Primary Surgical Resection Research Articles

Assessing the Efficacy of Imiquimod Use in Patients With Persistent Locally Advanced Melanoma In Sit.

The standard of care when treating melanoma in situ (MMIS) is an excision with at least 5 mm surgical margins.1 Some studies have suggested up to 9 mm margins to maximize local recurrence-free survival.2 This retrospective review aims to assess the efficacy of imiquimod as a topical treatment for persistently positive MMIS at the margins of prior excisions or where surgery is not an option. Retrospective study conducted at Moffitt Cancer Center between 2019 and 2021 with patients aged > 18 years with MMIS at the margins of excision of an invasive melanoma or MMIS. Included patients were not ideal candidates for primary or additional surgical resection due to non-feasibility of surgery because of comorbidity or cosmetically sensitive location and/or the need for repeated skin grafting, or due to patient's refusal. Patients received imiquimod on protocol for 16 weeks and were monitored for treatment response and side effects. Following completion of the treatment, scouting biopsies were performed to assess histological response, and dermoscopy was used to determine the clinical disease status. Ten patients completed 16 weeks of imiquimod. Seven (75%) had a median of 2 surgical resections, and 3 refused surgery despite discussion that surgery was standard of care. Seven were deemed free of disease on post-imiquimod treatment scouting biopsies, while 2 were found to be clinically free of disease following confocal microscopy, indicating a tumor clearance rate of 90% with imiquimod treatment. One patient was found to have persistent residual disease following 2 rounds of imiquimod and was taken for an additional surgical excision after which they were deemed free of disease. Median follow-up duration from the onset of imiquimod therapy to the last clinic visit was 18 months, without any recurrences to date. Imiquimod appears to demonstrate an encouraging tumor clearance among patients with persistent MMIS after surgery where further surgical resection may not be feasible. Although long-term durability has not been demonstrated in this study, a 90% tumor clearance rate is promising. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6987.

Our Experiences of Tertiary Referral Centers in the Management of Recurrent Colonic Cancer after an Initial Curative Right-sided Colonic Resection

Abstract Background: Colon cancer is one of the most common types of cancer. Oncological surgical resection is the most effective method to achieve a successful outcome, but the prognosis of recurrence is poor. Objectives: The objective of our study was to provide an insight into our management of patients who have experienced recurrences by first assessing the 5-year survival rate of patients who underwent curative surgery for right-sided colon cancer and then reporting on the rate and management of recurrences. Study Design: We conducted a retrospective study using a prospective database of patients with recurrent colon cancer following an initial curative right-sided resection. Setting: In the study, patients diagnosed and treated at King’s College Hospital for colorectal cancer between 2011 and 2015 were included. Patients and Methods: The study included patients with right-sided colonic adenocarcinoma (including the cecum, ascending colon, hepatic flexure, and proximal two-thirds of the transverse colon) who had undergone curative surgical resection and had completed follow-up. Main Outcome Measures: Our main outcome measures were survival after curative resection of right-sided colon cancers, recurrence, and survival after recurrence. Sample Size: Our study included 195 patients. Results: In this study, 195 patients with stages I–III right-sided colonic tumors were treated with primary curative surgical resection (R0), of which 173 (86.7%) were treated electively and 22 (11.3%) were treated as an emergency. A total of 104 men (53.3%) and 91 women (46.7%) participated in our study, and the mean age at diagnosis was 69.2 (12.8) years. After a 5-year follow-up period, 145 patients (74.4%) successfully completed the follow-up with no loss of patients. We noted that 88.7% of the patients had no recurrence, but 22 (11.3%) of 195 patients experienced recurrences and 28 (14.4%) died. Following further analysis of the patients with recurrences, we found that 13 (6.6%) had distant metastases, seven (3.5%) had local recurrences, and two (1.2%) had multiple recurrences. The mean time to recurrence was 15.1 (10.8) months. Recurrence was associated with a mean survival rate of 39.64 (19.2) months compared to 53.9 ± 15.1 for patients without recurrence (Log Rank P = 0.000). Among patients with recurrences, the 5-year survival rate was 31.8%; however, it was 80.9% (Log Rank P = 0.000) for those without recurrences. Patients with recurrent cancer who received curative treatment had a 5-year survival rate of 40.0% compared to 14.3% for those who received palliative treatments (Log Rank P = 0.068). Conclusion: In our study, right-sided colorectal cancer after oncological surgical resection was associated with a recurrence rate of 11.3%. The survival rate was inversely proportional to the stage of the disease at the time of diagnosis. Detection of recurrence and surgical intervention in a timely manner are associated with improved survival rates. Limitations: This study has limitations, including its retrospective nature. We collected data for this study from electronic records and databases of patients after completion of follow-up. Conflict of Interest: The authors have no conflict of interest to declare.

Neoadjuvant tyrosine kinase inhibitor therapy in locally advanced differentiated thyroid cancer: a single centre case series.

Primary surgical resection remains the mainstay of management in locally advanced differentiated thyroid cancer. Tyrosine kinase inhibitors have recently shown promising results in patients with recurrent locally advanced differentiated thyroid cancer. This study discussed four patients with locally advanced differentiated thyroid cancer managed with tyrosine kinase inhibitors used prior to surgery in the 'neoadjuvant' setting. Prospective data collection through a local thyroid database from February 2016 identified four patients with locally advanced differentiated thyroid cancer unsuitable for primary surgical resection commenced on neoadjuvant tyrosine kinase inhibitor therapy. All cases had T4a disease at presentation. Three cases tolerated tyrosine kinase inhibitor therapy for more than 14 months while the last case failed to tolerate treatment at 1 month. All patients subsequently underwent total thyroidectomy to facilitate adjuvant radioactive iodine treatment. Disease-specific survival remains at 100 per cent currently (range, 29-75 months). Neoadjuvant tyrosine kinase inhibitors in locally advanced differentiated thyroid cancer can be effective in reducing primary tumour extent to potentially facilitate a more limited surgical resection for local disease control.

Abstract P4-09-08: AI-based quantitation of cancer cell and fibroblast nuclear morphology reflects transcriptomic heterogeneity and predicts survival in breast cancer

Abstract Background: Morphological features of cancer cell nuclei are routinely used to assess disease severity and prognosis, and cancer nuclear morphology has been linked to genomic alterations. Quantitative analyses of the nuclear features of cancer cells and other tumor-resident cell types, such as cancer-associated fibroblasts (CAFs), may reveal novel biomarkers for prognosis and treatment response. Here, we applied a pan-cancer nucleus detection and segmentation algorithm and a cell classification model to hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of breast cancer specimens, enabling the measurement of morphological features of nuclei of multiple cell types within a tumor. Methods: Convolutional Neural Network models for 1) nucleus detection and segmentation and 2) cell classification were deployed on H&E-stained WSIs from The Cancer Genome Atlas (TCGA) breast cancer dataset (primary surgical resections; N=890). Separate models were trained to segment regions of stromal subtypes, such as inflamed and fibroblastic stroma. Nuclear features (area, axis length, eccentricity, color, and texture) were computed and aggregated across each slide to summarize slide-level nuclear morphology for each cell type. Next-generation sequencing-based metrics of genomic instability (N=774) and gene expression (N=868) were acquired and paired with TCGA WSIs. Gene set enrichment analysis was performed using the Molecular Signatures Database. Spearman correlation compared nuclear features to genomic instability metrics. Linear regression was used to assess the relationship between nuclear features and bulk gene expression. Multivariable Cox regression with age and ordinal tumor stage as covariates was used to find association between overall survival (OS) and nuclear features. All reported results were significant (p< 0.05) when adjusted for false discovery rate via the Benjamini-Hochberg procedure. Results: Variation in cancer cell nuclear area, a quantitative metric related to pathologist-assessed nuclear pleomorphism, was calculated by the standard deviation of the nuclear area of cancer cells across a WSI. This feature was associated with genomic instability, as measured by aneuploidy score (r=0.448) and homologous recombination deficiency score (r=0.382), and reduced OS. In contrast, the variability in fibroblast and lymphocyte nuclear areas did not correlate with either metric of genomic instability (all r< 0.1, p>0.05). Furthermore, an association between variation in cancer cell nuclear area with the expression of cell cycle and proliferation pathway genes was observed, suggesting that increased nuclear size heterogeneity may indicate a more aggressive cancer phenotype. Features quantifying CAF nuclear morphology were also assessed, revealing that CAF nucleus shape (larger minor axis length) was associated with lower OS, as well as the expression of gene sets involved in extracellular matrix remodeling and degradation. Conclusions: The nuclear morphologies of breast cancer cells and CAFs reflect underlying genomic and transcriptomic properties of the tumor and correlates with patient outcome. The application of digital pathology analysis of breast cancer histopathology slides enables the integrative study of genomics, transcriptomics, tumor morphology, and overall survival to support research into disease biology research and biomarker discovery. Citation Format: John Abel, Christian Kirkup, Filip Kos, Ylaine Gerardin, Sandhya Srinivasan, Jacqueline Brosnan-Cashman, Ken Leidal, Sanjana Vasudevan, Deepta Rajan, Suyog Jain, Aaditya Prakash, Harshith Padigela, Jake Conway, Neel Patel, Benjamin Trotter, Limin Yu, Amaro Taylor-Weiner, Emma L. Krause, Matthew Bronnimann, Laura Chambre, Ben Glass, Chintan Parmar, Stephanie Hennek, Archit Khosla, Murray Resnick, Andrew H. Beck, Michael Montalto, Fedaa Najdawi, Michael G. Drage, Ilan Wapinski. AI-based quantitation of cancer cell and fibroblast nuclear morphology reflects transcriptomic heterogeneity and predicts survival in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-09-08.

Association of Variation in US County-Level Rates of Liver Surgical Resection for Colorectal Liver Metastasis With Poverty Rates in 2010

Among patients with colorectal liver metastasis (CRLM) who are eligible for curative-intent liver surgical resection, only half undergo liver metastasectomy. It is currently unclear how rates of liver metastasectomy vary geographically in the US. Geographic differences in county-level socioeconomic characteristics may, in part, explain variability in the receipt of liver metastasectomy for CRLM. To describe county-level variation in the receipt of liver metastasectomy for CRLM in the US and its association with poverty rates. This ecological, cross-sectional, and county-level analysis was conducted using data from the Surveillance, Epidemiology, and End Results Research Plus database. The study included the county-level proportion of patients who had colorectal adenocarcinoma diagnosed between January 1, 2010, and December 31, 2018, underwent primary surgical resection, and had liver metastasis without extrahepatic metastasis. The county-level proportion of patients with stage I colorectal cancer (CRC) was used as a comparator. Data analysis was performed on March 2, 2022. County-level poverty in 2010 obtained from the US Census (proportion of county population below the federal poverty level). The primary outcome was county-level odds of liver metastasectomy for CRLM. The comparator outcome was county-level odds of surgical resection for stage I CRC. Multivariable binomial logistic regression accounting for clustering of outcomes within a county via an overdispersion parameter was used to estimate the county-level odds of receiving a liver metastasectomy for CRLM associated with a 10% increase in poverty rate. In the 194 US counties included in this study, there were 11 348 patients. At the county level, the majority of the population was male (mean [SD], 56.9% [10.2%]), White (71.9% [20.0%]), and aged between 50 and 64 (38.1% [11.0%]) or 65 and 79 (33.6% [11.4%]) years. The adjusted odds of undergoing a liver metastasectomy was lower in counties with higher poverty in 2010 (per 10% increase; odds ratio, 0.82 [95% CI, 0.69-0.96]; P = .02). County-level poverty was not associated with receipt of surgery for stage I CRC. Despite the difference in rates of surgery (mean county-level rates were 0.24 for liver metastasectomy for CRLM and 0.75 for surgery for stage I CRC), the variance at the county-level for these 2 surgical procedures was similar (F370, 193 = 0.81; P = .08). The findings of this study suggest that higher poverty was associated with lower receipt of liver metastasectomy among US patients with CRLM. Surgery for a more common and less complex cancer comparator (ie, stage I CRC) was not observed to be associated with county-level poverty rates. However, county-level variation in surgical rates was similar for CRLM and stage I CRC. These findings further suggest that access to surgical care for complex gastrointestinal cancers such as CRLM may be partially influenced by where patients live.

Relationship Between Worst Pattern of Invasion and Extranodal Extension in Oral Tongue Squamous Cell Carcinomas.

Oral tongue squamous cell carcinoma (OTSCC) is a common malignancy of the oral cavity with poor survival rates. The aim of this project is to investigate the relationship between certain histopathological factors such as Worst Pattern of Invasion (WPOI) and Extranodal Extension (ENE) in patients with oral tongue squamous cell carcinoma (OTSCC) who underwent surgical resection at Loyola University Medical Center. This was a retrospective cohort study at a tertiary care academic medical center. All patients that underwent primary surgical resection of OTSCC between 1/1/2015 and 1/1/2022 were reviewed. Patients were identified using the Cerner CoPath Laboratory Information System. A total of 82 patients met inclusion criteria and were included in the study. Higher grades of WPOI (WPOI 5) were not significantly associated with the presence of ENE in our study (P = 0.82), regardless of the presence of major or minor ENE. WPOI 5 was associated with a higher incidence of local recurrence (P = 0.011). Higher grades of WPOI were not found to correlate with the presence of ENE, a common histopathological factor that is used as an important prognostic indicator in OTSCC. It is important for clinicians to consider these factors separately when determining whether a patient is high-risk and would benefit from aggressive multimodal treatment.

Tumor Necrosis Factor Alpha: Implications of Anesthesia on Cancers.

Cancer remains a major public health issue and a leading cause of death worldwide. Despite advancements in chemotherapy, radiation therapy, and immunotherapy, surgery is the mainstay of cancer treatment for solid tumors. However, tumor cells are known to disseminate into the vascular and lymphatic systems during surgical manipulation. Additionally, surgery-induced stress responses can produce an immunosuppressive environment that is favorable for cancer relapse. Up to 90% of cancer-related deaths are the result of metastatic disease after surgical resection. Emerging evidence shows that the interactions between tumor cells and the tumor microenvironment (TME) not only play decisive roles in tumor initiation, progression, and metastasis but also have profound effects on therapeutic efficacy. Tumor necrosis factor alpha (TNF-α), a pleiotropic cytokine contributing to both physiological and pathological processes, is one of the main mediators of inflammation-associated carcinogenesis in the TME. Because TNF-α signaling may modulate the course of cancer, it can be therapeutically targeted to ameliorate clinical outcomes. As the incidence of cancer continues to grow, approximately 80% of cancer patients require anesthesia during cancer care for diagnostic, therapeutic, or palliative procedures, and over 60% of cancer patients receive anesthesia for primary surgical resection. Numerous studies have demonstrated that perioperative management, including surgical manipulation, anesthetics/analgesics, and other supportive care, may alter the TME and cancer progression by affecting inflammatory or immune responses during cancer surgery, but the literature about the impact of anesthesia on the TNF-α production and cancer progression is limited. Therefore, this review summarizes the current knowledge of the implications of anesthesia on cancers from the insights of TNF-α release and provides future anesthetic strategies for improving oncological survival.

The effect of insurance status on treatment modality in advanced oral cavity cancer

BackgroundInsurance status has been shown to impact survival outcomes. We sought to determine whether insurance affects the choice of treatment modality among patients with advanced (T4) oral cavity squamous cell carcinoma.MethodsThis is a retrospective, population-based cohort study using the Survival, Epidemiology, and End Results Program database. The population included all adult (age ≥ 18) patients with advanced (T4a or T4b) oral cavity squamous cell carcinoma diagnosed from 2007 to 2016. The main outcome was the odds of receiving definitive treatment, defined as primary surgical resection. Insurance status was categorized into uninsured, any Medicaid, and insured groups. Univariable, multivariable, and subgroup analyses were performed.ResultsThe study population consisted of 2628 patients, of whom 1915 (72.9%) were insured, 561 (21.3%) had Medicaid, and 152 (5.8%) were uninsured. The multivariable model showed that patients who were 80 years or older, unmarried, received treatment in the pre-Affordable Care Act (ACA) period, and who were on Medicaid or uninsured were significantly less likely to receive definitive treatment. Insured patients were significantly more likely to receive definitive treatment compared to those on Medicaid or uninsured (OR = 0.59, 95% CI 0.46–0.77, p < 0.0001 [Medicaid vs. Insured]; and OR = 0.48, 95% CI 0.31–0.73 p = 0.001 [Uninsured vs. Insured]), however these differences did not persist when considering only those patients treated following the 2014 expansion of the ACA.ConclusionsInsurance status is significantly associated with treatment modality among adults with advanced stage (T4a) oral cavity squamous cell carcinoma. These findings support the premise of expanding insurance coverage in the US.Graphical

Is there a Role for Primary Surgical Resection in the Palliative Rectal Cancer Setting: A Systematic Re-view

Introduction: There are over 42,000 new cases of colorectal cancer diagnosed every year in the UK alone, a third of those being rectal in origin. Although there has been significant progress in the treatment of rectal cancer, overall, 5-year survival can still be as low as 17% for those with advanced disease. We aimed to assess the impact on of overall survival and quality of life of primary tumour resection in the palliative setting. Method: A literature search was performed using Pubmed and Cochrane databases in March 2022. Bias was assessed using the Joanna Briggs institute checklist. Results: Seven papers were included in the review; all retrospective cohort. A total of 809 patients underwent rectal resection in the presence of metastatic disease +/- adjuvant therapy. The median age was 61years, 59.7% male. 68.6% of patients presented with liver metastasis at the time of diagnosis. The most commonly reported symptoms preoperatively were bleeding and tenesmus. 4-50% of patients in each cohort underwent neoadjuvant therapy. Highest 30-day mortality reported was 7.3%. Both studies comparing resection v none demonstrated a higher overall survival for those undergoing surgery, with one showing 1year overall survival 65v20%. Quality of life was not addressed across the literature. Conclusion: Although there is some evidence to show a favourable overall survival for patients undergoing primary tumour resection in the palliative setting, this data is mainly old and across a heterogeneous population. A larger scale prospective study would be required to assess its potential role and impact upon quality of life.

New trends in criteria indicative of neoadjuvant oncological therapy of lower and middle rectal cancers.

The indication for primary surgical resection or neoadjuvant therapy in lower and middle rectal cancers is often disputable. The aim of the study was to evaluate the occurrence of local recurrence of rectal cancer as for aperiod of at least 4 years after radical resection. The second aim was to evaluate and compare the results of preoperative magnetic resonance (MR) staging with definitive histology.From September 2013 to December 2017, we, at the 3rd Surgical Department Comenius University, Bratislava, prospectively evaluated patients with lower and middle rectal cancers with the distal tumor border being in a12-cm distance from the anal verge. All patients underwent MR examination at the same MRI department and were operated on at the 3rd Surgical Department, Comenius University, Bratislava. Inclusion criteria included parameters based on MRI examination, i.e., T-staging of T1-T3b, negative extramural vascular infiltration (EMVI), negative circumferential margin (CRM), no mesorectal fascia infiltration with a distance of more than 2 mm. We did not take lymph node staging into account in the indication for primary surgical resection. We performed a radical primary resection procedure (R0 resection) in all patients. The group consisted of 87 patients, of whom 49 were men and 38 were women. The mean age of the patients was 66 years (min. 36 - max. 86 years). Our study also shows significant differences in preoperative T and N staging as compared to definitive histology. The incidence of local recurrence during aperiod of at least 4 years after surgery was 6.76 %. Study also shows that the indication for preoperative radiotherapy for lower and middle rectal cancers based on N status is inaccurate and leads to unnecessary indications for preoperative radiotherapy which may decrease the patients´ quality of life and increase the post‑operative complications. We have also shown that leaving out the N-based radiotherapy from indications does not lead to an increase in the number of local recurrences in lower and middle rectal cancers (Tab. 1, Fig. 5, Ref. 22). Text in PDF www.elis.sk Keywords: rectal cancer, neoadjuvant therapy, local recurrence.

Frequency and accuracy of intraoperative bone margin sampling for T4a cancers of the head and neck at the QEII Health Sciences Centre: a retrospective chart review

BackgroundStage T4a cancers are associated with a 5-year survival of 21.6–59.0%. Adequate resection of these tumors is a critical factor in maximizing survival. Tumors invading bone pose a unique challenge to intraoperative bone margin assessment. Due to processing limitations, there had been no formal standardized protocol for intraoperative bone sampling at the QEII Health Sciences Centre. These resections often involve extensive reconstruction, making salvage surgery difficult if positive margins are detected post-surgically. The purpose of this study was to assess the accuracy and frequency of intraoperative bone margin assessment during the study period and to determine survival and recurrence rates associated with positive final bone margins.MethodsA retrospective chart review was conducted including patients with stage T4a head and neck cancer involving bone that underwent primary surgical resection in Nova Scotia between 2009 and 2019. Eligible patients were identified through the Cancer Care Nova Scotia registry. Exclusion criteria included patients with stage T4a tumors involving bone that did not receive primary surgical treatment with curative intent and patients with stage T4a tumors that did not invade bone.ResultsOf 67 patients included, 50 were amenable to intraoperative bone margin sampling while 18 had intraoperative sampling. Four patients had positive intraoperative margins and one had final positive bone margins. The incidence of final bone margin positivity was 7.5%. Median survival following surgery was 4.56 years for patients with final negative bone margins (n = 62) and 3.98 years for patients with positive final bone margins (n = 5). All patients with final positive bone margins received adjuvant radiation therapy. Of patients with negative final bone margins, 16.1% received no adjuvant therapy, 61.3% received adjuvant radiation therapy and 21.0% received adjuvant chemoradiation therapy.ConclusionIntraoperative bone margin sampling occurred in 26.8% of all cases and 36.0% of amenable cases. Median survival of patients with positive final bone margins was 0.58 years lower than those with negative final bone margins, although this difference did not reach statistical significance. This will provide baseline data for comparison of the standardized intraoperative bone margin sampling protocol implemented at the QEII Health Sciences Centre.Graphical

Treatment Outcomes of Adenoid Cystic Carcinomas of the Head and Neck Region-A Single-Institution Experience.

Malu RafiObjectives This study was undertaken to evaluate the characteristics and treatment outcomes of patients with adenoid cystic carcinomas of the head and neck region treated at a tertiary cancer center in south India. Materials and Methods This was a retrospective study done on patients treated at the institute between 2004 and 2011. Clinicopathological details and treatment outcomes were captured from the treatment records to estimate the treatment outcomes and factors affecting them. Results There were a total of 140 patients with mean age of presentation of 46 years and a median follow-up of 65 months. The most common single site of presentation was the oral cavity. One-hundred eighteen patients (84.3%) underwent primary surgical resection in which 38% had negative surgical margins. Ninety-nine patients were given adjuvant radiotherapy and 18 patients received radical radiotherapy, mostly for surgically inaccessible and inoperable tumors. Median time to recurrence and distant metastasis was 37 and 34 months, respectively. The overall survival and disease-free survival estimate using the Kaplan-Meier method were 92.3 and 71.9%, respectively, at 5 years. Surgical removal of the primary tumor and the nodal stage had the most significant impact on the overall survival outcomes of these patients. Conclusion Surgery remains the most impactful treatment modality in the management of these rare epithelial tumors. The use of adjuvant radiotherapy may help to tackle the issues of perineural spread and inadequate surgical margins in technically difficult sites. Radical radiotherapy also has impressive response rates.

Association of Primary Tumor Volume With Survival in Patients With T3 Glottic Cancer Treated With Radiotherapy

The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors. To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study. This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria. Tumor volume as measured on diagnostic imaging by expert neuroradiologists. Primary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study. The mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76). Increasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.

Spatial Analysis of NQO1 in Non-Small Cell Lung Cancer Shows Its Expression Is Independent of NRF1 and NRF2 in the Tumor Microenvironment.

Nuclear factor erythroid 2-related factor 1 (NFE2L1, NRF1) and nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) are distinct oxidative stress response transcription factors, both of which have been shown to perform cytoprotective functions, modulating cell stress response and homeostasis. NAD(P)H:quinone oxidoreductase (NQO1) is a mutual downstream antioxidant gene target that catalyzes the two-electron reduction of an array of substrates, protecting against reactive oxygen species (ROS) generation. NQO1 is upregulated in non-small cell lung cancer (NSCLC) and is proposed as a predictive biomarker and therapeutic target. Antioxidant protein expression of immune cells within the NSCLC tumor microenvironment (TME) remains undetermined and may affect immune cell effector functions and survival outcomes. Multiplex immunofluorescence was performed to examine the co-localization of NQO1, NRF1 and NRF2 within the tumor and TME of 162 chemotherapy-naïve, early-stage NSCLC patients treated by primary surgical resection. This study demonstrates that NQO1 protein expression is high in normal, tumor-adjacent tissue and that NQO1 expression varies depending on the cell type. Inter and intra-patient heterogenous NQO1 expression was observed in lung cancer. Co-expression analysis showed NQO1 is independent of NRF1 and NRF2 in tumors. Density-based co-expression analysis demonstrated NRF1 and NRF2 double-positive expression in cancer cells is associated with improved overall survival.

239P Prospective evaluation of difference in patient-reported swallowing outcomes and quality of life of tongue vs bucco-alveolar complex cancers treated with ablative surgery

Oral cancer surgery includes radical resections of the mandible and tongue, affecting the functional swallowing outcomes. However, risk factors and swallowing outcomes are not the same for all subsites of oral cancer. The present study aimed to assess the difference in patient-reported swallowing function and quality of life after primary surgical resection in tongue vs bucco- alveolar complex (BAC) malignancies.

Biobehavioral factors predict an exosome biomarker of ovarian carcinoma disease progression.

Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors. Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6months) versus more extended disease-free intervals following initial treatment. Samples from asecond subgroup of 24 patients were analyzed by mixed-effects linear models to determine whether the progression-predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms). An RNA-based molecular signature was identified that discriminated between individuals who had disease progression in ≤6months versus >6months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates. These data identified a novel exosome-derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring.

Role of immune-inflamed phenotype in the prognosis of hypopharyngeal carcinoma following primary surgery.

The immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined. We enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand-1 (PD-L1), and interferon (IFN)-γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non-inflamed tumors based on the presence or absence of parenchymal CD8+ T cells. We found that 74% of HPSCC cases in our cohort were characterized by an immune-inflamed TME. Immune-inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163+ tumor-associated macrophages and Foxp3+ regulatory T cells. Additionally, the inflamed tumor showed increased expression of PD-L1, without IFN-γ upregulation. The immune-inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment.

329. IMPROVED TUMOUR PURITY AND PLOIDY ESTIMATION FROM LASER CAPTURE MICRODISSECTED ESOPHAGEAL ADENOCARCINOMA SAMPLES

Abstract Large scale sequencing efforts by The Cancer Genome Atlas (TCGA), among others, have generated detailed genomic data for esophageal adenocarcinoma. However, samples with low cancer purity (i.e. high amounts of normal DNA) will limit accurate inference of copy number aberrations, a genomic hallmark of esophageal adenocarcinoma. This consequently restricts more advanced analysis such as quantifying intratumor heterogeneity or inferring tumor evolution. We have systematically collected biopsies from pre-treatment and post-induction esophageal adenocarcinoma tumors. Laser capture microdissection (LCM) was utilized to enrich for tumor cells for whole genome sequencing. Matching blood was utilized as germline control. Cancer purity and ploidy was estimated using a developed method tailored to the high genomic instability observed in EAC samples. This method uses both sequencing depth and minor allele frequencies to infer ploidy and purity. The esophageal adenocarcinoma dataset from TCGA were used as comparison. We achieved significantly higher tumor cellularity in surgical resection specimens (n = 8) compared to TCGA (71%+/−11 vs. 58%+/−18). Interestingly, tumor cellularity from biopsy specimens (n = 25) remained similar to TCGA despite LCM (65%+/−13), which is likely due to TCGA only using surgical resections that were pre-selected to have at least 60% cellularity, while we applied no histopathological cellular constraints on our samples. Estimated ploidy was similar between biopsy of primary tumors and surgical resection specimens compared to TCGA (2.67+/−0.58, 2.72+/−0.70, 2.64+/−0.75). There was a trend towards higher ploidy (3.07+/− 0.13) in metastatic biopsies (n = 3) but additional specimens are required. Laser capture microdissection of post-induction esophageal adenocarcinoma surgical resection specimens has resulted in significantly higher tumor purity in whole genome sequencing data. This will allow for improved inferences of phylogenetic trees between pre- and post- induction samples and quantification of subclonal copy number aberrations or intratumor heterogeneity.

Lobar versus sublobar resection in clinical stage IA primary lung cancer with occult N2 disease.

Sublobar resection is increasingly being utilized for early-stage lung cancers, but optimal management when final pathology shows unsuspected mediastinal nodal disease is unclear. This study tested the hypothesis that lobectomy has improved survival compared to sublobar resection for clinical stage IA tumours with occult N2 disease. The use of sublobar resection and lobectomy for patients in the National Cancer Database who underwent primary surgical resection for clinical stage IA non-small-cell lung cancer with pathologic N2 disease between 2010 and 2017 was evaluated using logistic regression. Survival was assessed with Kaplan-Meier analysis, log-rank test and Cox proportional hazards model. A total of 2419 patients comprised the study cohort, including 320 sublobar resections (13.2%) and 2099 lobectomies (86.8%). Older age, female sex, smaller tumour size and treatment at an academic facility predicted the use of sublobar resection. Patients undergoing lobectomy had larger tumours (2.40 vs 2.05 cm, P &lt; 0.001) and more lymph nodes examined (11 vs 5, P &lt; 0.001). Adjuvant chemotherapy use was similar between the 2 groups (sublobar 79.4% vs lobectomy 77.4%, P = 0.434). Sublobar resection was not associated with worse survival compared to lobectomy in both univariate (5-year survival 46.6% vs 45.2%, P = 0.319) and multivariable Cox proportional hazards analysis (hazard ratio 0.97, P = 0.789). Clinical stage IA non-small-cell lung cancer patients with N2 disease on final pathology have similar long-term survival with either sublobar resection or lobectomy. Patients with occult N2 disease after sublobar resection may not require reoperation for completion lobectomy but should instead proceed to adjuvant chemotherapy.

34902 Assessing the efficacy of imiquimod use in patients with persistent locally advanced melanoma in situ

Purpose: The standard of care (SOC) when treating melanoma in situ (MMIS) is excision with at least 5mm surgical margins. This retrospective review aims to assess the efficacy of imiquimod as a topical treatment for persistently positive MMIS at the margins of prior excisions or where surgery is not an option. Methods: Patients age >18 years with MMIS at the margins of excision of an invasive melanoma or MMIS were enrolled in this retrospective study at the Moffitt Cancer Center between 2019-2021. Included patients were not candidates for primary or additional surgical resection due to refusal and/or the need for repeated skin grafting. Patients received imiquimod on protocol for 16 weeks and were monitored regularly for inflammatory effects of the treatment. Following completion of the treatment, scouting biopsies were performed to assess response. Results: Eight patients completed 16 weeks of imiquimod with scout biopsies 4-8 weeks after. Six (75%) had a median of 2 surgical resections, and 2 refused surgery despite discussion that surgery was the SOC. Seven were deemed free of persistent disease on post-imiquimod treatment scout biopsy, indicating an 87.5% pathologic complete response (pCR). Median follow-up duration from the onset of imiquimod to the last clinic visit was 15 months, without any recurrences on examination. Conclusion: These results demonstrate that imiquimod appears to be an efficacious treatment for patients with persistent MMIS after surgery where further surgical resection may not be feasible. Although long-term durability has not been demonstrated in this study, an 87.5% pCR is promising.