Local-regional Recurrence Research Articles

The role of surveillance and salvage esophagectomy in previously treated esophageal cancer.

Esophageal cancer remains a significant cause of cancer-related mortality among men and women in the United States. The utility of surgery, as either an immediate or delayed resection in the form of esophagectomy following neoadjuvant therapy in local-regionally advanced esophageal cancer, remains controversial. While neoadjuvant therapy followed by immediate surgery is a guideline-concordant treatment, emerging data suggests that active surveillance with delayed resection at the time of local-regional recurrence may be considered.

Effect of Adjuvant Radiation Dose on Survival in Patients with Esophageal Squamous Cell Carcinoma.

Background: For patients with esophageal squamous cell carcinoma (ESCC) treated with surgery alone, the incidence of local-regional recurrence remains unfavorable. Postoperative radiotherapy (PORT) has been associated with increased local-regional recurrence-free survival (LRFS), although its application is limited by concerns of PORT-related toxicities. Methods: Among 3591 patients with ESCC analyzed in this study, 2765 patients with T3-4N0 and T1-4N1-3 lesions and specific local-regional status information were analyzed in a subsequent analysis of adjuvant radiation dose (aRTD) effect. Application of the restricted cubic spline regression model revealed a non-linear relationship between aRTD and survival/radiotoxicity. Linear regression analysis (LRA) was performed to evaluate correlations between LRFS and overall survival (OS)/ disease-free survival (DFS). Results: For patients staged T1−2N0, T1−2N1−3, T3−4N0, and T3−4N1−3, 5-year OS in PORT and non-PORT groups were 77.38% vs. 72.91%, p = 0.919, 52.35% vs. 46.60%, p = 0.032, 73.41% vs. 61.19%, p = 0.005 and 38.30% vs. 25.97%, p < 0.001. With aRTD escalation, hazard ratios (HRs) of OS/DFS declined until aRTD exceeded 50Gy, then increased, whereas that of LRFS declined until aRTD exceeded 50 Gy, then remained steady. HR of treatment-related mortality was stable until aRTD exceeded 50 Gy, then increased. LRA revealed strong correlations between LRFS and OS/DFS (r = 0.984 and r = 0.952, respectively). An absolute 1% advancement in LRFS resulted in 0.32% and 0.34% improvements in OS and DFS. Conclusions: An aRTD of 50Gy was well-tolerated, with favorable survival resulting from PORT-related LRFS improvement in patients staged T3−4N0 or T1-4N1−3. Further stratification analyses based on tumor burden would help determine potential PORT-beneficiaries.

Proton therapy for isolated local regional recurrence of breast cancer after mastectomy alone.

To assess adverse events (AEs) and disease-specific outcomes after proton therapy for isolated local-regional recurrence (LRR) of breast cancer after mastectomy without prior radiotherapy (RT). Patients were identified from a multi-institutional prospective registry and included if diagnosed with invasive breast cancer, initially underwent mastectomy without adjuvant RT, experienced an LRR, and subsequently underwent salvage treatment, including proton therapy. Follow-up and cancer outcomes were measured from the date of RT completion. Nineteen patients were included. Seventeen patients were treated with proton therapy to the chest wall and comprehensive regional lymphatics (17/19, 90%). Maximum grade AE was grade 2 in 13 (69%) patients and grade 3 in 4 (21%) patients. All patients with grade 3AE received > 60 GyE (p=0.04, Spearman correlation coefficient=0.5). At the last follow-up, 90% of patients were alive with no LRR or distant recurrence. For breast cancer patients with isolated LRR after initial mastectomy without adjuvant RT, proton therapy is well-tolerated in the salvage setting with excellent loco-regional control. All grade 3 AEs occurred in patients receiving > 60 GyE.

Estimating the incidence of breast cancer recurrence using administrative data.

Breast cancer is the most common cancer among women, but most cancer registries do not capture recurrences. We estimated the incidence of local, regional, and distant recurrences using administrative data. Patients diagnosed with stage I-IIIprimary breast cancer in Ontario, Canada from 2013 to 2017 were included. Patients were followed until 31/Dec/2021, death, or a new primary cancer diagnosis. We used hospital administrative data (diagnostic and intervention codes) to identify local recurrence, regional recurrence, and distant metastasis after primary diagnosis. We used logistic regression to explore factors associated with developing a distant metastasis. With a median follow-up 67months, 5,431/45,857 (11.8%) of patients developed a distant metastasis a median 23 (9, 42) months after diagnosis of the primary tumor. 1086 (2.4%) and 1069 (2.3%) patients developed an isolated regional or a local recurrence, respectively. Patients with distant metastatic disease had a median overall survival of 15.4months (95% CI 14.4-16.4months) from the time recurrence/metastasis was identified. In contrast, the median survival for all other patients was not reached. Patients were more likely to develop a distant metastasis if they had more advanced stage, greater comorbidity, and presented with symptoms (p < 0.0001). Trastuzumab halved the risk of recurrence [OR 0.53 (0.45-0.63), p < 0.0001]. Distant metastasis is not a rare outcome for patients diagnosed with breast cancer, translating to an annual incidence of 2132 new cases (17.8% of all breast cancer diagnoses). Overall survival remains high for patients with locoregional recurrences, but was poor following a diagnosis of a distant metastasis.

Role of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump

This study aimed to determine the effectiveness of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump, and to identify the candidates most likely to benefit. Newly diagnosed, non-metastatic cervical cancer patients treated in our hospital between January 2012 and November 2015 were retrospectively reviewed. Early stage patients receiving radical surgery and needing adjuvant external radiotherapy were included, but those with positive stump were excluded. All patients received external radiotherapy. They were divided into two groups: one group received vaginal brachytherapy and the other did not. The 5-year local-regional recurrence free survival (LRRFS) and overall survival (OS) rates in the two groups were compared. Two hundred and twenty-five patients were included in this study; while 99 received brachytherapy, 126 did not. The brachytherapy group had significantly superior 5-year LRRFS (87.7% vs. 72.5%, p = 0.004), but did not show a significant overall survival benefit (78.4% vs. 75.3%, p = 0.055). In multivariate analysis, brachytherapy, pathological type, high-risk factors, duration of radiotherapy, and transfusion were independent prognostic factors for 5-year LRRFS. In stratified analysis, the brachytherapy group showed superior LRRFS in those meeting Sedlis criteria (p = 0.017). The combination of external beam radiation therapy and brachytherapy can improve LRRFS in post-operative cervical cancer patients with risk factors other than positive stump. Therefore, brachytherapy should be considered for these patients.

PP03 Presentation Time: 9:20 AM: Patterns of Failure for Salvage HDR Prostate Brachytherapy in the Prostate PET Imaging Era

<h3>Purpose</h3> Although some patients who undergo prostate re-irradiation achieve long-term biochemical control, the majority of patients ultimately experience a biochemical recurrence. Furthermore, a small, but significant percentage of patients may experience significant toxicities. Prostate positron emission tomography (PET) may improve the management of radiorecurrent prostate cancer, by better delineating the systemic extent of disease prior to treatment. Furthermore, PET may allow for a more precise understanding of the patterns of failure after treatment. The purpose of this study is to analyze oncologic outcomes including patterns-of-failure for a contemporary cohort of patients who underwent salvage high-dose rate (HDR) prostate brachytherapy in the prostate PET imaging era. <h3>Materials and Methods</h3> We conducted a retrospective analysis of all patients, who underwent salvage HDR brachytherapy from 2017 onwards. 18F-fluciclovine and 18F-DCFPyL became available in 2017 and 2021, respectively. We utilized the Kaplan-Meier method to measure oncologic endpoints including biochemical progression-free survival (bPFS), clinical progression free survival (cPFS), and metastasis-free survival (MFS). We also implemented Cox regression analysis to identify factors associated with the development of bPFS and MFS. <h3>Results</h3> The median follow-up was 16.6 months. Of the 50 patients included in this study, 48 patients had 18F-fluciclovine (Axumin) imaging and two had 18F-DCFPyL (PSMA) imaging prior to treatment initiation. Six patients (12%) had oligometastatic disease prior to treatment and were treated with SBRT to those sites. Six patients (12%) had castrate-resistant prostate cancer at the time of salvage brachytherapy. The median brachytherapy dose was 1150 cGy in two treatments, and the entire prostate was treated. 43 (86%) patients were concurrently treated with androgen deprivation therapy. Six patients (12%) patients experienced a biochemical recurrence, and four patients (8%) experienced a local-regional recurrence by post-salvage PSMA or Auxmin imaging. Two patients (4%) experienced distant metastatic progression. No initial covariates were statistically associated with bPFS survival (Figure 1). However, increasing time to recurrence trended towards negative association (HR 0.77| CI 0.56 - 1.04, p = 0.091). The bPFS was 100% (CI 100% - 100%), 94% (CI 87% - 100%), and 90% (CI 81% - 100%) at 6 months, 12 months, and 18 months, respectively. <h3>Conclusion</h3> Patients undergoing HDR prostate brachytherapy to salvage recurrent disease in the prostate PET imaging era have durable bPFS. In this cohort, HDR salvage was equally effective regardless of initial treatment covariates (i.e. initial risk group), status of disease immediately prior to salvage (i.e. castrate resistance or oligometastases), or use of androgen deprivation therapy (ADT) during salvage. Therefore, prostate PET may identify candidates for whom HDR salvage will be effective.

Routine and interval detection of locoregional breast cancer recurrences and risk of subsequent distant metastasis

PurposeFollow-up for breast cancer survivors consists of after care and surveillance. The benefits of routine surveillance visits remain debatable. In this study we compared the severity of locoregional recurrences (LRRs) and the subsequent risk of a distant metastasis (DM) between LRRs detected at routine and interval visits.MethodsWomen diagnosed with early breast cancer between 2003 and 2008 in one of the 15 participating hospitals, and who developed a LRR as first event after primary treatment, were selected from the Netherlands Cancer Registry (Cohort A). Chi-squared tests were used to compare the severity of routine- and interval-detected local recurrences (LRs) and regional recurrences (RRs), using tumor size, tumor grade, and number of positive lymph nodes. Data on the development of a subsequent DM after a LRR were available for a subset of patients (Cohort B). Cohort B was used to estimate the association between way of LRR-detection and risk of a DM.ResultsCohort A consisted of 109 routine- and 113 interval-LRR patients. The severity of routine-detected LRs or RRs and interval-detected LRs or RRs did not significantly differ. Cohort B consisted of 66 routine- and 61 interval-LRR patients. Sixteen routine- (24%) and 17 (28%) interval-LRR patients developed a DM. After adjustment, way of LRR-detection was not significantly associated with the risk of a DM (hazard ratio: 1.22; 95% confidence interval: 0.49–3.06).ConclusionThe current study showed that routine visits did not lead to less severe LRRs and did not decrease the risk of a subsequent DM.

Primary Tumor Recurrence after Chemoradiotherapy in Limited Stage Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Accounting for 13-15% of lung cancer, small cell lung cancer (SCLC) is typically characterized by more extensive local invasion and more frequent metastases compared with other subtypes. Although SCLC is sensitive to chemoradiotherapy, 25% of the patients with limited stage SCLC would meet local regional relapse. Although thoracic radiation had significantly improved local control, primary tumor recurrence is common in clinic. So far, we had little acquaintance of the local relapse details to help us to make progress in the thoracic radiation. To investigate the patterns of patients with local regional recurrence and the prognosis of primary tumor recurrence, we proposed this study. <h3>Materials/Methods</h3> We searched patients with pathological diagnosis of SCLC, with disease of limited stage, received systemic chemotherapy and thoracic intensity modulate radiotherapy at our center with available follow-up records between August 1^st, 2006 and May 31^st,2014. Patients with intrapulmonary recurrence or regional lymph nodes recurrence by the last follow up time, without diffused lung metastasis were selected. All the patients received involved field thoracic radiotherapy with dose of 2Gy per fraction per day. Data regarding patient demographics and treatments. The first local recurrent sites were recorded. Local regional relapse time was calculated from the first day of the treatment delivery to the diagnosis of primary tumor or regional lymph nodes. Overall survival was calculated from the first day of the diagnosis of local relapse to the death using Kaplan Meir Method. <h3>Results</h3> We identified 482 patients with a diagnosis of limited stage SCLC. Among these, 125 patients fulfilled the eligibility criteria. The median dose of radiotherapy is 60Gy. The median local relapse time was 12.97 months. Primary tumor recurrence, ipsilateral hilar and/or mediastinal lymph node recurrence, contralateral hilar and/or lymph node recurrence, and supraclavicular lymph node recurrence, were observed in 92 patients (73.6%), 49 patients (39.2%), 1 patient (0.8%) and 13 patients (10.4%), respectively. There were 26 patients with multisite local recurrence. Out-field relapse was observed in 6 patients (4.8%). The median follows up time was 34.7 months. After second line therapies, the median survival time for these patients diagnosed as recurrent disease was 10.5 months. Of the 92 patients with primary tumor recurrence, 25 patient received re-radiation and 39 patients also met distant metastasis. Median survival time of patients with primary tumor recurrence is slightly shorter than the others (9.9months vs. 12.0months). <h3>Conclusion</h3> For patients with limited stage SCLC who received chemoradiotherapy, primary tumor recurrence is still the leading course in local regional relapses and accompanied by worse survival. Accordingly, simultaneous integrated boost might be taken into consideration to primary tumor. Involved field radiation is reasonable with low out-field local recurrence.

Dose Escalation SBRT in Patients with Localized Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Localized pancreatic cancer can benefit from local therapy with radiation therapy (RT); however, such tumors are often radioresistant, making low dose RT not effective. Here, we compare the use of low (<40Gy/5fx) versus high dose (40Gy or more in 5 fractions) stereotactic body radiation therapy (SBRT) in patients with localized pancreatic cancer. <h3>Materials/Methods</h3> We performed a retrospective analysis of patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC) treated with 5 fraction-SBRT at the University of Texas MD Anderson Cancer Center. Patients were divided into two cohorts: those that were treated with <40Gy/5fx, and those that received 40Gy or more in 5fx. Our main endpoint was local-regional recurrence (LRR) post-SBRT. <h3>Results</h3> A total of 89 patients (42 females, 47 males; median age: 69years) were included in our study: 58 patients (65.2%) were treated with <40Gy, and 31 patients (34.8%) were treated with 40Gy or more. In patients treated with lose dose SBRT, 35 (35/58; 60.3%) had BRPC, and in patients treated with high dose SBRT, 13 (13/31; 41.9%) had BRPC. For patients with BRPC, the 1- and 2-year post-SBRT LRR rates were 20.0% vs 0%, and 28.6% vs 7.7%, for the low vs high dose cohorts, respectively. Those results were not statistically significant on Cox regression (HR: 0.5, 95%CI 0.1-2.1, <i>P</i>=0.32). Moreover, in patients with LAPC, the 1- and 2-year LRR rates were 30.4% vs 16.7%, and 39.1% vs 27.8%, for the low vs high dose cohorts, respectively. Those results were also not statistically significant on Cox regression (HR: 0.8, 95%CI 0.3-2.5, <i>P</i>=0.75). <h3>Conclusion</h3> Escalating SBRT dose in patients with localized pancreatic cancer may lead to improved local control, however larger series are still needed to better assess this effect.

The Significance of Increased Dose in the Outcome of Definitive Chemoradiotherapy at Doses above 60Gy for cT3-4 Cervical Esophageal Cancer: A Report of 83 Cases from a Single Institution

<h3>Purpose/Objective(s)</h3> We investigated whether increasing the RT dose from 60 Gy to 67-68 Gy, which is comparable to the dose for squamous cell carcinoma of the head and neck, would improve the treatment outcome in cT3-4NxM0 patients enrolled for definitive chemoradiotherapy (CRT) for locally advanced cervical esophageal cancer based on late adverse events and recurrence patterns. <h3>Materials/Methods</h3> From 2004 to 2020, 83 patients with cT3-4bNxM0 squamous cell carcinoma of the cervical esophagus (including 22 cases of Ce, 8 cases of CePh, and 53 cases of CeUt, but not UtCe) were enrolled in a radical CRT (1.8-2.1 Gy/F, total dose >60 Gy, and concurrent CDDP80mg/m²x1 and 5-fluorouracil 800 mg/m²x5, 2 courses) protocol at our institution. Pretreatment imaging, including MRI and ultrasound tracheal endoscopy, showed that 71% of 59 patients were cT4 (89% tracheal invasion) and the rest were cT3. cN1 or higher was found in 73 patients (88%) and cN0 in 10 patients (12%). Thirty-six patients were in the cohort group for VMAT of 67-68 Gy/33 F/7 wks with D50 indication for PTV, and the rest were in the non-cohort group. In the remaining 47 patients in the non-cohort (3DCRT) group, 30 patients were completed at 60 Gy (or less than 60 Gy for surgery), and only 14 patients underwent 3DCRT of 62 Gy or more, which was presumably added due to poor response. A total of four patients were judged to be candidates for salvage surgery at 50 Gy intermediate assessment: one in the cohort group and three in the non-cohort group. The median observation period for survivors was 87.4 months (95% CI: 65.0-109.7). <h3>Results</h3> OS was 30.3% (SE 5.4%) at 5 years in all cT3-4NxM083 patients. cT3/T4, cN0/N1, age, gender ratio, and tumor occupying subsite CePh/CeUt types in cohort vs. non-cohort were not significantly skewed. There was no significant difference in OS between the cohort group and the non-cohort group in the ITT comparison of all patients, including the 4 patients who were converted to surgery (Breslow, p=0.84). Multivariate analysis showed that the two factors significant for OS were cT3 vs. cT4 (p=0.035, HR=2.12) and tumor occupation site Ce/CePh vs. CeUt (p=0.047, HR=1.91). There was no significant difference in local recurrence and regional recurrence, 41.5% and 12.2% in the cohort group and 39.5% and 7.9% in the non-cohort group, respectively. The main late adverse events Grade 3 or higher were esophageal stenosis in 6 cases and bilateral recurrent nerve palsy in 1 case, but there was no significant difference between the cohort group (3 cases) and the non-cohort group (4 cases), and it could not be said to occur at doses higher than 60 Gy by dose. <h3>Conclusion</h3> It has long been pointed out that cervical esophageal cancer may require higher doses than thoracic esophageal cancer. However, in advanced cancers of cT3 or higher, treatment planning to obtain an appropriate dose distribution of 60 Gy or higher in VMAT did not directly lead to improved OS.

Clinical Outcomes in Patients Receiving Pencil Beam Proton Re-Irradiation for New or Locoregionally Recurrent Breast Cancer

<h3>Purpose/Objective(s)</h3> Local-regional recurrence of breast cancer (BC) after prior radiation (RT) presents clinical and dosimetric challenges. Proton beam therapy (PBT), and in particular pencil beam scanning (PBS), offers a unique dosimetric advantage due to its lack of exit dose and high conformality, which may allow safer delivery of a second RT course. Recently, there has been a retrospective report of 46 patients (pts) treated with uniform or PBS PBT. Here, we present the largest series to date using PBS PBT. We analyzed treatment patterns, toxicities, and clinical outcomes of BC pts receiving PBS-proton reradiating (reRT). Our hypothesis was that PBS PBT reRT to breast/chest wall (CW) provides reasonable local control (LC) and toxicities. <h3>Materials/Methods</h3> A single-institution retrospective IRB-approved analysis was conducted of all pts who underwent reRT for recurrent or new BC, between 4/2017 and 11/2021. Descriptive statistics were used to describe pt, tumor and treatment characteristics. Local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were measured from reRT start to the first event, by Kaplan-Meier method. Pts who remained alive were censored at last follow-up. Toxicities were scored according to CTCAE v4.0. Comparisons of pts, tumor, and treatment characteristics between those with any grade ≥ 3 acute toxicity (AT) or any late toxicity (LT) vs. none were performed using two-sample t-tests and chi-square tests. Multivariable analysis for LFFS and OS was conducted using cox-proportional hazards models. Statistical software used for analysis. <h3>Results</h3> A total of 68 pts with breast/CW reRT with PBS PBT were identified. Only pts who completed treatment were included in analyses (3 pts were excluded; final N=65). Median follow-up was 26.6 months. The median age was 61 yrs (range 30-89). 60% of pts were white, 32% black and 8% from other races. 65% of treated BCs were hormone positive, 1% HER2/neu enriched and 34% triple negative. Median time between initial and reRT was 52 months (range 6-328). Median cumulative previous RT dose (EQD2) was 48.4 Gy (range 43.2-66.0). Median cumulative PBS PBT dose (EQD2) was 57.0 Gy (range 30.2-76.9). 8 pts (12%) underwent BID treatment, 22 pts (34%) received concurrent hyperthermia and 13 pts (20%) underwent concurrent chemotherapy. 14 pts (22%) experienced grade 3 AT, including 13 dermatitis (20%) and 1 fatigue and pain (1.5%). No grade 4/5 toxicities were observed. 6 pts were lost in follow-up. 33 pts (56%) experienced any grade LT (skin changes [N=21; 36%], soft tissue fibrosis [N=7; 12%], CW discomfort [N=10; 17%], arm discomfort [N=6; 10%], lymphedema [N=11; 19%] and rib fracture [N=3; 5%]). At 2 yrs, LFFS=93% and DMFS=88%. OS was 89%. No explanatory variables were associated with toxicity or survival outcomes <h3>Conclusion</h3> Our analysis indicates that PBS PBT reRT for BC is well tolerated and offers meaningful rates of LC, toxicities and survival.

Improving radiomic model reliability using robust features from perturbations for head-and-neck carcinoma.

BackgroundUsing high robust radiomic features in modeling is recommended, yet its impact on radiomic model is unclear. This study evaluated the radiomic model’s robustness and generalizability after screening out low-robust features before radiomic modeling. The results were validated with four datasets and two clinically relevant tasks.Materials and methodsA total of 1,419 head-and-neck cancer patients’ computed tomography images, gross tumor volume segmentation, and clinically relevant outcomes (distant metastasis and local-regional recurrence) were collected from four publicly available datasets. The perturbation method was implemented to simulate images, and the radiomic feature robustness was quantified using intra-class correlation of coefficient (ICC). Three radiomic models were built using all features (ICC > 0), good-robust features (ICC > 0.75), and excellent-robust features (ICC > 0.95), respectively. A filter-based feature selection and Ridge classification method were used to construct the radiomic models. Model performance was assessed with both robustness and generalizability. The robustness of the model was evaluated by the ICC, and the generalizability of the model was quantified by the train-test difference of Area Under the Receiver Operating Characteristic Curve (AUC).ResultsThe average model robustness ICC improved significantly from 0.65 to 0.78 (P< 0.0001) using good-robust features and to 0.91 (P< 0.0001) using excellent-robust features. Model generalizability also showed a substantial increase, as a closer gap between training and testing AUC was observed where the mean train-test AUC difference was reduced from 0.21 to 0.18 (P< 0.001) in good-robust features and to 0.12 (P< 0.0001) in excellent-robust features. Furthermore, good-robust features yielded the best average AUC in the unseen datasets of 0.58 (P< 0.001) over four datasets and clinical outcomes.ConclusionsIncluding robust only features in radiomic modeling significantly improves model robustness and generalizability in unseen datasets. Yet, the robustness of radiomic model has to be verified despite building with robust radiomic features, and tightly restricted feature robustness may prevent the optimal model performance in the unseen dataset as it may lower the discrimination power of the model.

Intraoperative radiation therapy for locally advanced and recurrent head and neck cancer.

The purpose of the present study was to present a single institution experience with intraoperative radiation therapy (IORT) for patients with head and neck cancer (HNC). The present study included all patients with HNC treated consecutively with IORT at Loyola University Medical Center between January 2014 and December 2018. Charts were reviewed for patient and tumor characteristics, IORT technical details, IORT-induced adverse events and treatment outcomes. The study included 23 eligible patients. Median patient age was 66 years (range, 34-91 years). Tumor sites included the parotid gland (43%), lymph nodes (43%), oral tongue (9%) and ear (4%). A total of 48% of patients received IORT upfront with or without postoperative adjuvant external beam radiation therapy (EBRT), whereas 52% received salvage IORT after local tumor recurrence. The median prescribed IORT dose was 7.5 Gy (range, 5-14 Gy) in a single fraction prescribed to 5 mm depth with flat applicators (median diameter, 5 cm). A total of 92% of patients did not experience wound healing complications. One patient (4%) developed postoperative acute thromboembolic stroke and a second patient (4%) experienced protracted wound healing. At a median follow up of 36 months (range, 2-81 months), overall survival was 52%. In addition, 48% of patients were reported to have no evidence of disease, and although two had died of unrelated causes, 13% of patients were alive with disease and 39% died with the disease. The local-regional recurrence rate was 39% (median time to local recurrence, 11 months; range, 1-34 months), the rate of distant metastasis was 35% (median time to distant metastasis, 16 months; range, 4-40 months), and 21% of patients had both local-regional recurrence and distant metastases. The percentages of local-regional recurrence and distant metastases among patients receiving salvage IORT were 58 and 50% respectively, compared with 18 and 18% respectively in those receiving upfront IORT with or without adjuvant EBRT. In the present single institution retrospective study, it was concluded that IORT for patients with locally advanced and recurrent HNC was a safe treatment modality, with tumor control comparable to historical IORT data. Larger prospective studies are needed to further assess the utility of IORT in the management of locally advanced and recurrent HNC.

361. EARLY RECURRENCE PATTERNS AFTER ESOPHAGECTOMY FOR ESOPHAGEAL CANCER IN PATIENTS UNDERGOING CROSS NEOADJUVANT THERAPY

Abstract Chemoradiotherapy (CROSS regimen) has been regarded as standard preoperative treatment for patients with locally advanced esophageal cancer, but some patients still developed early recurrence after such intensive therapy. The present study aimed to determine the factors associated with early recurrence for patients with ESCC treated by CROSS therapy within 6 months. Patients were identified from single institution from 2019 to 2021. All patients with locally advanced ESCC who underwent CROSS regimen NCRT and following R0 esophagectomy were reviewed. Total 115 patients were included. 19 patients (16.52%) recurred within 6 months post-surgery. 8 patients (6.96%) had local-regional recurrence with most common location was cervical lymphnodes; 11 patients (9.56%) had distant recurrence and most often occured in lung. In univariate analysis: BMI before CROSS (p = 0.03), tumor size regression (p = 0.03), ypN≧1 (p = 0.002) and neck metastases (p = 0.01) were significantly associated with local-regional recurrence. In multivariate analysis: ypN≧1 (HR = 9.08, p = 0.05) was only independent covariate. For distant recurrence, tumor size regression (p = 0.02), ypN≧1 (p &amp;lt; 0.0001) and TRG3/4 (p = 0.01) were risk factors in univariate analysis, ypN≧1 (HR = 15.60, p = 0.01) was also independent covariate in multivariate analysis. For patients after CROSS neoadjuvant therapy, if there are still positive lymph nodes in clinical evaluation, M staging should be performed more carefully to avoid ineffective surgery with early postoperative distant recurrence.

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial

Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. The presence of DCIS and EFS, DRFS, and LRR. The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. ClinicalTrials.gov Identifier NCT01042379.

698P Bilateral nodal drainage in early-stage oral cancers: The case for lymphatic mapping

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. 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. From 2014 to 2021, 54 patients were diagnosed with clinical T1/T2N0 OSCC and underwent a SLNB with SPECT-CT. 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. 11 patients (73.3%) from the bilateral drainage cohort completed appropriate SLN mapping with bilateral nodal assessments. 4 patients who had SPECT-CT evidence of bilateral drainage completed unilateral nodal assessment alone. 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. 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 28% 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.

799P A pilot study of the neo-adjuvant use of vemurafenib plus cobimetinib in patients with BRAF mutant melanoma with palpable lymph node metastases

Melanoma patients with palpable nodal metastases have a very poor prognosis with the majority recurring within the first 2-3 years with survival ranging from 20-50% at 5 years. We aimed to ascertain that patients with a BRAF V600 mutation that receive vemurafenib and cobimetinib before surgery (neoadjuvantly) will have a higher probability of resectability, pathologic complete response, a lower risk of local recurrence and a longer DFS, PFS and OS. This was a single arm, prospective, multi centre phase II study in patients with confirmed BRAF V600 mutated Stage IIIB and IIIC melanoma ( AJCC 7th Edition) with palpable nodal disease. Patients received vemurafenib 960mg PO BID and cobimetinib 60mg PO OD for 4 months prior to resection followed by 8 months of adjuvant therapy post-surgery. CTscans were performed at baseline and before resection and every 6 months for the first 3 years and yearly in year 4 and 5. Biopsies for correlative studies and diagnosis were performed at baseline prior to starting therapy. The primary outcomes were the proportion of patients achieving resectability, radiologic response as per RECIST and the proportion of patients achieving a pathological response. Secondary objectives were local-regional recurrence rates, DMFS, DFS and OS. Twenty-four patients were enrolled and received neoadjuvant vemurafenib and cobimetinib and 21 underwent resection. At time of surgery 1 (20%; 95% CI 0.15-24.87) had a complete response, 16 (80%; 95% CI 56.34-94.27) had a partial response, and 2 (10%; 95% CI 1.23-31.70) had stable disease. One patient progressed as per RECIST but had a partial response upon resection. Following resection and pathological evaluation 12 (57%; 95% CI 34.02-78.18)) patients achieved a complete pathologic response, 8 (38%; 95% CI 18.11-61.56) had a partial pathologic response. Treatment related Grade 3-4 events occurred in 10 patients with no deaths due to AEs. Only 2 patients had a local recurrence. OS at 60 months was 63.9% (95% CI 43.5-93.8). Neoadjuvant vemurafenib and cobimetinib led to all patients being resectable with a high response rate, pathologic response rate and low local recurrence rate in melanoma patients with palpable lymph nodes.

Systematic review: Oncological safety of reconstruction with fat grafting in breast cancer outcomes

Autologous fat grafting (AFG) has become a commonly used procedure for breast reconstruction (BR) after cancer removal. Nevertheless, oncological considerations remain for AFG after breast cancer surgery. This article aims to evaluate the oncological safety of AFG in BR and its effect on disease-free survival (DFS) and local-regional recurrences (LRR). A systematic review regarding the use of AFG in BR to identify a difference in incidence rates of LRR and DFS between patients who had AFG and controls was performed using PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus, and Cochrane databases. The protocol was developed following the Preferred Reporting for Items for Systematic Reviews-Protocols (PRISMA-P) guidelines. The included studies had to match predetermined criteria according to the PICOS approach. A total of 11 studies were included. Seven studies reported LRR, and 5 studies reported DFS in 5,886 patients. Our systematic review showed that AFG was not associated with increased LRR and DFS. Pooled hazard ratios (HRs) (95% confidence intervals [CIs]) for LRR and DFS were 1.26 (0.90-1.76) and 1.27 (0.96-1.69), respectively. AFG can, therefore, be performed safely in BR after breast cancer. Further, randomized controlled trials and related systematic reviews, as well as evidence-based medicine (EBM) studies of level 1, are required to consolidate the results of the studies identified in this systematic review.

Hidden local recurrence of colorectal adenocarcinoma diagnosed by endoscopic ultrasound: A case series

BACKGROUNDAlmost half of the patients with colorectal cancer (CRC) will experience local-regional recurrence after standard surgical excision. Many local recurrences of colorectal cancer (LRCC) do not grow intraluminally, and some may be covered by a normal mucosa so that they could be missed by colonoscopy. Early detection is crucial as it offers a chance to achieve curative reoperation. Endoscopic ultrasound (EUS) is mainly used in CRC staging combined with cross-section imaging study. EUS can provide an accurate assessment of sub-mucosal lesions by demarcating the originating wall layer and evaluating its echostructure. EUS fine-needle aspiration (FNA) provides the required tissue examination and confirms the diagnosis.CASE SUMMARYWe report a series of five cases referred to surveillance for LRCC with negative colonoscopy and/or negative endoscopic biopsies. EUS-FNA confirmed LRCC implanted deep into the third and fourth wall layer with normal first and second layer.CONCLUSIONAssessment for LCRR is still problematic and may be very tricky. EUS and EUS-FNA may be useful tools to exclude local recurrence.

A Nomogram Based on Hematological Parameters and Clinicopathological Characteristics for Predicting Local-Regional Recurrence After Breast-Conserving Therapy.

ObjectivesThe aim of this study was to identify the factors for local–regional recurrence (LRR) after breast-conserving therapy (BCT). We established a practical nomogram to predict the likelihood of LRR after BCT based on hematological parameters and clinicopathological features.MethodsA retrospective analysis was performed on 2,085 consecutive breast cancer patients who received BCT in Shandong Cancer Hospital from 2006 to 2016, including 1,460 patients in the training cohort and 625 patients in the validation cohort. Univariate and multivariate analyses were performed based on hematological parameters (fibrinogen, platelets, mean platelet volume, neutrophils, monocytes, and lymphocytes) and clinicopathological characteristics to identify the independent factors for LRR. Subsequently, a nomogram for predicting LRR was established by logistic regression analysis. The nomogram was validated in 625 patients in the validation cohort.ResultsDuring the median follow-up period of 66 months, 44 (3.01%) patients in the training cohort and 19 (3.04%) patients in the validation cohort suffered from LRR. Multivariate analysis showed six independent factors related to LRR, including molecular subtype, pathological N stage, re-resection, radiotherapy or not, platelet count*MPV*fibrinogen (PMF), and neutrophil count/lymphocyte count ratio (NLR). Six variables were entered into logistic regression to establish the nomogram for predicting LRR. The nomogram of LRR showed excellent discrimination and prediction accuracy. The area under the receiver operating characteristic curve (AUC) was 0.89 (p < 0.001, 95% CI = 0.83, 0.95) in the training cohort and 0.88 (p < 0.001, 95% CI = 0.8, 0.96) in the validation cohort. Calibration curves for the prediction model in the training and validation cohorts both demonstrated satisfactory consistency between the nomogram-predicted and actual LRR.ConclusionThe combination of hematological parameters and clinicopathological characteristics can predict LRR after BCT. The predictive nomogram based on preoperative and postoperative indicators of BCT might serve as a practical tool for individualized prognostication. More prospective studies should be performed to verify the model.