, analyzing retrospectively the oncologic outcomes, we observed a significant benefit for local control at 5 years for patients with TGS-dPCR negative results in all margins compared to pathologic negative margins (91.7% versus 64.1%, p=0.02). Conclusions: To our knowledge, this is the first report of local MRD assessment after surgery using NGS.Molecular analysis of resection margins for early OSCC lead to a better evaluation of MRD and personalized postoperative decision making to improve local control. Clinical trial information: NCT00232960 .