Risk Of Local Recurrence Research Articles

Patterns of local recurrence and risk of skin recurrence in soft tissue sarcomas after surgical resection.

Soft tissue sarcomas (STSs) are rare, heterogeneous tumors primarily managed surgically with radiotherapy (RT) added to improve local control. Although there is a theoretical risk of skin seeding at the time of surgery, current ASTRO Clinical Practice Guidelines recommend against routine use of bolus during pre-operative or post-operative radiotherapy for STS due to increased risk of skin toxicity without clear benefit. However, in the modern era with contemporary treatment planning techniques, the risk of skin recurrence has not been assessed. We performed a detailed analysis of the patterns of local recurrence (LR) in patients with STS treated with surgical resection with or without RT. We performed a retrospective analysis of 206 adult patients with extremity or trunk STSs evaluated in the Department of Radiation Oncology at our institution over 14 years (2007-2021) and identified all patients with LR. The depth of the recurrence and location relative to the radiation field in patients treated with radiotherapy was evaluated. Progression free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, and cumulative incidence of distant metastasis (CIDM) was calculated with competing risk analysis from the date of LR. Of the 206 patients evaluated, 20 experienced a LR after surgical resection with or without RT. Among patients with a LR, 5 patients (25.0%) were treated with surgery alone and 15 patients (75.0%) received surgery and RT. In patients treated with RT, 46.7% had pre-operative RT, 53.3% had post operative RT, and bolus was used in 5 patients (33.3%). Surgical margins were close (<1mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). Tumor grade was intermediate/high in 15 patients (75%) and the median tumor size was 9 cm (range 5-12). LR occurred in the muscle in 8 patients (40%), subcutaneous tissue in 11 patients (55.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone and the tumor involved the skin at presentation. In the patients treated with RT, LR occurred within radiation field in 10 patients (66.7%). Median follow up time after local recurrence was 12.9 months. At 3 years after LR, PFS was 43.9%, OS was 81.7%, and CIDM was 16.7%. Skin recurrences were exceedingly rare after surgical resection of STSs, and only occurred in a tumor that involved the skin at initial presentation. Due to the increased dose to the normal skin and subcutaneous tissues when bolus is used, which increases risk of toxicity, these findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

Characterizing First Events in LA-NSCLC Patients Treated with Chemoradiotherapy

Definitive chemoradiotherapy (CRT) is a standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). After treatment, patients are at risk for local disease recurrence, developing new sites of disease, and death without disease recurrence. Here, we characterize the rates of these events in a modern patient cohort and explore risk factors for each event. The hypothesis is that these rates and risk factors will better inform treatment strategies for local intensification and systemic therapy. We reviewed patients who underwent staging PET/CT and were treated for LA-NSCLC with definitive CRT at our institution between 2010 and 2022. Competing risks analyses were performed to calculate rates of disease progression and death without disease progression. Competing risks analyses were repeated after dividing disease progression into in-field recurrence versus out-of-field progression and after subdividing in-field recurrences into progression of high-risk (large) tumors or lymph nodes (defined as having metabolic tumor volume [MTV] >20 cc on staging PET/CT) versus progression of low-risk (small) tumors or lymph nodes. Predictors of each event type were identified using univariate and multivariable Fine and Gray competing risks regressions. A total of 210 patients met inclusion criteria, and the median follow-up duration is 43 months. Median age was 68 (IQR 60 to 74), and 77% of patients had ECOG performance status 0-1. Median progression-free survival and overall survival durations are 13 and 40 months, respectively. The 3-year cumulative incidence rate (CIR) of disease progression was 58%, and the 3-year CIR of death without disease progression was 18%. The 3-year CIR for out-of-field disease progression was 44%, and the 3-year CIR for in-field recurrence was 14%. The 3-year CIR for in-field recurrence of high-risk lesions was 11%, and the 3-year CIR for low-risk lesions was 4%. Multivariable analyses examining predictors of out-of-field progression revealed two statistically significant factors: total disease burden on PET (SHR 1.03 per 10 cc, p = 0.013) and durvalumab receipt (SHR 0.60, p = 0.031). Multivariable analyses also revealed two predictors of death without disease progression: age (SHR 1.06 per year, p = 0.018) and ECOG performance status (SHR 1.81, p = 0.012). For LA-NSCLC patients treated with definitive CRT, we found that developing new sites of disease is the most common first event, followed by death without disease recurrence. In-field disease recurrence is relatively uncommon, particularly when treating relatively small tumors and lymph nodes. These findings may inform prioritization of strategies to improve systemic therapy, intensify local therapy, and minimize treatment-related toxicity.

A Deep Learning Framework with Explainability for the Prediction of Lateral Locoregional Recurrences in Rectal Cancer Patients with Suspicious Lateral Lymph Nodes.

Malignant lateral lymph nodes (LLNs) in low, locally advanced rectal cancer can cause (ipsi-lateral) local recurrences ((L)LR). Accurate identification is, therefore, essential. This study explored LLN features to create an artificial intelligence prediction model, estimating the risk of (L)LR. This retrospective multicentre cohort study examined 196 patients diagnosed with rectal cancer between 2008 and 2020 from three tertiary centres in the Netherlands. Primary and restaging T2W magnetic resonance imaging and clinical features were used. Visible LLNs were segmented and used for a multi-channel convolutional neural network. A deep learning model was developed and trained for the prediction of (L)LR according to malignant LLNs. Combined imaging and clinical features resulted in AUCs of 0.78 and 0.80 for LR and LLR, respectively. The sensitivity and specificity were 85.7% and 67.6%, respectively. Class activation map explainability methods were applied and consistently identified the same high-risk regions with structural similarity indices ranging from 0.772-0.930. This model resulted in good predictive value for (L)LR rates and can form the basis of future auto-segmentation programs to assist in the identification of high-risk patients and the development of risk stratification models.

Omission of Chest Wall/Scar Boost and Skin Bolus Does Not Increase Risk of Local Recurrence for Breast Cancer Patients

For breast cancer patients receiving postmastectomy radiation (PMRT), little is known about the value of Chest Wall Boost (CWB) and Skin Bolus (SB) across different biological subtypes and patients with high-risk features. We reviewed 2,917 charts of breast cancer patients treated with mastectomy between 2000-2020 at our institution. Only patients treated with PMRT were included. Patients with and without reconstruction were included. Reconstruction types included autologous or single-stage-direct-implant or two stages expanders/implant. PMRT was delivered with 3D conformal technique using photons and conventional fractionation (50-50.4 Gy in 25-28 fractions). CWB using enface electrons and 3-5 mm SB applied every other day were delivered at the discretion of the physician. Primary objectives were locoregional failure (LF) rates between CWB and No CWB groups; SB and No SB groups. Different subgroup analyses exploring the benefits of CWB and SB in different biological subtypes, patients with lymphovascular invasion (LVI+), positive margins (PM) and nipple sparing mastectomy (NSM) were conducted. Secondary objectives were toxicity of CWB and SB on different reconstruction outcomes and PMRT side effects. Logistic and cox regressions were used. A total of 1,103 patients with an overall median follow-up of 7.8 years were available for analysis. Among the entire cohort, 55.4% received CWB, 76% received SB, 48% had LVI, 23% with PM, 41% with NSM, 67% with Luminal A, 15% with Luminal B, 7% with HER2 enriched and 11% with triple negative. The 10 years incidence of LF was 6.5% and 4.0% for CWB and NO CWB, respectively (HR 1.6, p = 0.1); and 5.6% and 5.1% for SB and NO SB respectively (HR 0.9, p = 0.8). Multivariable analysis of LF adjusted for LVI, ECE, grade, tumor size, number of malignant nodes, and biological subtype showed no association of CWB and SB with local control (HR:1.4, p = 0.2 and HR:0.9, p = 0.8), respectively. Subgroup analyses confirmed no association of CWB or SB with improved local control across different biological subtypes, (LVI+), PM and NSM patients. On multivariable level CWB significantly increased reconstruction complications (OR 2.3, p = 0.001, OR 1.7, p = 0.008) for infection/necrosis (I/N) and overall reconstruction failure (ORF), respectively; while SB did not (OR 1.1, p = 0.8, OR 1.0, p = 0.9) for I/N and ORF, respectively. 56 patients needed treatment break, 49 of them (87%) had SB. Both CWB and SB significantly increased the risk of higher grade radiation dermatitis (2-4) in the entire cohort OR 2.1 p = 0.01, and OR 2.3, p = 0.02 for CWB and SB, respectively. CWB and SB did not improve local control across different biological subtypes, patients with LVI, Positive Margins and NSM. CWB significantly increased reconstruction complications and SB increased treatment breaks and radiation dermatitis. These findings do not support routine usage of CWB and SB.

Comparison of Early Outcomes of Stereotactic Accelerated Partial Breast Irradiation vs. Volumetric Modulated Arc Therapy-Based FAST-FORWARD Whole Breast Irradiation for Breast Cancer

Despite evidence supporting APBI from 8 published prospective randomized trials enrolling over 10,000 women, the uptake of APBI in clinical practice is surprisingly low. This is being exacerbated by a new, convenient, and safe shortened WBI schedule. Here, we report the dosimetric and early outcome analyses of the first >1000 patients treated at our institution since the first adoption of stereotactic APBI and the ultra-hypofractionated WBI regimen. From 2016 to 2022, 801 women with breast cancers in the suitable or cautionary categories according to the ASTRO APBI consensus panel guidelines, received 30 Gy in 5 fractions (92%) either using a robotic stereotactic radiation system (83%) or stereotactic volumetric-based arc therapy (VMAT, 17%). Between 2020 and 2022, 468 women, who were not candidates for APBI and not undergoing any regional irradiation received 26 Gy in 5 fractions using VMAT to the whole breast with the addition of cardiac sparing technique in left-sided breast cancer patients. Tumor bed boosts were delivered in 99% of FF-WBI patients. We evaluated dose-volume histogram parameters for target volumes and organs-at-risk and radiation-related toxicities during RT or within 6 months after the end of RT. Target volume coverage was acceptable in both groups, with mean 96% of the target volumes receiving 95% of the prescribed doses and 0 cm3 within target volumes exceeding 105% of the prescribed doses. S-APBI resulted in small, but statistically significant, reductions in the radiation dose delivered to the ipsilateral breast, contralateral breast, lungs, heart, and coronary artery compared with FF-WBI. Comparing WBI to APBI, the mean contralateral breast dose, ipsilateral lung V20 Gy, mean contralateral lung dose, and mean heart dose, were reduced by 89%, 78%, 73%, and 29%, respectively. With median follow-up periods of 32 months for s-APBI and 19 months for FF-WBI, acute toxicity was assessable in all patients. The risks of any grade acute toxicity were 21% for s-APBI and 25% for FF-WBI (p = .117). Among them, grade 2 rates were 1.3% in both groups and no severe toxicity has been reported. We found s-APBI and VMAT-based FF WBI were associated with favorable dosimetric and acute toxicity profiles. However, considering significantly less irradiated volume in the breast, lungs, and heart, APBI with advanced available technique options should be considered over any WBI-based approach for patients at low risk for local recurrence.

Clinical Outcomes Following Postoperative Cavity Stereotactic Radiosurgery for Brain Metastases

We evaluated outcomes of patients with brain metastases (BM) treated with surgical resection and postoperative cavity stereotactic radiosurgery (SRS) to identify which baseline characteristics and treatment factors may increase risk for local recurrence (LR). From June 2017 to December 2021, 68 patients underwent surgical resection for BM followed by single-fraction SRS (n = 15) or fractionated SRS (FSRS) in 3 (n = 24) or 5 (n = 29) fractions to the postoperative cavity using frameless LINAC-based technique. Patients treated with surgery alone or surgery with postoperative whole brain radiotherapy (WBRT) were excluded. Median prescription doses were 1600 cGy (range: 1440-1875) in 1 fraction, 2400 cGy (range: 2100-2700) in 3 fractions, and 3000 cGy (range: 2500-3000) in 5 fractions. Local control (LC) and overall survival (OS) were estimated by the Kaplan-Meier method. Cox proportional hazards models were used to compare groups. Median follow-up was 19.5 months (IQR: 9.0-34.7). Median patient age was 62.5 years (range: 24-80), and 38 (55.9%) patients were male. Primary tumors were lung (n = 29), including NSCLC (n = 28) and SCLC (n = 1), melanoma (n = 12), breast (n = 11), and other (n = 16). Median preoperative tumor maximal dimension was 3.5cm (range: 1.1-6.3). Median planning treatment volume (PTV) was larger in the FSRS group (26.2cc (range: 6.5-151.8)) than in the SRS group (7.7cc (range: 1.1-11.5)) (p<0.001). Median number of concurrently treated intact lesions was 0 (range: 0-13). Median time from surgery to SRS was 32 days (range: 14-77). Forty-eight (70.6%) patients were treated with immunotherapy or targeted therapy. Median OS was 22.3 months (95% CI: 14.4-30.9). The 1-year and 2-year OS rates were 70% and 48%, respectively. The 1-year and 2-year LC rates were 86% and 73%, respectively. Median time to LR was 8.4 months (95% CI: 4.4-11.0). Among the 14 patients with LR, 11 had undergone salvage therapy at last follow-up which included repeat SRS (n = 4), WBRT (n = 3), palliative local radiotherapy (n = 2), surgery followed by repeat SRS (n = 1), and systemic therapy (n = 1). Eleven (16.2%) patients ultimately underwent WBRT post-SRS for local and/or distant failure. No difference in LC was observed based on primary tumor, time interval between resection and SRS, PTV volume, prescription dose, or fractionation regimen (SRS v. FSRS). However, all LR in the 3-fraction group occurred in patients who received less than 2700 cGy. Favorable LC and OS outcomes were observed following postoperative cavity SRS for resected BM in a modern cohort with a large percentage of patients receiving immunotherapy or targeted therapy. No prognostic factors were identified for LC which may be attributable to the cohort size and small number of events observed. However, our findings suggest that patients who undergo 3-fraction FSRS should be treated to a total dose of 2700 cGy to maximize LC.

Partial Tongue Sparing without Marginal Failures: The Dosimetric Advantages for Oral Tongue Squamous Cell Carcinoma

Due to a lack of internal barriers, many radiation oncologists believe whole tongue (WT) irradiation is warranted in the adjuvant setting for oral tongue cancer. Our institutional practice is to include the resection bed and flap with a 5-10 mm margin, attempting to spare unaffected oral tongue. We hypothesize that partial tongue (PT) irradiation, when feasible, results in decreased dose to surrounding normal structures without an increased risk of local recurrence (LR). Patients with a new diagnosis of squamous cell carcinoma of the oral tongue treated with adjuvant IMRT between 2010 and 2021 were collected from an IRB approved database. PT was defined as <80% of residual tongue in the clinical target volume (CTV). Recurrence was deemed local if in the tongue or floor of mouth, and in field if within the CTV or marginal if outside of CTV. Mean dose to mandible, pharyngeal constrictors, and oral cavity were evaluated. Comparisons between groups were made using parametric one-way ANOVA. Multivariable linear regression was used to predict mean radiation dose. Local control and overall survival were estimated using Kaplan-Meier. A total of 130 patients are included with median follow up 34.1 months (IQR 13.5-64.6). Radiation dose was 48-72 Gy in 24-36 fractions, most commonly 60-66 Gy in 30-33 fractions (84.6%). All were treated to oral cavity, and neck irradiation included bilateral 96 (72%), unilateral 31 (24%), and none 3 (4%). PT sparing was feasible in 91 (70%) and 39 (30%) required WT. Primary tumor stage in PT included 20 pT1, 50 pT2, 17 pT3, and 4 pT4, and WT included 3 pT1, 8 pT2, 15 pT3, and 13 pT4. 3-year local control for PT and WT was 96% and 87%, respectively. LR occurred in 14 patients overall (10.8%), 6.6% (6) of patients treated with PT and 20.5% (8) treated with WT (p = 0.072). Of the LR for PT, stage was 2 pT1, 3 pT2, and 1 pT3, and all occurred within the radiation field. Of the LR for WT, stage was 1 each of pT1 and pT2, 2 pT3, and 4 pT4. Overall survival was 57%, regional and distant recurrence was each 17.7%. Dosimetric analysis for PT vs WT is described in Table 1, demonstrating lower mean dose when the primary tumor CTV is limited to PT. Unilateral neck irradiation also resulted in a lower mandible [-8.5 Gy (-11.2 - -5.8)], pharyngeal constrictor [-14.3 Gy (-18.1 - -10.5)], and oral cavity [-9.0 Gy (-13.0 - -5.0)] dose (all p<0.001). Limiting the primary tumor CTV to PT for adjuvant radiotherapy resulted in significant sparing of the mandible and pharyngeal constrictors, and a routinely lower oral cavity mean dose of ≥3.5 Gy. There was a low risk of LR when implementing PT, and all LR occurred in field. Given the increased sparing of normal structures, and low risk of LR outside of PT radiation field, sparing a portion of unaffected oral tongue should be considered.

A Genomic Score to Predict Local Control among Patients with Brain Metastases Managed with Radiation

Clinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. As a result, radiation doses and fractionation schemes are relatively homogeneous and prescribed with a "one-size-fits-all" approach. We hypothesized that tumor-specific genomic alterations may underlie radiation sensitivity among patients with BrM and sought to develop a DNA-based signature of radiation-based efficacy in this patient population, utilizing genes that are readily testable in modern-day assays, to identify subpopulations at greater vs. lesser risk of recurrence. We identified 570 patients with 1,487 distinct BrM managed with whole-brain (WBRT) or stereotactic radiation therapy (SRS/SRT) at a tertiary cancer center (2013-2020) for whom next-generation sequencing panel data (OncoPanel, 239 genes) were available on at least one extracranial or intracranial tumor specimen. Fine/Gray's competing risks regression was utilized to compare local recurrence on a per-metastasis level among patients with vs. without somatic alterations of likely biological significance across 84 OncoPanel genes with a mutational frequency of >0.5%. Genes with a q-value<0.10 were utilized to develop a numeric "Brain-Radiation Prediction Score" ("Brain-RPS") to quantify local recurrence risk. Genomic alterations of potential biological relevance in 11 (ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, MDM4) and two genes (FBXW7 and AURKA) were associated with a decreased or increased risk of local recurrence, respectively (q-value<0.10). Weighted scores corresponding to the strength of association with local failure for each gene were summed to calculate a patient-level Brain-RPS. On multivariable Fine/Gray's competing risks regression, Brain-RPS [1.66 (1.44-1.92, p<0.001)], metastasis-associated edema [1.89 (1.38-2.59), p<0.001], and receipt of WBRT without SRS/SRT or neurosurgical resection [2.73 (1.78-4.20), p<0.001] were independent predictors of local failure. Utilizing a targeted panel of genes with a known role in cancer pathogenesis, we developed a genomic score that can be calculated from an extracranial or intracranial site to quantify local recurrence risk following brain-directed radiation. Prior attempts to develop a biomarker-based radiation response signature have not focused on patients with BrM and have primarily relied on RNA-based measures of radiosensitivity, limiting their utility in real-world clinical practice for this patient population. To our knowledge, this represents the first study to systemically correlate DNA-based alterations with radiation-based outcomes among patients with BrM. If validated, Brain-RPS has potential to facilitate clinical trials aimed at genome-based personalization of radiation treatment among patients with BrM.

Neoadjuvant Stereotactic MR-Guided Ablative Radiation Therapy (SMART) and Surgical Outcomes in Patients with Pancreatic Cancer

The benefit of neoadjuvant radiation therapy for patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC) remains unclear. Stereotactic MR-guided adaptive radiation therapy (SMART) treatment to ablative doses is a newer technique that is well tolerated and has increased local control in unresectable pancreatic cancer. For resectable pancreatic cancer, neoadjuvant SMART has the potential to decrease local recurrence risk and positive margin rates. However, there is concern for perioperative risks associated with ablative dose treatments. We report the efficacy and safety of surgical resection in patients who have received neoadjuvant SMART at our institution. We conducted a retrospective analysis of all consecutive patients diagnosed with PDAC who had noted vascular involvement of the celiac axis, superior mesenteric, and/or portal vessels between January 2016 and December 2022 at a single, high-volume, academic institution. Perioperative events were defined according to the Clavien-Dindo classification. The Kaplan Meier method was applied to estimate disease free survival (DFS) and overall survival (OS). Seventeen patients with PDAC and vessel involvement at time of diagnosis who received SMART were included. Median follow-up time was 14.3 months; all patients underwent surgery, at a median time after radiation of 28 days (range: 15 - 90). Median length of postoperative stay was 7 days (range: 3 - 15). Five patients (29%) underwent vascular resection. Fifteen patients (88%) achieved R0 resection, with two R1 resections noted at the SMA and pancreatic neck respectively. Seven patients (41%) had adverse events attributable to surgery, with the majority being defined as abscess or infection (n = 5; 29%). One (6%) Clavien-Dindo grade III or higher toxicity was observed - a cortical cerebrovascular event following surgery. No major bleeding events requiring surgical intervention were noted. At time of event censorship, there were no observable locoregional failures. The median DFS and OS were not reached; however, 1-year DFS and OS were 62% and 87%, respectively. Neoadjuvant SMART appears to be safe, with low rates of surgical complications and promising outcomes. Further identification of patients for this approach requires additional investigation.

Failure Patterns Within Different Histological Types in Sinonasal Malignancies: Making the Complex Simple.

To analyze the failure patterns in patients with different histological subtypes of sinonasal malignancies (SNMs). Retrospectively gathered data. Academic university hospital. Patients with SNMs treated at a tertiary referral center between January 1999 and January 2019 were included. We assessed the failure patterns within different histological subtypes. The study included 897 patients. The median follow-up time was 100 months. Adenoid cystic carcinoma (ACC) had a moderate risk of developing local recurrence (LR) and distant metastasis (DM). Compared with ACC, squamous cell carcinoma (SCC), adenocarcinoma (AC), soft tissue sarcoma (STS), and mucosal melanoma (MM) were classified as a high LR risk group. For DM, neuroendocrine carcinoma (NEC), STS, and MM were in the high-risk group. ACC had intermediate local and distant failure risks, while SCC, AC, STS, and MM were at high LR risks. NEC, STS, and MM were at high DM risk.

Prediction model of the risk for lateral local recurrence in locally advanced rectal cancer without enlarged lateral lymph nodes: Lessons from a Japanese multicenter pooled analysis of 812 patients.

Although the oncological impact of lateral lymph node dissection on enlarged lateral lymph nodes has been gradually accepted over the last decade, that on lateral lymph nodes without swelling remains doubtful. This study aimed to develop a prediction model for the future risk of lateral local recurrence and to clarify the value of adding lateral lymph node dissection in locally advanced rectal cancer without enlarged lateral lymph nodes. This retrospective, multi-institutional study recruited 812 patients with cStage II/III low rectal cancer without enlarged lateral lymph nodes <7 mm. Total lateral local recurrence was a hypothetical value of future risk of lateral local recurrence when lateral lymph node dissection was never performed. Overall, total lateral local recurrences were observed in 67 patients (8.3%). In the multivariate analyses, the strongest risk factor for total local recurrences was no preoperative chemoradiotherapy (odds ratio [OR][95%Cl]: 33.2 [4.56-241.7], P < 0.001), followed by tumor distance ≤40 mm (OR [95%Cl]: 2.71 [1.51-4.86], P < 0.001) and lateral lymph node 5-7 mm (OR[95%Cl]: 2.38 [1.26-4.48], P = 0.007). In patients with lateral lymph nodes of 5-7 mm, the total lateral recurrence rate was 4.8% after preoperative chemoradiotherapy. Lateral lymph node dissection could reduce from a total lateral local recurrence of 21.6% to an actual lateral local recurrence of 8.0% in patients without preoperative treatment. We introduce a novel prediction model of future risk of lateral local recurrences, which has the potential to enable us to indicate lateral lymph node dissection selectively according to the patients' risks.

Predictive value of lesion morphology in rectal cancer based on MRI before surgery

ObjectiveTo explore the relationship of MRI morphology of primary rectal cancer with extramural vascular invasion (EMVI), metastasis and local recurrence.Materials and methodsThis retrospective study included 153 patients with rectal cancer. Imaging factors and histopathological index including nodular projection (NP), cord sign (CS) at primary tumor margin, irregular nodules (IN) of mesorectum, MRI-detected peritoneal reflection invasion (PRI), range of rectal wall invasion (RRWI), patterns and length of tumor growth, maximal extramural depth (EMD), histologically confirmed local node involvement (hLN), MRI T stage, MRI N stage, MRI-detected extramural vascular invasion (mEMVI) and histologically confirmed extramural vascular invasion (hEMVI) were evaluated. Determining the relationship between imaging factors and hEMVI, synchronous metastasis and local recurrence by univariate analysis and multivariable logistic regression, and a nomogram validated internally via Bootstrap self-sampling was constructed based on the latter.ResultsThirty-eight cases of hEMVI, fourteen cases of synchronous metastasis and ten cases of local recurrence were observed among 52 NP cases. There were 50 cases of mEMVI with moderate consistency with hEMVI (Kappa = 0.614). NP, CS, EMD and mEMVI showed statistically significant differences in the negative and positive groups of hEMVI, synchronous metastasis, and local recurrence. Compared to patients with local mass growth, the rectal tumor with circular infiltration had been found to be at higher risk of synchronous metastasis and local recurrence (P < 0.05). NP and IN remained as significant predictors for hEMVI, and mEMVI was a predictor for synchronous metastasis, while PRI and mEMVI were predictors for local recurrences. The nomogram for predicting hEMVI demonstrated a C-index of 0.868, sensitivity of 86.0%, specificity of 79.6%, and accuracy of 81.7%.ConclusionNP, CS, IN, large EMD, mEMVI, and circular infiltration are significantly associated with several adverse prognostic indicators. The nomogram based on NP has good predictive performance for preoperative EMVI. mEMVI is a risk factor for synchronous metastasis. PRI and mEMVI are risk factors for local recurrence.

Comparative efficacy of intraoperative radiotherapy and external boost irradiation in early-stage breast cancer: a systematic review and meta-analysis.

External boost radiotherapy (EBRT) and intraoperative radiotherapy (IORT) are shown to be effective in patients with early-stage breast cancer. However, the difference between IORT and EBRT for patients' prognosis remains to be elucidated. The purpose of this meta-analysis is to investigate differences in local recurrence (LR), distant metastases, disease free survival (DFS), and overall survival (OS) between these two therapies. We searched the Cochrane Library, PubMed, Web of Science and Embase, from inception to Jan 10th, 2022. We used The Cochrane risk-of-bias assessment tool to assess the risk of bias of the included studies, and the STATA15.0 tool was used for the meta-analyses. Eight studies were ultimately included. Meta-analysis demonstrated that there was an inconsistent finding in the long-term risk of LR between the two radiotherapies, and there was no significant difference in short-term risk of LR, the metastasis rate, DFS, and OS IORT would be more convenient, less time-consuming, less costly, and more effective at reducing side effects and toxicity. However, these benefits must be balanced against the potential for increased risk of LR in the long term.

Single-Fraction Versus Fractionated Preoperative Radiosurgery for Resected Brain Metastases: A PROPS-BM International Multicenter Cohort Study

Preoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS for resected brain metastases (BM). Most reported studies of preoperative SRS used single-fraction SRS (SF-SRS). The goal of this study was to compare outcomes and toxicity of preoperative SF-SRS with multifraction (3-5 fractions) SRS (MF-SRS) in a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases-PROPS-BM). Patients with BM from solid cancers, of which at least 1 lesion was treated with preoperative SRS followed by planned resection, were included from 8 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included prior or planned whole brain radiation therapy. Intracranial outcomes were estimated using cumulative incidence with competing risk of death. Propensity score matched (PSM) analyses were performed. The study cohort included 404 patients with 416 resected index lesions, of which SF-SRS and MF-SRS were used for 317 (78.5%) and 87 patients (21.5%), respectively. Median dose was 15 Gy in 1 fraction for SF-SRS and 24 Gy in 3 fractions for MF-SRS. Univariable analysis demonstrated that SF-SRS was associated with higher cavity local recurrence (LR) compared with MF-SRS (2-year: 16.3% vs 2.9%; P=.004), which was also demonstrated in multivariable analysis. PSM yielded 81 matched pairs (n=162). PSM analysis also demonstrated significantly higher rate of cavity LR with SF-SRS (2-year: 19.8% vs 3.3%; P=.003). There was no difference in adverse radiation effect, meningeal disease, or overall survival between cohorts in either analysis. Preoperative MF-SRS was associated with significantly reduced risk of cavity LR in both the unmatched and PSM analyses. There was no difference in adverse radiation effect, meningeal disease, or overall survival based on fractionation. MF-SRS may be a preferred option for neoadjuvant radiation therapy of resected BMs. Additional confirmatory studies are needed. A phase 3 randomized trial of single-fraction preoperative versus postoperative SRS (NRG-BN012) is ongoing (NCT05438212).

Oral squamous cell carcinoma - do we always need elective neck dissection? evaluation of clinicopathological factors of greatest prognostic significance: a cross-sectional observational study.

With regard to TPS, FOM appeared to be the most metastatic. However, the recurrence rate was similar to TC tumors, which were characterized by higher G than those in other locations. When analyzing G, the highest percentage of LR (40.5%) and NM (34.5%) was observed among patients with G2. As G increased, so did the number of pENE G1 - 7.4%; G2 - 31%; G3 - 35.7%; LVI: G1 - 25.9%; G2 - 50%; G3 - 57.1%; PNI: G1 - 29.6%; G2 - 47.6%; G3 - 92.9%; NR G1 - 14.8%; G2 - 32.1%; G3 - 21.4%. Grading did not affect the type of growth and did not directly affect the occurrence of NR. pT and DOI increased the frequency of NM but we did not observe any effect of pT and DOI on LR, PNI, and LVI. NY in the study group did not increase the risk of NR. Tumor primary sites within the FOM, TC, and pT classification are the factors that increase the risk of NM and LR. However, apart from the primary site predisposing to the occurrence of NM, the histological structure of the tumor turned out to be the most important feature affecting the patient's prognosis. The number of cases of pENE+, LVI+, PNI+, NM+, and NR+ increased with the increase in G. Although the pT, DOI increased the frequency of NM, we did not observe the effect of the pT and DOI on LR, PNI and LVI. Thus, even in the case of a small tumor of the FOM and TC with at least G2, elective neck dissection should be performed each time.

Factors Influencing Recurrence in Medial Breast Cancer Tumors After Skin Sparing Mastectomy and Immediate Breast Reconstruction

BackgroundSkin sparing mastectomy (SSM) with immediate breast reconstruction (IBR) has been established as a safe option for curative-intent surgical resection. Prior studies have shown that medial location of the primary tumor is associated with increased risk of local recurrence. The purpose of this study is to determine the factors associated with recurrence and survival in individuals with breast cancers located in the inner quadrants (medial) who underwent SSM with IBR. MethodsA retrospective chart review was done on individuals with medial breast cancer who received SSM with IBR in British Columbia between 1980 and 2012. ResultsOf 136 individuals with medial breast cancer undergoing SSM with IBR, 27.9% experienced local recurrence and 42.6% overall recurrence. Factors associated with recurrence were T-stage (44.8 vs. 22.4% with T2 disease, P = .02), transverse rectus abdominis muscle (TRAM) flap reconstruction (48.3 vs. 29.5%, P = .00395), prior breast surgery (87.9 vs. 63%, P = .002), and prior radiation therapy (74.1 vs. 38.5%, P < .0001). LR was associated with higher mortality (OR 2.78, 95% CI: 1.26-6.09). ConclusionFor patients with medial tumors undergoing SSM with IBR, potential risk factors for recurrence are T-stage, TRAM flap reconstruction, prior breast surgery, and prior radiation therapy. Local recurrence is associated with poor survival.

Oncoplastic breast conserving surgery versus standard breast conserving surgery for early and locally advanced breast cancer: a retrospective analysis from Sri Lanka

BackgroundBreast aesthetics is becoming increasingly important in breast cancer surgery due to changes in patient expectations and greater emphasis been placed on the psychosocial outcomes. Studies have shown no difference in local recurrence risk between mastectomy and breast conserving surgery (BCS) and also a higher overall survival rate after BCS. Breast preservation improves the quality of life substantially compared to mastectomy. Oncoplastic breast-conserving surgery (O-BCS) involves tumour excision whilst overcoming the limitations of standard breast conserving surgery (S-BCS) by allowing larger resection volumes, avoiding deformities with better aesthetic results. Our study aims to compare the oncosurgical and aesthetic outcomes of O-BCS versus S-BCS among women in Sri Lanka.MethodsWe conducted a retrospective study over a 4-year period including patients who underwent breast conservation surgery for primary non-metastatic breast cancer in two tertiary care units. We assessed outcomes in terms of re-excision rates, resection margin, complications and aesthetic outcomes using a Likert scale questionnaire to grade specific outcomes such as symmetry, volume, nipple position, scar visibility. Non-parametric tests were used for statistical analyses.ResultsFifty-four and seventy-three patients underwent S-BCS and O-BCS respectively. The median specimen volume and the maximum tumour diameter were significantly higher in O-BCS [160(range:65–220); 4.2(range: 1.2–5.2)] compared to S-BCS [65(range:45–86); 2.4(range: 1.0-2.6)]. The median closest tumour margin was 16 mm (range:4-25 mm) in O-BCS while 6 mm (range:<1 – 12 mm) in S-BCS (p = 0.01). Close (< 1 mm) and positive margins needing re-excision were seen mostly in S-BCS. Superior aesthetic outcomes with statistical significant difference were reported in the O-BCS compared to S-BCS group with better symmetry, volume, nipple position and scar visibility. The re-excision rates were significantly lower in O-BCS group. There was no significant difference in the operative time and complications while the aesthetic outcomes were significantly superior in OBCS.ConclusionsOverall, Level 2 perforator flap based reconstruction had superior aesthetic outcomes. O-BCS is safe and more aesthetically acceptable with no difference in oncological outcome and operative time. More consideration should be given to aesthetic parameters such as scar visibility, nipple position, breast volume and shape when considering the best surgical option for the patients.

Role of GATA3 in Early-Stage Urothelial Bladder Carcinoma Local Recurrence.

Background One of the most characteristic features of non-invasive urothelial carcinoma (UC) is its high recurrence rate. Guanine-adenine-thymine-adenine nucleotide sequence-binding protein 3 (GATA3), as a transcription factor, correlates with urothelial differentiation and has been reported with poor prognosis in high-grade UC and recurrence in breast malignancies. As such, we set out to study the specifics of GATA3 in non-invasive UC, emphasizing on prediction for recurrence. Methods The cohort comprised 163 patients, with a follow-up period of five years, including 109 pTa cases and 54 pT1 cases. Immunohistochemical expression of GATA3 was assessed using a histo score (H-score). Kaplan-Meier test was conducted for the time to recurrence, according to the level of expression of GATA3 and the indicators studied. Receiver operating characteristic (ROC) curve analysis was done to determine the role of accuracy and specificity of predictability of the indicators. Results Recurrence within the follow-up period was noted in 41.72% of cases. No recurrence relationship was established for age and gender. GATA3 expression showed a varying H-score. Using ROC curve analysis, a cut-off value of 155 divided UC expression levels into low and high, with a sensitivity of 72.7% and specificity of 78.7% (area under the curve=0.800, 95% confidence interval: 0.696-0.904, p<0.001), further showing an association between high levels of nuclear expression and risk of local recurrence (p<0.0001). Conclusion Herein we have described the sensitivity of high GATA3 expression in non-invasive UC of the urinary bladder and its relation to local recurrence, independent of gender, age, tumor differentiation, and stage.

Oncologic outcomes after breast-conserving surgery with radiotherapy versus mastectomy in patients with Paget's disease of the breast: systematic review and meta-analysis.

The conventional approach to treatment for Paget's disease of the breast has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) followed by radiotherapy (RT) in these patients. This study aimed to provide an updated systematic review and meta-analysis comparing outcomes after BCS with RT versus mastectomy in the treatment of Paget's disease of the breast. Studies before May 2021 were included. Primary outcomes were overall survival and local recurrence. Separate analyses of Paget's disease associated with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were undertaken. Meta-regression was used to adjust for imbalance in the proportion of IDC among patients selected to undergo BCS versus mastectomy. Overall survival in patients with Paget's disease who underwent BCS with RT was higher than for those who underwent mastectomy with pooled mortality hazard ratio (HR) of 0.68, (95% per cent c.i. 0.45 to 1.01). Patients with Paget's disease with DCIS had higher overall survival after BCS with or without RT versus mastectomy, with adjusted HR of 0.14 (0.10 to 0.20) and 0.28 (0.22 to 0.36), respectively. For patients with Paget's disease and IDC, overall survival was lower for BCS with or without RT versus mastectomy, with adjusted HR of 0.84 (0.57 to 1.25) and 1.64 (1.04 to 2.58), respectively. In Paget's disease and IDC, local recurrence risk was much higher for BCS with RT, RR 26.8 (1.60 to 456) versus without RT, RR 51.8 (6.80 to 391). In patients with Paget's disease and DCIS, risk of local recurrence versus mastectomy was lower for BCS with RT 0.72 (0.11 to 4.50) but slightly higher for BCS alone 1.38 (0.09 to 21.20). BCS with RT may be a comparable treatment alternative to mastectomy for patients with Paget's disease with DCIS, and for selected patients with Paget's disease and IDC.

Updated Austrian treatment algorithm for metastatic triple-negative breast cancer.

Approximately 15% of newly diagnosed breast cancer patients have neither hormone receptors expression nor HER2 overexpression and/or HER2/neu gene amplification. This subtype of breast cancer is known as Triple Negative Breast Cancer (TNBC), and carries a significantly elevated risk of local and distant recurrence. In comparison with other breast cancer subtypes, there is a higher rate of visceral and brain metastases. The majority of metastases of TNBC are diagnosed within three years after initial breast cancer diagnosis. While there have been major advances in hormone-receptor- positive and in human epidermal growth factor receptor 2 (HER2)-positive disease over the past two decades, only limited improvements in outcomes for patients with triple negative breast cancer (TNBC) have been observed. A group of Austrian breast cancer specialists therefore convened an expert meeting to establish a comprehensive clinical risk-benefit profile of available mTNBC therapies and discuss the role sacituzumab govitecan may play in the treatment algorithm of the triple-negative breast cancer patients.