Locoregional Disease Research Articles

Survival Outcomes in Patients Undergoing Pelvic Exenteration for Pelvic Mucosal Melanomas: Retrospective Single Institution Australian Study.

Pelvic mucosal melanomas, including anorectal and urogenital melanomas, are rare and aggressive with a median overall survival of up to 20 months. Pelvic mucosal melanomas behave differently to its cutaneous counterparts and presents late with locoregional disease, making pelvic exenteration its only curative surgical option. This study aimed to evaluate the survival outcomes post pelvic exenteration in pelvic mucosal melanomas at Royal Prince Alfred Hospital. Retrospective case series from a prospectively collected pelvic exenteration database from October 1994 to November 2023. Royal Prince Alfred Hospital (quaternary institution), Camperdown, New South Wales, Australia. Seven patients undergoing pelvic exenteration for pelvic mucosal melanoma. Overall survival, disease-free survival, and complication rates. Of the seven patients, most were female (n = 5, 71.4%) and had a median age of 65 years (range, 36-79). Five patients (71.4%) underwent pelvic exenteration for primary pelvic mucosal melanoma; 3 of which were anorectal and 2 vaginal melanomas. Two patients (28.6%) had recurrent anorectal melanoma and received neoadjuvant radiotherapy following an initial wide local excision. Three patients (42.9%) required total pelvic exenteration, while 2 required a central pelvic exenteration (28.6%). The remaining procedures were a central and lateral pelvic exenteration; along with anterior, central and lateral pelvic exenteration. Median length of hospital stay was 19.7 days. Five patients had postoperative complications with one major complication (Clavien-Dindo IIIa). At the study's completion, there were 4 mortalities. Mean survival was 23.6 months (range, 2-100) with a recurrence rate of 83%. Median time to recurrence was 3 months, despite 6 patients (85.7%) having R0 resections. Distant recurrence, i.e. to bone, lung and liver was most common. Small study cohort due to rarity of disease, limiting generalizability. Pelvic exenteration for pelvic mucosal melanoma appears to help control local disease as recurrence is most commonly distant or regional. See Video Abstract.

Profound, durable benefit from external beam radiotherapy for primary, in transit and locoregional disease from Merkel cell carcinoma in the frail elderly: illustrative clinical vignettes

Profound, durable benefit from external beam radiotherapy for primary, in transit and locoregional disease from Merkel cell carcinoma in the frail elderly: illustrative clinical vignettes

Abstract B028: Analytical validation of tumor-informed whole genome sequencing analyses for detection of molecular residual disease in solid tumors

Abstract Introduction: Across all patients diagnosed with solid tumors, approximately two-thirds initially present with locoregional disease and are potentially eligible for curative-intent intervention. However, there is a significant subset of patients for which residual tumor cells remain afterwards, potentially leading to disease recurrence. It has been reported that these residual tumor cells, representative of molecular residual disease (MRD), can be detected through analyses of circulating tumor DNA (ctDNA), often earlier than can be achieved through radiographic imaging or clinical presentation. Methods: Labcorp Plasma Detect was utilized to analyze patient-matched tumor, germline (white blood cells), and cell-free or contrived DNA samples through whole genome sequencing at approximately 80x, 40x, and 30x depth, respectively. Raw sequencing data were demultiplexed and trimmed for read quality, then aligned to the hg19 human reference genome. Tumor-specific single nucleotide variants were identified from the tumor and germline datasets and used to determine the presence of cancer within cell-free or contrived DNA samples through a random forest machine learning model. ctDNA status was determined based on the level of signal compared to a reference cohort of noncancerous donor plasma samples (n=80). Results: Analytical specificity was determined through analysis of five noncancerous donor plasma samples with five replicates each, evaluated against 60 somatic mutation profiles obtained from patients with stage III colon cancer, demonstrating a specificity of 99.4% (835/840). Analytical sensitivity was assessed using three contrived cell line models from breast and melanoma tumors, analyzed across three tumor content levels with five replicates at each level and resulted in a limit of detection of 0.005% tumor content using a 100% hit-rate model. Precision, repeatability, and reproducibility were demonstrated within and across runs, operators, and instruments, resulting in a 100% detection rate at 0.05% tumor content with a coefficient of variation of 8.5%. Finally, analytical accuracy compared to an independent tumor-informed ctDNA MRD approach was determined through analysis of 39 clinical cases obtained from patients with bladder, breast, colorectal, and lung cancer, yielding a positive percent agreement of 91% (10/11) and negative percent agreement of 100% (24/24). The prognostic value of ctDNA MRD was demonstrated in stage III colon cancer and clinical validation results for HPV-negative head and neck squamous cell carcinoma will be presented separately. Conclusions: There is significant potential for tumor-informed, non- bespoke MRD approaches for ctDNA detection across a broad range of solid tumor types and curative-intent clinical settings. These data demonstrate the analytical performance of Labcorp Plasma Detect in a CAP/CLIA laboratory for pan-solid tumor research use together with investigational use in early stage colon cancer to support the interventional MEDOCC-CrEATE clinical trial. Citation Format: Kaitlin Victor, Andrew Georgiadis, Ellen Verner, Antoine Simmons, David Riley, James R White, Christopher Greco, Liam Cox, Jesse Fox, Jennifer B Jackson, Eric A Severson, Brian J Caveney, Marcia Eisenberg, Taylor J Jensen, Shakti Ramkissoon, Samuel V Angiuoli, Amy Greer, Kenneth Valkenburg, Mark Sausen. Analytical validation of tumor-informed whole genome sequencing analyses for detection of molecular residual disease in solid tumors [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 B028.

OGC SO13 - Recurrence Patterns after Minimally Invasive vs. Left Thoracoabdominal Oesophagectomy for distal oesophageal and junctional adenocarcinomas

Abstract Background Oesophageal cancer is a leading cause of cancer-related death worldwide, with oesophagec-tomy being the primary treatment for curable disease. This study compares loco-regional and distal disease recurrence patterns between minimally invasive oesophagectomy (MIO) and left thoracoabdominal oesophagectomy (LTAO) using a matched dataset. The definition of loco-regional recurrence remains unclear in the literature. In this study, loco-regional recur-rence is categorised as recurrence in the oesophageal bed, anastomosis, or local nodes in the mediastinum and upper abdomen. Method Patients from 2014 to 2021 were identified and followed until 31/12/2023. Data on MIOs and LTAO were collected from a prospectively maintained database. Gastroesophageal junction and distal oesophagus adenocarcinomas were included, and all received neoadjuvant chemotherapy. Out of 302 eligible patients, 104 were successfully matched. The primary outcome was overall cancer recurrence. Categorical variables were compared using chi-square tests, and non-parametric contin-uous variables with Mann-Whitney U tests. Propensity score matching, accounted for baseline differences. Logistic regression generated propensity scores for age, gender, and tumour stage. Operative approach was the dependant variable. The groups were then selected using ‘nearest neighbour’ matching. Results The study compared 52 cases each of LTAO and MIO. Postoperative complications were similar, LTAO (58%) and MIO (52%) P=0.554. The R0 resection rate was higher in LTAO (90%) compared to MIO (81%) P=0.163. Recurrence was significantly higher in LTAO (42%) than MIO (23%) P=0.037. Local recurrence rates were 15% for LTAO and 8% for MIO P=0.22. Distant recurrence was 35% for LTAO and 21% for MIO P=0.111. Notably, peritoneal recurrence was significantly higher in LTAO (12%) P=0.012. There was no difference in median time to recurrence. Mortality rate was similar: 38% for LTAO and 35% for MIO P=0.684. Conclusion The study found that while postoperative complications and mortality rates were similar between LTAO and MIO, LTAO had a significantly higher overall recurrence rate and notably higher peritoneal recurrence. There was no significant difference in median time to recurrence between the two groups. These findings suggest that MIO may be associated with better long-term outcomes in terms of recurrence.

Abstract B014: Prospective analysis of circulating tumor cell dynamics during preoperative radiotherapy in locally advanced breast cancer

Abstract Introduction: This is a per-protocol interim analysis of circulating tumor cell (CTC) dynamics among patients diagnosed with locally advanced breast cancer receiving preoperative radiotherapy (RT) on the TOPAz trial (“Trial of Preoperative Radiation”) with concurrent enrollment on a prospective observational cohort study (2022-0601). Methods: Eligible patients with clinical or pathologic T3-4 or node-positive non-metastatic breast cancer were prospectively enrolled. All patients received preoperative RT followed by mastectomy and were randomized to conventional fractionation (CFx, 50Gy/25Fx) versus hypofractionation (HFx, 40Gy/15Fx). CTCs were enumerated using the CellSearch® assay immediately prior to RT (Pre-RT) and within 1 week of completing RT (End of RT). Rates of CTC detection and clearance with RT were calculated. Results: As of August 2024, 46 enrolled patients had a Pre-RT assessment for CTCs, of which 45 (98%) received neoadjuvant chemotherapy (NAC), 30 (65%) had clinical T3-4 disease, 10 (22%) had advanced nodal (cN3) disease, 39 (85%) had estrogen receptor (ER)- positive disease, 3 (7%) overexpressed Her2, and 6 (13%) had triple negative disease. Prior to RT, 15 (33%) patients had ≥1 detectable CTC (median [IQR] = 2 cells [1-2.5]). Of the 14 CTC- positive patients with a completed “End of RT” blood draw to date, 11 (79%) achieved CTC clearance, while 3 patients had persistent CTCs (median [IQR] = 2 cells [1.5-2.5]). Patients who achieved CTC clearance had significantly lower median initial CTC count compared to patients who had persistent CTCs ((2 [1-2]) versus 8 [5-19], Kruskal-Wallis test, p<0.05). CTC status at either time point was not significantly associated with clinicopathologic or treatment variables. Of the 9 CTC-positive patients who achieved CTC clearance and completed surgery, 1 experienced pCR (11%) while all 3 patients with persistent CTCs had residual disease. The median RCB index score for patients without detectable CTCs at End of RT (n=33) was 2.9 [1.4- 3.4] versus 3.3 [2.2-3.4] for the 3 patients with persistent CTCs. In a subgroup of 37 patients with ER+ Her2- disease, 11 (30%) patients had detectable CTCs prior to RT. Of the 10 with completed “End of RT” blood draw to date, 8 (80%) achieved CTC-clearance. The median RCB index score for patients without detectable CTCs at End of RT (n=27) was 3.0 [1.5-3.6] versus 3.4 [3.4-3.4] for the 2 patients with persistent CTCs. Conclusion: In this prospective analysis of CTC dynamics during preoperative RT for patients with locally advanced breast cancer, one- third of patients had detectable CTCs prior to RT (33%). Following comprehensive RT, 79% of patients with detectable CTCs prior to RT experienced CTC clearance prior to surgical resection. All patients with persistent CTCs had residual disease at surgery. These interim results support further study of longitudinal monitoring of circulating tumor material as a potential real-time biomarker for residual locoregional disease in the preoperative setting. Citation Format: Chelain R Goodman, Simona F Shaitelman, Saleh Ramezani, Jonathan B. Strauss, Anam Zia, Nathan Comeaux, Ritupreet Virk, Ruitao Lin, Kevin Nead, Melissa P Mitchell, Karen E Hoffman, Eric Strom, Michael Stauder, George Perkins, Valerie Reed, Elizabeth Bloom, Melissa Joyner, Pamela Schlembach, Vicente Valero, Bora Lim, Carlos H Barcenas, Anthony Lucci, Wendy A Woodward, Benjamin D Smith. Prospective analysis of circulating tumor cell dynamics during preoperative radiotherapy in locally advanced breast 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 B014.

Patterns of loco-regional progression and patient outcomes after definitive-dose radiation therapy for anaplastic thyroid cancer

BackgroundThe aim of this study is to characterize the patterns of loco-regional progression (LRP) and outcomes after definitive-dose intensity modulated radiation therapy (IMRT) for anaplastic thyroid cancer (ATC) with macroscopic neck disease at the time of IMRT. MethodsDisease/treatment characteristics and outcomes for patients with unresected or incompletely resected ATC who received IMRT (≥45 Gy) were retrospectively reviewed. For those with LRP after IMRT, progressive/recurrent gross tumor volumes (rGTV) were contoured on diagnostic CTs and co-registered with initial planning CTs using deformable image registration. rGTVs were classified based on established spatial/dosimetric criteria. ResultsForty patients treated between 2010–2020 formed the cohort. Median IMRT dose was 66 Gy (45–70 Gy); altered fractionation (AF) was used in 24 (60 %). All received concurrent chemotherapy. In addition to areas of gross disease, target volumes (TVs) commonly included: central compartment/upper mediastinum (levels VI/VII), neck levels II-V in an involved, and levels III-IV in an uninvolved lateral neck. Median overall survival was 7.1 m. Median progression free survival was 7.4 m for patients with locoregional disease and 1.8 m for patients with distant metastasis at the time of IMRT. Twenty-one patients (53 %) developed LRP at median of 10.9 m; freedom from LRP at 3 m and 12 m was 71 % (95 %CI 58–87 %) and 47 % (95 %CI 32–68 %). Forty-one individual rGTVs were identified and most occurred within the high dose (HD) TVs: Type A/central HD (n = 29, 71 %) and B/peripheral HD (n = 3, 7 %). ConclusionsDespite an intensive treatment schedule, including AF and concurrent chemotherapy, classic radio-resistant and rapid Type A failures predominated; isolated extraneous dose failures were rare. While these findings support the IMRT and TV delineation strategies described herein, they highlight the importance of identifying novel strategies to further improve LRC for patients with unresectable disease without targetable mutations for contemporary neo-adjuvant strategies.

Clinical Outcomes, Patterns of Failure, and Salvage Therapies of a Large Modern Cohort of Patients With Anal Squamous Cell Carcinoma Treated With Definitive-Intent Intensity-Modulated Radiation Therapy

PurposePatterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy are not well described. Patients and MethodsWe identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure (LRF), distant failure (DF), progression-free survival (PFS), colostomy-free survival (CFS), and overall survival (OS)), patterns of failure, and salvage therapies were collected. Failures were analyzed by competing risks methods, whereas survival endpoints were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months from completing IMRT. Results375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for AJCC stage 0-I, II, and III, respectively. Six-year rates of LRF, DF, PFS, CFS, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse six-year OS than patients without LRF (44% versus 86%, P<0.0001). Approximately 30% of patients who underwent salvage therapy were alive ten years after recurrence, compared with none of the patients who were managed with chemotherapy alone or best supportive care. ConclusionsThis large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment.

A Randomized, Multicenter, Phase 2 Trial of Camrelizumab With or Without Metastasis-directed Stereotactic Body Radiation Therapy in Recurrent or Metastatic Nasopharyngeal Carcinoma

PurposeTo investigate the efficacy of metastasis-directed therapy (MDT) when added to camrelizumab (Cam) in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). MethodsWe conducted a randomised, controlled, multicentre, phase II trial in 3 centres from China (NCT04830267). Patients with R/M-NPC, without prior exposure to immunotherapy, who presented with ≥2 lesions, and at least 1 measurable lesion were randomised 1:1 to either Cam alone or Cam plus MDT (Cam+MDT). Patients randomised to the MDT group must have 1 lesion that is amendable to stereotactic body radiotherapy (SBRT) prescribed to 27Gy in 3 fractions every other day. Primary endpoint was objective response rate (ORR) of unirradiated lesions by RECIST v1.1. ResultsBetween April 2021 and August 2023, 39 patients were randomly assigned to receive either Cam (n=20) or Cam+MDT (n=19). 17/39 (43.6%) patients had oligometastatic disease (≤3 lesions); 18/39 (46.2%) had liver involvement; 3/39 (7.7%) had locoregional recurrent disease. ORR of unirradiated lesions did not differ between the treatment groups (26.3% [Cam+MDT] vs 30.0% [Cam], P=1.0). DCR of unirradiated lesions was 73.7% in the Cam+MDT group compared with 60.0% in the Cam group (P=0.571). After a median follow-up of 25.8 months, median progression-free survival was 9.3 (95% CI: 6.2-NR) months in the Cam+MDT group and 8.8 (95% CI: 3.3-NR) months in the Cam group (P=0.750). Exploratory analyses suggested a longer overall survival (OS) with Cam+MDT for patients with >3 lesions (HR 0.23 [95% CI: 0.07-0.77], P=0.009). G3 and above adverse events were comparable between the treatment groups (15.8% [Cam+MDT] vs 20.0% [Cam]). Overall rate of capillary proliferation was 17.9% (7/39) on the trial. ConclusionsOur study did not meet its primary endpoint of superior ORR of unirradiated lesions with the addition of MDT to Cam in patients with R/M-NPC.

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.

Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery.

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) is evolving as a new treatment modality for patients with early biochemical recurrence of prostate cancer and disease limited to locoregional lymph nodes on PSMA-ligand PET/CT. Nevertheless, the pattern of failure (locoregional vs. systemic) after PSMA RGS remains unknown. Therefore, the aim of this retrospective analysis was to evaluate the pattern of disease using PSMA-ligand PET in patients experiencing relapse after PSMA RGS. Methods: We evaluated 100 patients with biochemical recurrence after previous PET-guided PSMA RGS who underwent PSMA-ligand PET (median prostate-specific antigen [PSA], 0.9 ng/mL; range, 0.2-14.2 ng/mL). All suspicious lesions for recurrent prostate cancer were grouped according to the molecular imaging TNM classification system. Detection rates and lesion localization were determined and stratified by PSA values and the International Society of Urological Pathology grade group. Further, lesion localization was compared before and after PSMA RGS. Results: The median time between PSMA RGS and PSMA-ligand PET for relapse was 11.4 mo (range, 5.5-25.6 mo). In total, 91 of 100 (91%) patients showed PSMA-ligand-positive findings. PSMA PET detection rates were 82.6%, 92.6%, 91.3%, and 96.3% for PSA levels of 0.2-0.49, 0.5-0.99, 1-1.99, and at least 2 ng/mL, respectively. More than half of the patients (53%; 48/91) showed local recurrence or pelvic lymph node metastases only. Extrapelvic lymph node metastases, bone metastases, and visceral metastases were present in 22% (20/91), 16% (15/91), and 9% (8/91) of the patients, respectively. With increasing International Society of Urological Pathology grade group, the percentage of patients with bone and visceral metastases increased, whereas the number of patients with only locoregional disease decreased. Conclusion: PSMA-ligand PET is a useful method to detect and localize recurrent disease in patients with biochemical failure after PSMA RGS, with more than half of the patients presenting with locoregional recurrence, offering the potential for a second local therapy (e.g., radiation therapy or repeated surgery).

Abstract B135: Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors

Abstract Background: Disparities in pediatric cancer outcomes by race and ethnicity may be influenced by neighborhood characteristics, particularly residential economic and racial segregation. Prior to a new cancer diagnosis, pediatric patients are vulnerable to structural barriers embedded in their neighborhoods. In particular, residential economic and racial segregation may impede access to initial care for early cancer detection, increasing the likelihood of presenting with distant metastatic disease at diagnosis that can translate to excess morbidity and mortality. This study assesses the association of residential economic and racial segregation as measured by the Index of Concentration at the Extremes (ICE) with the likelihood of presenting with distant metastatic disease (as compared to local or locoregional disease) among children newly diagnosed with cancer. Methods: We studied a cohort of pediatric patients diagnosed with solid tumors at Children’s Healthcare of Atlanta between 2010 and 2016. Patients’ ZIP codes were linked to the ICE, which was constructed at the ZIP code level using American Community Survey 2012-2016 five-year estimates. The ICE was categorized into tertile 1 (most deprived) through tertile 3 (most privileged). Multivariable logistic regression models were used to assess the association between residential economic and racial segregation, defined by tertiles of the ICE, and the likelihood of presenting with distant metastatic disease, as determined by initial cancer staging. All models adjusted for patient- and disease-level covariates, including age, sex at birth, health insurance type, and cancer type. Results: Among 829 patients identified in our analytic sample, 27.6% had distant metastatic disease at diagnosis. Living in the most deprived (ICE tertile 1) versus the most privileged (ICE tertiles 2/3) neighborhoods was significantly associated with a higher likelihood of presenting with distant metastatic disease at diagnosis (adjusted odds ratio [OR] = 1.46; 95% confidence interval [CI] = 1.03 to 2.07; p=0.03). Additionally, non-Hispanic Black patients living in the most deprived neighborhoods were more likely to have distant metastatic disease at diagnosis compared to non-Hispanic White patients living in the most privileged neighborhoods (adjusted OR = 1.83; 95% CI = 1.15 to 2.92; p=0.002). Conclusion: This study provides new insights into how residential economic and racial segregation is associated with metastatic disease at diagnosis among children presenting with a new solid tumor. Our findings highlight the need for geographically targeted interventions to improve community care, resource allocation and investment, and public policies aimed at supporting this vulnerable patient population. Citation Format: Alexandra Cathcart, Sharon M. Castellino, Lu Zhang, Karen Wasilewski-Masker, Andrew L. Hong, Heeju Sohn, Xu Ji. Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B135.

Marginal Mandibulectomy in Oral Cavity SCC: Experience in a Tertiary Care Centre.

Marginal mandibulectomy is indicated for oral cavity squamous cell carcinomas that involve floor of mouth, abut or minimally erode the mandible without gross invasion. Successful outcomes after Marginal mandibulectomy is predicated on accurate patient selection and appropriate adjuvant treatment based on specific host and tumor characteristics. To study the onclogical outcomes in terms of loco-regional recurrence free survival and disease specific survival of marginal mandibulectomy done for oral squamous cell carcinomas. Study Design-Retrospective study. Setting-The study was done from January 2018 to January 2021 at our tertiary care centre Madras Medical College, Chennai. Subjects-30 cases were included in our study who underwent Marginal Mandibulectomy for oral cavity SCC. Methods-The decision to perform a marginal mandibulectomy was taken based on preoperative clinical examination, contrast enhanced computed tomography (CECT) findings and intra-operative assessment under anesthesia. Disease-free survival, cause-specific survival, and local control rates were plotted using the Kaplan-Meier method. Oncologic outcomes in terms of Overall survival and Disease-specific survival at the end of 1 year and 3 years for the gingival, buccal, tongue, floor of mouth cancers were analyzed. Independent impacts including the site of tumor, T and N stage, microscopic bony invasion, grade of differentiation, adjuvant radiotherapy on the loco-regional control and cause-specific survival were evaluated using Kaplan meier method. Our study group was comprised of 20(66.67%) males and 10 (33.33%) females of mean age 54 years. None of them had prior radiotherapy to the head and neck region. A total of 7 (23.33%) marginal mandibulectomies were carried out for SCC in the gingival region, 11(36.67%) for buccal mucosa, 8(26.67%) for tongue, 2(6.67%) for floor of mouth SCC, 1(3.33%) involving lip, 1(3.33%) in Retromolar trigone. Clinically 2 (6.67%) patients had T1 cancer, 18 (54.54%) had T2, 6 (18.18%) had T3, 4(13.33%) had T4 tumor. Clinically Neck nodes were not palpable in 17 (56.67%) patients, 10 (33.33%) had N1 disease and 3 (10%) had N2 disease. T and N stage distributions for tongue/floor of mouth and gingival buccal complex cancers are summarized in the table and there were no statistically significant differences between the 2 groups. 19 (63.33%) had selective neck dissection (levels I-III), and 11 (36.67%) had comprehensive neck dissection. Well-differentiated tumors were encountered in 12 (40%) cases, moderately differentiated tumors in 16 (53.33%) cases, and poorly differentiated tumors in 2 (6.67%) cases. Bone was microscopically involved in 4 (13.33%) cases and mucosal margin of excision was less than 5 mm from the tumor in 2 (6.67%) cases. Cumulative hazard of local recurrence was not significantly affected by mandibular involvement. On histopathologic examination, positive nodes were seen in 6(20%) cases that included 3 (10%) with pN1 and the rest with pN2 disease. Adjuvant radiotherapy (56 to 64 Gy) was given to 13 (43.33%) patients. In carefully selected patients, marginal mandibulectomy in oral squamous cancer achieves good oncological outcome in terms of locoregional control and overall survival rates.

The added value of 68Ga-PSMA PET/CT in anatomical staging of prostatic carcinoma in correlation with the histopathological zonal staging

BackgroundProstate cancer is well known as the commonest cancer in men and the second leading cause of cancer-related death. CT, MRI and bone scintigraphy are considered the commonly widely used imaging diagnostic tools for detection, staging and follow-up of prostate cancer. Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, that can be concentrated in prostate cancer cells up to 100 times higher than in normal cells. PSMA-targeted imaging modalities have now proven their efficacy in diagnosis, staging and follow-up of prostate cancer. The use of 68Ga PSMA PET-CT has efficiently improved the detection of loco-regional and metastatic disease. 68Ga PSMA PET-CT also has an effective role in the primary diagnosis, staging, and detecting biochemical recurrence after curative treatment and in metastasis-targeted therapy. This work aims to review the role of 68Ga PSMA PET-CT in anatomical staging of prostate cancer in correlation with histopathological staging.ResultsZonal correlation between 68Ga PSMA findings and biopsy results showed sensitivity ranging between 76.9 and 90.6% and specificity ranging from 85.7 to 100%. There was high significant correlation between the SUVmax uptake and the biopsy results, between the SUVmax uptake and the local staging as well as between the Gleason score and 68Ga PSMA PET/CT findings.Conclusions68Ga PSMA PET/CT is a highly promising imaging modality with an effective role in detection of prostate cancer showing high sensitivity and specificity in prediction of zonal histopathological results and loco-regional Gleason score staging with significant positive correlation between the SUV uptake results, Gleason score and the PSA levels.

WP3.2 - Craniectomy With Soft Tissue Reconstruction for Locally Advanced Non-Melanoma Skin Cancer of Scalp with Calvarial Invasion: the Nottingham experience

Abstract Introduction Locally advanced non-melanoma skin cancer (NMSC) involving the periosteum or calvarium remain clinically challenging for patients unfit for immunotherapy due to medical comorbidities and/or frailty. This case series aims to explore outcomes for patients that underwent craniectomy and soft tissue reconstruction. Method Patients underwent craniectomy and soft tissue reconstruction for invasive NMSC with calvarium or periosteal invasion from 2016 to 2022 were included. Data including demographics, operative details, and clinical outcomes were sourced from Nottingham University Hospitals digital health record and the histopathology electronic database. Result 8 patients (Age: 78.4, 3F 5M) with significant comorbidities and varying degrees of periosteal or bone invasion fulfilled the inclusion criteria. These included four squamous cell carcinoma, two basal cell carcinoma and two pleomorphic dermal sarcomas. Five patients had a history of prior incomplete deep margin excision. The median soft tissue defect, tumour and bone defect size was 51.83cm2, 34.63cm2 and 42.25cm2 respectively. Intraoperative complications included one dural tear. Four patients underwent local flap reconstruction and with split thickness skin grafting, four patients underwent free flap reconstruction. Adjuvant radiotherapy was administered to three. Complications comprised partial graft loss in two and complete graft loss in one. There was partial flap loss in one case. One patient required subsequent parotidectomy due to regional progression before achieving disease control. All patients achieved lasting locoregional disease control (average follow up 29.7 months). Conclusion Craniectomy with soft tissue reconstruction is a safe and effective treatment option in advanced NMSC of the scalp in patients unsuitable for immunotherapy due to frailty or medical co-morbidity.

Carboplatin and Paclitaxel Chemoradiation for Localized Anal Cancer in Patients Not Eligible for Mitomycin and 5-Fluorouracil.

Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Ten patients were included; eight were female, and the median age was 75.5 years (54-87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40-100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4-50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials.

785. MANAGEMENT OF ESOPHAGEAL CANCER WITH CONCURRENT CERVICAL NODE METASTASIS: A NATIONWIDE POPULATION-BASED COHORT STUDY

Abstract Background In the Netherlands, the standard treatment of locally advanced, resectable esophageal cancer without metastasis is neoadjuvant chemoradiotherapy followed by esophagectomy. There is a small subset of patients that present with concurrent cervical lymph node metastasis (LNM). Historically this was seen as distant metastasis and surgical intervention has usually not been an option for these patients. The contemporary TNM classification now categorizes these lymph node stations as locoregional disease. Our current study aims to describe current treatment paradigms in the Netherlands for patients presenting with esophageal cancer and concurrent cervical LNM. Methods This population-based cohort study utilized data from the Netherlands Cancer Registry (NCR), encompassing patients with locally advanced thoracic esophageal or gastroesophageal junction cancer and concurrent cervical lymph node metastasis. Treatment modalities were categorized into five options: neoadjuvant therapy followed by surgery (Neo + S), definitive chemoradiotherapy (dCRT), chemotherapy with or without radiotherapy &amp;lt; 30 Gray (CT), radiotherapy (RT), and best supportive care (BSC). Overall survival (OS) was assessed using the Kaplan-Meier method and compared via the log-rank test. Hazard rates were computed using Cox proportional hazards regression, with adjustment for confounding achieved through inverse probability of treatment weighting (IPTW). Results Between 2015 and 2021, a cohort of 412 patients was identified from the NCR database. Median survival durations were observed as follows: 24.2 months for Neo + S, 18.0 months for dCRT, 14.5 months for CT, 7.0 months for RT, and 3.2 months for BSC (Figure). A comparison between the Neo + S group and dCRT demonstrated a significant improvement in survival (p=0.02). Further subdivision of the surgical group into neoadjuvant CRT or chemotherapy did not reveal a significant difference in survival (p=0.6). Utilizing IPTW to adjust for confounding factors, Neo + S maintained its survival advantage. Conclusion The retrospective cohort findings suggest that neoadjuvant therapy followed by surgery may represent the optimal approach for managing esophageal cancer patients with cervical LNMs Yet, it's vital to recognize the influence of confounding by indication, which statistical adjustments may not entirely rectify. Furthermore, immortal time bias notably skews results favorably toward surgery. Nevertheless, the results emphasize the importance of considering surgery as a viable option for these patients. These limitations underscore the critical need for a prospective study, prompting the launch of the NODE-II trial.

776. THREE-FIELD LYMPHADENECTOMY IN ESOPHAGEAL CANCER: EXPERIENCE OF A PORTUGUESE TERTIARY CENTER

Abstract Background The American Joint Committee for Cancer (AJCC) and the Japanese Esophagus Society (JES) differ in the N classification for esophageal cancer, with the former considering the presence of disease in the supraclavicular lymph nodes as M1, and the latter classifying it as loco-regional disease in thoracic esophageal tumors. Patients who would be excluded from a curative intent treatment strategy by the AJCC classification may be candidates for surgery with lymphadenectomy of nodal groups 101 and 104 (JES). Our goal is to understand the impact of three-field lymphadenectomy on morbidity, loco-regional control and overall survival in patients with esophageal cancer. Methods A retrospective cohort study was conducted using data from a prospective database from a single center, which included all consecutive patients undergoing esophagectomy for cancer with either two-field total thoracic lymphadenectomy or three-field lymphadenectomy, between January 2019 and December 2023. Three-field lymphadenectomy was performed for clinical supraclavicular and recurrent nerve nodal involvement and for proximal third tumors. We assessed the morbidity and mortality of both types of surgery, and loco-regional and distant recurrence and overall survival for both groups. Results Of the 279 esophagectomies for cancer, 137 were included for analysis. The median age was 65 years, with 84% males. 58,4% had squamous cell carcinoma and 41,6% adenocarcinoma. 34.3% of the patients had a 3-field lymphadenectomy, 27,7% of these for supraclavicular N+ and 34% for recurrent nerve N+. Conclusion In this large single-center cohort, patients with significant lymph node involvement, treated with esophagectomy and three-field lymphadenectomy, demonstrated comparable loco-regional control and overall survival to more favorable cases, with no statistically significant increase in morbidity and mortality.

Definitive Radiation Therapy is a Viable Treatment for Locally Advanced Basal Cell Carcinoma Otherwise Requiring Radical or Disfiguring Resection

BackgroundStandard treatment for basal cell carcinoma (BCC) is surgical resection. However, a subset of locally advanced BCCs may be unresectable, or surgery would result in unacceptable functional or cosmetic defects. Outcomes after definitive radiotherapy for locally advanced BCC in the contemporary era are not well established. ObjectiveWe sought to determine locoregional control and disease specific survival after definitive radiotherapy for locally advanced BCC. MethodsPatients with locally advanced BCC treated with definitive radiotherapy between 2005-2020 from 4 academic tertiary care institutions were included. Locally advanced BCCs were defined as patients with unresectable disease, or locations where margin negative resection would lead to unacceptable cosmetic or functional deficit. Additionally, a set of 5 risk factors (size ≥4 cm, the presence of bone invasion, PNI, immunocompromised patient, and recurrent disease) was separately defined and outcomes were investigated. Results608 locally advanced BCC cases were identified, of which 140 were treated with definitive radiotherapy. Median follow up was 22.9 months (1.5-207.2 months). 101 (72.1%) tumors were treated with upfront definitive radiotherapy, while 39 (27.9%) were treated for a recurrence. 5-year Kaplan-Meier estimated locoregional control was 78%. The majority of locoregional failures were local recurrences (95.5%). Larger tumor diameter was a risk factor for locoregional failure (p=0.045), while recurrent disease was not (p=0.29). Cumulative incidence of BCC related mortality at 5 years was 9.5%. Patients with 0 risk factors had a 5-year FF-LRF of 92.4%, whereas those with 1+ risk factors had a 5-year FF-LRF of 68.5% (p=0.004). ConclusionDefinitive radiotherapy for locally advanced BCC has excellent locoregional control, with tumor size representing the only risk factor for recurrence in this study.

Conventional chemoradiation versus accelerated chemoradiation: A prospective study in oropharyngeal cancer

Background: Squamous-cell carcinoma of the head and neck is predominantly a loco regional disease, and the primary treatment methods are surgery and radiotherapy. For patients with locally-regionally advanced oropharyngeal cancer, concurrent chemoradiotherapy is the standard treatment. Material and Method: The aim and objectives of study were a) to compare locoregional response in two arms, b) to compare acute and chronic treatment-related toxicities in the two arms, and c) to compare the quality of life. The study was conducted between August 2014 and April 2016, with 86 patients of histologically proven squamous-cell carcinoma of oropharynx. This is a prospective trial to assess the suitability of five versus six weekly radiotherapy fractions, along with concurrent cisplatin, given to the same total dose, in all stages of oropharyngeal cancer patients. Result: Patients were randomized into two arms: conventional arm (Arm A), which received 5 fractions per week RT -70GY/7 weeks/35#, and accelerated arm (Arm B), which received 6 fractions per week RT -70GY/6 weeks/35. Locoregional squamous-cell carcinoma improved significantly in the accelerated fractionation group compared with that in the conventional RT group. Conclusion: Accelerated RT enhances improvement of locoregional control in the squamous-cell carcinoma of head and neck region, with reduction in overall treatment time and concurrent chemotherapy. Locoregional control of carcinoma improved significantly in the accelerated fractionation group compared with that in the conventional RT group.

Evaluation of Image-Defined Risk Factor (IDRF) Assessment in Patients With Intermediate-risk Neuroblastoma: A Report From the Children's Oncology Group Study ANBL0531

BackgroundThe International Neuroblastoma Risk Group (INRG) classifier utilizes a staging system based on pretreatment imaging criteria in which image-defined risk factors (IDRFs) are used to evaluate the extent of locoregional disease. Children's Oncology Group (COG) study ANBL0531 prospectively examined institutional determination of IDRF status and compared that to a standardized central review. MethodsBetween 9/2009-6/2011, patients with intermediate-risk neuroblastoma were enrolled on ANBL0531 and had IDRF assessment at treating institutions. Paired COG pediatric surgeons and radiologists performed blinded central review of diagnostic imaging for the presence or absence of IDRFs. Second blinded review was performed in cases of discordance. Comparison of local and central review was performed using the Kappa coefficient to determine concordance in IDRF assessment. Results211 patients enrolled in ANBL0531 underwent IDRF assessment; 3 patients were excluded due to poor image quality. Central reviewer pairs agreed on the presence or absence of any IDRF in 170/208 (81.7%; κ = 0.48) cases. Thirteen (6.3%) cases could not be adjudicated after second blinded review. Radiologists were more likely to identify IRDFs as present than surgeons (p < 0.001). Local and central reviewers agreed on the presence or absence of any IDRF in only108/208 (51.9%; κ = 0.06) cases. ConclusionsAmong experienced pediatric surgeons and radiologists participating in central review, concordance was moderate, with agreement in 81.7% of cases. On comparison of local and central assessment of IDRFs, concordance was poor. These data indicate that greater standardization, education, technology, and training are needed to improve the assessment of IDRFs in children with neuroblastoma. Level of EvidenceTreatment Study, Level III.