Local-regional Recurrence Rate Research Articles

A Prospective Pilot Study of Pencil Beam Scanning Proton Radiation Therapy as a Component of Trimodality Therapy for Esophageal Cancer

PurposeTo evaluate the safety and efficacy of pencil beam scanning (PBS) proton radiotherapy (RT) in trimodality therapy for esophageal cancer. MethodsThis prospective pilot study was planned to accrue 30 patients with locally advanced esophageal or gastroesophageal junction (GEJ) carcinoma, medically suitable for chemoRT (CRT) followed by esophagectomy. PBS proton RT consisted of 25 fractions, 50 Gy to tumor + 1 cm and 45 Gy to a 3.5 cm mucosal expansion and regional lymph nodes. Chemotherapy was weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m2). At 4-8 weeks after CRT, patients underwent restaging and potential esophagectomy. The primary endpoint was acute grade 3+ adverse events (AEs) attributed to CRT. Overall (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier methodology; local-regional recurrence (LRR) and distant metastases (DM) rates were assessed by cumulative incidence methodology. The Functional Assessment of Cancer Therapy-Esophagus (FACT-E) assessed quality of life. ResultsThirty eligible patients enrolled June 2015-April 2017. Median age was 68 years. Histology was adenocarcinoma in 87% and location was distal esophagus/GEJ in 90%. Stage was T3-4 in 87% and N1-3 in 80%. All patients completed the planned RT dose. Acute grade 3+ AEs occurred in 30%, most commonly leukopenia and neutropenia. Acute grade 3+ non-hematologic AEs occurred in 3%. Esophagectomy was performed in 90% of patients (R0 in 93%). Pathologic complete response rate was 40%. Major post-operative complications (Clavien-Dindo score ≥ III) occurred in 34%. Postoperative mortality at 30 days was 3.7%. Median follow-up was 5.2 years. 5-year outcome estimates were OS 46%, PFS 39%, LRR 17%, and DM 40%. FACT-E scores (medians) were baseline (145), end of CRT (136, p=0.0002 vs. baseline), before esophagectomy (144), 12 months (146), and 24 months (157). ConclusionsPBS proton RT is feasible and safe as a component of trimodality therapy for esophageal cancer.

Total neoadjuvant therapy with split-course hypofraction radiotherapy combined with CAPOX and envafolimab followed by local excision for locally advanced very low rectal cancer (TRACE-LE): An open-label, single-arm, multicenter, phase II trial.

TPS3647 Background: In the treatment of patients with locally advanced very low rectal cancer, neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) is considered a standard therapeutic approach. Short-course hypofractionated radiotherapy, in combination with subsequent chemotherapy, has been shown to be comparable to long-term chemoradiotherapy in terms of neoadjuvant therapy effects in rectal cancer. Additionally, it has been observed that hypofractionated radiotherapy, when combined with programmed death L-1 (PD-L1) blockade, can enhance the immune response. This study aims to investigate efficacy and safety of organ preservation in patients with locally advanced very low rectal cancer by utilizing total neoadjuvant therapy involving split-course hypofraction radiotherapy in conjunction with CAPOX and Envafolimab (a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment). Methods: TheTRACE-LE trail is an open-label, single-arm, multicenter, phase II trial. The target sample is 72 participants. Key eligibility criteria include individuals aged 18-75, confirmed rectal adenocarcinoma, cT3-4N0/cT1-4N1-2 with lower margin ≤ 2cm from anorectal ring's upper edge (MRI) and ECOG performance status of 0-2. The treatment protocol include preoperative split-course hypofractionated radiotherapy (5×7Gy), in conjunction with 6 cycles of CAPOX chemotherapy and Enverolimab (300 mg subcutaneous injections) administered in a 3-week treatment cycle. The primary outcome measure is organ preservation, specifically the rectum intact, owing to no radical total mesorectal excision (TME), no locoregional regrowth unless amenable to limited, curative (R0) salvage surgery by local excision (LE) and no permanent stoma (including a never reversed protective stoma, or a stoma owing to toxicities and/or poor functional outcomes). The secondary outcome measures encompass ypT0-1 rate, pathological complete response (pCR) rate, acute and late toxicity as per NCICTCAE V.5.0, local recurrence rate, local regional recurrence rate, disease-free survival, quality of life, and anorectal function. Clinical trial information: NCT05970900 .

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

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

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

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

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

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

Margin Assessment Methods in Oral Cavity Squamous Cell Carcinoma and Recurrence

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

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

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

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

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

Low Rates of Local-Regional Recurrence Among Inflammatory Breast Cancer Patients After Contemporary Trimodal Therapy.

Inflammatory breast cancer (IBC) represents a rare (2-3 %) but aggressive subset of breast cancer with a historically reported 5-year overall survival rate of 50 % and a 3-year local-regional recurrence (LRR) rate of 20 %. This study aimed to evaluate long-term LRR in a contemporary cohort of non-metastatic IBC patients undergoing trimodal therapy at a single institution and identify factors associated with local and distant failure. The study identified 262 patients with non-metastatic IBC who received trimodal therapy (neoadjuvant chemotherapy, modified radical mastectomy, adjuvant radiation) from an institutional prospective database (2007-2019). Long-term outcomes of local-regional and distant metastasis were reported. Survival outcomes were analyzed using the Cox proportional hazards regression model. The median age at diagnosis was 52 years, and the median follow-up period was 5.1 years. In this cohort, 82 (31.3 %) patients achieved a pathologic complete response (pCR) in the breast and axilla. Local-regional recurrence was observed in 18 (6.9 %) patients (11 isolated to the chest wall, 4 isolated to regional nodes, and 3 involving chest wall and ipsilateral axillary nodes). Distant metastasis was observed in 92 (35.1 %) patients. During the follow-up period, 90 deaths occurred. In the multivariate analysis, pCR was associated with improved disease-free survival (hazard ratio [HR], 0.26; 95 % confidence interval [CI], 0.13-0.51; p = 0.001) and overall survival (HR,0.31; 95 % CI, 0.15-0.65;p = 002). During a median follow-up period longer than 5 years, the local-regional relapse rate for the IBC patients treated with contemporary trimodal therapy was 6.9%, similar to that for the non-IBC patients. After chemotherapy, surgical resection with modified radical mastectomy to negative margins and postmastectomy radiation therapy resulted in excellent long-term local-regional control.

Extremely Low Incidence of Local-Regional Recurrences Observed Among T1-2 N1 (1 or 2 Positive SLNs) Breast Cancer Patients Receiving Upfront Mastectomy Without Completion Axillary Node Dissection.

Completion axillary node dissection (CLND) is routinely omitted in cT1-2 N0 breast cancer treated with upfront, breast-conserving therapy and sentinel node biopsy (SLNB) showing one to two positive sentinel nodes (SLNs). The purpose of this study was to determine the incidence and impact of axillary treatment among patients treated with mastectomy in a contemporary cohort. A prospective, institutional database was reviewed from 2006 to 2015 to identify patients with T1-2 breast cancer treated with upfront mastectomy and SLNB found to have one to two positive SLNs. Patients were stratified by axillary therapy [including CLND and/or post-mastectomy radiation therapy (PMRT)], and clinicopathologic factors and incidence rates of local-regional and distant recurrence were analyzed. A total of 548 patients were identified, including 126 (23%) without CLND. Rates of PMRT were similar between those with and without CLND (35.3% vs. 28.6%, p = 0.16). On multivariate analysis, two rather than one positive SLN, larger SLN metastasis size, frozen-section analysis of the SLNB, and adjuvant chemotherapy were significantly associated with receipt of CLND. At a median follow-up of 7 years, there were only two local-regional recurrences in the no-CLND group, of which only one was an axillary recurrence. The 5-years incidence rate of LRR was not significantly different for those with and without CLND (1.3% vs. 1.8%, p = 0.93). We found extremely low rates of local-regional recurrence among those with T1-2 breast cancer undergoing upfront mastectomy with 1-2 positive SLNs. Further axillary surgery may not be indicated in selected patients treated with a multidisciplinary approach, including adjuvant therapies.

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.

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.

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.

Comparable Clinical Outcome Using Small or Large Gross Tumor Volume-to-Clinical Target Volume Margin Expansion in Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.

The purpose of this study was to evaluate the feasibility of small primary gross tumor volume (GTV)-to-clinical target volume (CTV) margin expansion in neoadjuvant chemoradiation for esophageal squamous cell carcinoma. Medical records of 139 patients with locally advanced esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiation and radical esophagectomy were retrospectively reviewed. Patients treated with longitudinal primary GTV-to-CTV margin expansion of 2 cm and no additional expansion of the CTV through the esophagus were classified into a small margin (SM) group (37 patients). The remaining 102 patients were classified as a large margin (LM) group. Patterns of recurrence including local and out-field regional recurrence rates were compared between the two groups. Clinical outcomes including rates of local control, regional control, failure-free survival, and overall survival were also compared. More patients in the SM group underwent paclitaxel + carboplatin, Mckeown esophagectomy, and intensity-modulated radiation therapy than in the LM group. With a median follow-up of 25.6 months, there was no significant difference in the crude rate of local recurrence (10.8% vs. 6.9%, P=0.694), out-field regional recurrence (27.0% vs. 19.6%, P=0.480), or out-field regional recurrence without in-field recurrence (10.8% vs. 12.7%, P=0.988) between the two groups. There was no significant difference in failure-free survival (5-year, 34.4% vs. 30.6%, P=0.652) or overall survival (44.1% vs. 38.5%, P=1.000), either. Esophageal fistula was not reported in the SM group (0.0% vs. 7.9%, P=0.176). In conclusion, a radiation field with 2 cm of longitudinal primary GTV-to-CTV was feasible in the neoadjuvant setting for esophageal squamous cell carcinoma treatment.

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

6058 Background: Intraoperative Radiation Therapy (IORT) allows precise delivery of radiation therapy (RT) to a limited target area at high risk of cancer recurrence while minimizing RT to nearby organs at risk. IORT may be particularly beneficial for patients with locally recurrent head and neck cancer (HNC) in a previously irradiated field and for locally advanced HNC cases, in which obtaining negative surgical margins may be difficult. This study aims to present a single institution experience with IORT for HNC patients. Methods: This study included HNC patients treated consecutively with IORT at our institution between 2014 and 2018. Charts were reviewed for patients’ and tumors’ characteristics, IORT technical details, IORT-induced adverse events, and treatment outcomes. Results: The study included 23 eligible patients. Median patient age was 66 (range 33-91). Tumor sites included parotid gland (43%), lymph nodes (43%), oral tongue (9%), and ear (4%). 52% of patients received IORT upfront with or without postoperative adjuvant external beam radiation therapy (EBRT), while 48% 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 of 5 cm). 92% of patients did not experience wound healing complications. One patient (4%) developed postoperative acute thromboembolic stroke, a second patient (4%) experienced protracted wound healing. At a median follow-up of 36 months (range 2-81), 42% of patients presented with no evidence of disease (NED), overall survival was 54%, 13% of patients were alive with disease, and 46% died with disease. Local-regional recurrence rate was 39% (median time to local recurrence was 18 months, range 2-60), rate of distant metastasis was 43% (median time to distant metastasis was 23 months, range 5-60), and 30% of patients had both local-regional recurrence and distant metastases. The percent of local-regional recurrence and distant metastases among patients receiving salvage IORT was 64% and 73% respectively, compared to 23%, and 15% respectively in those receiving upfront IORT with or without adjuvant EBRT. Conclusions: In this single institution chart review study, IORT to locally advanced and recurrent HN cancer patients was a safe treatment modality, with tumor control comparable to historical EBRT data. Larger prospective studies are needed to further assess the utility of IORT in the management of locally advanced and recurrent HN cancer.

Hyperfractionation versus Conventional Fractionation of Preoperative Intensity-Modulated Radiotherapy with Oral Capecitabine in Locally Advanced Mid-Low Rectal Cancer: A Propensity Score Matching Study.

Purpose In theory, the hyperfractionated radiotherapy can enhance biological effect dose against tumor and alleviate normal tissue toxicity. This study is to assess the efficacy and safety of preoperative hyperfractionated intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced rectal cancer (LARC). Methods We retrospectively screened patients with LARC from January 2015 to June 2016. Patients that received hyperfractionated IMRT or conventional fractionated IMRT were eligible in the hyperfractionation (HF) group or conventional fractionation (CF) group, respectively. The primary outcome was the complete response rate. Secondary outcomes included toxicity, postoperative complications, anus-reservation operation rate, local recurrence and distant metastases rate, overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Results 335 patients were included in the analysis. The complete response rate for the hyperfractionated and conventional fractionated IMRT was 20.41% vs. 23.47% (P = 0.583). The anus-reservation operation rate was 68.37% vs. 65.31% (P = 0.649). There were no cases of grade 4 toxicity during radiotherapy; the rate of grade 3 toxicity and postoperative complications was both comparable between groups. However, in the CF group, more patients had a second operation due to complications (0.0% vs. 5.68%, P = 0.011). The cumulative local regional recurrence and distant metastases rates of the HF group and CF group were 5.10% vs. 9.18% (P = 0.267) and 22.45% vs. 24.49% (P = 0.736), respectively. The 5-year OS, CSS, and DFS in the HF group and CF group were 86.45% vs. 73.30% (P = 0.503), 87.34% vs. 75.23% (P = 0.634), and 70.80% vs. 68.11% (P = 0.891), respectively. Conclusions The preoperative hyperfractionated IMRT with oral capecitabine, with an acceptable toxicity and favorable response and survival, could reduce the rate of secondary surgery.

Abstract P3-19-08: Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk?

Abstract Background: Breast-cancer related lymphedema (BCRL) is a devastating treatment complication driven by the extent of axillary surgery (axillary lymph node dissection [ALND] versus sentinel lymph node biopsy [SLNB]). Regional nodal irradiation (RNI) may increase the risk of BCRL by up to 5%. Recently, investigators identified a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) as a potential organ-at-risk (OAR) demonstrating that increasing radiation dose to the ALTJ was associated with a higher risk of BCRL. Here, we set to validate whether radiation dose to the ALTJ is associated with BCRL. Materials/Methods: We identified patients with stage II-III breast cancer treated with adjuvant RNI after M or L from 2013-2018 excluding those with BCRL pre-radiation. RNI treatment planning included delineation of clinical target volumes (CTVs): breast or chest wall and regional lymph nodes per the RTOG Breast Cancer Atlas. The CTVs were expanded by 5mm to create the planning target volume (PTV). Dose delivered was 50 Gy/25 fractions with goal of 47.5 Gy (95%) to 95% of each PTV. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb &amp;gt;2.5 cm at any 1 visit or ≥2 cm on at least 2 visits. All patients suspected of having BCRL at routine follow-up visits were evaluated by physical therapy. The ALTJ was retrospectively contoured and the following metrics collected: maximum/minimum/mean dose; V10Gy-V50Gy. Follow-up time was defined as the time from surgery to the development of BCRL or last follow-up. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. All variables with p&amp;lt;0.10 on univariate analysis were entered in the final multivariate model (p&amp;lt;0.05 considered statistically significant). Results: Population includes 378 patients with median age 53 years (interquartile range [IQR], 45-61 years), median body mass index (BMI) 28.4 kg/m2 (IQR, 24.3-33.4 kg/m2), 60% HR+/HER2-, 89% chemotherapy, 53% stage III, 71% underwent M, and 82% underwent ALND with median of 18 nodes removed (IQR, 11-25) and median of 2+ nodes (IQR, 1-5). Median follow-up time was 54.5 months (IQR, 40.3-72.2 months). The ALTJ and axilla PTV overlapped in 91% of the patients. BCRL developed in 97 patients (25.7%) at a median of 18.9 months (IQR, 9.9-30.6 months). The 4-year cumulative incidence of BCRL was 23.5% (26.6% ALND vs. 8.7% SLNB, p=0.002). On univariate analysis, increasing age (HR=1.02, p=.039), increasing BMI (HR=1.04, p=0.002), increasing number of nodes removed (HR=1.04, p&amp;lt;0.0001), and use of IMRT vs. 3DCRT (HR=1.50, p=0.041) were all significantly associated with developing BCRL while increasing size of the axilla PTV (HR=0.96, p=0.047) was associated with a lower risk. None of the ALTJ metrics were associated with developing BCRL. Increasing ALTJ V45 was marginally associated with a lower risk of BCRL (HR=0.96, p=0.091). On multivariate analysis, increasing age (HR=1.02, p=0.021), increasing BMI (HR=1.04, p=0.004), and increasing number of nodes removed (HR=1.03, p=0.001) were associated with a higher risk of developing BCRL while use of IMRT (HR=1.24, p=0.338), size of the axilla PTV (HR=0.96, p=0.110) and ALTJ V45 (HR=0.99, p=0.708) were not. There were 10 local-regional recurrence (LRR) events as a first failure, 8 of which occurred with simultaneous distant metastases (DM). Of these LRRs, 5 included an axillary nodal component (all with DM) resulting in a 2.6% 4-year LRR rate (1.4% axillary recurrence rate). Conclusion: In this analysis, ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL given the low LRR and inability to validate ALTJ as an OAR. Citation Format: Erin Healy, Sachin Jhawar, Sasha Beyer, Julia R White, Jose G Bazan. Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-08.

Comparison of efficacy and safety between simultaneous integrated boost intensity-modulated radiotherapy and standard-dose intensity-modulated radiotherapy in locally advanced esophageal squamous cell carcinoma: a retrospective study

ObjectiveThis study aimed to evaluate the efficacy and safety of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) versus standard-dose intensity-modulated radiotherapy (SD-IMRT) in the treatment of locally advanced esophageal squamous cell carcinoma.MethodsFrom July 2003 to March 2014, 1748 patients in a single center who received definitive chemoradiotherapy were included in the analysis. A total of 109 patients who underwent SIB-IMRT and fulfilled all inclusion and exclusion criteria were identified as the study group. A total of 266 patients who underwent SD-IMRT (60 Gy/30 fractions, 2 Gy/fraction, 1 time/day, 5 times/week) during the same period were selected as the control group. Propensity score matching (PSM) was used to balance the baseline characteristics. Survival status, treatment failure mode, and the occurrence of adverse events were compared between the two groups.ResultsThere were more women and more cervical and upper thoracic cancers (P = 0.038, < 0.001, respectively) in the SIB-IMRT group before case matching. The median progression-free survival (PFS) in the SD-IMRT and SIB-IMRT groups was 22 and 19 months, respectively, and the median overall survival duration was 24 and 22 months, respectively, with χ2 = 0.244 and P = 0.621. After PSM of 1:1, 138 patients entered the final analysis (69 cases from each group). The median PFS of the SD-IMRT group and the SIB-IMRT group was 13 and 18 months, respectively, with χ2 = 8.776 and P = 0.003. The 1‑, 3‑, and 5‑year overall survival rates were 66.7, 21.7, and 8.7% and 65.2, 36.2, and 27.3%, respectively, and the median overall survival duration was 16 and 22 months, respectively, with χ2 = 5.362 and P = 0.021. Treatment failure mode: 5‑year local regional recurrence rates of SD-IMRT and SIB-IMRT were 50.7 and 36.2%, respectively, with χ2 = 2.949 and P = 0.086. The 5‑year distant metastasis rates of the two groups were 36.2 and 24.6%, respectively, with χ2 = 2.190 and P = 0.139. Adverse events: 3 patients experienced grade 4–5 toxicity (2.2%), including one case of grade 4 radiation esophagitis and two cases of grade 5 radiation pneumonitis, all in the SD-IMRT group; 14 patients experienced grade 3 adverse events (10.1%), primarily including radiation esophagitis, radiation pneumonitis, and hematological toxicity.ConclusionThe technique of SIB-IMRT was safe and reliable compared with SD-IMRT. In addition, SIB-IMRT had locoregional control advantages and potential survival benefits.

Oncological safety of breast conserving surgery in breast cancer

Background/Aim: Breast-conserving surgery is a type of surgery used as a treatment option for breast cancer. It was introduced at the end of the 20th century following and in accordance with relevant clinical studies. With heightened public awareness of breast cancer and the introduction of new diagnostic procedures, despite the proven oncological safety of this type of surgery, a growing number of women choose to undergo total mastectomy. The aim of this study was to confirm the oncological safety of breast-conserving surgery performed on breast cancer patients at the University Clinical Centre of the Republic of Srpska. Methods: This study analysed 305 female patients with I and II stage of breast cancer, operated on between March 2009 and December 2013. One group of patients underwent breast-conserving surgery (BCS), followed by adjuvant radiation therapy and the other total mastectomy (MX). The patients were followed up for 5 years after the surgery. Analysed herein were the local-regional recurrence, distant metastases, disease-free survival and overall survival rates. Results: After a five-year follow-up, the local-regional recurrence rate for patients in the BCS group was 4.3 %, while for the MX group it was 4.2 %. The overall survival rate of patients in the BCS group was 90.9 %, as opposed to 89.1 % for MX patients. Conclusion: After a five-year follow-up, no statistically significant difference was observed between the two groups of patients regarding the local-regional recurrence (p = 0.967) and overall survival rates (p = 0.610). Breast-conserving surgery is an oncologically safe surgical treatment for breast cancer.

Breast cancer outcomes following immediate breast reconstruction with implants versus autologous flaps: a propensity score-matched study.

A large proportion of patients with breast cancer who had mastectomy had undergone breast reconstruction with implants or autologous flaps. However, only a few studies have compared the breast cancer outcomes between the implant-based reconstruction (IBR) and autologous flap reconstruction (AFR). In this study, we retrospectively compared the local recurrence rates, distant metastasis rates, and survival outcomes between immediate IBR and AFR. A total of 1530 patients with primary breast cancer who underwent IBR or AFR with nipple-/skin-sparing mastectomy were included. Patients who underwent neoadjuvant systemic therapy were excluded from the study. After propensity score matching by age at diagnosis, T stage, N stage, molecular subtype, mastectomy type, adjuvant radiotherapy status, and follow-up period, 938 patients were 1:1 matched, comprising the well-balanced IBR and AFR groups. Locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were compared between the matched groups. After matching, the median follow-up periods were 68months and 71months for the IBR and AFR groups, respectively. No significant differences were observed between the IBR and AFR groups regarding the local recurrence (7.2% vs. 5.1%; P = 0.175), regional recurrence (2.1% vs. 1.5%; P = 0.463), or distant metastasis (3.2% vs. 3.2%; P = 1.000) rates. Moreover, no significant difference was observed between the IBR and AFR groups in the LRRFS (hazard ratio, 0.691; 95% CI, 0.433-1.102; P = 0.118), DFS (hazard ratio, 0.709; 95% CI, 0.468-1.076; P = 0.104), DMFS (hazard ratio, 1.006; 95% CI, 0.491-2.059; P = 0.987), or BCSS (hazard ratio, 0.445; 95% CI, 0.111-1.786; P = 0.659). In this propensity score-matched analysis of oncologic outcomes in patients with primary breast cancer who underwent immediate breast reconstruction with nipple-/skin-sparing mastectomy, no significant differences were observed between the IBR and AFR groups.