Abstract
Objective
To assess the impact of surgical margin status and re‐resection on local recurrence (LR) in early‐stage oral cavity squamous cell carcinoma (OCSCC).
Study Design
Retrospective analysis of 352 patients with cT1‐2N0 OCSCC.
Setting
Tertiary care center from 2005 to 2024.
Methods
Patients were stratified by margin status: initial negative (n = 325), re‐resected to negative (RRN) (n = 20), and positive (n = 7). Initial margin status was determined intraoperatively with frozen sections using specimen‐based or tumor bed–based sampling. Primary outcome was 3‐year LR. Chi‐square tests and Cox proportional hazards models evaluated differences across groups, accounting for potential confounders, for example, adjuvant treatment.
Results
The most common subsite was the tongue (60.2%). 75.9% underwent elective neck dissection. 5.7% had an initial positive margin RRN. 4.8% and 22.7% received adjuvant chemoradiotherapy and radiotherapy, respectively. LR rates were 10.5% for initial negative, 35.0% for RRN, and 42.9% for positive margins despite re‐resection. Compared to patients with initial negative, those with positive (hazard ratio [HR] 5.67, 95% CI 1.74‐18.61) and RRN (HR 3.32, 95% CI 1.47‐7.49) margins showed higher rates of LR. There was no significant difference in LR rates between positive versus RRN margins (P = .374). After controlling for adjuvant therapy and margin assessment method, positive (aHR 8.32, 95% CI 2.31‐29.9) and RRN (aHR 3.82, 95% CI 1.68‐8.68) margins remained associated with higher LR. Adjuvant therapy trended toward a protective effect (aHR 0.53, 95% CI 0.24‐1.17, P = .117).
Conclusion
RRN margins should not be considered oncologically equivalent to initial negative margins, as demonstrated by higher 3‐year LR rates.
Keywords: adjuvant therapy, Early‐stage, oral cavity, squamous cell carcinoma, surgical margins
Head neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally, accounting for an estimated 890,000 new cases and 450,000 deaths worldwide annually. 1 The largest contributing site is the oral cavity (OC) with approximately 380,000 new cases each year. 1 According to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database, about 54,000 new cases of HNSCC were diagnosed in 2022 in the United States, with an estimated 11,230 deaths. 2 5‐year survival varies by stage, but for localized disease is 86.6%. This number drops substantially to 69% for regionally metastatic and 40.4% for distant metastatic disease. Therefore, it is critical for optimization of oncological outcomes to attempt to capture and successfully treat patients at an early stage. 3
Surgical resection with a healthy margin of tissue, with or without adjuvant therapy, is the standard of care for patients with OCSCC. 4 Adjuvant radiation therapy is indicated for pT4 tumors and/or if ≥2 neck nodes are positive and considered for pT2 and 3‐tumors with adverse features. 5 Adjuvant chemoradiotherapy is indicated in cases with extranodal extension or positive margins. 6
The National Comprehensive Cancer Network (NCCN) guidelines recommend re‐resection for positive margins when feasible because current treatment paradigms suggest that adjuvant therapy may be avoided if the final pathologic margin is sufficient. 7 Especially in early‐stage OSCC, re‐resection is guided by intraoperative frozen‐section. The adverse impact of positive margins is well‐established. 8 , 9 , 10 , 11 , 12 , 13 , 14 However, the equivalency of re‐resected negative (RRN) margins and initially negative margins has not been definitively identified.
This study aims to evaluate 3‐year local recurrence (LR) among patients with clinical early‐stage OCSCC stratified by final margin status, specifically comparing outcomes between those with initial negative margins, RRN margins, and positive margins. We hypothesize that patients with final margins RRN have worse oncologic outcomes than patients with initial negative margins and therefore should not be treated as oncologically equivalent. We also examine whether adjuvant treatment plays a role in modifying outcomes, hypothesizing that even when adjuvant therapy is controlled for, patients with RRN margins display worse oncologic outcomes compared to their initial negative counterparts.
Methods
We conducted a retrospective analysis of patients with early‐stage OCSCC who underwent surgical resection at the University of Kansas Medical Center (KUMC) from 2005 to 2024. The study was approved by the KUMC institutional review board (STUDY 00161315). Informed consent was waived because the study utilized retrospective deidentified data.
Patients aged 18 years or older with clinically staged T1‐T2 OCSCC without clinical or radiographic evidence of nodal disease (cN0) who were treated with surgical extirpation of the primary tumor were identified. Patients were included if they had complete pathologic data including final margin status and re‐resectiondata. Patients with synchronous primaries, distant metastases, history of head and neck radiation, or resection that was not en bloc or done without curative intent, were excluded. Additionally, patients who had multiple OCSCCs with numerous cancer resections over time in whom it was impossible to distinguish a recurrence from a second primary were excluded.
Patient demographics, tumor characteristics, and pathology reports, treatment details, recurrence data, follow up time, and vital status, were collected from the electronic medical record. Margin status was categorized as: initial negative (lack of invasive carcinoma at frozen and final margins), RRN (invasive carcinoma at initial frozen margin, RRN by additional tissue removal), or positive (invasive tumor at final specimen edge despite re‐resection). Final margin status was determined by pathologic evaluation of formalin‐fixed tissues. Of note, if re‐resection was performed for “close margins” or carcinoma in situ/dysplasia we counted the margin as initial negative not RRN. Initial margin status was determined by frozen section analysis as documented in the pathology report. The intraoperative margin assessment method was classified as specimen‐based margin (SBM) sampling or tumor bed‐based margin (TBBM) sampling based on operative and pathology reports.
The primary outcome was 3‐year LR‐free survival (LRFS). We defined LR as invasive cancer occurring within 3 years of primary surgical resection at a contiguous site. Regional and distant recurrences were also recorded. Secondary outcomes included 3‐year disease‐free survival (DFS) and overall survival (OS). Any patient without a recurrence who did not survive or have a follow‐up within 6 months of surgery was not included in the calculation of LR. All statistical analyses were performed using SPSS 27.0, Chicago, IL. Chi‐square tests were used for categorical comparisons between groups. The outcome metrics of 3‐year LRFS, DFS, and OS were determined by the Kaplan‐Meier method and compared using the log‐rank (Mantel‐Cox) test. A multivariate Cox proportional hazards model was built to assess the independent impact of margin status on LRFS while controlling for adjuvant radiation with or without chemotherapy and margin assessment method. Survival analyses were developed using time from initial surgery date to date of death, date of recurrence, or last known follow‐up. A P value < 0.05 was considered statistically significant.
Results
A total of 352 patients met inclusion criteria. The mean age was 61.2 years (SD = 14.0); 94.9% of patients were white, and 50.6% were male. 196 (55.7%) patients were current or former smokers. The clinical T‐classification distribution was 55.4% cT1 (n = 195) and 44.6% cT2 (n = 157). Some patients were upstaged based on pathologic examination. Pathologic T‐classification distribution was 55.4% pT1 (n = 195), 36.1% pT2 (n = 127), and 8.5% T3/T4 (n = 30). Clinically, all patients were N0. Occult disease was captured by pathologic N‐stage with distribution: 65.3% N0 (n = 230), 5.7% N1 (n = 20), 5.4% N2 (n = 19), 1.7% N3 (n = 6). The overall distribution of subsites included oral tongue (60.2%; n = 212), floor of mouth (11.4%; n = 40), alveolus (9.9%; n = 35), and other OC subsites (18.5%; n = 65). Baseline patient and tumor characteristics were similar between groups. The study population characteristics are summarized in Tables 1 and 2.
Table 1.
Demographic Characteristics
| Margin status | |||||
|---|---|---|---|---|---|
| Overall (N = 352) | Initial negative (N = 325) | Re‐resected to negative (N = 20) | Positive (N = 7) | P‐value | |
| Age, mean (SD) | 61.2 (14.0) | 61.2 (13.8) | 62.0 (1) | 58.7 (22.7) | .855 |
| Sex | .939 | ||||
| Male | 178 (50.6%) | 164 (50.5%) | 10 (50.0%) | 4 (57.1%) | |
| Female | 174 (49.4%) | 161 (49.5%) | 10 (50.0%) | 3 (42.9%) | |
| Race | .954 | ||||
| White | 334 (94.9%) | 307 (94.5%) | 20 (100%) | 7 (100%) | |
| Black | 3 (0.9%) | 3 (0.9%) | 0 | 0 | |
| AAPI | 5 (1.4%) | 5 (1.5%) | 0 | 0 | |
| Other | 10 (2.8%) | 10 (3.1%) | 0 | 0 | |
| Smoking status | .814 | ||||
| Current | 71 (20.2%) | 65 (20.0%) | 4 (20.0%) | 2 (28.6%) | |
| Former | 125 (35.5%) | 118 (36.3%) | 5 (25.0%) | 2 (28.6%) | |
| Never | 156 (44.3%) | 142 (43.7%) | 11 (55.0%) | 3 (42.9%) | |
Abbreviation: AAPI, Asian American and Pacific Islander.
Table 2.
Pathologic Characteristics
| Margin status | |||||
|---|---|---|---|---|---|
| Overall (N = 352) | Initial negative (N = 325) | Re‐resected to negative (N = 20) | Positive (N = 7) | P‐value | |
| Subsite | .339 | ||||
| Tongue | 212 (60.2%) | 200 (61.5%) | 10 (50.0%) | 2 (28.6%) | |
| FOM | 40 (11.4%) | 35 (10.8%) | 3 (15.0%) | 2 (28.6%) | |
| Alveolus | 35 (9.9%) | 31 (9.5%) | 2 (10.0%) | 2 (28.6%) | |
| Other | 65 (18.5%) | 59 (18.2%) | 5 (25.0%) | 1 (14.3%) | |
| Clinical T classification | .086 | ||||
| T1 | 195 (55.4%) | 183 (56.3%) | 11 (55.0%) | 1 (14.3%) | |
| T2 | 157 (44.6%) | 142 (43.7%) | 9 (45.0%) | 6 (85.7%) | |
| Pathological T classification | <.001 | ||||
| T1 | 195 (55.4%) | 186 (57.2%) | 8 (40.0%) | 1 (14.3%) | |
| T2 | 127 (36.1%) | 118 (36.3%) | 7 (35.0%) | 2 (28.6%) | |
| T3 | 19 (5.4%) | 14 (4.3%) | 4 (20.0%) | 1 (14.3%) | |
| T4 | 11 (3.1%) | 7 (2.2%) | 1 (5.0%) | 3 (42.9%) | |
| Pathological N classification | .001 | ||||
| N0 | 230 (65.3%) | 217 (66.8%) | 9 (45.0%) | 4 (57.1%) | |
| N1 | 20 (5.7%) | 19 (5.8%) | 1 (5.0%) | 0 | |
| N2 | 19 (5.4%) | 13 (4.0%) | 5 (25.0%) | 1 (14.3%) | |
| N3 | 6 (1.7%) | 5 (1.5%) | 0 | 1 (14.3%) | |
| Nx | 77 (21.9%) | 71 (21.8%) | 5 (25.0%) | 1 (14.3%) | |
Abbreviation: FOM, floor of mouth.
The timing of re‐resection was intraoperative for 11.9% of patients (n = 42), at a close later date based on positive specimen margins on final pathology report for 0.6% (n = 2), and both intraoperative and delayed for 0.9% (n = 3). Margin assessment method was TBBM in 86.6% (n = 305) of the cohort and SBM in the rest. After surgery, 97 (27.6%) patients received adjuvant treatment, with 80 (22.7%) receiving adjuvant radiation and 17 (4.8%) receiving adjuvant chemoradiation. In total, 44 (12.5%) patients subsequently developed LR within 3 years. The overall recurrence rate, including local, regional, and distant failure, was 19.6% (n = 69). Among patients who developed local recurrence, adjuvant therapy was administered to 23.5% (n = 8) of those with initially negative margins, none of those with RRN margins, and 33.3% (n = 1) of those with positive margins (P = .316).
Recurrence rates are summarized in Table 3. Median follow‐up for patients was 46.5 months. Overall, 3‐year LRFS was 87.5% (Figure 1). Patients with positive margins had a significantly higher risk of LR compared with those with initial negative margins (hazard ratio [HR] 5.67, 95% CI 1.74‐18.61, P = .001). Patients with RRN margins demonstrated increased risk of LR compared to those with initial negative margins (HR 3.32, 95% CI 1.47‐7.49, P = .001). 3‐year DFS was 75.3% overall with a significant difference observed for positive versus initial negative margins (HR 5.95, 95% CI 2.58‐13.73, P < .001) and for RRN vs. initial negative margins (HR 2.15, 95% CI 1.08‐4.23, P = .026). Regarding 3‐year OS, the rate was 88.1% in the overall cohort with significant differences between positive versus initial negative margins (HR 5.17, 95% CI 1.58‐16.85, P = .006). No difference was observed between RRN and initial negative margins. Margin sampling method (SBM vs TBBM) was not associated with LR (HR 1.14, 95% CI 0.53‐2.99, P = .766).
Table 3.
Clinical Characteristics
| Margin status | |||||
|---|---|---|---|---|---|
| Overall (N = 352) | Initial negative (N = 325) | Re‐resected to negative (N = 20) | Positive (N = 7) | P‐value | |
| END timing | .825 | ||||
| Initial surgery | 260 (74.9%) | 240 (73.8%) | 15 (75.0%) | 5 (71.4%) | |
| Delayed | 7 (2.8%) | 6 (1.8%) | 0 | 1 (14.3%) | |
| None | 85 (24.1%) | 79 (24.3%) | 5 (25.0%) | 1 (14.3%) | |
| ND laterality | .015 | ||||
| Ipsilateral | 234 (66.5%) | 217 (88.2%) | 14 (93.3%) | 3 (50.0%) | |
| Bilateral | 33 (9.4%) | 29 (11.8%) | 1 (6.7%) | 3 (50.0%) | |
| Margin assessment | .663 | ||||
| Tumor bed‐based | 305 (86.6%) | 283 (87.1%) | 16 (80.0%) | 6 (85.7%) | |
| Specimen‐based | 47 (13.4%) | 42 (12.9%) | 4 (20.0%) | 1 (14.3%) | |
| Adjuvant treatment | .020 | ||||
| Radiation | 80 (22.7%) | 72 (22.2%) | 5 (25.0%) | 3 (42.9%) | |
| Chemoradiation | 17 (4.8%) | 14 (4.3%) | 1 (5.0%) | 2 (28.6%) | |
| None | 255 (72.4%) | 239 (73.5%) | 14 (70.0%) | 2 (28.6%) | |
| Local recurrence | <.001 | ||||
| Yes | 44 (12.5%) | 34 (10.5%) | 7 (35.0%) | 3 (42.9%) | |
| No | 308 (87.5%) | 291 (89.5%) | 13 (65.0%) | 4 (57.1%) | |
| Regional recurrence | .663 | ||||
| Yes | 33 (9.4%) | 31 (9.5%) | 1 (5.0%) | 1 (14.3%) | |
| No | 319 (90.6%) | 294 (90.5%) | 19 (95.0%) | 6 (85.7%) | |
| Distant recurrence | <.001 | ||||
| Yes | 4 (1.1%) | 2 (0.6%) | 1 (5.0%) | 1 (14.3%) | |
| No | 348 (98.9%) | 323 (99.4%) | 19 (95.0%) | 6 (85.7%) | |
Abbreviations: END, elective neck dissection; ND, neck dissection.
Figure 1.
Local recurrence–free survival stratified by margin status. Comparisons were performed using the log‐rank test.
After controlling for adjuvant radiation therapy and chemotherapy in multivariable analysis, compared to initial negative margins, positive margin status (adjusted HR [aHR] 8.32, 95% CI 2.31‐29.90, P = .001) and RRN margin status (aHR 3.82, 95% CI 1.68‐8.68, P = .001) both remained independently associated with increased LR. Radiation therapy demonstrated a trend towards an independent protective effect (aHR 0.53, 95% CI 0.24‐1.17, P = .117). Multivariable model results are summarized in Table 4.
Table 4.
Multivariable Cox Hazards Model for Local Recurrence
| Hazard ratio | 95% CI | P‐value | |
|---|---|---|---|
| Margin status | |||
| Initial negative | 1 [Reference] | ||
| Re‐resected to negative | 3.82 | 1.68–8.68 | .001 |
| Positive | 8.32 | 2.31–29.9 | .001 |
| Adjuvant treatment | |||
| None | 1 [Reference] | ||
| (C)RT | 0.53 | 0.24–1.17 | .117 |
| Margin assessment method | |||
| Tumor bed‐based | 1 [Reference] | ||
| Specimen‐based | 1.14 | 0.48–2.73 | .766 |
Abbreviations: CI, confidence interval; (C)RT, radiation therapy with or without chemotherapy.
Discussion
In this study, we sought to analyze the impact of final margin status and re‐resection on local recurrence among patients with early clinical stage OCSCC. Local recurrence was defined as invasive cancer occurring within 3 years of primary surgical resection at a contiguous site. 352 patients were included in the study with 44 (12.5%) patients developing local recurrence as defined above. Local recurrence occurred in 34 patients with initial negative margins, 7 patients with margins RRN, and 3 patients with positive final margins despite re‐resection. Difference in 3‐year LRFS rates was significant between initial negative and positive margins as well as initial negative and RRN margins. Multivariable Cox hazards analysis confirmed that both positive and RRN margin status were independently associated with increased risk of recurrence after adjusting for radiation with or without chemotherapy and margin sampling method.
For early‐stage OCSCC, surgery is the primary treatment modality, with adjuvant therapy predicated on final pathology. 7 Tumor resection aims to completely remove the tumor and achieve a cancer‐free margin beyond the macroscopic boundaries in order to ensure microscopically tumor‐negative margins. 15 If no high‐risk pathologic features are identified on final pathology, patients with assured clear margins can often be treated with surgery alone, avoiding the morbidity of multimodality treatment. This point is especially salient in the case of early‐stage cancers where adjuvant therapy is often driven by the primary tumor alone, in comparison to locoregionally advanced cancers where other factors, including lymph node involvement can trigger the addition of adjuvants. Therefore, the majority of early OCSCC patients with involved margins undergo re‐resection to achieve negative margins in order to avoid radiation. While positive final margin status is a well‐known risk factor for local recurrence and poor survival in OCSCC, 8 , 9 , 10 , 11 , 12 , 13 , 14 the oncologic significance of initial positive margin status, ultimately RRN, is inconclusive.
This ambiguity is especially important to unveil as the data regarding adjuvant radiation even in the setting of positive margins has been mixed. A 2021 big data analysis from the National Cancer Database reported that radiation did not improve survival in positive margin cases among patients with cT1‐2N0 OCSCC. 16 This finding begs the question of why; might this be because re‐resection is the superior modality of disease control or perhaps tumors with initially positive margins, whether RRN ultimately or not, represent a biologically unique entity.
In any case, the current overall opinion about management of positive resection margins is to achieve microscopically complete surgical resection with negative margins on frozen section, especially in the setting of early OCSCC. However, there remains controversy regarding repeated resection on improved oncologic outcomes. Though intraoperative frozen section analysis has long been recognized as an important means of attempting to achieve instant negative margins and predicting final margin status after initial resection, more recent studies have shown questionable efficacy of further resection guided by frozen sectioning in patients with OCSCC.
Several studies have demonstrated that re‐resection guided by frozen section does not improve oncologic outcomes. Kwok et al. reported comparable recurrence‐free survival and OS between cases with initially negative margins and those with initially positive RRN margins in a heterogeneous cohort of floor of mouth and pharyngeal cancers across varying tumor stages and adjuvant treatment statuses. 17 In another study of 547 patients with OCSCC, an initial positive margin was a poor prognostic factor for local control despite margin revision surgery. 18 In a retrospective analysis of 441 patients with pT1‐2N0 OCSCC who did not receive adjuvant radiation, Kim et al showed significantly improved LRFS in the initially negative margins group as compared to the RRN group. 19 There were no statistically significant differences in age, sex, T stage, depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), or SUV max between groups. In the same vein, a meta‐analysis demonstrated that revision of initially positive margins to clear margins based on frozen section guidance does not confer oncologic equivalence to initially negative margins and does not significantly improve local control in early OCSCC. 20
In contrast, other studies have demonstrated comparable local tumor control rates between revised clear margins and initial negative margins. 21 , 22 However, these studies included patients with variations in tumor stage, adjuvant therapy, and neck dissection as well as those with an unclear resection margin status. Such methodological and clinical heterogeneity likely contributes to the conflicting results observed across the literature.
Our results align with the studies suggesting that tumors RRN are not oncologically equivalent to tumors with initially negative margins. Previous studies have indicated that patients with OCSCC who exhibit positive initial margins tend to have more aggressive tumor biology, such as poorly differentiated tumors, higher T/N stages, a greater burden of nodal metastasis, and extracapsular spread. 16 , 23 , 24 , 25 Biologically aggressive tumors are further characterized by features such as high tumor grade, DOI exceeding established thresholds, PNI, LVI, and specific molecular alterations. 26 For example, mutations in tumor suppressor genes like TP53 and overexpression of epidermal growth factor receptor have been linked to heightened invasive potential and worse prognosis. 27 , 28 These features can lead to infiltrative growth patterns that extend beyond visible or palpable tumor margins, complicating complete excision and increasing the likelihood of residual disease after surgery. 29 Such biological behavior aligns with the observed requirement for re‐resection in cases where initial margins are positive or close.
Anatomical challenges inherent to tumor location are worth considering as having an influence on the feasibility of achieving clear margins and therefore LR outcomes. Tumors situated in anatomically complex regions such as the tongue, floor of mouth, and retromolar space often infiltrate surrounding tissues extensively, making it difficult to delineate tumor borders intraoperatively. 29 The proximity of critical neurovascular structures limits the extent of resection permissible without excessive morbidity, which in turn increases the risk of residual disease requiring re‐excision. 30 In these scenarios, even tumors with less aggressive biology may necessitate additional surgery due to the limitations imposed by anatomy.
The interplay between tumor biology and challenging anatomy complicates surgical decision‐making. It is worth noting that tumors exhibiting aggressive features are often more infiltrative, further complicating complete resection and predisposing to residual disease. 31 Additionally, intraoperative factors such as limited visibility, submucosal spread, and difficulty in defining tumor boundaries contribute to positive margins and subsequent re‐resection (Table 1).
It is challenging to parse whether the primary driver of re‐resection is biological aggressiveness or anatomical complexity and the reality may in fact be both are contributors. 13 , 29 , 32 Of specific concern is the idea of macroscopic versus microscopic disease. The term “tumor margin” refers to the tumor's outer boundary, which can be further divided into clinical/gross, histological, and molecular margins. The “clinical/gross margin” represents the macroscopic boundary ascertainable via clinical examination such as visual inspection and palpation. Histological margin demarcates the boundary between tumor cells (or morphologically abnormal cells) and normal cells. The molecular margin, on the other hand, refers to the boundary between genetically abnormal cells and their normal counterparts.
In our study, there were no differences across subsites in terms of prevalence of re‐resection, which suggests that the location of a mass (ie, a less physically accessible mass, eg, floor of mouth vs anterior tongue) does not deter re‐resection. This observation may prompt future studies that consider tumor characteristics, as patients who have tumors with more aggressive features (ie, presence of LVI and PNI, increased DOI) may be more likely to recur despite re‐resection to a negative margin (Table 2).
Finally, the role of intraoperative margin sampling technique warrants consideration. In our cohort, margin assessment method (TBBM vs SBM) was not significantly associated with final margin status or with LRFS. Prior studies have reported mixed findings, with some demonstrating improved margin clearance and lower LR rates with SBM sampling likely due to enhanced intraoperative localization of close or positive margins. 33 , 34 However, other studies have shown comparable outcomes between sampling techniques, consistent with our findings. 35 , 36 , 37 Margin sampling technique was not evenly distributed across our cohort, with some surgeons predominantly using a single approach. Consequently, our ability to draw definitive conclusions regarding sampling method is limited by the predominance of TBBM sampling (86.6%), limited statistical power, and potential confounding by surgeon‐related factors. Despite these limitations, we demonstrated that positive and RRN margins remained independently associated with worse 3‐year LRFS after controlling for margin sampling technique.
The limitations of this study include the retrospective design and relatively small sample sizes in the re‐resected and positive margin groups. Additionally, we could not control for all potential confounders in adjuvant therapy decisions. Multi‐institutional studies with larger cohorts are needed to validate these findings.
Conclusions
RRN margins should not be considered oncologically equivalent to initial negative margins in early OCSCC, as demonstrated by significantly higher local recurrence rates even after adjusting for adjuvant radiation and chemotherapy. Tumors requiring re‐resection may embody a spectrum where biological aggressiveness and challenging anatomy often coexist, leading to residual disease and subsequent surgical intervention. Future efforts should focus on integrating molecular profiling with advanced imaging and intraoperative guidance to better predict and mitigate these challenges, ultimately enhancing surgical precision and patient outcomes.
Author Contributions
Hannah J. Brown, MD: study conceptualization, data collection, analysis, manuscript writing; Naomi C. Wang, MD: data collection, analysis, manuscript writing; Rahul Alapati, MD: data collection; Uma Ramesh, MD: data collection; Ameen M. Amanian, MD: editing; Andrés M. Bur, MD: study conceptualization, oversight, and guidance.
Disclosures
Competing interests
None.
Funding source
This work was supported by the Kansas Institute for Precision Medicine (P20GM130423).
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.