Risk Of Local-regional Recurrence Research Articles

RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1–3 node-positive breast cancer (RIGAIN): a study protocol for a multicentre, open-label, randomised controlled prospective, phase III trial

IntroductionPostoperative radiotherapy in patients with breast cancer with one to three lymph node metastases, particularly within the pT1–2N1M0 cohort with a low clinical risk of local–regional recurrence (LRR), has incited...

The Presence of Extensive Lymphovascular Invasion is Associated With Higher Risks of Local-Regional Recurrence Compared With Usual Lymphovascular Invasion in Curatively Treated Breast Cancer Patients

Purpose/objectives: Several datasets have demonstrated a correlation between lymph-vascular invasion (LVI) and local-regional recurrence (LRR). Whether the observation of "extensive LVI" is a further and 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).Materials/Methods: Between 12/2009 and 8/2021, 8837 patients with early-stage breast cancer 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. A matched propensity score analysis compared outcomes between patients with LVI vs. E-LVI.Results: Of the 8837 patients studied, 5584 were neg, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. Patient with E-LVI had an adverse risk profile compared to the other groups.The 5- and 10-year local regional recurrence (LRR) cumulative incidence estimates in patients with E-LVI were 9.6% (95% CI: 7.1-13) and 13% (95% CI: 10-17), which were significantly higher than observed in the usual LVI group (6.8% [5.7-7.9] and 10% [8.8-12], respectively). A statistically significant difference in LRR was demonstrated on univariable (HR 1.4, 95% CI [1.03-1.89], p-value 0.029) and multivariable regression analysis (HR 1.62, 95% CI [1.15-2.27], p-value 0.005) when compared to non-extensive LVI.In an alternative approach, we performed a 2:1 propensity-matched analysis comparing LVI to E-LVI patients. The hazard ratio for LRR (HR 1.47 (CI 1.02-2.14, p=0.041) was suggestive of a higher risk with E-LVI.Conclusions: Our work suggests that patients with E-LVI are at a higher risk for LRR than those with usual LVI. For patients who are borderline candidates for regional nodal irradiation or PMRT, the finding of E-LVI might be decisive in favor of intensified treatment.

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.

A subregion-based prediction model for local–regional recurrence risk in head and neck squamous cell carcinoma

Background and purposeGiven that the intratumoral heterogeneity of head and neck squamous cell carcinoma may be related to the local control rate of radiotherapy, the aim of this study was to construct a subregion-based model that can predict the risk of local–regional recurrence, and to quantitatively assess the relative contribution of subregions. Materials and methodsThe CT images, PET images, dose images and GTVs of 228 patients with head and neck squamous cell carcinoma from four different institutions of the The Cancer Imaging Archive(TCIA) were included in the study. Using a supervoxel segmentation algorithm called maskSLIC to generate individual-level subregions. After extracting 1781 radiomics and 1767 dosiomics features from subregions, an attention-based multiple instance risk prediction model (MIR) was established. The GTV model was developed based on the whole tumour area and was used to compare the prediction performance with the MIR model. Furthermore, the MIR-Clinical model was constructed by integrating the MIR model with clinical factors. Subregional analysis was carried out through the Wilcoxon test to find the differential radiomic features between the highest and lowest weighted subregions. ResultsCompared with the GTV model, the C-index of MIR model was significantly increased from 0.624 to 0.721(Wilcoxon test, p value < 0.0001). When MIR model was combined with clinical factors, the C-index was further increased to 0.766. Subregional analysis showed that for LR patients, the top three differential radiomic features between the highest and lowest weighted subregions were GLRLM_ShortRunHighGrayLevelEmphasis, GRLM_HghGrayLevelRunEmphasis and GLRLM_LongRunHighGrayLevelEmphasis. ConclusionThis study developed a subregion-based model that can predict the risk of local–regional recurrence and quantitatively assess relevant subregions, which may provide technical support for the precision radiotherapy in head and neck squamous cell carcinoma.

Postoperative Radiotherapy for Cutaneous Melanoma in Patients at High Risk of Local-Regional Recurrence after Surgery Alone

We evaluated outcomes in 131 patients with cutaneous melanoma (median follow-up, 3.6 years) considered at high risk of recurrence after surgery alone treated with surgery and postoperative radiotherapy. Eligible patients had one or more of the following: recurrence after surgery, positive lymph nodes, extracapsular extension, incomplete regional node dissection, microscopically positive margins, gross residual disease, or in-transit metastases. 102 patients received hypofractionated radiotherapy and 29 had conventional fractionation. 10-year outcomes were: in-field local-regional control, 87%; local regional control, 72%; distant metastasis-free survival, 48%; cause-specific survival, 44%; and overall survival, 31%. Three patients experienced acute toxicities while 6 experienced late toxicities.

Treatment for Early-Stage Lung Cancer Should Never Be “Just a Wedge”

Anatomic resection with lobectomy and complete mediastinal lymph node dissection has been considered the gold-standard early-stage lung cancer surgery since the Lung Cancer Study Group showed a higher risk of local-regional recurrence for sublobar resections.1 Nevertheless, evidence guiding lung cancer surgery has evolved since that study was published, possibly from increased radiology study use that has shifted the presentation of early-stage lung cancer such that patients are generally discovered with smaller tumors.

MRI Changes in Breast Skin Following Preoperative Therapy for Patients with Inflammatory Breast Cancer

Preoperative systemic therapy (PST) followed by mastectomy and radiation improves survival for patients with inflammatory breast cancer (IBC). Residual disease within the skin post-PST adversely impacts surgical outcome and risk of local-regional recurrence (LRR). We aimed to assess magnetic resonance imaging (MRI) breast skin changes post-PST with pathologic response and its impact on surgical resectability. We retrospectively reviewed 152 baseline and post-PST breast MRIs of 76 patients with IBC. Using the ACR-BIRADS MRI lexicon, we correlated skin thickness, qualitative enhancement, and kinetic analysis with pathologic response in the skin at mastectomy. Baseline MRI showed skin thickening in all 76 patients, 75/76 (99%) showed skin enhancement, 54/75 (72%) had medium/fast initial kinetics, usually with persistent delayed kinetics in 49/54 (91%). Following PST, 66/76 (87%) had residual skin thickening with 64/76 (84%) showing a decrease; 33/76 (43%) had persistent enhancement. The median thickness post-PST was 4.7 mm with residual tumor in the skin, and 3.0 mm without residual tumor (p=0.008). Regardless of pathologic response, the majority of patients had persistent skin thickening on MRI following PST (100% [14/14] with residual tumor and 84% [52/62] without residual tumor). There was no association between post-PST skin thickness on breast MRI and rate of LRR. Patients with IBC have skin thickening and enhancement on baseline breast MRI, with a statistically significant reduction in skin thickness following successful PST. Despite persistent skin changes on MRI, patients achieving a partial or complete parenchymal response to PST may proceed to mastectomy with low LRR rates.

Identification of Patients With Locally Advanced Gastric Cancer Who May Benefit From Adjuvant Chemoradiotherapy After D2 dissection: A Propensity Score Matching Analysis.

BackgroundOne of the most controversial areas in gastrointestinal oncology is the benefit of postoperative chemoradiotherapy (CRT) over chemotherapy (CT) alone after D2 dissection of locally advanced gastric cancer (LAGC). We aimed to identify the LAGC patients who may benefit from adjuvant CRT.MethodsWe analyzed retrospectively 188 patients receiving radical gastrectomy with D2 dissection for LAGC in our hospital. Patients were divided into two balanced groups by using propensity score matching: CRT group (n = 94) received adjuvant CRT, and CT group received adjuvant CT alone.ResultsAt a median follow-up of 27.10 months, 188 patients developed 79 first recurrence events (36 in CRT group and 43 in CT group). Our results showed that adjuvant CRT significantly decreased the risk of developing local regional recurrence (LRR) when compared to CT alone (14.9% vs. 25.5%, p = 0.044), while the estimated 3-year disease-free survival (DFS) was comparable between the CRT and CT groups (59.3% vs. 50.9%, p = 0.239). In the subgroup analysis, a significantly decreased LRR rate was also observed in LAGC patients with N1-3a stage after adjuvant CRT (p = 0.046), but not for N3b. Para-aortic lymph nodes (station No. 16) were the most frequent sites of LRR. After receiving radiotherapy, recurrence of 16 a2 region and 16 b1 region were significantly deceased (p = 0.026 and p = 0.044, respectively). Patients who received irradiation more than 4 months after surgery showed an increased risk of LRR (p = 0.022).ConclusionsThis study showed that adjuvant CRT significantly reduced LRR after D2 dissection of LAGC. Early initiation of adjuvant RT with clinical target volume encompassing a2 and b1 regions of para-aortic lymph nodes is recommended for pN1-3a patients after D2 dissection.

A microRNA-based signature predicts local-regional failure and overall survival after pancreatic cancer resection.

Resectable pancreatic adenocarcinoma (PC) is generally managed with surgery followed by chemotherapy, but the role of postoperative chemoradiation (pCRT) is controversial. We sought to identify a microRNA (miRNA) expression profile associated with higher risk for local-regional recurrence (LRR), which might help identify patients that may benefit from pCRT. Total RNA was isolated from viable tumor from 88 patients who underwent PC resection with or without chemotherapy, but did not receive radiation. Digital miRNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated miRNAs, and dichotomized about the median to detect correlations between risk group, LRR and overall survival (OS). Two cohorts from The Cancer Genome Atlas (TCGA) and Seoul National University (SNU) were used for validation. Patients with high-risk scores had significantly worse LRR (p = 0.001) and worse OS (p = 0.034). Two-year OS rates for the high- and low-risk groups were 27.7% and 52.2%, respectively. On multivariable analysis, the risk score remained significantly associated with LRR (p = 0.018). When validated on TCGA data, a high-risk score was associated with worse OS on univariate (p = 0.03) and multivariable analysis (p = 0.017). When validated on the SNU cohort, a high-risk score was likewise associated with worse OS (p = 0.042). We have developed a 4-miRNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts. This signature has the potential to select patients most likely to benefit from pCRT, and should be tested further.

Infiltrates of M2-Like Tumour-Associated Macrophages Are Adverse Prognostic Factor in Patients with Human Papillomavirus-Negative but Not in Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

Introduction: Human papillomavirus with a high oncogenic potential (HR-HPV) is responsible for more than a half of squamous cell carcinomas of the oropharynx. The HR-HPV-dependent cases of this tumour have a better prognosis compared to the HR-HPV-negative cases, despite the usually more advanced disease at the time of diagnosis. In addition to genetic and epigenetic factors, the causes of this more favourable course of the disease are also seen in the participation of the tumour microenvironment, including the patient’s immune system. Macrophages are one of the most important elements of the immunocompetent cells landscape that make up the tumour microenvironment. Traditionally, they are divided into 2 groups: inflammatory macrophages with the M1 phenotype and tumour-associated macrophages known as M2 phenotype macrophages. Objective: The aim of this study was to investigate the impact of the macrophage infiltrates intensity of the M1/M2 and M2 phenotype separately on the clinical outcome of patients with squamous cell carcinoma of the oropharynx (OPSCC), taking into account the HR-HPV status of tumours. Methods: The study involved 85 patients with OPSCC in which HR-HPV status in tumour tissue was determined using a double-check algorithm including the detection of viral DNA by RT-PCR method with subsequent confirmation of its biological activity by immunohistochemical demonstrating the P16^INK4A protein overexpression. In each of the groups formed on the basis of HR-HPV status, macrophages were discriminated using CD68 and CD163 proteins as markers of pan-macrophage and M2 phenotype. The intensity of infiltrates was quantified by means of computer-assisted analysis in digital images of whole slides (virtual slides) separately in tumour tissue and stroma. Results: In HPV-positive patients, significantly more intense infiltration of both M1/M2 and M2 macrophages was found in the tumour stroma compared to HPV-negative patients. The infiltrates from both types of macrophages in the tumour tissue were less intense and did not differ between these groups. Intensive infiltration of CD68⁺ macrophages in the tumour front was associated with higher rate of nodal failures and a shorter nodal control in both HR-HPV groups. In the group of HR-HPV-negative patients, heavy infiltration of CD163⁺ macrophages was associated with significantly shorter: loco-regional control (LRC), metastasis-free survival and overall survival (OS). These parameters and prognosis in patients with scanty CD163⁺ infiltration were similar to favourable outcomes in HR-HPV-positive patients. The relative risk of local-regional recurrence, distant metastases and disease-related death in HR-HPV-negative patients with intense CD163⁺ infiltrates was, respectively, 4.7, 5.4 and 5.7 compared to patients with scanty infiltrates. Conclusions: Tumours with a positive HR-HPV status demonstrate intense infiltrations of total pool M1/M2 and M2 macrophages. In the group of HPV-negative patients, intensive M1/M2 macrophage infiltrates correlate with higher risk of nodal failures, and intensive M2 infiltrates are an adverse prognostic factor for LRC, metastasis-free survival and OS.

Local-regional recurrence risk after autologous fat grafting in breast cancer patients: A systematic review and meta-analysis.

This meta-analysis aims to determine whether autologous fat grafting (AFG) affects the risk of local-regional recurrence (LRR) in breast cancer patients. In pooled analyses of 11 eligible studies, AFG was not associated with increased LRR. Subgroup analyses showed that AFG did not increase the risk of LRR in patients undergoing breast-conserving surgery or mastectomy, in patients with in situ carcinomas or invasive carcinomas, or in patients undergoing postoperative radiotherapy.

Clinical significance of S100A7 protein in predicting recurrence of breast cancer in patients undergoing breast-conserving surgery with radiotherapy*

Abstract Objective To investigate the relationship between the expression of S100A7 protein and prediction of recurrence and prognosis of breast cancer in patients undergoing breast-conserving surgery combined with radiotherapy. Methods 349 samples of carcinoma tissue wax blocks were selected from January 2011 to January 2014 in Qingdao Central Hospital. All the patients had undergone breast-conserving surgery. We analyzed S100A7 expression in tumor tissue by immunohistochemical staining. Using univariate and multivariate analyses, we evaluated the relationship between S100A7 and clinical results, to explore independent risk factors for local regional recurrence (LRR). Results The positive expression of S100A7 in the recurrence group (66.7%) was significantly higher than in the non-recurrence group (38.4%), P = 0.025. A log-rank test showed that high S100A7 expression was significantly correlated with 5-year regional recurrence free survival rate (RFS) (94.9% vs 89.5%, P = 0.0408), distant metastasis free survival rate (DFS) (95.4% vs 83.5%, P &lt; 0.001), and overall survival rate (OS) (99.0% vs 92.5%, P = 0.0011). Histological grade, vessel carcinoma embolus, lymph node metastasis, S100A7 expression, and tumor size were factors that influenced RFS. Multivariate analysis of the Cox proportional hazard model showed that high S100A7 expression was an independent risk factor that affected breast cancer RFS (HR = 6.864, 95 % CI: 1.575 - 29.915, P = 0.01). Thus, we concluded that high S100A7 expression is associated with increased risk of LRR and distant metastasis of breast cancer after breast-conserving surgery and postoperative radiotherapy. S100A7 can be used as a molecular marker to screen for patients with high recurrence risk after breast-conserving surgery.

Development and Validation of a MicroRNA Signature Predictive of Local-Regional Recurrence and Overall Survival after Resection of Pancreatic Ductal Adenocarcinoma (PDAC)

Prognosis for PDAC remains poor despite oncologic resection and adjuvant chemotherapy, with local-regional recurrence (LRR) rates as high as 60-70% at 2 years and 5-year overall survival (OS) of less than 30%. The use of postoperative radiotherapy (RT) is controversial, and identification of novel molecular markers may assist in selecting patients at high risk for LRR who might benefit from RT. We hypothesized we could identify a novel microRNA (miRNA) expression profile associated with LRR and OS in resectable PDAC. We isolated total RNA from formalin-fixed, paraffin-embedded tumor and adjacent normal tissue from patients who underwent surgery and adjuvant chemotherapy at 3 institutions. We created equal-sized training and validation cohorts balanced by institution and LRR events. MiRNA expression was analyzed using a multiplex analysis platform human miRNA v3 platform. Using mixed modeling, we identified miRNAs differentially expressed in tumor and normal tissue in the full dataset and used elastic net modeling to identify miRNAs predictive of LRR and OS in the training dataset. Risk scores were generated using Cox coefficients for each miRNA. For multivariable analysis (MVA), we evaluated the association of risk score with LRR and OS using Cox proportional hazards, accounting for age, pathologic T and N stage, histologic grade, postoperative CA 19-9, and margin status. For Kaplan-Meier analysis, each cohort was dichotomized by its median risk score. There were 90 patients in the training and 93 patients in the validation cohort. Most (96.2%) patients received no RT. Risk score predicted LRR in the training (hazard ratio [HR] = 1.4; 95% confidence interval [CI] 1.1 - 1.8; p = 0.002) and validation cohort (HR = 1.3; 95% CI 1.0 - 1.6; p = 0.046). It did not predict OS in the training cohort (p = 0.4), but was predictive in the validation cohort (HR = 1.2; 95% CI 1.0 - 1.4; p = 0.04). After dichotomization, binary risk score predicted LRR in the training (HR = 3.3; 95% CI 1.5 - 7.0; p = 0.002) and validation cohort (HR = 2.1; 95% CI 1.1 - 4.0; p = 0.03). It trended toward association with OS in the training cohort (HR = 1.6; 95% CI 0.98 - 2.5; p =0.058) and was significant in the validation cohort (HR = 1.6; 95% CI 1.0 - 2.5; p = 0.04). On MVA, binary risk score independently predicted LRR (HR = 3.7; 95% CI 1.2 - 11.2; p = 0.02) and OS (HR = 2.1; 95% CI 1.0 - 4.4; p = 0.039) in the training cohort. In the validation cohort, there was a trend toward association with LRR (HR = 2.2; 95% CI 0.98 - 5.1; p = 0.056) and OS (HR = 1.8; 95% CI 0.9 - 3.4; p = 0.09). Using a multi-institutional dataset, we identified and validated a miRNA signature associated with LRR and OS in patients with resectable PDAC. This signature may be useful in selecting patients at higher risk of LRR who would benefit from adjuvant RT, and should be tested in prospective clinical trials.

Abstract ES7-3: Indications for radiation treatments after neoadjuvant chemotherapy while awaiting the results of clinical trials

Abstract Using systemic therapy prior to surgery has become an accepted standard for patients with lymph node-positive disease at presentation. Studies demonstrate that this approach can eradicate the disease in lymph nodes prior to local-regional interventions. This occurs particularly frequently for patients with HER2/neu-positive disease and to a relevant degree for those with triple negative disease. Patients with an excellent pathological response to treatment have improved outcomes compared to those with extensive residual disease. However, it is less clear whether local-regional therapies can be diminished or omitted in patients with an excellent pathological response. Accordingly, such questions are currently being investigated in phase III clinical trials. Unfortunately, local-regional therapeutic trials require long-term outcome data, particularly for the endpoints of distant disease control and overall survival. Therefore, the ongoing studies addressing whether regional lymph node radiation can be omitted in selected patients after neoadjuvant chemotherapy will not provide clinically useful information in the near term. This is unfortunate because such questions arise with a high degree of frequency in oncology practices. This topic has also become increasingly important because completed clinical trials indicate that regional lymph node radiation combined with treatment of the chest wall/breast improves the outcome of patients with pathologically positive lymph node(s) and who are treated with surgery first followed by adjuvant systemic therapy. While the sequencing of chemotherapy and surgery does not affect the risk of local-regional recurrence for populations of patients, it does affect an individual patient's risk. For example, patients with clinically stage II, lymph node-positive disease (who do not receive radiation) will have lower risk of local-regional recurrence if they achieve a pathological complete response to neoadjuvant chemotherapy compared to those with residual positive lymph nodes. This is also true for patients with clinical stage III disease, although patients with locally advance breast cancer have a high enough risk for local recurrence even with a complete pathological response to warrant adjuvant radiation. Based on the data outlined above, the current standard outside the setting of clinical protocols is to recommend regional lymph node radiation with chest wall/breast radiation for all patients with residual positive lymph nodes after neoadjuvant chemotherapy and all patients who present with clinically stage III disease. For patients with stage II disease who achieve a pathological complete response, the available evidence suggests that their predicted local regional recurrence risk without regional or postmastectomy radiation is 10% or less. Therefore the benefit from radiation is likely low and it is reasonable weigh out these small potential benefits in the context of associated treatment morbidities and costs. It is also important to further consider additional local-regional risk factors such as patient age, tumor biology, plans for prolonged systemic therapies, and other pathological factors at presentation in making radiation treatment decisions for such patients. Citation Format: Buchholz T. Indications for radiation treatments after neoadjuvant chemotherapy while awaiting the results of clinical trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES7-3.

Is there a role for salvage re-irradiation in pediatric patients with locoregional recurrent rhabdomyosarcoma? Clinical outcomes from a multi-institutional cohort

Background and purposeLimited data exist detailing the role of salvage reirradiation following local-regional recurrence (LR) in previously irradiated pediatric patients with rhabdomyosarcoma (RMS). Materials and methodsWe evaluated outcomes and prognostic factors in a multi-institutional cohort of 23 patients with LR-only (N = 19) or LR with distant failure (N = 4) RMS managed with (N = 12) or without (N = 11) re-irradiation who were treated from 1996 to 2012. ResultsAt a median follow-up of 4.6 years from LR, 7 (30%) patients were alive and 5 (22%) had no evidence of disease. Median OS and PFS from LR were 19.3 and 16.9 months, respectively. LFFS and DFFS at 3 years from relapse were 54% and 56%, respectively. Salvage re-irradiation occurred in 12 (52%) patients, with 9 (75%) receiving resection before re-irradiation. Patients classified as low-risk at diagnosis with favorable primary tumor location had improved 3-year PFS 80% (95% CI 51.6–100%) vs. 47.1% (95% CI 27.3–81.2%), p = 0.066], and OS 80% [(95% CI 22.4–100%) vs. 47.1% (95% CI 27.3–81.3%), p = 0.051] following LR. Median LFFS and OS in unirradiated vs. re-irradiated patients was 12.4 vs. 19.6 (p = 0.1) and 18.8 vs. 26.1 months (p = 0.46). No patients experienced ≥grade 4 acute toxicity from re-irradiation. LR failure was a component of cancer-related death in 60% vs. 40% of the unirradiated and re-irradiated group (p = 0.02). ConclusionSalvage re-irradiation appears tolerable with acceptable morbidity and may reduce the risk of subsequent LR as a component of death in patients with LR RMS.

CT-Based Radiomic Biomarker Features Predict Prognosis in Patients with Limited Stage Small Cell Lung Cancer

Limited stage small cell lung cancer (LS-SCLC) has a poor prognosis (5-year survival <20%). Despite being initially sensitive to chemoradiation (CRT), most patients develop recurrences with limited salvage options. Early stratification of risk of local-regional recurrence (LRR)/poor survival may provide valuable information for selective intensification of treatment. Radiomics, large-scale quantitative imaging features, may be used as a potential biomarker to identify patients at higher risk of recurrence. We investigate the ability of radiomic features extracted from CT images to predict overall survival (OS), LRR, and distant metastases (DM). Between 2000 and 2013, 105 patients with biopsy-proven LS-SCLC treated with CRT were analyzed retrospectively. Planning CT scans were reviewed, and the gross tumor volume (GTV) was manually contoured. Based on unsupervised selection, we evaluated 18 stable and non-redundant radiomic features, and compared these with conventional features (volume and maximum diameter). Cox regression hazard ratio (HR) and concordance index (CI) were computed for clinical and imaging features, respectively. P-values were computed by comparing significance from random prediction. Clinical and treatment data are described in the table. With a median follow-up of 21.3 months (range, 0.6-113.4), 2-year local control was 62% (n = 38 failures; median time to failure of 8.6 months), 2-year metastasis-free survival was 48% (n = 55 events, median time to metastasis of 20.6 months), and 2-year OS was 47% (median survival of 22.3 months). One conventional imaging feature (maximum diameter) was found to be significantly associated with LRR (0.61 CI, P = 0.008). GTV volume did not show any association with clinical outcomes (CI range 0.5-0.58, P-values > 0.09). One radiomic feature capturing tumor elongation (shape) was associated with OS, LRR, and DM (CI 0.58, 0.63, 0.61, respectively, P-values< 0.05). Two textural radiomics features (patterns) were associated with LRR and OS with one sensitive to homogeneity (informal measure of correlation, CI = 0.58, P-value = 0.05) and one sensitive to tumor heterogeneity (entropy, CI = 0.43, P-value = 0.02), respectively. For LS-SCLC, we found several radiomic features associated with treatment outcomes after CRT. In particular, tumor elongation at time of treatment planning was established as a potential biomarker for LRR, DM, and OS. These features need further validation but demonstrate promise in the era of precision medicine.Tabled 1Abstract 27; Table 1 Clinical and treatment dataCharacteristicN (%)GenderFemale42 (40%)Male63 (60%)AgeMedian (range)63.8 (44.4-87.5)Performance score032 (30%)≥172 (70%)Smoking HistoryCurrent56 (53%)Former46 (44%)Never3 (3%)Pack-yearsMedian (range)45 (1.3-127.5)Tumor size (cm)Median (range)4.5 (0.7-11.5)Concurrent CRT92 (88%)Median RT dose (range)45 (20-66.6) Open table in a new tab

Abstract P5-16-08: Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy

Abstract Purpose: We seek to investigate the prognostic factors that could possibly affect the local-regional recurrence (LRR) of breast cancer patients who do not achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NCT), and to build a prognostic nomogram to predict patients' outcome. Methods: The retrospective analysis included 510 patients who had received NCT followed by surgery and radiotherapy. The NCT regimens included anthracycline-containing, vinorelbinecontaining, and taxane-containing regimens for a median of 3 cycles. The clinical responses to neoadjuvant chemotherapy were evaluated based on MRI and ultrasound examinations and in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Miller-Payne (MP) grading system was employed to evaluate the decrease in cancer cellularity. Multivariate analyses were used to identify independent predictors of LRR. Results: The median follow-up for the entire study population was 61 months (range 5-128 months). There were 40 isolated local recurrences, 17 regional-only recurrences and 5 patients with local and regional recurrences. Sixteen patients (25.8%) occurred synchronously with distant metastasis, and no LRR was detected after distant failure. Fifteen patients had recurrences in the supraclavicular field. The 5-year cumulative LRR-free survival rate was 88.0% (95% CI: 85.2%-90.1%). The 5-year overall survival and disease-free survival rates were 79.0% (75.5%-82.6%) and 63.1% (58.9%-67.3%), respectively. Multivariate analysis revealed that positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% were independent factors for LRR-free recurrence. The prognostic model was established based on the sum of both independent prognostic factors, with positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% individually contributing 1 point to the risk score. The patients in the validation set were assigned to a low-risk group (0 point), median-risk group (1 point) and high-risk group (2 points). The 5-year LRR-free survival rates in the low, intermediate, and high-risk groups were 95.5%, 89.1%, and 67.1%, respectively (p &amp;lt; 0.001). We also show the annual LRR rate among these 3 groups using our single-institution data, as well as to review relevant literature-based data to compare with our observations. Four publications that reported ARR (annual recurrence rate) after surgery for primary breast cancer were identified as eligible. In the relevant literature, the annual risk of local-regional recurrence peaked between two and three years after the initial diagnosis. In contrast, the ARR curve of the high risk subgroup for neoadjuvant patients exhibited one peak near 1 year (17% per annum). The median and low-risk subgroups did not have an obvious recurrence peak. Conclusion: This prognostic model has considerable clinical value in predicting local-regional recurrence, which could help clinicians to design appropriate local-regional treatment specifically and to perform surveillance individually. Citation Format: Chen S, Huang L, Shao Z-M. Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-08.

Impact of age, intrinsic subtype and local treatment on long-term local-regional recurrence and breast cancer mortality among low-risk breast cancer patients

Aim: To evaluate the long-term prognostic impact of age, local treatment and intrinsic subtypes on the risk of local-regional recurrence (LRR) and breast cancer mortality among low-risk patients.Material and methods: Cohort study with prospectively collected data, balanced five-year age groups, including 514 Danish lymph node negative breast cancer patients diagnosed between 1989 and 1998, treated with mastectomy (N = 320) or breast-conserving therapy (BCT) (N = 194) and without systemic treatment. Intrinsic subtype approximation was performed by combining information on estrogen-, progesterone-, HER2 receptor and Ki67.Results: The majority of the tumors had a luminal subtype: 70% Luminal-A (LumA), 16% Luminal-B (LumB), and 10% Luminal-HER2 + (Lum-HER2+). The distribution of intrinsic subtypes between younger (≤45 years) and older (>45 years) patients was similar. Intrinsic subtypes had no prognostic impact on the 20-year LRR risk, regardless of age. A distinct 20-year mortality pattern was observed among the younger patients: 11% of patients with LumB tumor died of breast cancer within the first five years after primary surgery, 23% of patients with Lum-HER2+ tumor died within a 5–10-year period, whereas patients with LumA tumor died with a constant low rate throughout the 20-year period. After 20 years of follow-up, patients with LumA tumor had breast cancer mortality comparable to that of patients with LumB tumor (20%) and lower than Lum-HER2+ tumor (39%). Among the older patients, no distinct mortality pattern was observed, and the 20-year breast cancer mortality was not associated with intrinsic subtypes.Conclusion: Among low-risk patients, 96% of the tumors were Luminal and the distribution of intrinsic subtypes between younger (≤45 years) and older (>45 years) patients was similar. The observed higher frequency of LRR among younger low-risk BCT patients was not associated intrinsic subtype. The 20-year breast cancer mortality was non-significant for LumA tumors among the older patients, whereas among the younger patients, LumA tumors had a comparable mortality with LumB, but lower than for Lum-HER2 + tumors.

Current treatment of lacrimal gland carcinoma.

The traditional treatment for lacrimal gland carcinoma is orbital exenteration followed by radiation therapy. However, orbital exenteration does not prevent distant relapse and death, and some patients experience local-regional recurrence after exenteration. More recently, eye-sparing surgery and adjuvant radiation therapy and chemotherapy have gained popularity in the treatment of lacrimal gland carcinoma. Preliminary studies show that these approaches are associated with reasonable local control rates and ocular toxicity profiles. In this review, we discuss recent studies of treatment of lacrimal gland carcinoma, including studies of potential molecular treatment targets. Recent studies suggest promising results for neoadjuvant intra-arterial chemotherapy followed by orbital exenteration and adjuvant intravenous chemotherapy, but only in patients with an 'intact lacrimal artery'. Recent studies of globe-sparing surgery followed by adjuvant proton radiation therapy or concurrent chemoradiation suggest good local control, reasonable rates of eye preservation, and low risk of serious ocular toxic effects. Larger tumor size and predominant basaloid histology seem to be associated with higher risk of local-regional recurrence and distant metastasis. One study showed oncogenic mutations in more than half of cases of lacrimal gland adenoid cystic carcinoma, with KRAS mutations in 10 of 24 patients, suggesting potential benefit of treatments targeting the EGFR-RAS-RAF cascade. In selected patients with lacrimal gland carcinoma, eye-sparing surgery with eye-sparing radiation therapy offers preservation of visual function with good local control and minimal radiation-induced ocular toxic effects. In patients with recurrent or metastatic disease, a search for actionable cancer-associated mutations may be prudent.