Close Margins Research Articles

Margin-to-depth ratio as an independent prognostic factor in resected oral cavity squamous cell carcinoma: A nationwide cohort study

BackgroundThe prognostic significance of margin-to-depth ratio (MDR) in oral cavity squamous cell carcinoma (OCSCC) remains unclear, particularly in comparison to traditional margin status. We aimed to examine the association between MDR and clinical outcomes in a large Taiwanese cohort. MethodsA total of 18,324 patients with first primary OCSCC were categorized by margin status: positive (1013), <5 mm (8371), and ≥ 5 mm (8940). Disease-specific survival (DSS) and overall survival (OS) served as the main outcome measures. ResultsAfter excluding patients with positive margins (MDR = 0), the optimal MDR cutoff value for DSS and OS was 0.6. Patients with MDR > 0.6 showed significantly better 5-year DSS and OS rates (87 %, 81 %) compared to those with MDR ≤ 0.6 (71 %, 63 %) and MDR = 0 (53 %, 43 %). Multivariable analysis identified MDR ≤ 0.6 as independently associated with both DSS and OS in the entire cohort (hazard ratio [HR] = 1.34/1.32). This finding was consistent in the subgroups with surgical margins < 5 mm (HR = 1.39 for DSS and 1.38 for OS) and margins ≥ 5 mm (HR = 1.21 for both DSS and OS). In subgroups with surgical margins < 5 mm and ≥ 5 mm, an MDR > 0.6 was associated with better survival outcomes. ConclusionsAn MDR (cutoff: 0.6) is independently associated with prognosis in OCSCC, offering improved risk stratification compared to margin status alone. While MDR may guide surgical margin modification, further research is needed to determine whether MDR could serve as a postoperative indicator for adjuvant therapy in patients with close or clear margins.

Disease recurrence in patients undergoing mastectomy for ductal carcinoma in situ.

With DCIS incidence on the rise, up to 30% of patients undergo mastectomy for Ductal carcinoma in situ (DCIS) (Nash and Hwang, in: Ann Surg Oncol 30(6):3206-3214, 2023). Local recurrence rates after mastectomy for DCIS are reportedly low, but risk factors for recurrence are not known (Kim et al., in: J Cancer Res Ther 16(6):1197-1202, 2020). We aim to define risk factors associated with ipsilateral breast cancer recurrence in patients undergoing mastectomy for DCIS. We aimed to identify risk factors that may contribute to recurrence of breast cancer following mastectomy for pure DCIS. We hypothesized that close or positive mastectomy margins, age at diagnosis, extent of breast disease and mutation carriers would be associated with increased risk of recurrence. We performed a retrospective chart review of patients who underwent unilateral or bilateral mastectomies for pure DCIS at a single academic tertiary referral center from 2013 to 2023. There were 165 patients who met inclusion criteria with an average length of follow-up of 39.9months. On final surgical pathology, the average span of DCIS was 33.7mm (± 24.6mm). Hormone receptor positive disease was identified in 80.6% of the patient cohort. For margin status, 23 patients (14%) had < 1mm margins on final pathology and of those, 1 received adjuvant radiation therapy and 4 returned to the OR for re-excision. Only 1 (0.6%) patient had ipsilateral disease recurrence during the study period. Recurrence after mastectomy for pure DCIS is a rare event and in our study sample, only one recurrence occurred. Risk factors for recurrence appear unrelated to margin status, age, extent of DCIS, or pathogenic mutation (ElSherif et al., in Am J Surg 226(5):646-651, 2023).

Determining Factors Which Limit Resectability in Advanced Hypopharyngeal Malignancy.

Preoperative radiological findings of hypopharyngeal cancers are used to determine suitability for surgical resection. We sought to examine preoperative imaging characteristics to determine how well imaging findings predicted surgical resectability. A retrospective case-control study of patients undergoing a pharyngolaryngectomy in a tertiary referral center over a 2-year period was completed. Demographic details, previous treatment, subsite, TNM staging, imaging characteristics, and operative characteristics were collected. A total of 78 patients met initial inclusion criteria, of which 71 patients ultimately underwent successful surgical resection (91.1%). Preoperative images identified suspicion of prevertebral fascia invasion in 24 (30.7%) cases and carotid artery involvement in 14 (17.9%) cases. In cases of suspicion of prevertebral fascia invasion (24), 19 cases (79.2%) were resectable, and in those with carotid artery involvement (14), 11 (78.6%) were resectable. Concern for prevertebral fascia invasion on radiology led to a higher likelihood of a close margin (42% vs. 17%) in those without concerning features (p = 0.088). The present study demonstrated a high rate of resectability of hypopharyngeal and upper esophageal cancers despite imaging findings suspicious for factors that could limit resectability. In patients with advanced hypopharyngeal, especially in the salvage setting, surgery should be considered.

Visual pathology reports for communication of final margin status in laryngeal cancer surgery

BackgroundPositive margins are frequently observed in total laryngectomy (TL) specimens. Effective communication of margin sampling sites and final margin status between surgeons and pathologists is crucial. In this study, we evaluate the utility of multimedia visual pathology reports to facilitate interdisciplinary discussion of margin status in laryngeal cancer surgery. MethodsEx vivo laryngeal cancer surgical specimens were three-dimensional (3D) scanned before standard of care pathological analysis. Using computer-aided design software, the 3D model was annotated to reflect inking, sectioning, and margin sampling sites, generating a visual pathology report. These reports were distributed to head and neck surgeons and pathologists postoperatively. ResultsFifteen laryngeal cancer surgical specimens were 3D scanned and virtually annotated from January 2022 to December 2023. Most specimens (73.3%) were squamous cell carcinomas (SCCs). Among the cases, 26.7% had final positive surgical margins, whereas 13.3% had close margins, defined as <5 mm. The visual pathology report demonstrated sites of close or positive margins on the 3D specimens and was used to facilitate postoperative communication between surgeons and pathologists in 85.7% of these cases. Visual pathology reports were presented in multidisciplinary tumor board discussions (20%), email correspondences (13.3%), and teleconferences (6.7%), and were referenced in the final written pathology reports (26.7%). Conclusions3D scanning and virtual annotation of laryngeal cancer specimens for the creation of visual pathology reports is an innovative approach for postoperative pathology documentation, margin analysis, and surgeon–pathologist communication.

Adjuvant chemoradiotherapy plus pembrolizumab for locally advanced esophageal squamous cell carcinoma with high risk of recurrence following neoadjuvant chemoradiotherapy: a single-arm phase II study

BackgroundAdjuvant nivolumab reduces recurrence in patients with locoregional esophageal cancer who had pathological residual disease after neoadjuvant chemoradiotherapy and R0 resection. However, the efficacy of adjuvant anti-PD-1 therapy in patients at higher risk of recurrence remains unclear.MethodsThis phase II trial (ClinicalTrials.gov identifier: NCT03322267) enrolled patients with locally advanced esophageal squamous cell carcinoma (ESCC) received neoadjuvant chemoradiotherapy plus esophagectomy but still had various risk factors for recurrence, such as involved or close margins (≤ 1 mm), extranodal extension of the involved lymph nodes, and the ypN2-3 stage. Patients received adjuvant therapy composed of a course of cisplatin-based chemoradiotherapy and pembrolizumab (200 mg, IV every 3 weeks) for 18 cycles. The primary endpoint was 1-year relapse-free survival (RFS) rate.ResultsTwenty-five patients were enrolled. The risk factors were tumor margins of ≤ 1 mm (18 patients), extranodal extension of the involved lymph nodes (9 patients), and the ypN2-3 stage (9 patients). The median follow-up duration was 21.6 months (95% CI: 18.7–33.2). The rate of 1-year RFS was 60.0%. The median duration of RFS and overall survival was 14.3 (95% CI: 9.0–19.5) and 21.6 (95% CI: 0.0–45.5) months, respectively. Treatment-emergent adverse events of any grade and those of ≥ 3 grade occurred in 56% and 8% of all patients receiving cisplatin-based chemoradiotherapy and in 79.2% and 12.5% of those receiving pembrolizumab.ConclusionsAdjuvant chemoradiotherapy followed by pembrolizumab is feasible and may be associated with improved 1-year RFS rate in patients at high risk of recurrence after trimodality therapy for locally advanced ESCC.Trial registration number ClinicalTrials.gov (No. NCT03322267).

Single pre-operative radiation therapy (SPORT-CK) trial for low-risk breast cancer: Early results of a phase 2 study

Background and purposePreoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI. Materials and MethodsIn this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1–2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence. ResultsTwenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences. ConclusionPreoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population.

Clinical Variables Influencing Outcomes in Patients with Atypical Intradermal Smooth Muscle Neoplasms (Formerly Cutaneous Leiomyosarcomas): Single-Institution Study of 95 Surgical Patients.

Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity. A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n=95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm. Median age at diagnosis was 58 years (range 22-86), and 74% were male. Ninety-five percent (n=90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n=44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day-18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%. In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited.

Assessment of the bony resection margin distance in bone-invasive oral cancer using laser-induced breakdown spectroscopy

ObjectivesInadequate resection margins of less than 5 mm impair local tumor control. This weak point in oncological safety is exacerbated in bone-infiltrating tumors because rapid bone analysis procedures do not exist. This study aims to assess the bony resection margin status of bone-invasive oral cancer using laser-induced breakdown spectroscopy (LIBS).Materials and methodsLIBS experiments were performed on natively lasered, tumor-infiltrated mandibular cross-sections from 10 patients. In total, 5,336 spectra were recorded at defined distances from the tumor border. Resection margins < 1 mm were defined as very close, from 1–5 mm as close, and > 5 mm as clear. The spectra were histologically validated. Based on the LIBS spectra, the discriminatory power of potassium (K) and soluble calcium (Ca) between bone-infiltrating tumor tissue and very close, close, and clear resection margins was determined.ResultsLIBS-derived electrolyte emission values of K and soluble Ca as well as histological parameters for bone neogenesis/fibrosis and lymphocyte/macrophage infiltrates differ significantly between bone-infiltrating tumor tissue spectra and healthy bone spectra from very close, close, and clear resection margins (p < 0.0001). Using LIBS, the transition from very close resection margins to bone-infiltrating tumor tissue can be determined with a sensitivity of 95.0%, and the transition from clear to close resection margins can be determined with a sensitivity of 85.3%.ConclusionsLIBS can reliably determine the boundary of bone-infiltrating tumors and might provide an orientation for determining a clear resection margin.Clinical relevanceLIBS could facilitate intraoperative decision-making and avoid inadequate resection margins in bone-invasive oral cancer.

Comparison of 3D-printed multichannel non–co-planar vaginal applicators and single-channel vaginal applicators for brachytherapy with positive or close surgical margins in cervical cancer

OBJECTIVEThis study was conducted to compare the differences between 3D-printed multichannel non-coplanar vaginal applicators and single-channel vaginal applicators in cervical cancer patients with positive or close surgical margins. METHODSBetween January 2015 and June 2023, 104 cervical cancer patients who underwent radical surgery with positive or close surgical margins were enrolled to receive concurrent intensity-modulated chemoradiotherapy combined with 3D-printed multichannel non-coplanar vaginal applicators (3D-printed group, 41 patients) or single-channel vaginal applicators (single-channel group, 63 patients) guided brachytherapy. The dosimetric parameters, 5-year local control (LC), progression-free survival (PFS), overall survival (OS) of two groups were retrospectively analyzed. RESULTSThe high-risk clinical target volume (D90, D100) and high-dose volume fraction (V150) in 3D-printed group were significantly higher than those in single-channel group (p<0.05), and the homogeneity index (HI) and conformal index (COIN) were equally better in 3D-printed group. In 3D-printed group, the D2cc, D1cc, and D0.1cc of the bladder and rectum were significantly lower than those of the single-channel group (p<0.05). The 3D-printed group had significantly superior 5-year LC (70.0% vs. 51.3%, P=0.041) and PFS (63.0% vs. 44.2%, P=0.045), but OS were not significantly different between treatment groups (75.4% vs. 59.7%, P=0.112). The incidence of radiation enteritis and cystitis was lower in the 3D-printed group than in the single-channel group, but no statistical difference was noted. CONCLUSIONSThe 3D-printed multichannel non-coplanar vaginal insertion applicators shows the advantage of target dose, improve the LC and PFS in patients with positive or close surgical margins after cervical cancer surgery. Thus, the popularization of this method and its application may be of value.

Histological deep margins in cutaneous squamous cell carcinoma of the scalp and risk of recurrence.

Consensus is lacking on adequate deep histological margins in cutaneous squamous cell carcinoma (cSCC). Deep clearance for tumours located on the scalp is limited by anatomic constraints. To determine whether clear but close deep histological margins (<1 mm) confer a higher risk of recurrence in cSCCs of the scalp treated by wide local excision, compared to deep histological margins ≥1 mm. Multicentre retrospective observational cohort study and multivariate competing risk analysis to evaluate risk factors for recurrence. In total, 295 patients with 338 cSCCs were included. Close deep histological margins were not associated with an increased cumulative incidence of recurrence (subhazard ratio [SHR] 1.96 [95% CI 0.87-4.41]). However, an increased risk of recurrence was observed for those tumours that presented concurrent invasion of the galea aponeurotica and close deep margins, as opposed to patients without these factors (SHR 3.52 [1.24-10.01]). Tumours with clear but close peripheral margins (<1 mm) also had higher risk of recurrence (SHR 5.01 [1.68-14.97]). Retrospective observational study based on pathology reports. Deep histological margins <1 mm do not confer a greater risk of recurrence as long as the tumour is completely excised and the galea aponeurotica is not involved. Surgical excision of cSCC on the scalp should include the galea to ensure proper assessment of deep margins.

A Phase 2 Multicenter Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer with a pH-Activatable Nanoprobe.

Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer. Recently, a probe has been developed that only fluoresces when activated in an acidic pH, which is common to many malignancies. We report the first multicenter Phase 2 trial of a pH-activatable nanoprobe (pegsitacianine, ONM-100) for IMI of lung cancer. Patients with suspected or biopsy-confirmed lung cancer scheduled for sublobar resection were administered a single intravenous infusion of pegsitacianine (1mg/kg) one to three days prior to surgery. Intraoperatively, the patients underwent a white light thoracoscopic evaluation, and then were imaged with an NIR thoracoscope to detect tumor fluorescence. The primary study endpoint was the proportion of patients with a clinically significant event (CSE) which was defined as an intraoperative discovery during IMI that led to a change in the surgical procedure. Possible CSEs included (i) localizing the index lung nodule that could not be located by white light, (ii) identifying a synchronous malignant lesion, or (iii) recognizing a close surgical margin (< = 10mm). Secondary endpoints were sensitivity, specificity, NPV, and PPV of pegsitacianine in detecting tumor-containing tissue. The safety evaluation was based on adverse event reporting, clinical laboratory parameters, and physical examinations. Twenty patients were confirmed as eligible and administered pegsitacianine. Most of the patients were female (n = 12 [60%]), middle-aged (mean age 63.4years), and former smokers (n = 13 [65%], 28.6 mean pack years). Mean lesion size was 1.9cm, and most lesions (n = 17 [85%]) were malignant. The most common histologic subtype was adenocarcinoma (n = 9). By utilizing IMI with pegsitacianine, one patient had a CSE in the detection of a close margin and another had localization of a tumor not detectable by traditional surgical means. Six of 19 (31.6%) malignant lesions fluoresced with mean tumor-to-background ratio (TBR) of 3.00, as compared to TBR of 1.20 for benign lesions (n = 3). Sensitivity and specificity of pegsitacianine-based IMI for detecting malignant tissue was 31.6% and 33.3%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of pegsitacianine-based IMI was 75% and 7.1%, respectively. Pegsitacianine-based imaging was not effective in differentiating benign and malignant lymph nodes. From a safety perspective, no drug-related serious adverse events occurred. Four patients experienced mild pegsitacianine-related infusion reactions which required discontinuing the study drug with complete resolution of symptoms. Pegsitacianine-based IMI, though well tolerated from a safety perspective, does not consistently label lung tumors during resection and does not provide significant clinical benefit over existing standards of surgical care. The biology of lung tumors may not be as acidic as other solid tumors in the body thereby not activating the probe as predicted.

Surgical Margins After Neoadjuvant Radiation for Locally Advanced Vulvar Carcinoma: What is an Adequate Margin?

We aim to explore whether the surgical tumor free margin is important for overall survival (OS) and local control in patients who undergo neoadjuvant radiation (RT) for vulvar cancer. A retrospective review from 2004 to 2021 of patients who underwent RT followed by surgical resection was performed. Patients were categorized into groups based on margin status (no residual disease, >8mm, close margins defined as 1 to 7mm, or positive). Local control and OS were analyzed using the Kaplan-Meier with log rank test. Multivariate analysis was performed with cox hazards model. Eighty-three patients were included. A complete pathologic response (pCR) was found in 56% (n=46) of patients. The median follow-up time was 35 months (range: 4 to 216). The median OS for the entire cohort was 46 months (95% CI: 32.3-59.7). Having a pCR improved both OS and disease-free survival (DFS) compared with residual disease by 81 and 91 months, respectively (P<0.001). In the 2 patients with a margin >8mm, there was no statistical difference in survival between those with close margins (46 vs. 25mo, P=0.485). Factors that significantly impacted both OS and DFS were depth of invasion (DOI) and LVSI. On multivariate analysis of those with residual disease, there was no difference in OS or DFS by margin status but having a DOI >9mm showed decreased OS (HR: 3.654; 95% CI: 1.317-10.135). In this cohort, response to RT, not margin status drives survival and recurrence. Given residual disease, the optimal margin is not clear, as there were only 2 patients with >8mm margins. A close or positive margin had no impact on OS or local recurrence. A DOI >9mm significantly impacts both OS and local recurrence even when accounting for other factors.

Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

Margin status, adjuvant treatment and recurrence in buccal cancer

ObjectiveTo assess the prognostic importance of margin in resected buccal cancer within a framework of risk factor-driven postoperative adjuvant treatment. Materials and MethodsConsecutive, treatment naïve patients undergoing primary surgical treatment for buccal cancer. Margin was defined as clear (≥5 mm), close (1–4 mm) and involved (<1 mm). Main outcome was association of margin with local recurrence free survival (LRFS). Subgroup analysis of close margin was performed according to receipt or no receipt of adjuvant treatment. A numerical margin cut-off in mm that could independently predict LRFS was sought to be identified. ResultsOf the 167 patients included, the frequency of clear, close and involved margins was 50 (30 %), 78 (47 %) and 39 (23 %) respectively, among whom 52 %, 44 % and 98 % received postoperative adjuvant treatment respectively. Clear and close margins had similar 3-year LRFS (89 % and 96 % respectively), while involved margin had worse 3-year LRFS at 65 %. Involved margin was confirmed to be strongly and independently associated with worse LRFS. Within close margin, receipt and no receipt of adjuvant treatment had similar 3-year LRFS (92 % and 100 % respectively). A margin cut-off of 2 mm was identified at or above which LRFS approximated that of clear margin. ConclusionsThis single center cohort study of patients with resected buccal cancer suggests that close margin is distinct from and has a better LRFS than involved margin. A subset of close margin, with margin size ≥ 2 mm and no other adverse features, might be spared adjuvant treatment without compromising outcomes.

Prognostic effect of microscopically negative but close resection margin in gastric cancer

IntroductionMicroscopically positive resection margin (RM) following curative surgery has been linked to disease recurrence in gastric cancer (GC), but the impact of microscopically negative but close RM (CRM) remains unclear. This study aimed to evaluate the prognostic implications of a CRM of ≤0.5 cm in GC patients. MethodsA retrospective review of the institutional GC database identified 1958 patients who underwent curative gastrectomy for pathologically proven GC between January 2011 and December 2015. The patients were categorized into CRM (RM ≤0.5 cm) and sufficient RM (SRM, RM >0.5 cm) groups. The impact of CRM on recurrence-free survival (RFS) and overall survival (OS) was analyzed compared to the SRM group. ResultsThe cohort comprised 1264 patients with early GC (EGC, 64.6%) and 694 with advanced GC (AGC, 35.4%). Forty-four patients (2.2%) had RM of ≤0.5 cm. CRM was associated with worse RFS in AGC (5-year RFS in the CRM vs. SRM groups; 41.6% vs. 68.7%, p = 0.011); however, the effect on OS was not significant (p = 0.159). Multivariate analysis revealed that CRM was an independent prognostic factor for RFS (hazard ratio [HR] 2.035, 95% confidence interval [CI] 1.097–3.776). In AGC, the locoregional recurrence rate was significantly higher in the CRM group than in the SRM group (15.4% vs. 4.9%, p = 0.044). ConclusionCRM of ≤0.5 cm was a significant prognostic factor for RFS in GC patients and was associated with a significant increase in locoregional recurrence in AGC.

The Trans-facial Approach for Simultaneous Resection and Reconstruction of Retromolar Trigone Tumors: A Pilot Study

IntroductionEarly retromolar trigone (RMT) lesions are difficult to access and free tissue transfer is often an overkill for such small lesions. The aim was to devise a novel surgical approach that would aid the resection without raising a cheek flap and simultaneously provide a local reconstructive option for small lesions in the RMT.MethodologyThis study was to demonstrate the outcomes of the “trans-facial” approach used to simultaneously access and reconstruct small RMT tumors through an islanded nasolabial flap. Patients with histologically proven squamous cell carcinoma of RMT requiring surgery were included from January 2021 to September 2022. Case selection was done based on the location of the disease and its size (cT1/T2). All needed bone and soft tissue resection via per oral trans-facial approach, along with an ipsilateral neck dissection. The technique is described along with their post-operative and pathologic outcomes.ResultsOut of the eight patients included in this study, six underwent a bi-alveolar marginal resection and reconstructed using the trans-facial approach. No major complications were noted in the post-operative period. 50% were pT1 tumors and 75% were pN0 status. One patient had a close margin; while, the others had adequate resection margins. All patients were followed up for a median of 18 months with a locoregionally controlled status.ConclusionThe trans-facial approach can be a suitable option with a reasonable oncologic outcome to address small RMT lesions.

Clinical validation of the accuracy of an intra-operative assessment tool using 3D ultrasound compared to histopathology in patients with squamous cell carcinoma of the tongue

BackgroundHistopathological analysis often shows close resection margins after surgical removal of tongue squamous cell carcinoma (TSCC). This study aimed to investigate the agreement between intraoperative 3D ultrasound (US) margin assessment and postoperative histopathology of resected TSCC.MethodsIn this study, ten patients were prospectively included. Three fiducial cannulas were inserted into the specimen. To acquire a motorized 3D US volume, the resected specimen was submerged in saline, after which images were acquired while the probe moved over the specimen. The US volumes were annotated twice: (1) automatically and (2) manually, with the automatic segmentation as initialization. After standardized histopathological processing, all hematoxylin-eosin whole slide images (WSI) were included for analysis. Corresponding US images were found based on the known WSI spacing and fiducials. Blinded observers measured the tumor thickness and the margin in the caudal, deep, and cranial directions on every slide. The anterior and posterior margin was measured per specimen.ResultsThe mean difference in all measurements between manually segmented US and histopathology was 2.34 (SD: ±3.34) mm, and Spearman’s rank correlation coefficient was 0.733 (p < 0.001). The smallest mean difference was in the tumor thickness with 0.80 (SD: ±2.44) mm and a correlation of 0.836 (p < 0.001). Limitations were observed in the caudal region, where no correlation was found.ConclusionThis study shows that 3D US and histopathology have a moderate to strong statistically significant correlation (r = 0.733; p < 0.001) and a mean difference between the modalities of 2.3 mm (95%CI: -4.2; 8.9). Future research should focus on patient outcomes regarding resection margins.

Biomarker-driven radiation therapy dose reduction after transoral robotic surgery for the treatment of HPV-positive oropharyngeal cancer.

TPS6119 Background: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is a highly curable cancer with a considerable burden of treatment-related toxicities. Transoral surgery (TOS) is a treatment option for patients with early-stage disease; however, adjuvant radiotherapy (RT) is often recommended and can add to these late toxicities. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive marker of tumor recurrence, and undetectable post-operative ctHPVDNA is associated with improved recurrence-free survival. We hypothesize that patients with undetectable post-TOS ctHPVDNA without high risk pathologic factors can safely undergo de-escalation of adjuvant RT to 36 Gy, and this reduction will improve long-term swallowing function. Methods: We opened a multi-institutional phase II study (NCT05387915) including patients with pT1-2, N0-1, M0 HPV-related OPSCC who had TOS resection of their primary site and at least ipsilateral neck dissection. Pertinent inclusion criteria include a &lt;10 pack-year smoking history, or a &lt;30 pack-year smoking history if &gt;10 years since last tobacco consumption, and pathologic findings of one or more intermediate risk factors: close margin (1 – 4 mm), perineural invasion, 2 – 4 positive lymph nodes or a single lymph node &gt;3 cm. Patients with high risk factors (positive margin, extranodal extension, 5 or more positive lymph nodes) are excluded. Patients must have a detectable pre-operative ctHPVDNA and a post-operative ctHPVDNA drawn 7-14 days after TOS; if negative, patients receive 36 Gy of adjuvant RT in 15 fractions of 2.4 Gy delivered daily; if positive, they receive care per the discretion of the treating radiation oncologist. If the final surgical margins at the site of the primary tumor are &gt;2mm, patients are eligible for omission of the primary tumor post-operative bed from the radiation volume. Our primary endpoint is 1-year swallowing function as measured by the composite MD Anderson Dysphagia Index (MDADI) score. Secondary endpoints include overall/progression-free survival and other quality of life metrics. The study is powered to detect an 8.5-point improvement in MDADI composite score at one year over the historical control from ECOG 3311 Arm B. With an alpha of 0.05 and a power of 0.90 we require 27 evaluable patients. Accounting for dropout and patients lost to follow-up, we aim to enroll 35 total patients. Since accrual began in June 2022, we have enrolled 18 patients as of January 2024. We recently opened the study at a second institution and are in the process of opening at a third institution. Clinical trial information: NCT05387915 .

Close margin of adverse histologic factors with a negative primary tumor margin is not associated with increased locoregional recurrence in colon cancer

PurposeLocoregional recurrence after resection of colon cancer is increased when primary tumor margin is positive (<1 ​mm). Data is limited regarding the risk of locoregional recurrence with close margin (<1 ​mm) of histologic factors, such as intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension. We hypothesized that close margin of these factors doesn't affect locoregional recurrence. MethodsA retrospective review of all colon cancer surgical resections for adenocarcinoma from 2007 to 2020 was performed. Inclusion criteria were specimens with a negative primary tumor margin but a close margin of adverse histologic factors, defined as intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension within 1 ​mm of a mesenteric or circumferential margin. ResultsAmong 4435 pathology reports reviewed, 45 (1 ​%) of cases met inclusion criteria. Average follow-up was 38 months. The adverse histologic factor was identified as intranodal tumor in 24 (53 ​%) cases, intravascular tumor in 8 (17.8 ​%), tumor deposits in 5 (11.1 ​%), and more than one pathologic feature in 6 (13.3 ​%). There were 9 (20 ​%) recurrences; 6 (13 ​%) had distant recurrences only, 2 (4 ​%) patients had locoregional recurrences only, and 1 (2 ​%) patient had both locoregional and distant recurrence. The adverse histologic factor in these three patients was intravascular in two and both intravascular and intranodal in one. ConclusionBased on our results, we do not have evidence that the presence of intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension within 1 ​mm of a mesenteric or circumferential margin is associated with increased risk of locoregional recurrence.

Adjuvant chemotherapy following concurrent chemoradiation (CRT) in patients with high-risk early-stage cervical carcinoma following radical hysterectomy: Results of NRG oncology/RTOG 0724/GOG-0724.

5504 Background: To assess the efficacy of adjuvant systemic chemotherapy following CRT for patients (pts) with high-risk early-stage cervical carcinoma. Methods: Pts with clinical stage IA2, IB, or IIA cervical carcinoma with at least one of the following high-risk features after radical hysterectomy: positive pelvic nodes, positive parametrium, and/or positive para-aortic nodes were stratified by intention to use brachy (yes v no), RT (Standard v IMRT); and RT dose (45 v 50.4 Gy) then randomized 1:1 to CRT or CRT and 4 cycles of adjuvant chemotherapy with paclitaxel and carboplatin (CRT + chemo). Primary endpoint was disease-free survival (DFS: death, local or regional failure, or distant mets). Reported secondary endpoints are OS (death due to any cause) and AEs (CTCAEv4). Sample size was 235 pts (50 DFS events, HR=0.47, corresponding to an increase in 4-year DFS from 80% to 90% for the CRT + chemo arm, 80% power, 1-sided log-rank α=0.05). Multivariable analysis (MVA) used Cox regression models. Results: From 9/16/2009 to 3/2/2022, this phase III international trial enrolled 236 pts, with 212 eligible/analyzed (109 CRT and 103 CRT + chemo). Median age was 46 yrs (min-max: 25-77) and median follow-up for all pts was 4.5 yrs (min-max: 0.02-12.8). Fifty-one percent of pts identified as white, 39% as Asian, and 6% Black. Most pts had squamous cell carcinoma (76%), with 18% adenocarcinoma and 5% adenosquamous. 56% of pts had open radical hysterectomy, 23% laparoscopic, and 22% robotic. Most pts had stage IB (87%) and 74% had positive pelvic nodes. Four (4%) pts on the CRT arm and 1 (1%) patient on CRT + chemo did not receive RT. The median (min-max) RT dose delivered was 50.4 Gy (7.2-60.4). Four pts (2 on each arm) did not receive concurrent cisplatin and 27 (26%) pts did not receive adjuvant carboplatin and paclitaxel on the CRT + chemo arm. Grade 3 and 4 events occurred in 36% and 7% of CRT pts; 44% and 21% in the CRT + chemo arm. There were 50 failures, 26 and 24 on the CRT and CRT + chemo arms, respectively, with 4-yr DFS estimates of 76% (90% CI: 69%, 83%) and 77% (90% CI: 70%, 84%) for the CRT and CRT + chemo arms, respectively (HR=1.05 [90% CI: 0.65, 1.68], p=0.56). Thirty-seven of 50 first failures were distant [74%], 20 (40%) and 17 (34%) in CRT and CRT + chemo arms, respectively. On MVA, factors that were statistically significant for worse DFS were receiving vaginal brachy (p&lt;0.0001), RT dose ≥50 Gy (p=0.0021), and adenocarcinoma histology (p=0.03). Pts receiving brachy had close or positive margins. The estimated 4-yrs OS is 87% (90% CI: 82%, 93%) and 89% (90% CI: 84%, 94%) for the CRT and CRT +chemo arms, respectively (HR=0.91 [90% CI: 0.49 to 1.69]; 1-sided log-rank p=0.40). Conclusions: The addition of systemic chemotherapy following CRT didn't improve DFS or OS in cervical cancer patients with high-risk factors after radical hysterectomy. Clinical trial information: NRG Oncology/RTOG 0724/GOG-0724.