Local-regional Recurrence Research Articles

Clinical outcomes after post-operative radiotherapy for breast cancer patients presenting with ipsilateral supraclavicular metastasis: considerations on the cranial border of irradiation field.

Disease recurrence at lower neck adjacent to ipsilateral supraclavicular (SCV) region represents a concern in locally advanced breast cancer patients presenting with SCV metastasis at diagnosis. This study aims to report the outcomes following post-operative radical radiation therapy and discuss the reasonable cranial border of the irradiation field for N3c patients. Between July 2016 and January 2022, a total of 268 patients were eligible for analysis. The endpoints included in-field and out-field cervical failures, local-regional recurrence-free survival (LRRFS), SCV recurrence-free survival (SRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS). During a median follow-up of 37months (range 3-89months), 17 patients (6.3%) developed local-regional recurrence as the first recurrence event, with 13 having concomitant distant-metastasis (DM); 56 patients (20.9%) had DM alone. The 3-year rates of LRRFS, SRF, DMFS, RFS, and OS were 92.3%, 94.5%, 74.5%, 73.0%, and 90.0%, respectively. 89.2% of patients received RT with the cranial border at the top of hyoid bone, and 95.1% of patients received a boost not exceeding the level of cricoid cartilage. A total of 11 patients (4.1%) developed ipsilateral SCV failure, and 3 patients (1.1%) experienced cervical failure, including 2 in-field failures and 1 out-field failure. Neoadjuvant systemic therapy (NST) was administered to 234 patients (87.3%). In the multivariate analysis, non-ypN0, triple-negative subtype and cT4 at diagnosis were predictors of worse SRFS and RFS in NST subgroup. Our findings suggest that radical RT with cranial border of irradiation field at the hyoid bone level lead to excellent local-regional control, and out-field cervical failure was rare. The irradiation field might not extend to mastoid process.

Outcomes and failure patterns after chemoradiotherapy for locally advanced rectal cancer with positive lateral pelvic lymph nodes: a propensity score-matched analysis

PurposeThis study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN).Materials and methodsPatients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. 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.ResultsA total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), 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 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. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109).ConclusionsOur study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

Long-term outcomes and risk profile of cT3N0 breast cancer treated with neoadjuvant chemotherapy and curative surgery.

We evaluated the treatment outcomes and failure patterns in cT3N0 breast cancer patients classified for rigorous pretreatment evaluation and treated with neoadjuvant chemotherapy (NAC) and curative surgery. We reviewed the records of 87 cT3N0 breast cancer patients who received NAC and curative surgery between 2000 and 2015. The clinical high-risk group was defined as having two or more risk factors: age < 40, histologic grade 3, lymphovascular invasion, hormone receptor negativity, and Ki-67 labeling index >20%. Of the patients, 84 (96.6%) and 79 (90.8%) were initially evaluated using magnetic resonance imaging and positron emission tomography/computed tomography. Most patients received anthracycline based NAC regimen (n = 69, 79.3%) and modified radical mastectomy (n = 61, 70.1%). During a 91.5-month median follow-up, ten patients experienced distant metastasis (DM) only, two had isolated local recurrence, one had local recurrence and DM, and another had local recurrence, regional recurrence, and DM. The 5-year rates of locoregional recurrence, DM, any recurrence (AR), and overall survival (OS) were 1.2%, 11.6%, 11.6%, and 90.8%, respectively. The risk group was an independent prognostic factor of recurrence, and the high-risk group had worse rates of DM (19.2% vs. 0%, P = 0.009), AR (19.2% vs. 0%, P = 0.016) and OS (82.8% vs. 100%, P = 0.001). Patients with cT3N0 breast cancer classified for rigorous pretreatment evaluation and treated with NAC and radical surgery had favourable oncological outcomes. A clinical risk group based on clinical and immunohistochemical risk factors was an excellent predictor of survival and recurrence.

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction

Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. To compare HF and CF PMRT outcomes after implant-based reconstruction. This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02). In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction. ClinicalTrials.gov Identifier: NCT03422003.

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...

HPV status and immunohistochemical analysis of p16, p53 and PD‑L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

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.

Evaluating the efficacy of chemoradiotherapy combined with immunotherapy for local-regional recurrent esophageal cancer patients after esophagectomy: A retrospective analysis.

e16085 Background: Chemoradiotherapy has been the standard-of-care for esophageal cancer patients with local-regional recurrent disease after esophagectomy without prior chemoradiation. Recent studies have demonstrated that immune checkpoint inhibitors confer survival benefits to patients with esophageal cancer. However, the effectiveness of chemoradiotherapy combined with immunotherapy remains undetermined in patients experiencing local-regional recurrence. Methods: Esophageal cancer patients treated at our institution were screened retrospectively for the following inclusion criteria: histological confirmation of squamous cell carcinoma; loco-regional recurrence after surgery-based first-line treatment; received chemoradiotherapy combined with immunotherapy regimen after loco-regional recurrence. Patients with prior radiotherapy were excluded. The endpoints of the study were overall survival (OS) and progression-free survival (PFS). Loco-regional recurrence was defined as recurrences from below the hyoid to the lower margin of the first lumbar vertebra, including supraclavicular, mediastinal, abdominal lymph nodes, and the tumor bed. PFS was defined as the time from the date of postoperative recurrence until disease progression, recurrence, death, or the last follow-up day; OS was determined as the duration from postoperative recurrence to the date of death from any cause or the last follow-up date. Results: Between January 2020 and July 2023, 685 patients were screened and 61 patients were finally enrolled in this study. The median follow-up period was 14 months (2.9~45.5 months). Regarding the regions of recurrence, 31 patients experienced exclusive mediastinal recurrence, and 30 patients had recurrence beyond the mediastinum (supraclavicular lymph node [n = 21], abdominal lymph node [n = 8], both supraclavicular and abdominal lymph node [n = 1]). In these cases, 26 patients (43%) experienced recurrence after receiving chemoradiotherapy combined with immunotherapy (loco-regional failure [n = 15], distant metastasis [n = 3], and both loco-regional failure and distant metastasis [n = 8]). Fourteen (23%) patients died from disease progression. The median PFS was 18 months (95%CI, 9.6-26.4) and the median OS was not reached. The 2-year OS rate was 65%. In univariate analysis, patients with recurrence in supraclavicular/abdominal lymph nodes had a worse prognosis (P = 0.014, HR = 2.765). Conclusions: Chemoradiotherapy combined with immunotherapy showed a favorable efficacy in radiotherapy-free esophageal cancer patients experiencing loco-regional recurrence post-surgery. Additionally, the regions of recurrence may influence patient outcomes.

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 .

Second primary squamous cell cancers in the HPV de-escalation Quarterback Trials.

e18049 Background: Patients with HPV oropharyngeal cancer (HPVOPC) have a cure rate approaching 90%, and will live for decades with the sequelae of therapy. Trials evaluating treatments for HPVOPC select patients by p16 status rather than using more accurate molecular testing; a fraction of these patients, approaching 5%, are HPV16 negative. Recurrent cancers are often not tested molecularly and may not be tested for p16. Applying molecular diagnostics for HPV at diagnosis and relapse can avoid significant mis-assignment, mistreatment, and inaccurate results in clinical trials. We reviewed and report results from the Quarterback Trials (QT) where molecular testing confirmed HPV status at diagnosis and recurrence. Methods: Patients entered on the QT were required to have &lt; 20 py smoking history, not be active smokers, have non-metastatic locally advanced disease, and have a molecularly confirmed HPV status, including genotype (PCR based DNA Sequencing). Subjects were treated with TPF chemotherapy for 3 cycles and patients with an adequate response were eligible for de-escalation of chemoradiotherapy (CRT) to 5600 cGy (RD). The first 20 patients were randomized to standard dose (SD) 7000 cGy (8) or RD (12). Patients who withdrew from the study or had an inadequate response to TPF, were treated with SD. Patients were monitored for recurrent disease by routine surveillance with physical examination and PET scan. Recurrences were confirmed with tissue biopsy. We performed a retrospective analysis of 2nd in-field primaries (SP) and compared them to local regional recurrences (LRF) in the entire eligible population. Results: 62 patients were consented on to the QTs. 2 patients failed screening and are not considered any further. 14 patients received 7000 cGy: 8/14 were randomized to SD, 5/14 had an inadequate response to TPF and 1/14 patient withdrew consent. One patient randomized to SD withdrew consent and stopped CRT at 5200cGy. There were 7 HPV+ LRF: (1 SD and 6 RD); and 4 molecularly documented in-field non-HPV SP squamous cell cancers: 2/14 SD (14%) and 2/46 RD (4%). 1 of 4 SP tumors was p16+; all were molecularly negative for HPV and had documented p53 mutations. Median time to LRF was 8 mo. (4-49) and 66 mo. (35-84) for SP. Median survival after LRF is 11 (4-72+) and after SP 18+ (3-36+). 4/11 (36%) of post treatment local regional squamous cancer events were not HPV related. Conclusions: Non-HPV SP SCC were not rare events in this documented HPV+, non-smoking population. SP were more common in the SD than the RD treated patients suggesting an RT dose dependency and causality, although other biologic explanations are possible. SP will increase and be a major cause of mortality in this population indicating a need for awareness during surveillance. p16 is inaccurate for determining HPV16 status at diagnosis and recurrence in HPV critical clinical trials and in-field cancer events should be molecularly assessed to determine if they are LRF or SP.

Association of MammaPrint index and 3-year outcome of patients with HR+HER2- early-stage breast cancer treated with chemotherapy with or without anthracycline.

511 Background: The MammaPrint (MP) risk of distant recurrence signature identifies hormone receptor-positive (HR+), HER2-negative early-stage breast cancer (EBC) patients (pts) with increased or decreased chemosensitivity and chemotherapy (CT) benefit. The MINDACT trial demonstrated excellent outcomes for MP Low Risk tumors without CT, and previous studies show MP High Risk tumors exhibit higher sensitivity and benefit with CT. There remains an unmet clinical need for identifying biomarkers to inform specific regimen planning for pts who qualify for CT. Here, the association of MP index and 3-year (yr) Recurrence-Free Interval (RFI) was evaluated in pts with HR+HER2-, genomically High Risk Luminal B-Type EBC treated with taxane and cyclophosphamide (TC) vs anthracycline + TC (AC-T). Methods: The prospective, observational FLEX Study (NCT03053193) includes stage I-III breast cancer pts who received MP testing, with or without BluePrint (BP) molecular subtyping, and consented to full transcriptome and clinical data collection. Pts with HR+HER2- MP High Risk and BP Luminal B-Type tumors who received chemotherapy with 3-yr follow-up data (N = 614) were included. High Risk tumors were further classified into High 1 (H1; 0.000 to -0.569) or High 2 (H2; -0.570 to -1.000). Differences in 3-year RFI, defined as time from diagnosis to a local-regional recurrence, distant recurrence, or breast cancer specific death per STEEP 2.0 criteria, between H1 and H2 tumors were evaluated by Kaplan-Meier analysis and log-rank test, stratified by CT regimen. Results: Patients had similar age, menopausal status, race, and lymph node status between H2 vs H1 tumors. H2 tumors were more likely Grade 3, compared to H1 tumors. 86% of tumors were classified as H1 Luminal B-Type (N = 530) and 14% were classified as H2 Luminal B-Type (N = 84). AC-T treated tumors had non-significant differences in 3-yr RFI between H1 Luminal B-Type (95.3% [95% CI, 91.8-98.8]; N = 184) and H2 Luminal B-Type (97.7% [95% CI, 93.4-100.0]; N = 44). In contrast, pts with H2 Luminal B-Type (N = 40) tumors treated with TC demonstrated a significantly worse RFI of 86.4% (95% CI, 74.2-100.0) compared with 97.1% (95% CI, 95.1-99.2) in pts with H1 Luminal B-Type (N = 346) tumors, with an absolute difference of 10.7% (p = 0.0076). Conclusions: These data show that among pts with Luminal B-Type tumors, MP H2 have significantly worse 3-yr RFI than pts with MP H1 tumors when treated with TC. This further supports ongoing research demonstrating the significant benefits of anthracycline-based CT for treating H2 Luminal B-Type tumors. Conversely, MP H1 tumors do not appear to benefit from the addition of anthracycline to CT regimen. These FLEX data add to the growing evidence identifying MammaPrint as a comprehensive genomic signature regarding both prognosis as well as selection of systemic therapy for HR+HER2- EBC pts. Clinical trial information: NCT03053193 .

Abstract ED11-03: Approaches to radiation therapy for inflammatory breast cancer

Abstract Inflammatory breasst cancer ((BC) is an uncommon and highly agressive form of breast cancer, with a predilection for both distant metastases and local regional recurrence. In this talk we will review challenges in radiation therapy planning and execution unique to IBC. These include staging studies and photographs to define the full extent of disease prior to systemic therapy, as well as current thoughts on dose and fractionation. We will also discuss pros and cons of local therapy in patients with metastatic disease, as well as ongoing research studying ways to optimize local regional control with concurrent systemic therapy and radiation. Citation Format: J. Bellon. Approaches to radiation therapy for inflammatory breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED11-03.

Abstract PS01-06: The relationship between margin status of &amp;lt;2mm and local recurrence in DCIS patients

Abstract Background: There has been controversial evidence regarding adequate margin in breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS). However, the consensus is a surgical margin distance of 2 mm. Moreover, recent recommendations advised on ‘’clinical judgement’’ approach to re-excision in cases of margin distance &amp;lt; 2mm. The ongoing controversy in DCIS margin compared to invasive cancer margin is due to the differences in post operative management. This is important as margin status is one of the modifiable risk factor for local regional recurrence in DCIS. In our study we evaluated margin distance in patient diagnosed with DCIS who underwent BCS on local recurrence Methods: Patients who underwent breast conserving surgery between February 2000 and December 2018 at Asan Medical Center were retrospectively reviewed. Patients with involved resection margins were excluded. Kaplan-Meier survival analysis and Cox proportional hazard models were applied to determine the relationship between negative margin width and local recurrence. Results: A total of 1,858 patients were included in the study. Almost half of the patients had a tumor size of 1cm or smaller (n=876, 47.1%). Only 98 (5.3%) patients did not undergo radiation therapy. A negative margin width of &amp;lt; 1mm, &amp;lt; 2mm, &amp;lt; 5mm were all not associated with local recurrence (log-rank test p-value 0.1, 0.1, 0.078, respectively). For patients who underwent radiation therapy, a negative margin of any width was not related to local recurrence. Whereas, for patients who did not undergo radiation therapy, those with margins ≤2mm were significantly more likely to develop local recurrence than those with margins &amp;lt; 2mm (10-yr local recurrence rate, 16.4% vs 5.5%, respectively; hazard ratio, 5.709; 95% CI, 1.106-29.46, p=0.038). Conclusion: A negative margin is not related to local recurrence in DCIS patients who undergo breast conserving surgery with radiation therapy. Routine additional surgery for wider negative margin may only be needed for patients who do not undergo radiation therapy. Citation Format: Sarah Al Safi, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Hee Jin Lee, Gyungyub Gong. The relationship between margin status of &amp;lt;2mm and local recurrence in DCIS patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-06.

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.

O78: Risk of recurrence after surgical resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia (IPMN) with patterns of distribution and treatment

Abstract Introduction Recurrence patterns and treatment of recurrence post resection of invasive IPMN are poorly explored. This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for invasive IPMN. Method Patients undergoing pancreatic resection for invasive IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). Results Four hundred and fifty-nine patients were included (median, 70years; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 months). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1year], 20.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;p=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (p&amp;lt;0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (p=0.401). Conclusion Recurrence after pancreatic resection for invasive IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Effects of VDR and CYP24A1 gene polymorphisms on the outcome of supraglottic larynx cancer.

Vitamin D has been demonstrated to play a protective role in carcinogenesis. Polymorphisms of the vitamin D receptor (VDR) genes and 24-α-hydroxylase (encoded by CYP24A1) may affect the outcome of some cancers. This study examines the effects of the VDR gene and CYP24A1 single nucleotide polymorphisms on the outcome of supraglottic larynx cancer. Patients diagnosed with supraglottic larynx cancer between 2017 and 2022 were enrolled. Single nucleotide polymorphisms of the VDR gene (rs2228570, rs731236, rs7975232, rs11574113, rs11168267 and rs11168266) and CYP24A1 gene (rs4809960, rs6022999, rs6068816, rs2259735 and rs2296241) were investigated. All patients were followed up for any evidence of local recurrence, regional recurrence, distant metastasis, and second primary tumor development. Cox regression analysis was performed to evaluate the prognostic value of single-nucleotide polymorphisms (SNPs). Kaplan-Meier method was used for survival analysis. 87 patients were included. The mean follow-up time was 45.02±24.47 months. Cox regression analysis for locoregional recurrence revealed that the hazard ratio of rs731236 GG was 2.098 (95% CI, range: 1.047-4.202, p=0.037). Locoregional recurrence for rs731236 AA, AG, and GG were 38.6%, 23.1%, and 53.3%, respectively. In the presence of rs731236 GG polymorphism, disease-specific survival was significantly shorter (47.63±7.48 months, p=0.015), and disease-free survival (45.71±6.3 months) was significantly shorter (p=0.040). Rates of metastases and second primary tumors were not significantly different between SNPs. This study has demonstrated the possible effects of VDR rs731236 SNP on the locoregional recurrence and prognosis of supraglottic larynx cancer.

Early Postoperative Complications after Pelvic Exenteration

Background. Radiation therapy is an integral part of the treatment of most malignant neoplasms of the pelvic organs, which in 25–30% of cases can cause the development of late radiation complications; in addition, 2–8% of patients have severe complications with an outcome in fistulas of various localization. Also, tumors of this localization are prone to local-regional recurrence, which can be combined with late radiation injuries. One of the most radical, and, often, the only method of treating this extremely severe and prognostically unfavorable pathology is to perform evisceration of the pelvic organs; however, its implementation against the background of radiation damage to normal tissues, leading to a significant decrease in the reparative potential, inevitably leads to a high risk of postoperative complications.&#x0D; Methods. A retrospective analysis of early postoperative complications on the Clavien–Dindo scale was carried out in 136 patients after pelvic evisceration performed at the A.F. Tsyba MRSC in 2019–2021. All patients in the perioperative period underwent complex conservative therapy, including nutritional support.&#x0D; Results. Pelvic evisceration was performed due to the progression of the underlying disease in 57% of cases, in 29% — due to the development of severe late radiation injuries with an outcome in the fistula, in 14% — due to a combination of local recurrence of the underlying disease with radiation complications). Complications of grade I on the Clavien–Dindo scale were noted in 50%; II — in 20.5%; III — in 3.6%; grade IV — in 3%. There were no cases of postoperative mortality.&#x0D; Conclusions. Conducting active preoperative preparation of patients aimed at correcting anemia, dysproteinemia, pain syndrome, etc.; as well as modifying surgical techniques and improving the management tactics of postoperative patients can minimize the risk of postoperative complications in patients after pelvic evisceration.

Comparisons of the oncological results of transoral laser surgery and radiotherapy for early stage laryngeal squamous cell cancer: single-center long-term results.

In the treatment of early stage laryngeal cancers, surgery (transoral laryngeal surgery (TOLS), open partial laryngeal surgery (OPLS) and radiotherapy (RT) are used. Compare the oncological results of patients with early stage laryngeal squamous cell carcinoma (LSCC) treated with TOLS or RT. Retrospective. Tertiary training and research hospital. The participants were divided into patients who underwent TOLS and RT treatment. The groups were compared with each other in terms of local recurrence, regional recurrence, distant metastasis, 3 and 5-year overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS) and laryngectomy-free survival rates (LFS). The effects of TOLS and RT treatment on local control, regional control, OS, DFS, DDS and LFS in early stage laryngeal cancers. 261. The mean follow-up time was 48 (26) months. There were 186 patients who underwent TOLS and 75 patients who underwent RT treatment. Gender, cigarette/alcohol consumption, tumor localization, anterior commissure involvement, tumor grades, recurrence rates and recurrence localizations of the groups were similar. The 5-year overall, disease specific, disease free and laryngectomy-free survival rates were 85.9%, 88%, 79.4%, 96.3% in the TOLS group and 74.3%, 76.7%, 72.3%, 85.2% in the RT group (P=.034, .065, .269, .060, respectively). TOLS had equal and good oncological outcomes on OS and DFS compared to RT. Anterior commissure involvement was statistically significant independent prognostic risk factor for DFS in both groups. The 5-year OS rate was greater in the TOLS groups (P=.034). Retrospective, but to the best our knowledge, this is the first study in Turkey with a high patient volume and a long follow-up time.

Clinical Outcomes Among Patients Treated With Stereotactic Body Radiation Therapy to Femur Metastases for Oligometastatic Disease Control or Reirradiation: Results From a Large Single-Institution Experience

There are limited data regarding outcomes after stereotactic body radiation therapy (SBRT) for femur metastases, which was an exclusion criteria for the Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) trial. We aimed to characterize clinical outcomes from a large single institution experience. Forty-eight patients with 53 lesions were consecutively treated with femur SBRT from May 2017 to June 2022. The Kaplan-Meier method and Cox proportional hazard models were used to characterize time-to-event endpoints and associations between baseline factors and clinical outcomes, respectively. Local control and locoregional control were defined as the absence of tumor progression within the radiation treatment field or within the treated femur, respectively. Most patients had Eastern Cooperative Oncology Group performance status 0 to 1 (90%), prostate (52%) or breast/lung (17%) cancer, and 1 to 3 lesions (100%), including 29 proximal and 5 distal. Fifty-seven percent of the lesions were treated with concurrent systemic therapy. Median planning target volume was 49.1 cc (range, 6.6-387 cc). Planning target volume V100 (%) was 99% (range, 90-100). Fractionation included 18 to 20 Gy/1F, 27 to 30 Gy/3F, and 28.5-40 Gy/5F. Forty-two percent had Mirels score ≥7 and most (94%) did not have extraosseous extension. Acute toxicities included grade 1 fatigue (15%), pain flare (7.5%), nausea (3.8%), and decreased blood counts (1.9%). Late toxicities included fracture (1.9%) at 1.5 years and osteonecrosis (4%) from dose of 40 Gy in 5F and 30 Gy in 5F (after prior 30 Gy/10F). One patient (2%) required fixation postradiation for progressive pain. With median follow-up 19.4 months, 1- and 2-year rates of local control were 94% and 89%, locoregional control was 83% and 67%, progression-free survival were 56% and 25%, and overall survival were 91% and 73%. Fifty percent of local regional recurrence events occurred within 5 cm of gross tumor volume. Femur SBRT for oligometastatic disease control in well-selected patients was associated with good outcomes with minimal rates of acute and late toxicity. Patterns of local regional recurrence warrant consideration of larger elective volume coverage. Additional prospective study is needed.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial

BackgroundSupraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients.MethodsThe SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants.DiscussionThe results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer.Trial registrationClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www.clinicaltrials.gov/ct2/show/NCT05059379.