Local-regional Recurrence Research Articles

Level-2 Oncoplastic Surgical Techniques for Breast Cancer: A Preliminary Vietnamese Report.

Breast cancer is the most common malignancy and remains the first cause of death related to cancer among Vietnamese women, with an incidence of 21,555 cases in 2020. Most breast cancer patients present with invasive disease and relatively large tumor sizes. While oncoplastic surgery (OPS) are commonly applied in Western countries, data on Asian population remains relatively limited. This study aims to assess the outcomes of level-2 oncoplastic techniques in breast-conserving surgeries at the Vietnam National Cancer Hospital. From January 2017 to June 2021, a cohort of 257 breast cancer patients who underwent breast-conserving surgery with OPS techniques were examined. Surgical complications, cosmetic outcome, recurrence and survival rates were assessed. The mean age was 47.6±9.4 years, most patients had breast cup sizes B and C. The mean tumor size upon pathological examination was 2.00 ± 0.74 cm. Only 7 cases required reoperation, resulting in a mastectomy rate of 1.17%. The overall complication rate was low at 11.46%, with 9 cases (3.56%) experiencing delayed complications. Cosmetic results were rated as "excellent" in 20.6% and "good" in 60.5%, with a statistically significant difference. The rates of local recurrence, regional recurrence, and distant metastasis at five years were 2.78%, 1.19%, and 2.36%, respectively. The level 2 oncoplastic techniques had low complication rates, favorable oncological outcomes, and cosmetically satisfying results.

Stereotactic Body Radiotherapy Reirradiation Is Safe in Patients With Lung Cancer With In-Field Enlarged Tumor Recurrence.

Introduction: Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for reirradiation. Materials and Methods: Fifteen patients with recurrent stage III lung cancer treated with stereotactic body radiotherapy (SABR) between October 2013 and December 2017 were retrospectively evaluated for local control as a first endpoint; overall survival, disease-free survival, and treatment-related toxicity were secondary endpoints. Results: The median age was 68 (IQR: 50-71) years, and the median tumor size was 3.3 cm (IQR: 3.0-4.5). The radiation field was all within the previous radiation (previous 80%-90% isodose line), and the median dose was 66 Gy/(2 Gy × 33 standard fractionation). For SABR, the median biologically effective dose at an α/β ratio of 10 (BED10) was 60.0 Gy (IQR: 39.38-85.0) and given in 3 to 5 fractions. Three patients experienced grade 3 or 4 toxicity but none experienced grade 5. The median follow-up period was 14 (IQR: 10-23) months. The local control rate was found as 86.7% in the first year, 80% in the second year, and 80% in the third year. The median disease-free survival was 8 (IQR: 6-20) months and the median overall survival was 14 (IQR: 10-23) months. The rate of overall survival was 66.6% for the first year and 33.3% for the second and third years. The disease-free survival rate was 46.6% for the first year and 40% for the second and third years. Nine patients who received doses of BED10 ≥ 50 Gy developed no local recurrence (P = .044). Discussion: In local local-regional recurrence of lung cancer, radiosurgery as reirradiation can be used at doses of BED10 ≥ 50 Gy and above to provide local control for radical or palliative purposes. SABR is an important and relatively safe treatment option in such recurrences.

Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study

BackgroundBased on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge.MethodsFrom 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).ResultsAfter post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02).ConclusionIn patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor’s hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.

Role of Lymphovascular Invasion in Oral Cavity Squamous Cell Carcinoma Regional Metastasis and Prognosis.

The overall 5-year survival for oral squamous cell carcinoma (OSCC) has not changed in the last 20 years despite advances in treatment. Lymphovascular invasion (LVI) has been shown to be a negative prognostic factor in other cancers, however its role in the prognosis of OSCC remains unclear. This study aims to determine if LVI is a predictor of cervical lymph node metastasis and/or recurrence in OSCC. We conducted a retrospective cohort review of patients from our institutional cancer registry who were treated for OSCC between 2004 and 2018. Patient demographics, surgical pathology results, and clinical outcome data were collected. A multivariable logistic regression analysis was performed to determine if LVI was an independent predictor of cervical lymph node metastasis and/or recurrence. 442 patients were included, 32.8% were female and median age at time of diagnosis was 61.2 years. LVI was present in 32.8% of patients. When controlled for age, sex, t-classification, perineural invasion, depth of invasion (DOI), and margin status, LVI was a significant predictor of the presence of cervical node metastasis (OR: 3.42, CI: 2.17-5.39, P < .001). There was no significant association found between LVI and local recurrence (OR: 1.03, CI: 0.57-1.84, P = .92), regional recurrence (OR: 1.10, CI: 0.57-2.11, P = .78), or distant recurrence (OR: 1.59, CI: 0.87-2.94, P = .13). The results of this study suggest that LVI is a significant predictor of the presence of cervical lymph node metastasis at presentation independent of other known prognostic factors. LVI, however, was not found to be a significant independent predictor of locoregional or distant recurrence.Level of Evidence: Level III.

Risk of Recurrence After Surgical Resection for Adenocarcinoma Arising From Intraductal Papillary Mucinous Neoplasia (IPMN) With Patterns of Distribution and Treatment: An International, Multicenter, Observational Study (ADENO-IPMN Study).

This international multicenter cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasm (IPMN). Recurrence patterns and treatment of recurrence postresection of adenocarcinoma arising from IPMN are poorly explored. Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 and December 2020 at 18 pancreatic centers were identified. Survival analysis was performed using the Kaplan-Meier log-rank test and multivariable logistic regression by Cox-Proportional Hazards modeling. End points were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). Four hundred fifty-nine patients were included (median, 70 years; interquartile range, 64-76; male, 54%) with a median follow-up of 78.1 months. Recurrence occurred in 209 patients [45.5%; median time to recurrence, 12.8 months; early recurrence (within 1 years), 23.2%]. Eighty-three (18.1%) patients experienced a local regional recurrence, and 164 (35.7%) patients experienced a distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (hazard ratio 1.09; P =0.669) One hundred twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months ( P <0.001), with no significant difference between treatment modalities. There was no significant difference in survival between locations of recurrence ( P =0.401). Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Oncotype Recurrence Score (RS) at the Extremes of Tumor Size: Which Drives Clinical Outcomes?

Tumor size is an established and independent risk factor for local-regional recurrence (LRR) and distant recurrence (DM). More recently, the recurrence score calculated from a 21-gene expression assay (Oncotype DXTM, Exact Sciences) has also been correlated with LRR and DM. We sought to determine the impact of the interaction between tumor size and Oncotype RS, particularly when the variables are in discrepancy with each other. More specifically, we evaluated clinical outcomes in patients with small tumors (≤1 cm) and high RS (≥26) and, separately, in patients with large tumors (>5 cm) with low RS. Between 2008 and 2020, 310 patients were identified retrospectively as having been treated for early-stage, hormone-receptor positive, Her2-negative breast cancers with tumor size ≤1 cm that were node-negative and had RS ≥ 26 at our institution. In addition, 64 patients were identified with tumor size >5 cm and RS < 26 (irrespective of nodal status). Locoregional recurrence rates (LRR) and invasive recurrence rates (composite of LRR and distant recurrence) were estimated using the Kaplan-Meier method. Patient characteristics are shown in Table 1. In the group of patients with small tumors and high RS, the 5- and 10-year invasive recurrence rates with 95% CI were 8% (4.2-12) and 17% (8.2-26). The 5- and 10-year locoregional recurrence rates with 95% CI were 5.8% (2.7-8.8) and 15% (6.2-23). In the group of patients with large tumors and low RS, 10-year rates could not be estimated with the available data. The 5- and 8-year invasive recurrence rates with 95% CI were 3.2% (0-7.5) and 3.2% (0-7.5). The 5- and 8-year locoregional recurrence rates with 95% CI were 1.6% (0-4.7) and 1.6% (0-4.7). Our findings suggest that patients with small tumors and high RS are at a higher risk for LRR compared to the average ≤1 cm node-negative breast cancer based on published data on the effect of tumor size on LRR and DM. Similarly, tumors larger than 5 cm with low RS appear to behave indolently and in a manner consistent with more favorable risk (despite their large size). These findings may have important implications for the tailoring of local-regional treatment strategies.

The Presence of Extensive Lymphovascular Invasion (LVI) is Associated with Higher Risk of Recurrence in Curatively Treated Breast Cancer Patients

Lymphovascular invasion (LVI) is a pathological feature seen in breast cancer that may be an important step in cancer metastasis. Multiple datasets have demonstrated a correlation between LVI and local-regional recurrence (LRR). Whether the extent of LVI is an incremental determinant of LRR risk is unknown. We describe clinical outcomes in women with invasive breast cancer stratified by: 1) absence of LVI (neg), 2) LVI focal or suspicious (FS-LVI), 3) usual (non-extensive) LVI (LVI) and 4) extensive LVI (E-LVI). Between December 2009 and August 2021, there were 8,837 patients with early-stage breast cancer (T1-2 and N0-2a) were treated with curative intent and were evaluable. Clinical-pathological details were abstracted by retrospective review. The description of LVI was abstracted from pathology reports. Recurrence and survival outcomes were compared based on the extent of LVI. Of the 8837 patients studied, 5584 were neg, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. The E-LVI cohort had baseline characteristics suggestive of higher risk such as younger median age, higher proportion of grade 3, more nodal positivity, more mastectomy (67% vs 48%), and higher use of chemotherapy compared to LVI. The cumulative incidence of LRR and DM was highest in the E-LVI group. Using LVI as the reference, the presence of E-LVI, age, tumor size, ER status, grade, mastectomy, and close/positive margins were independent variables for LRR on Cox multivariable regression (Table 1). To assess the effect with an alternate statistical method, we created propensity matched cohorts (matched for age, size, receptors, grade, surgery type, margins and chemotherapy/RT use); a statistical difference in OS was noted between groups with LVI vs E-LVI (HR 1.44 (CI 1.06-1.96, p = 0.018), but not in LRR (HR 1.31 (CI 0.87-1.97, p = 0.2) or DM (HR 1.16 (CI 0.88-1.53, p = 0.3). Our work suggests that patients with E-LVI are at a higher risk for LRR compared to patients with usual LVI, despite maximal standard of care treatment. This is important because E-LVI can be determined from breast specimens, and may help define indications for RNI/PMRT when nodal information is not available.

Outcomes and Failure Patterns after Chemoradiotherapy for Locally Advanced Rectal Cancer with Positive Lateral Pelvic Lymph Nodes: A Propensity Score-Matched Analysis

Locally advanced rectal cancer (LARC) combined with positive lateral pelvic lymph nodes (LPLN) tends to present worse prognosis. However, for those patients it remains unclear whether other combination high-risk factors affect the prognosis. This study aimed to use propensity score matching (PSM) to examine long-term outcomes and failure patterns in patients with positive vs. negative LPLN. Patients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. LPLN-positivity was defined as lymph node short diameter greater than or equal to 7 mm with specific morphological features. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local-regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan-Meier method and log-rank tests. Prior to PSM, a total of 651 LARC patients were included. The LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P<0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P<0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up time was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. Among 10 patients with LRR, seven (70.0%) had lateral pelvic recurrence, among them, five patients were LPLN-positive, and four (80.0%) of these patients did not receive simultaneous integrated boost intensity-modulated radiotherapy (SIB- IMRT).45 patients were diagnosed with DM, 11 (40.7%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109). Our study shows there is a tendency of worse PFS and DM in LPLN-positive than LPLN-negative patients, for LPLN-positive patients, oligometastases account for a large proportion of all distant metastases.

Risk Stratification of Postoperative Adjuvant Therapy for Endometrial Cancer (POAT-ENDORISK) Based on Bayesian Network Model: A Development and Validation Study

To establish a Bayesian network (BN) model for postoperative adjuvant treatment of early endometrial carcinoma (EC) patients. We retrospectively analyzed the data of 1280 early EC patients treated by multiple institutions in China from 1999 to 2017. All patients received primary hysterectomy/bilateral salpingo-oophorectomy and adjuvant radiotherapy. The FIGO 2009 stage of all patients is stage I and stage II EC, and the median age is 57 years old. All patients are grouped according to the ESMO-ESGO-ESTRO risk stratification. The clinicopathologic factors, treatment-related factors, local regional recurrence, distant metastasis and cancer-specific survival rate (CSS) of all patients were reviewed. We divide the original data set into training set and Validation set according to the ratio of 7:3. The training of the Bayesian network model is completed on Netica, and the test of the model effect is finally completed on the test set. After variable screening, a total of 14 characteristic variables entered the final model. A total of 896 patients were used for the development of BN model, and 384 patients were used for the validation of BN model. The results of the model showed that the factors directly related to CSS were locoregional failure (LRF), radiotherapy mode, distant metastasis (DM). Factors directly related to DM were chemotherapy, LRF, CSS. The factors directly related to LRF were risk stratification, preoperative serum CA125 and preoperative HB. The accuracy, sensibility, specificity, micro-f1, micro-f1, weighted-f1 and AUC of BN model in predicting DM and CSS were better than XGBoost model. In this study, we integrated almost all clinical pathology and treatment information related to postoperative adjuvant treatment of early EC patients and established a BN model for personalized clinical decision-making of postoperative adjuvant treatment of early EC patients. The results showed the complex correlation among the variables, and the overall prediction ability and visualization effect of BN model was significantly better than XGBoost model. Prospective research is needed before clinical implementation.

Evaluation of Sentinel Lymph Node Drainage Patterns in Early-Stage Oral Cavity Cancer

Surgery is the mainstay for squamous cell carcinoma of the oral cavity (OSCC), which includes an elective neck dissection. To limit morbidity of neck dissection, sentinel lymph biopsy (SLNB) has been introduced to identify patients at risk for nodal metastasis. While the data has thoroughly examined the relationship between SLNB in patients with unilateral lymph node drainage, little information exists on the rate of bilateral lymph node drainage patterns in lateralized OSCC. This study sought to examine the incidence of bilateral lymph node drainage patterns using sentinel node mapping in early stage OSCC. This retrospective review of the electronic medical records at Rush University Medical Center focused on patients who underwent a SLNB based on CPT codes 38724, 38900, 38542, and 38510. From this cohort, we limited our analysis to patients with primary clinical T1 or T2 OSCC. Primary outcome was the rate of bilateral nodal drainage on sentinel node mapping based on the SPECT-CT. A total of 54 patients were diagnosed with clinical T1/T2N0 OSCC and underwent a SLNB with SPECT-CT. (1) From the cohort of 54, 15 patients (27.78%) had bilateral sentinel lymph node drainage on SPECT-CT, while 39 patients (72.22%) had unilateral sentinel lymph node drainage. (2) Eleven patients (73.3%) from the bilateral drainage cohort completed appropriate SLN mapping with bilateral nodal assessments. (3) Four patients who had SPECT-CT evidence of bilateral drainage completed unilateral nodal assessment alone. (4) Of the patients with bilateral nodal assessment, 1 (9.1%) patient had a positive sentinel node on the ipsilateral side, 2 (18.2%) were found to have a positive sentinel node in the contralateral neck. (5) Overall, 3 patients (20%) had local-regional recurrence in the bilateral sentinel lymph drainage cohort. Management of early-stage OSCC has evolved to include SLN mapping and biopsy. Our results found that contralateral drainage occurs in 18% of our patients with 2 patients having positive sentinel node in the contralateral neck. Therefore, the rate of contralateral drainage is not clinically insignificant and this result furthers the importance of lymphatic mapping in the early-stage OSCC treatment algorithm.

Accelerated Partial Breast Irradiation (APBI) For HER2+ Early-Stage Breast Cancer

Historically, HER2+ breast cancer exhibited poor outcomes and, hence, has not been well-studied among trials of accelerated partial breast irradiation (APBI). We hypothesized that in contemporary practice with effective HER2-targeted agents, patients with HER2+ breast cancer now have excellent disease control and survival outcomes when treated with adjuvant APBI. Using a prospectively-maintained institutional database, we identified all HER2+ breast cancer patients treated with breast conserving surgery (BCS) and adjuvant APBI from 2000 - 2022. Salient clinicopathologic parameters were collected, as were receipt of systemic and endocrine therapies. All patients received external beam APBI to a total dose of 40Gy in 10 daily fractions over 2 weeks. We analyzed outcomes including local recurrence (LR), regional recurrence, distant recurrence, and death. Cumulative incidence functions were calculated to estimate the incidence of LR with the competing risk of death. All statistical analyses were performed in R version 4.2.2. The study cohort comprised 52 patients with HER2+ breast cancer (median age 64 years; range 44-87). Nearly all had T1 tumors (98%; median size 15 mm; range 1 - 21 mm). Approximately 10% had multifocal disease, with one exhibiting suspicion for lymphovascular invasion. Most patients had ER+ disease (88%). All patients had negative final surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. 42 (81%) received chemotherapy, 40 (77%) endocrine therapy, and 42 (81%) HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range 7 - 226 months for each patient), we observed two LR events, at 14 and 26 months, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any contralateral invasive breast cancer events or breast-specific mortality events. Two deaths were noted in the cohort, both without evidence of disease. Among a cohort of HER2+ early-stage breast cancer patients managed with BCS and APBI, we observed a 2-year LR rate of 3.8% with no regional or distant recurrences, and excellent overall survival. These findings merit longer term follow-up among larger cohorts, although are thus far consistent with the results of contemporary randomized trials of APBI unselected for HER2-status.

Mismatch Repair Status is an Effective Prognostic Factor for Early-Stage Endometrial Carcinoma

This study is to evaluate the impact of mismatch repair (MMR) status on prognosis among patients with stage I to II (FIGO 2009) endometrial carcinoma (EC) treated with hysterectomy and adjuvant RT. Between Oct. 2017 and Dec. 2020, patients with stage I to II (FIGO 2009) EC who had undergone hysterectomy followed by adjuvant RT in our institution were retrospectively reviewed. Clinical characteristics were compared between patients with proficient and deficient mismatch repair (pMMR and dMMR) using Pearson Chi-Square test for categorical variables. Kaplan-Meier method and log-rank test were used to compared overall survival (OS), disease-free survival (DFS), local-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). Statistically significant difference was set as p<0.05. Totally 276 stage I to II EC patients with known MMR status were included in this study. Among them, 211 patients were classified as pMMR while 65 patients were classified as dMMR. When compared to pMMR, patients with dMMR were more likely to have grade 3 and non-endometrioid type(37.8% vs. 20.8%, p = 0.014), lympho-vascular invasion (36.7% vs. 16.3%, p = 0.000), young age (<60) (28.6% vs. 17.2%, p = 0.027), HIR to HR classification(30.9% vs. 16.1%, p = 0.004). Of all the 276 patients, the median follow-up time was 31 months. Two-year DMFS was superior for pMMR compared to dMMR patients (96.3% vs. 95.0%, p = 0.048). Two-year DFS tended to be better for pMMR than dMMR patients with survival curves not crossed over each other (93.0% vs. 86.8%, p = 0.074). Two-year OS (98.9% vs. 98.4%, p = 0.716) and LRFS (96.3% vs. 95.0%, p = 0.815) were not different between pMMR/dMMR patients. For HIR to HR group, we reached the similar conclusion while for LR to IR group, survival statistics were not different between pMMR/dMMR patients. As to failure pattern, dMMR were more likely to have distant failure while local and regional failure were not different between the two groups. For stage I to II EC, patients with dMMR have poorer DMFS and DFS compared to pMMR patients especially in HIR to HR risk classification. The combination of MMR status and other clinical and pathological factors may establish a new prognostic model and form a new risk stratification system.

Margin Assessment Methods in Oral Cavity Squamous Cell Carcinoma and Recurrence

Positive margins and margin clearance are risk factors for recurrence in oral cavity squamous cell carcinoma (OCSCC), and these features are used to guide decisions regarding adjuvant radiation treatment. However, the prognostic value of intraoperative tumor bed vs resection specimen sampling is not well defined. To determine the prognostic implications of intraoperative margin assessment methods (tumor bed vs resection specimen sampling) with recurrence among patients who undergo surgical resection for OCSCC. This was a retrospective study of patients who had undergone surgical resection of OCSCC between January 1, 2000, and December 31, 2021, at a tertiary-level academic institution. Patients were grouped by margin assessment method (tumor bed [defect] or resection specimen sampling). Of 223 patients with OCSCC, 109 patients had localized tumors (pT1-T2, cN0), 154 had advanced tumors, and 40 were included in both cohorts. Disease recurrence after surgery was estimated by the cumulative incidence method and compared between cohorts using hazard ratios (HRs). Data analyses were performed from January 5, 2023, to April 30, 2023. Recurrence-free survival (RFS). The study population comprised 223 patients (mean [SD] age, 62.7 [12.0] years; 88 (39.5%) female and 200 [90.0%] White individuals) of whom 158 (70.9%) had defect-driven and 65 (29.1%) had specimen-driven margin sampling. Among the 109 patients with localized cancer, intraoperative positive margins were found in 5 of 67 (7.5%) vs 8 of 42 (19.0%) for defect- vs specimen-driven sampling, respectively. Final positive margins were 3.0% for defect- (2 of 67) and 2.4% for specimen-driven (1 of 42) margin assessment. Among the 154 patients with advanced cancer, intraoperative positive margins were found in 29 of 114 (25.4%) vs 13 of 40 (32.5%) for defect- and specimen-driven margins, respectively. Final positive margins were higher in the defect-driven group (9 of 114 [7.9%] vs 1 of 40 [2.5%]). When stratified by margin assessment method, the 3-year rates of local recurrence (9.7% vs 5.1%; HR, 1.37; 95% CI, 0.51-3.66), regional recurrence (11.0% vs 10.4%; HR, 0.85; 95% CI, 0.37-1.94), and distant recurrence (6.4% vs 5.0%; HR, 1.10; 95% CI, 0.36-3.35) were not different for defect- vs specimen-driven sampling cohorts, respectively. The 3-year rate of any recurrence was 18.9% in the defect- and 15.2% in the specimen-driven cohort (HR, 0.93; 95% CI, 0.48-1.81). There were no differences in cumulative incidence of disease recurrence when comparing defect- vs specimen-driven cases. The findings of this retrospective cohort study indicate that margin assessment methods using either defect- or specimen-driven sampling did not demonstrate a clear association with the risk of recurrence after OCSCC resection. Specimen-driven sampling may be associated with reduced surgical margin positivity rates, which often necessitate concurrent chemotherapy with adjuvant radiation therapy.

Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma

PurposeOral adenoid cystic carcinoma (OACC) has high rates of both local–regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention.Experimental designWe investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC–MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein–protein interaction networks) to illustrate how Khib modification interfere with OACC evolution.ResultsCompared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression.Conclusions and clinical relevanceKhib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.

Clinical and dosimetric outcomes of image-guided, dose-painted radiotherapy in muscle invasive bladder cancer

Purpose/ObjectiveDefinitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT.Material/MethodsThis was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS.Results117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5–89.2) and 46% (95% CI 36.5–57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%.ConclusionPartial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.

Temporal and spatial patterns of recurrence in oral squamous cell carcinoma, a single-center retrospective cohort study in China

BackgroundOral squamous cell carcinoma (OSCC) is an invasive cancer with a high recurrence rate. Most clinical studies have focused on the prognosis of patients with OSCC, few have investigated the causes and interventions that affect the recurrence. Our study is to explore the temporal and spatial patterns of recurrence in OSCC.Methods234 OSCC patients with recurrence in our hospital and 64 OSCC patients with recurrence in TCGA database were included in the study. Log-rank test and Multivariate Cox Regression Analysis were used to determine whether there was a significant difference between each selected demographic or clinical factors and recurrence. The Kaplan–Meier method was used to plot survival curves for each recurrence interval.ResultsThe proportion of OSCC patients in clinical and TCGA with early recurrence was 93.6% and 84.4%, respectively. Age, chewing betel nut, previous radiotherapy, histopathological grading of the primary tumor (poorly differentiated), lymph node metastasis and postoperative infection were found to be associated with the timing of recurrence. It was found that tongue cancer has more regional recurrences, while buccal cancer is mostly local and loco-regional recurrences. The earlier the recurrence, the greater the possibility of local-regional recurrence and the worse the prognosis.ConclusionMost of recurrent OSCC patients present early recurrence (< 18 months) with poor prognosis, and early recurrence is more prone to local recurrence. Moreover, recurrence site is related with primary site of OSCC.

ASO Visual Abstract: Extremely Low Incidence of Local-Regional Recurrences Observed among T1-2N1 (one or two Positive SLNs) Breast Cancer Patients Receiving Upfront Mastectomy without Completion Axillary Node Dissection.

ASO Visual Abstract: Extremely Low Incidence of Local-Regional Recurrences Observed among T1-2N1 (one or two Positive SLNs) Breast Cancer Patients Receiving Upfront Mastectomy without Completion Axillary Node Dissection.

ASO Author Reflections: Low Rates of Local-Regional Recurrence in Inflammatory Breast Cancer Patients After Contemporary Trimodal Therapy.

ASO Author Reflections: Low Rates of Local-Regional Recurrence in Inflammatory Breast Cancer Patients After Contemporary Trimodal Therapy.

Superior sulcus non–small cell lung cancers (Pancoast tumors): Current outcomes after multidisciplinary management

ObjectiveDespite neoadjuvant chemoradiotherapy, Pancoast tumors still present surgical and oncologic challenges. To optimize outcomes, we used a multidisciplinary care paradigm with medical and radiation oncology, and involvement of spine neurosurgery for most T3 and all T4 tumors. Spine neurosurgery permitted resection of transverse process for T3 and vertebral body resection for T4 tumors. MethodsRetrospective analysis of single institution, prospective database of patients undergoing resection for cT3 4M0 Pancoast tumors. Patients were grouped as cT3 with combined resection with spine neurosurgery (T3 Neuro), cT3 without spine neurosurgery (T3 NoNeuro), and cT4. Overall survival, progression-free survival were analyzed by Kaplan-Meier and compared between groups using log-rank test. Cumulative incidence of local-regional and distant recurrence were compared using Gray test. P value <.05 was considered significant. ResultsFrom 2000 to 2021, 155 patients underwent surgery: median age was 58 years, and 81 were (52%) men. Most patients received neoadjuvant platinum-based neoadjuvant chemoradiotherapy (n = 127 [82%]). Operations were 48 cT3 Neuro, 41 cT3 NoNeuro, 66 cT4. R0 resection was achieved in 49 (94%) cT3 NoNeuro, 35 (85%) cT3 Neuro, and 57 (86%) cT4 patients (P = .4). Complete or major pathologic response occurred in 71 (55%) patients. Lower local-regional cumulative incidence was seen in cT3 Neuro versus cT3 NoNeuro (P = .05) and after major pathologic response. Overall survival and progression-free survival were associated with complete response, pathologic stage, and nodal status but not cT category. ConclusionsThis treatment paradigm was associated with a high frequency of R0 resection, complete response, and major pathologic response. cT3 and cT4 tumors had similar outcomes. Novel therapies are needed to improve complete response.

ASO Visual Abstract: Low Rates of Local-Regional Recurrence in Inflammatory Breast Cancer Patients After Contemporary TrimodalTherapy.

ASO Visual Abstract: Low Rates of Local-Regional Recurrence in Inflammatory Breast Cancer Patients After Contemporary TrimodalTherapy.