Pathological Margin Research Articles

Abstract P1-01-05: Intraoperative three-dimensions MiniiSCANR for determine adequate margin in breast cancer specimens before histopathological examination

Abstract Background: 20-30% of breast conserving surgery patients undergo a second re-excision procedure due to tumor-positive margins at final histopathology. Various modalities are used to assess the adequacy of surgical resection to minimize positive margin and reoperation rates. MiniiSCAN™ is a method of intraoperative specimen radiography that allows for margin evaluation following excisional breast lesion either BI-RADS 4 and 5. The mechanism of MiniiSCAN™ is similar to computer tomography but specimen is rotated on the plate instead circular rotating frame with an x-ray tube mounted on 1 side and a detector on the opposite side in conventional computerized tomography scan. It is easily and short time to reconstructed into 3 dimensions. This machine was developed by Songklanagarind hospital and National Science and Technology Development Agency, Thailand. Objective: To evaluate the efficacy of MiniiSCAN™ as a surgical margin guidance tool compared with pathological margin in breast cancer specimens. Materials & Methods: A retrospective review was designed, 62 consecutive cases of abnormal mammogram (BI-RADS 4,5) with or without wire localization from 1 June 2016 to 30 June 2019 were identified from the electronic medical records at Prince of Songkla University. Results: Of the 62 specimens imaged, 17 had invasive cancer and ten had in-situ pathological diagnoses. Of these, 10 patients had a positive tumor margin and 17 a negative tumor margin at final histopathology. Margin status evaluation by MiniiSCAN™ reconstruction were calculated in 4 minutes (acquisition and reconstruction time). Of the 27 specimens readings, the margin status in 24 patients was correctly predicted by MiniiSCAN™. There were two false-negative predictions. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of MiniiSCAN™ in margin status prediction were 88.89%, 80%, 94.11%, 88.89% and 88.89%, respectively. Conclusion: MiniiSCAN™ could be integrated into routine care, enabling the surgical team to perform and interpret specimen radiographs rapidly and make immediate surgical decisions. Keywords: Abnormal mammography, Breast cancer, CT scan, Specimen radiography Citation Format: Suphawat Laohawiriyakamol, Piyanun Wangkulankul, Piyanoot Woodtichartpreecha, Puttisak Puttawibul. Intraoperative three-dimensions MiniiSCANR for determine adequate margin in breast cancer specimens before histopathological examination [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-05.

Augmented Reality during Open Liver Surgery Using a Markerless Non-rigid Registration System

IntroductionIntraoperative navigation during liver resection remains difficult and requires high radiologic skills because liver anatomy is complex and patient-specific. Augmented reality (AR) during open liver surgery could be helpful to guide hepatectomies and optimize resection margins but faces many challenges when large parenchymal deformations take place. We aimed to experiment a new vision-based AR to assess its clinical feasibility and anatomical accuracy. Patients and MethodsBased on preoperative CT scan 3-D segmentations, we applied a non-rigid registration method, integrating a physics-based elastic model of the liver, computed in real time using an efficient finite element method. To fit the actual deformations, the model was driven by data provided by a single RGB-D camera. Five livers were considered in this experiment. In vivo AR was performed during hepatectomy (n = 4), with manual handling of the livers resulting in large realistic deformations. Ex vivo experiment (n = 1) consisted in repeated CT scans of explanted whole organ carrying internal metallic landmarks, in fixed deformations, and allowed us to analyze our estimated deformations and quantify spatial errors. ResultsIn vivo AR tests were successfully achieved in all patients with a fast and agile setup installation (< 10 min) and real-time overlay of the virtual anatomy onto the surgical field displayed on an external screen. In addition, an ex vivo quantification demonstrated a 7.9mm root mean square error for the registration of internal landmarks. ConclusionThese first experiments of a markerless AR provided promising results, requiring very little equipment and setup time, yet providing real-time AR with satisfactory 3D accuracy. These results must be confirmed in a larger prospective study to definitively assess the impact of such minimally invasive technology on pathological margins and oncological outcomes.

Surgery for Pancoast tumors—the role of combined approaches

Background: The surgical techniques for Pancoast tumors are as variable as the clinical pictures. Involved structures and location/size of the tumor deeply affect the choice of technique and surgical approaches. Methods: Results of the surgical therapy in 23 consecutive patients with Pancoast tumor over an eighteen-year period was reviewed. Disease free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Results: Clinical stage was cT3N0M0 in 17 patients, cT3N1M0 in 2 and cT4N0M0 in 4. No cN2 patients were considered for surgery. Eighteen patients underwent induction chemoradiotherapy. The posterior approach was performed in 61%, the transmanubrial approach in 22% and an original “double step” approach in 17% of patients. A combined approach was performed in 39.1% of patients, mostly through an additional thoracotomy; a combined VATS approach was chosen just in one patient. The prosthetic stabilization of the chest wall was performed in 5 cases. No postoperative mortality was observed with a total complication rate of 48%. The type of approach did not influence the complication rate. Median follow-up was 52.24 months with IQR 13.16–85.39 months (range, 1.48–164.7 months). Median OS was 62.3 months (95% CI, 18.39–104.21 months). The 5-year OS was 55.6% (95% CI, 31.7–74.1%). Median DFS was 65.9 months (95% CI, 12.1–104.2 months); 5-year DFS was 51.5% (95% CI, 28.2–70.7%). Patients with R1 resection had a median OS of 13.1 months (95% CI, 12.2–18.4 months). Conclusions: Complete resection of the tumor represents one of the strongest prognostic factors of OS and DFS, along with T status and complete pathological response to therapy. Every effort should be made to obtain pathologic negative margin and combined approaches may facilitate this goal in anterior Pancoast tumors.

Neoadjuvant PD-1 Immune Checkpoint Blockade Reverses Functional Immunodominance among Tumor Antigen-Specific T Cells.

Surgical resection of primary tumor with regional lymphadenectomy remains the treatment of choice for patients with advanced human papillomavirus-negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse remains high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting the use of neoadjuvant or adjuvant treatment clinically are sparse. Two syngeneic models of oral cavity carcinoma with defined T-cell antigens were treated with programmed death receptor 1 (PD-1) mAb before or after surgical resection of primary tumors, and antigen-specific T-cell responses were explored with functional and in vivo challenge assays. We demonstrated that functional immunodominance developed among T cells targeting multiple independent tumor antigens. T cells specific for subdominant antigens expressed greater levels of PD-1. Neoadjuvant, but not adjuvant, PD-1 immune checkpoint blockade broke immunodominance and induced T-cell responses to dominant and subdominant antigens. Using tumors lacking the immunodominant antigen as a model of antigen escape, neoadjuvant PD-1 immune checkpoint blockade induced effector T-cell immunity against tumor cells lacking immunodominant but retaining subdominant antigen. When combined with complete surgical excision, neoadjuvant PD-1 immune checkpoint blockade led to formation of immunologic memory capable of preventing engraftment of tumors lacking the immunodominant but retaining subdominant antigen. Together, these results implicate PD-1 expression by T cells in the mechanism of functional immunodominance among independent T-cell clones within a progressing tumor and support the use of neoadjuvant PD-1 immune checkpoint blockade in patients with surgically resectable carcinomas.

Increased Preoperative Plasma Level of Microbial 16S rDNA Translocation Is Associated With Relapse After Prostatectomy in Prostate Cancer Patients.

Background: The environmental factors for promoting prostate cancer (PCa) recurrence remain unknown.Methods: A retrospective cross-sectional study was conducted in healthy men (n = 12) and PCa patients undergoing prostatectomy (n = 27). Plasma preoperative level of total cell-free bacterial 16S rDNA, a marker of microbial translocation, was evaluated by qPCR. Plasma levels of prostate-specific antigen (PSA) were evaluated by ELISA.Results: Similar degrees of microbial translocation were found in healthy men and patients. However, the levels of microbial 16S rDNA were increased in patients with cancer relapse (n = 10) compared to patients without relapse (n = 17) after prostatectomy. Furthermore, the levels of microbial 16S rDNA were marginally increased in patients with pT3 or pT4 tumors compared to those with pT 2 or less. The levels of microbial 16S rDNA tended to increase in patients with higher pathologic tumor stage, Gleason score, and margin and lymph node involvements; but these differences did not reach significance.Conclusion: The plasma 16S rDNA levels increased in patients with PCa who have biochemical recurrence and 16S rDNA levels were higher in patients with higher-grade PCa.

Performance of CT-based radiomics in diagnosis of superior mesenteric vein resection margin in patients with pancreatic head cancer.

To accurately identify the relationship between a portal radiomics score (rad-score) and pathologic superior mesenteric vein (SMV) resection margin and to evaluate the diagnostic performance in patients with pancreatic head cancer. A total of 181 patients with postoperatively and pathologically confirmed pancreatic head cancer who underwent multislice computed tomography within one month of resection between January 2016 and December 2018 were retrospectively investigated. For each patient, 1029 radiomics features of the portal phase were extracted, which were reduced using the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. Multivariate logistic regression models were used to analyze the association between the portal rad-score and SMV resection margin. Patients with negative (R0) and positive (R1) margins accounted for 70.17% (127) and 29.83% (54) of the cohort, respectively. The rad-score was significantly associated with the SMV resection margin status (p < 0.05). Multivariate analyses confirmed a significant and independent association between the portal rad-score and SMV resection margin (OR 4.62; 95% CI 2.19-9.76; p < 0.0001). The portal rad-score had high accuracy (area under the curve = 0.750). The best cut point based on maximizing the sum of sensitivity and specificity was -0.741 (sensitivity = 64.8%; specificity = 74.0%; accuracy = 71.3%). Decision curve analysis indicated the clinical usefulness of radiomics score. The portal rad-score is significantly associated with the pathologic SMV resection margin, and it can accurately and noninvasively predict the SMV resection margin in patients with pancreatic cancer.

Impact of the Proportion of Biopsy Positive Core in Predicting Biochemical Recurrence in Patients with Pathological Pt2 and Negative Resection Margin Status after Radical Prostatectomy.

This study aimed to determine the prognostic factors associated with biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with pathological T2 (pT2) prostate cancer (PCa) and negative resection margin (RM) status at a single institution. In this retrospective study, we examined 386 patients who were diagnosed with pT2 PCa with negative RM after RP. The length of the tumor was provided for each biopsy core and the overall percentage of PCa was calculated by a pathologist at our institution. We estimated the BCR-free survival (BRFS) in these patients. Univariate and multivariate analyses were performed using the Cox proportional hazard model to determine the risk factors of BCR. The median age of the participants was 68years, and their initial prostate-specific antigen level was 6.55ng/mL. The median follow-up period was 85.7months. The 5-year BRFS rate of the participants was 89.0%. The 5-year BRFS rates were 89.8% in patients with a biopsy Gleason score of 6, 90.4% in those with 7, and 64.1% in those with ≥8 (P = 0.007). The BRFS rate was 93.3% in patients who had a biopsy positive core ≤20% and 82.0% in those who had ≥21% (P = 0.001). Based on the multivariate analysis, the proportion of biopsy positive core was significantly associated with BCR. The proportion of biopsy positive core may predict preoperative covariates in patients with pT2 PCa and negative RM status after RP.

Pathological assessment of endoscopic resections of the gastrointestinal tract: a comprehensive clinicopathologic review.

Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.

Can micro-computed tomography imaging improve interpretation of macroscopic margin assessment of specimen radiography in excised breast specimens?

Peri-operative macroscopic margin assessment with standard intraoperative specimen radiography (IOSR) results in improved re-excision rates in excised breast tissue specimens but is limited. This study sought to improve the intraoperative margin assessment on standard IOSR techniques by utilizing noninvasive X-ray micro-computed tomography (micro-CT) imaging of breast tissue specimens to compare margins in three-dimensional with two-dimensional IOSR.Patients with impalpable breast carcinoma, or suspected breast carcinoma, who were eligible for breast-conserving surgery were recruited. Margins were assessed within each specimen using standard IOSR, micro-CT, and histology techniques.Six malignant and three benign lesions were included for the analysis in this study. Micro-CT identified the same positive margin as IOSR in 3 out of 6 malignancies. However, margin status identified by micro-CT was concordant with pathological assessment in only one specimen. In comparison, margin assessment by IOSR correctly correlated with pathological margin status in three malignant specimens.The use of micro-CT imaging in this study did not improve margin assessment in impalpable breast specimens when compared to standard specimen radiography (SR) assessment. However, future improvements in sample preparation and CT image acquisition processes may enhance the potential of micro-CT as a valuable imaging tool for improving margin assessment.

Recurrent basal cell carcinoma with maxillary bone invasion

Background: Basal cell carcinoma (BCC) is a malignant, slow growing, and locally invasive skin tumor. Advanced and neglected BCC may invade adjacent structures. The 5-year recurrence rates of facial BCCs are 4.1% after excision and 2.5% after Mohs Micrographic Surgery (MMS) . The number of BCC cases invading the bones of the head and neck region is limited. Case Illustration: A 75-year-old male complained of bleeding and ulcer enlargement on the right cheek expanding to the right nasal ala for 1 month. The patient had a history of an enlarged and painful lenticular nodule with a hyperpigmented spot that appeared 10 years ago on the right cheek and was diagnosed as BCC. The patient was treated with a wide excision having a negative pathological margin 3 years ago. He noticed that the similar lesion reappeared at the same location 2.5 years ago. Post-operative histopathological results showed nodular infiltrative BCC and maxillary bone invasion. Discussion: Based on history taking, physical examination, and diagnostic evaluation, the diagnosis of the patient was recurrent nodular infiltrative BCC. The final histopathology confirmed that tumor cells invaded the maxillary bone. After considering the treatment options, the patient opted to proceed with radiotherapy. Conclusion: Recurrent nodular BCC with invasion to the maxillary bone is a rare and interesting case. Among 140 BCC cases that we treated with MMS in our hospital from June 2014 to September 2019 , this case is the first recurrent BCC with maxillary bone invasion. Keywords: basal cell carcinoma, skin tumor, MMS, bone invasion

Cell cycle progression score improves risk stratification in prostate cancer patients with adverse pathology after radical prostatectomy.

To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010-2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards model. Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0-1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006-1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy.

Intraoperative Radiographic Assessment of Bone Resection Margins During Mandibulectomy: A Case Series

Mandibulectomy remains the treatment of choice for oral cavity squamous cell carcinoma with infiltration of bone and for benign tumors with full mandibular thickness involvement. Although bone resection margins are critical for patient outcomes, intraoperative immediate bone margins assessment is inadequate, and few alternative options have been described. The purpose of this study was to describe the use of an existing intraoperative radiographic system for objective determination of bone resection margins during mandibulectomy. We conducted a retrospective case series of all patients at the Greater Baltimore Medical Center who underwent mandibulectomy and received intraoperative Faxitron radiography from January 1, 2016, to March 1, 2019. Patient characteristics including age, sex, diagnosis, tumor location, clinical and pathologic stage, procedure performed, and bone resection margins were reviewed. A total of 10 patients underwent mandibulectomy with intraoperative radiography. Nine (90%) received surgery for squamous cell carcinoma, with 1 (10%) for ameloblastoma. Out of those with squamous cell carcinoma, tumor location varied, and all were clinically stage T4. Final pathologic margins were negative in all cases (10/10), though in 2 cases, close margins were assessed intraoperatively, leading to further resection or change in operative plan. Intraoperative radiographic assessment of bone resection margins is a promising technique, though further validation is required.

Perioperative adverse events following surgery for primary bone tumors of the spine and en bloc resection for metastases.

Surgical treatment of primary bone tumors of the spine and en bloc resection for isolated metastases are complex and challenging. Operative care is fraught with complications, though the true incidence and predictors of adverse events (AEs), length of stay (LOS), and mortality in this population remain poorly understood. The primary objective of this study was to describe the incidence and predictors of perioperative AEs in these patients. Secondary objectives included the determination of the incidence and predictors of admission to the intensive care unit (ICU), unanticipated reoperation during the same admission, hospital LOS, and mortality. In this retrospective analysis of prospectively collected data, the authors included consecutive patients at a single quaternary care referral center (January 1, 2009, to September 30, 2018) who underwent either surgery for a primary bone tumor of the spine or an en bloc resection for an isolated spinal metastasis. Information on perioperative AEs, demographic data, primary tumor histology, neurological status, surgical variables, pathological margins, Enneking appropriateness, LOS, ICU stay, reoperation during the same admission period, and in-hospital mortality was collected prospectively in the institutional database. The modified frailty score was extracted retrospectively. One hundred thirteen patients met the inclusion criteria: 98 with primary bone tumors and 15 with isolated metastases. The cohort was 59% male, and the mean age was 49 years (SD 19 years). Overall, 79% of the patients experienced at least 1 AE. The median number of AEs per patient was 2 (IQR 0-4 AEs), and the median LOS was 16 days (IQR 9-32 days). No in-hospital deaths occurred in the cohort. Thirty-two patients (28%) required an ICU stay and 19% underwent an unanticipated second surgery during their admission. A longer surgical duration was associated with a higher likelihood of AEs (OR 1.21/hour, 95% CI 1.06-1.37, p = 0.005), longer ICU stay (OR 1.35/hour, 95% CI 1 1.20-1.52, p < 0.001), and reoperation (OR 1.001/hour, 95% CI 1.0003-1.003, p = 0.012). Longer hospital LOS was independently predicted by older age, female sex, upper cervical and sacral location of the tumor, surgical duration, preoperative neurological deficit, presence of AEs, and higher modified frailty index score. Surgeries for primary bone tumors and en bloc resection for metastatic tumors are associated with a high incidence of perioperative AEs. Surgical duration predicts complications, reoperation, LOS, and ICU stay.

Mucin Pools Following Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Marker of Response or Epiphenomenon?

Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Morphologic changes such as fibrosis, inflammatory infiltrates, and the formation of extracellular mucin pools can be identified in the resection specimen after neoadjuvant CRT. The association of mucin pool formation with clinicopathologic variables and outcomes is unclear. The aim of this study was to meta-analyze all available evidence with regard to mucin pool formation and clinicopathologic outcomes following neoadjuvant CRT for rectal cancer. A comprehensive search for published studies analyzing outcomes between patients who formed mucin pools and patients who did not following neoadjuvant CRT for rectal cancer was performed. A random-effects model was used to combine the data. This study adhered to the recommendations of the MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. Data from 11 studies describing 1947 patients were included. Mucin pool formation was not associated with sex, T stage, N stage, tumor regression, pathologic complete response rate, lymphovascular invasion, perineural invasion, differentiation, margin status, local or distant recurrence, and disease-free or overall survival. Mucin pool formation is not associated with tumor response or downstaging; furthermore, on the basis of these data, it is not associated with local or systemic recurrence rate or survival.

Oncoplastic Central Partial Mastectomy and Neoareolar Reduction Mammoplasty with Immediate Nipple Reconstruction: An Initial Report of a Novel Option for Breast Conservation in Patients with Subareolar Tumors.

Breast-conserving therapy (BCT) has been associated with better quality of life and cosmetic outcomes than mastectomy. However, subareolar cancers abutting the nipple-areolar complex (NAC) present a unique cosmetic and oncologic challenge. Oncoplastic central partial mastectomy and neoareolar reduction mammoplasty with immediate nipple reconstruction is a novel technique that can permit BCT for these patients. This study enrolled consecutive patients with central tumors during 2017-2018 who underwent central partial mastectomy reconstructed with neoareolar reduction mammoplasty and immediate nipple reconstruction. Patient demographics, imaging and pathology size, margin width, mastectomy and reexcision rates, and cosmesis were evaluated. The study identified 23 sequential patients. The average patient age was 60.5 ± 12.3years, and the average body mass index was 29.4 ± 5.7kg/m2. The mean lesion size was 51.5 ± 43.0mm on preoperative imaging, and the average disease span shown by the final pathology was 59.5 ± 45.3mm. "No ink on tumor" was achieved for 22 patients (95.7%). In 13 patients (56.5%), the margins were inadequate for ductal carcinoma in situ (DCIS) (n = 12) or invasive cancer (n = 1). Good to excellent cosmetic results were achieved for 21 patients (95.5%). Complications occurred for six patients (26.1%), including three patients with ischemia of the reconstructed NAC. The single-stage operation described in this report can allow patients with cancers abutting the NAC to consider BCT. This technique allows patients to avoid mastectomy and to minimize the number of operations required for reconstruction while maximizing cosmetic outcomes. In the study cohort, the presence of extensive DCIS resulted in a significant need for reexcision, which could be performed successfully without compromise to cosmetic outcome.

Pathologic Outcomes of Systemic Therapy Followed By Stereotactic Body Radiation Therapy for Pancreatic Cancer in a Novel Lateral Decubitus Treatment Position

Outcomes of multi-fraction stereotactic body radiotherapy (SBRT) for pancreatic cancer (PC) report low rates of toxicity and high local control, improving feasibility for combination with more intensive systemic therapy regimens. However, SBRT in the ablative range poses risk to adjacent normal structures, excluding this option for tumors within 1 cm of a mucosal organ. In this study, we report our initial experience with treatment outcomes in the lateral decubitus position. An IRB retrospective query identified all patients with pancreatic body adenocarcinoma treated with systemic chemotherapy followed by SBRT in the lateral decubitis position. SBRT was delivered to the entire gross disease with 30 Gy in 5 fractions with focal dose escalation up to 40 Gy to the tumor/vessel interface (TVI) as long as constraints were met. Patients were explored for resection if no metastasis or progression was imaged on restaging scans. The primary endpoints were pathologic response and margin status. Descriptive analysis was performed with statistical software. The median age of the cohort was 68.9 (range, 50-83 yrs), with a white (94%) and male (56%) predominance. Initial staging of the 18 patients who met criteria included 10 (56%) patients diagnosed with borderline resectable disease (BRPC) and 8 (44%) with locally advanced disease (LAPC). 7 (44%) patients were treated with FOLFIRINOX, 5 (28%) with gemcitabine/nab-paclitaxel, 4 (22%) with gemcitabine/capecitabine/docetaxel, and 1 (6%) with gemcitabine/paclitaxel preceding SBRT. A median dose of 40 Gy (range, 33-40 Gy) was delivered to the TVI for all patients. 5 BRPC (28%) and 3 LAPC (17%) patients went to surgery, with 7 of these patients undergoing an R0 resection (88%) and 1 BRPC patient with an R1 resection. Pathologic tumor regression grades by the College of American Pathologists guidelines were 12.5% Grade 1, 75% Grade 2, and 12.5% Grade 3. Lateral decubitus treatment expands inclusion of pancreatic body patients for SBRT with focal TVI dose escalation leading to margin negative resection and significant partial tumor response, warranting future studies exploring ablative dosing in this position.

Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma: A Comparison of Three Platinum-based Regimens

Concurrent chemoradiotherapy (CRT) improves outcomes for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and high-risk postoperative patients. Current data support cisplatin at a dose of 100 mg/m2 every 3 weeks (Q3WC). Other regimens including weekly cisplatin (QWC) and weekly carboplatin/paclitaxel (CP) have been reported. We aim to compare survival, disease control, and post-treatment nutritional status between these regimens. We identified patients with HNSCC treated with CRT between 2010 and 2017. Patient, tumor, and treatment factors were abstracted from the medical record. Severe comorbidity was defined as Charlson comorbidity index ≥3. Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) and cumulative incidence (CI) of locoregional (LRF) and distant failure (DF) with death as a competing risk were generated from the date of RT completion. Multivariate models adjusting for baseline factors were performed. Gastrostomy tube dependence (GTD) at 6 months was defined as a Functional Oral Intake Scale ≤3. In total, 236 patients were treated with definitive (78%) or postoperative (28%) CRT with Q3WC (n=63), QWC (n=127) and CP (n=46). The Q3WC group had fewer patients >65 years old (10% v. 20% QWC v. 37% CP) or severe comorbidity (32% v. 39% v. 57%) and more frequent use of induction chemotherapy (3% v. 8% v. 20%). Primary sites included oropharynx (56%), larynx (27%), oral cavity (12%), and hypopharynx (5%) and 95% had stage III-IV disease. There were no baseline differences in gender, ECOG performance status, tobacco/alcohol use, clinical or pathologic stage, HPV status, extracapsular extension, or margin status. Cumulative dose ≥200 mg/m2 was achieved in 89% with Q3WC versus 73% with QWC (p=0.02). Twelve Q3WC patients converted to QWC due to one or more toxicity: nausea/vomiting (8), cytopenia (4), acute kidney injury (3), dehydration/weight loss (2), mucositis (1) and dermatitis (1). Median follow-up was 27 months. Three-year OS and DFS were 84%, 62% and 59% (p=0.01) and 74%, 58% and 48%, respectively (p=0.01). Compared to Q3WC, QWC (aHR 2.77) and CP (aHR 3.04) were associated with worse OS on multivariate analysis. Disease-specific survival also favored Q3WC (p=0.05). At 3 years, CI of LRF was 14% for Q3WC, 17% for QWC and 20% for CP (p=0.63); 3-year DF was 10%, 15% and 17%, respectively (p=0.81). No differences in weight change (mean -13% v. -12% v. -10%, p=0.29) or GTD (32% v. 20% v. 31%, p=0.31) were observed. Every-3-week cisplatin was associated with improved survival in patients treated with chemoradiotherapy for HNSCC. No significant differences were detected in locoregional or distant control. This may be related to cumulative dose, competing comorbidity and/or selection biases. There were no significant differences in nutritional outcomes.

Surgical Management of Primary Pulmonary Mucoepidermoid Carcinoma of the Proximal Left Mainstem Bronchus

A 29-year-old non-smoking female with a history of recurrent AML presented with worsening dyspnea. A CT scan revealed an 8 X 7 mm polypoid soft tissue nodule 8 mm distal to the carina in the left mainstem bronchus. She was brought to the operating room and a nearly obstructing soft fleshy tumor in the left mainstem bronchus just distal to the carina was removed with bronchoscopy. Pathology revealed a low grade mucoepidermoid carcinoma 0.8 cm in largest dimension with negative margins. The patient returned for a resection and was intubated with a right mainstem double lumen tube and placed in left lateral decubitus. After posterolateral thoracotomy, the azygos vein was divided to mobilize the esophagus and retract it laterally. Level 4 and 7 lymph node dissection were performed to obtain access to the anterior tracheal and subcarinal spaces. There was minimal dissection lateral to the trachea to minimize risk of ischemia. One centimeter of trachea just proximal to the carina was circumferentially isolated with umbilical tape for retraction. We bronchoscopically confirmed the location for transection and advanced a jet ventilator catheter distally. We resected one centimeter of left mainstem bronchus. We inspected the lumen of the airway to confirm no gross residual disease and confirmed negative pathologic margin before performing an end-to-end anastomosis with interrupted absorbable sutures under both jet and cross-table ventilation. Postoperatively, the patient had an uncomplicated course and was discharged without any supplemental oxygen on postoperative day 6. Final pathology was low grade mucoepidermoid carcinoma, T1aN0.

MRI-Based Use of Neoadjuvant Chemoradiotherapy in Rectal Carcinoma: Surgical Quality and Histopathological Outcome of the OCUM Trial.

Preoperative magnetic resonance imaging (MRI) allows highly reliable imaging of the mesorectal fascia (mrMRF) and its relationship to the tumor. The prospective multicenter observational study OCUM uses these findings to indicate neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. nCRT was indicated in patients with positive mrMRF (≤ 1mm) in cT4 and cT3 carcinomas of the lower rectal third. A total of 527 patients (60.2%) underwent primary total mesorectal excision, and 348 patients (39.8%) underwent long-term nCRT followed by surgery. The mrMRF was involved in 4.6% of the primary surgery group and 80.7% of the nCRT group. Rates of resections within the mesorectal plane (90.8%), sparing of pelvic nerves on both sides (97.8%), and number of regional lymph nodes (95.3% with ≥ 12 lymph nodes examined) are indicative of high-quality surgery. Resection was classified as R0 in 98.3%, the pathological circumferential resection margin (pCRM) was negative in 95.1%.Patients in the nCRT group had more advanced carcinomas with a significantly higher rate of abdominoperineal excision. Independent risk factors for pCRM positivity were advanced stage (T4), metastatic lymph nodes, resection in the muscularis propria plane, and location in the lower third. The risk classification of rectal cancer patients by MRI seems to be highly reliable and allows the restriction of nCRT to approximately half of the patients with clinical stage II and III rectal carcinoma, provided there is a high-quality MRI diagnostic protocol, high-quality surgery, and standardized examination of the resected specimen.

Factors Associated with Reoperation in Breast-Conserving Surgery for Cancer: A Prospective Study of American Society of Breast Surgeon Members

BackgroundMore than 20% of patients undergoing initial breast-conserving surgery (BCS) for cancer require reoperation. To address this concern, the American Society of Breast Surgeons (ASBrS) endorsed 10 processes of care (tools) in 2015 to be considered by surgeons to de-escalate reoperations. In a planned follow-up, we sought to determine which tools were associated with fewer reoperations.MethodsA cohort of ASBrS member surgeons prospectively entered data into the ASBrS Mastery® registry on consecutive patients undergoing BCS in 2017. The association between tools and reoperations was estimated via multivariate and hierarchical ranking analyses.ResultsSeventy-one surgeons reported reoperations in 486 (12.3%) of 3954 cases (mean 12.7% [standard deviation (SD) 7.7%], median 11.5% [range 0–32%]). There was an eightfold difference between surgeons in the 10th and 90th percentile performance groups. Actionable factors associated with fewer reoperations included routine planned cavity side-wall shaves, surgeon use of ultrasound (US), neoadjuvant chemotherapy, intra-operative pathologic margin assessment, and use of a pre-operative diagnostic imaging modality beyond conventional 2D mammography. For patients with invasive cancer, ≥ 24% of those who underwent reexcision did so for reported margins of < 1 or 2 mm, representing noncompliance with the SSO-ASTRO margin guideline.ConclusionsAlthough ASBrS member surgeons had some of the lowest rates of reoperation reported in any registry, significant intersurgeon variability persisted. Further efforts to lower rates are therefore warranted. Opportunities to do so were identified by adopting those processes of care, including improved compliance with the SSO-ASTRO margin guideline, which were associated with fewer reoperations.