Locoregional Failure Rate Research Articles

A retrospective study on the comparision of pathological tumour necrosis of conventional versus ultrahypofractionated preoperative radiotherapy in localised extremity soft tissue sarcoma and its correlation with clinical outcomes: A retrospective study on the comparision of pathological tumour necrosis of CONV-RT versus UHYPO-RT preoperative radiotherapy in localised extremity soft tissue sarcoma and its correlation with clinical outcomes

Background and PurposeWe aimed to determine if ultra-hypofractionated radiotherapy (UHYPO-RT) delivering 6Gy x 5 fractions yields similar tumour necrosis compared to conventional radiotherapy (CONV-RT) with 2Gy x 25 fractions in soft tissue sarcoma (STS). The clinical significance of tumor necrosis on loco-regional recurrence-free survival (LRFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed. Materials and methodsPatients with localised STS treated with CONV-RT or UHYPO-RT followed by surgery were included. Good response was defined as tumour necrosis ≥ 90%, and poor response as < 90%. Mann-Whitney U-test compared median tumour necrosis. Chi-squared analysis was used for categorical variables. Kaplan-Meier function estimated LRFS, DDFS, and OS. ResultsA total of 64 patients received CONV-RT, and 45 received UHYPO-RT. The median tumour size was 7.0 cm, with the lower extremity being the most common site (55%). Myxofibrosarcoma (39%) and undifferentiated pleomorphic sarcoma (16%) were the most frequent histologies. The median time from radiotherapy to surgery was 35 days. There was a significant difference in median tumour necrosis between CONV-RT and UHYPO-RT, with rates of 40% and 60%, respectively (p = 0.022). Patients receiving UHYPO-RT had a higher percentage of tumour necrosis at the 90% cutoff, achieving 27% compared to 6% for CONV-RT (p = 0.003). In a median follow-up of 32 months, 12 patients (9%) experienced loco-regional recurrence, 24 patients (19%) faced distant failure, and 19 patients (15%) died from metastatic disease. Patients with < 90% necrosis had higher rates of loco-regional (13% vs. 0%, p = 0.207) and distant failure (25% vs. 0%, p = 0.021). Three-year LRFS was 86% for < 90% necrosis and 100% for ≥ 90% necrosis (p = 0.160). DDFS was 75% for < 90% necrosis versus 100% for ≥ 90% (p = 0.036). OS rates were 79% and 93%, respectively (p = 0.290). ConclusionPreoperative RT with UHYPO-RT was associated with a higher rate of tumour necrosis ≥ 90% than CONV-RT. Our data suggest that more extensive necrosis is associated with better clinical outcomes.

Non-irradiated area of intraoperative radiotherapy with electron technique: outcomes and pattern of failure in early-stage breast cancer from a single-center, registry study

IntroductionIntraoperative radiotherapy (IORT) with electrons has revealed to have higher rates of ipsilateral breast tumor recurrence (IBTR) than external beam radiotherapy in updated large-scale, randomized controlled trials in 2021. This study details the oncological outcomes of IORT with electron beams using our strict IORT policies. We have found new and important observations regarding the location of recurrence.Methods and materialsThis is a single institution registry of early-stage breast cancer patients who underwent lumpectomy and electron beam IORT with appropriate cone size. All patients met our pre-excision requirements. The primary endpoint was 5-year IBTR rate, with secondary endpoints being 5-year locoregional failure rate, 5-year distant metastasis rate, 5-year overall survival and, importantly, the failure patterns.ResultsBetween January 2011 and December 2022, 124 patients were recruited. The median follow-up was 6.7 years. The 5-year IBTR rate was 1.87% (95% CI 0.47–7.29%), which is much lower than the ELIOT trial and comparable with other accelerated partial breast irradiation (APBI) techniques. The 5-year locoregional failure rate was 3.68% (95% CI 1.40–9.52%), and the 5-year distant metastasis rate was 0.88% (95% CI 0.13–6.12%), while the 5-year overall survival rate was 97.52% (95% CI 92.44–99.19%). Six patients experienced IBTR. All recurrences were in surgical area, occurring superficial to the tumor bed and within 1 cm of the skin dermis. This failure pattern is very unique and might be explained by our hypothesis of the non-irradiated area beneath the skin.ConclusionsIORT with electron beams with strict patient selection criteria and strict large cone size is still an acceptable treatment for select patients with early-stage breast cancer. However, our new findings support extreme caution in the non-irradiated area beneath the skin around the tumor cavity. Given the constraints of our sample size, these findings should be interpreted cautiously and warrant further investigation in larger, more comprehensive studies.

Randomized clinical trial on accelerated preoperative hyperfractionated radiotherapy versus preoperative hyperfractionated radio-chemotherapy in locally advanced rectal cancer.

The aim of this study was to compare pathological response rates after preoperative hyperfractionated radiotherapy with co-administration of chemotherapy based on 5FU (HART-CT) versus preoperative hyperfractionated radiotherapy (HART) in patients with resectable rectal cancer. Patients with T2/N+ or T3/any N rectal cancer were randomized either to HART twice a day (28 fractions of 1.5 Gy) to total dose 42 Gy or to HART-CT. Tumour regression grade was postoperatively assessed according to the 4-point scale as recommended by the American Joint Committee on Cancer (AJCC). The secondary endpoints included overall survival (OS), disease-free survival (DFS), toxicity of preoperative treatment, locoregional, and distant failure rates. There were 187 patients eligible for analysis: 95 in HART and 92 in the HART-CT. Median follow-up was 5.6 years. The analysis demonstrated a significantly higher chance of achieving pathologic complete response in HART-CT arm: complete response was achieved in 4/95, 4% (HART) and 11/92, 12% (HART-CT) (P = .045). The differences in OS and DFS, while tending to favour HART-CT, were not significant: OS (P = .13, hazard ratio [HR] = 0.82, 95% CI, 0.63-1.06) and DFS (P = .32; HR = 0.88, 95% CI, 0.69-1.13). The locoregional failure and distant metastases rates did not statistically differ between the trial arms. The rate of late complications was similar (P = .51), grade 3+ being 8% versus 11% in the HART/HART-CT group, respectively. The hyperfractionated preoperative radiotherapy with concurrent 5-Fu-based chemotherapy (HART-CT) improved pathological response rate compared to HART. This translated into favourable OS and DFS in HART-CT, but the differences did not reach the threshold for significance. A new hyperfractionated chemo-RT scheme is proposed. Histopathological major response (TRG 0-1) is associated with better clinical outcome.

Weekly Image Guidance in Patients With Cervical Cancer Treated With Intensity-Modulated Radiation Therapy: Results of a Large Cohort Study.

Image guidance is recommended for patients undergoing intensity-modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long-term outcomes in a large cohort of patients. The study enrolled patients with Stage IB-IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed. The median follow-up periods were 63.4 months. The incidence rates of loco-regional and distant failure were 9.9% and 13.6%. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5-year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5-year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para-aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty-six (4.0%) patients experienced late Grade 3/4 chronic toxicities. IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources.

Pre-treatment magnetic resonance imaging in anal cancer: large-scale evaluation of mrT, mrN and novel staging parameters

BackgroundIn patients with squamous cell carcinoma of the anus (SCCA), magnetic resonance (MR) imaging is recommended for pre-treatment staging prior to chemo-radiotherapy (CRT), but large-scale evaluation of its staging performance is lacking.MethodsWe re-characterised pre-treatment MRs from 228 patients with non-metastatic SCCA treated consecutively by CRT (2006–2015) at one UK cancer centre. We derived TN staging from tumour size (mrTr) and nodal involvement (mrN), and additionally characterised novel beyond TN features such as extramural vascular invasion (mrEMVI) and tumour signal heterogeneity (mrTSH). Primary outcomes were 5-year overall survival (OS) and 3-year loco-regional failure (LRF). Time-to-event analyses used Kaplan-Meier estimates; Hazard Ratios (HRs) with confidence intervals (CIs) were derived from Cox models.ResultsWith a median follow up of 60.9 months, 5-year OS was 74%. Poor OS was associated with increasing mrT (HR: 1.12 per cm [95% CI: 1.07–1.33]), nodal positivity (HR 2.08 [95% CI 1.23–3.52]) and mrEMVI (HR 3.66 [95% CI: 1.88–7.41]). 3-year LRF rate was 16.5%. Increased LRF was associated with increasing mrT (HR: 1.43 per cm [95% CI: 1.26–1.63]), nodal positivity (HR 2.70 [95% CI 1.39–5.24]) and mrTSH (HR 2.66 [95% CI 1.29–5.48]).ConclusionsIn SCCA, the study demonstrates that mrT and mrN stages are prognostic, while mrEMVI and mrTSH may be novel prognostic factors.

Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review.

To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC). We searched Medline®, Embase®, and CENTRAL®, between January 1, 2000- March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias (RoB) and overall strength of evidence (SOE) were evaluated for a prespecified outcome list using standardized methods. We identified 33 eligible studies and extracted data. Six were deemed low/moderate RoB. Compared with radiotherapy (RT) alone, chemoradiotherapy (CRT) with 5-fluorouracil (FU) and mitomycin C (MMC) probably shows a benefit in locoregional failure (LRF), disease-specific (DSS), and colostomy-free survival (CFS) (moderate SOE) yet may result in greater overall and acute hematologic toxicity, with no difference in late harms (low SOE). CRT with 5FU+MMC may show a benefit in LRF, DSS, and CFS rates compared with 5FU alone (low SOE). CRT with 5FU+cisplatin vs 5FU+MMC probably results in no differences in several effectiveness outcomes or overall acute or late harms, and probably increases hematologic toxicity with MMC (moderate SOE). Compared with CRT using capecitabine+MMC, CRT with capecitabine+MMC+paclitaxel may improve OS, DSS, and CFS, yet cause more acute harms (low SOE). Evidence was insufficient for remaining comparisons. CRT with 5FU+MMC or 5FU+cisplatin is likely more effective yet incurs greater acute hematologic toxicity than RT alone or single-agent CRT. Adding paclitaxel to capecitabine+MMC may increase treatment efficacy and toxicity. Evidence is insufficient comparing post-treatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Diffusion-weighted magnetic resonance imaging as an early prognostic marker of chemoradiotherapy response in squamous cell carcinoma of the anus: An individual patient data meta-analysis

Background and purposeSquamous cell carcinoma of the anus (SCCA) can recur after chemoradiotherapy (CRT). Early prediction of treatment response is crucial for individualising treatment. Existing data on radiological biomarkers is limited and contradictory. We performed an individual patient data meta-analysis (IPM) of four prospective trials investigating whether diffusion-weighted (DW) magnetic resonance imaging (MRI) in weeks two to three of CRT predicts treatment failure in SCCA. Material and methodsIndividual patient data from four trials, including paired DW-MRI at baseline and during CRT, were combined into one dataset. The association between ADC volume histogram parameters and treatment failure (locoregional and any failure) was assessed using logistic regression. Pre-defined analysis included categorising patients into a change in the mean ADC of the delineated tumour volume above and below 20%. ResultsThe study found that among all included 142 patients, 11.3 % (n = 16) had a locoregional treatment failure. An ADC mean change of <20 % and >20 % resulted in a locoregional failure rate of 16.7 % and 8.0 %, respectively. However, no other ADC-based histogram parameter was associated with locoregional or any treatment failure. ConclusionsDW-MRI standard parameters, as an isolated biomarker, were not found to be associated with increased odds of treatment failure in SCCA in this IPM. Radiological biomarker investigations involve multiple steps and can result in heterogeneous data. In future, it is crucial to include radiological biomarkers in large prospective trials to minimize heterogeneity and maximize learning.

Sequential neoadjuvant chemotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma.

TPS4209 Background: Patients with borderline resectable (BRPC) and locally advanced unresectable (LAPC) pancreatic cancer have a median OS of 8-20 months unless they undergo margin negative resection. Despite advances in systemic therapy, the prognosis is dismal. The locoregional and distant failure rates are high in post-surgery and therefore neoadjuvant chemotherapy emerged as standard-of-care practice to select the patients for surgery and improve overall clinical outcomes. An effective and tolerable neoadjuvant regimen can facilitate R0 resection by tumor down staging and mitigating the risk for positive margins. A recent SEQUENCE-2 study on sequential treatment with combination of Gemcitabine and nab-paclitaxel (GA) GA followed by modified FOLFOX (mFOLFOX) improved OS (13.2 months) and PFS (9.5 months) in patients with metastatic PDC, compared with the standard GA regimen, with comparable safety profile. Current guidelines suggest modified FOLFIRINOX (mFFX, infusional 5-fluorouracil, oxaliplatin, irinotecan) or GA as the first-line systemic chemotherapeutic regimen in neoadjuvant, adjuvant and palliative setting. These regimens are associated with modest pathological complete response rate. However, there is significant unmet need for management of BRPC and LAPC as the optimal treatment strategy remains undefined. As both of the aforementioned regimens are active and feasible in BRPC and LAPC, we conceptualize that by using both regimens alternating in sequence the rate of R0 resection and pathological response could be improved by overcoming possible resistance to a single backbone. Methods: The aim of this study is to demonstrate the efficacy and feasibility of sequential chemotherapy (GA followed by mFFX) in patients with BRPC (n=34) and LAPC (n=30). To achieve this, we are conducting a non-randomized prospective interventional clinical study with BRPC and LAPC patients treated with alternating cycles of GA and mFFX for 4 months and assessed for clinical outcomes, feasibility and toxicity. The primary objective of this study is to evaluate the efficacy of sequential GA followed by mFFX in improving R0 resection rate in patients with BRPC and LAPC. After four months of sequential neoadjuvant therapy, the patients will proceed to surgery, radiation, or extended course of chemotherapy, off study, as determined by multidisciplinary tumor board consensus or the treating physician. These results will have high translational potential for providing mechanistic insight into tumor response, optimizing current management strategies for pancreatic cancer that could be generalizable to other stages of this cancer. The key eligibility criteria include treatment naive histologically diagnosed BRPC or LAPC with measurable disease, ECOG 0,1, optimal organ function. Clinical trial information: NCT05776524 .

Standard versus fractionated high-dose cisplatin plus radiation for locally advanced head and neck cancer: Results of the CisFRad (GORTEC 2015-02) randomized phase II trial

BackgroundChemoradiotherapy with high-dose cisplatin (HD-Cis: 100 mg/m2 q3w for three cycles) is the standard of care (SOC) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Cumulative delivered dose of cisplatin is prognostic of survival, even beyond 200 mg/m2 but high toxicity compromises its delivery. AimCisplatin fractionation may allow, by decreasing the peak serum concentration, to decrease toxicity. To date, no direct comparison was done of HD-Cis versus fractionated high dose cisplatin (FHD-Cis). MethodsThis is a multi-institutional randomized phase II trial, stratified on postoperative or definitive chemoradiotherapy, comparing HD-Cis to FHD-Cis (25 mg/m2/d d1-4 q3w for 3 cycles) in patients with LA-HNSCC. The primary endpoint was the cumulative delivered cisplatin dose. ResultsBetween December 2015 and April 2018, 124 patients were randomized. Median cisplatin cumulative delivered dose was 291 mg/m2 (IQR: 251;298) in the FHD-Cis arm and 274 mg/m2 (IQR: 198;295) in the HD-Cis arm (P = 0.054). The proportion of patients receiving a third cycle of cisplatin was higher, with a lower proportion of grade 3–4 acute AEs in the FHD-Cis arm compared to the HD-Cis arm: 81 % vs. 64 % (P = 0.04) and 10 % vs. 17 % (P = 0.002), respectively.With a median follow-up of 48 months (IQR: 41;55), locoregional failure rate, PFS and OS were similar between the two arms. ConclusionAlthough the primary endpoint was not met, FHD-Cis allowed more cycles of cisplatin to be delivered with lower toxicity, when compared to SOC. FHD-Cis concurrently with RT is a treatment option which deserves further consideration.

Abstract 961: Detection of minimal residual disease in lymph predicts recurrence in HPV-negative head and neck cancer patients

Abstract Background: Locoregional cancer relapse remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC), particularly for HPV-negative patients whose 2-year locoregional failure rate is up to 50%. There is unmet need for an accurate diagnostic test that predicts risk of recurrence prior to adjuvant therapy selection. We present a novel proximal assay for minimal residual disease (MRD) profiled in lymphatic exudate collected via surgical drains (“lymph”). Methods: Lymph, plasma, and blood were collected from 46 HPV-negative HNSCC patients postoperatively at 24 hours along with resected tumor. Cell-free DNA was extracted from lymph and plasma and sequenced using the TruSeq Oncology 500 panel to a depth of &amp;gt;100 million reads. Somatic mutations were identified by exome sequencing (200x) tumor and blood. Five patients had &amp;lt;2 mutations in tumor and were excluded. Two patients were censored due to lack of clinical data, yielding 18 patients with disease recurrence (REC) and 21 with no evidence of disease (NED) with &amp;gt;1 year of follow-up. Tumor-specific variants were force-called in lymph and plasma using a custom pipeline. Patients were considered MRD positive if the mean variant allele fraction (mVAF) was greater than 0.015% (the estimated limit of detection). The Kaplan-Meier (KM) estimator with log-rank test and Cox proportional-hazards model were used for survival analyses. Logistic regression model was performed with 5-fold cross-validation. Results: KM survival analyses showed lymph accurately predicts recurrence (sensitivity (SN) = 78%, specificity (SP) = 67%; p = 0.003, Hazard ratio (HR) = 4.7), while plasma was not significant (p = 0.92) at this postoperative timepoint. Performance was enhanced for locoregional relapse (SN = 92%, SP = 67%; p = 0.001, HR = 13.9. N=33). We also observed accurate recurrence prediction (SN = 83%, SP = 69%, p = 0.03, HR = 7.7) in the 19 N0 patients (node-negative by pathology). Lymph MRD outperformed individual pathology features (extranodal extension, perineural invasion, lymphovascular invasion, and nodal disease status) for recurrence prediction (HR = 3.4, 0.88, 2.5, 2.4, respectively). A logistic regression model combining lymph MRD with these 4 high-risk pathologic features showed superior performance over lymph alone or pathology alone (SN = 89%, SP = 67%; p = 0.0007, HR = 8.6). Conclusions: ctDNA analysis of lymph from surgical drains represents a novel proximal MRD approach in HPV-negative HNSCC. Postoperative lymph significantly outperforms plasma for prediction of recurrence, particularly in patients with locoregional relapse. Accurate MRD identification in patients with lower risk pathologic features suggests that lymph MRD testing has potential to augment traditional pathology and provide more personalized adjuvant treatment decision-making in patients with HPV-negative HNSCC. Citation Format: Wendy Winckler, Zhuosheng Gu, Damion Whitfield, Noah Earland, Adam Harmon, Megan Long, Peter Harris, Zhongping Xu, Ricardo Ramirez, Sophie Gerndt, Maciej Pacula, Marra S. Francis, Jose P. Zevallos, Aadel A. Chaudhuri. Detection of minimal residual disease in lymph predicts recurrence in HPV-negative head and neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 961.

Local control and toxicity outcomes following consolidative radiation therapy in patients with high-risk neuroblastoma: a 20-year experience at a single center.

Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.

Pathologic Exploration of the Axillary Soft Tissue Microenvironment and Its Impact on Axillary Management and Breast Cancer Outcomes.

Axillary soft tissue (AXT) involvement with tumor cells extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) has been overlooked in breast pathology specimen analysis. We analyzed 2,162 LN+ patients, dividing them into four groups on the basis of axillary pathology: (1) LN+ only, (2) LN+ and ECE only, (3) LN+ and AXT without ECE, and (4) LN+ with both AXT and ECE. The primary end points were 10-year locoregional failure (LRF), the 10-year axillary failure, and 10-year distant metastasis rates. Multivariable Cox models, accounting for clinical factors, were fitted using the entire cohort, and subgroups analyses were conducted. The median follow-up was 9.4 years. The 10-year distant metastasis incidence was 42% for LN + AXT + ECE, 23% for both LN + AXT and LN + ECE only, and 13% for LN+ only. The 10-year axillary failure rates were 4.5% for LN + AXT + ECE, 4.6% for LN + AXT, 0.8% for LN + ECE only, and 1.6% for LN+ only. The 10-year LRF rates were 14% for LN + AXT + ECE, 10% for LN + AXT, 5.7% for LN + ECE only, and 6.2% for LN+ only. Multivariable analysis revealed that AXT was significantly associated with distant metastasis (hazard ratio [HR], 1.6; P < .001), locoregional failure (HR, 2.3; P < .001), and axillary failure (HR, 3.3; P = .003). Subgroup analyses showed that regional LN radiation (RLNR) improved locoregional tumor outcomes with AXT, ECE, or both (HR, 0.5; P = .03). Delivering ≤50 Gy to the axilla in the presence of AXT/ECE increased axillary failure (HR, 3.0; P = .04). Moreover, when delivering RLNR, axillary LN dissection could be de-escalated to sentinel node biopsy even in the presence of features such as AXT or ECE without significantly increasing any failure outcome: (HR, 1.0; P = .92) for LRF, (HR, 1.1; P = .94) axillary failure, and (HR, 0.4; P = .01) distant metastasis. Routine reporting of axillary tissue involvement, beyond LNs and ECE, is crucial in predicting breast cancer outcomes. Ruling out the presence of AXT is imperative before any form of axillary de-escalation, especially RLNR omission.

Different benefits of adaptive radiotherapy for different histologies of NSCLC

Background Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the most frequent histological subtypes of non-small cell lung cancer (NSCLC). The aim of this study was to investigate how patients with AC and SCC benefit from image-guided adaptive radiotherapy (ART) with tumour match. Material and methods Consecutive patients diagnosed with AC or SCC of the lung treated with definitive chemo-radiotherapy before and after the implementation of ART and tumour match were retrospectively included for analyses. Data collection included baseline patient and treatment characteristics in addition to clinical data on radiation pneumonitis (RP), failure, and survival. Patients were divided into four categories based on their histology and treatment before (n = 173 [89 AC and 84 SCC]) and after implementation of ART (n = 240 [141 AC and 99 SCC]). Results Median follow-up was 5.7 years for AC and 6.3 years for SCC. Mean lung dose decreased for both histologies with ART, whereas mean heart dose only decreased for patients with AC. Incidences of grade 3 and 5 RP decreased for both histologies with ART. Loco-regional failure (LRF) rates decreased significantly for patients with SCC after ART (p = .04), no significant difference was observed for AC. Overall survival (OS) increased significantly for SCC after ART (p < .01): the 2-year OS increased from 31.0% (95% confidence interval [CI] [22.5–42.6]) to 54.5% (95% CI [45.6–65.3]). No significant effect on OS was observed for patients with AC. Conclusion ART and tumour match in the radiotherapeutic treatment of patients with locally advanced NSCLC primarily led to decreased LRF and improved OS for patients with SCC.

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

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

Patterns of Locoregional Failure After Ablative 5-Fraction Stereotactic MR-Guided on-Table Adaptive Radiation Therapy for Pancreatic Cancer

SBRT for pancreatic ductal adenocarcinoma (PDAC) is routinely delivered with non-ablative dose to only gross disease resulting in locoregional failure (LRF) rates of >50%, most commonly near the celiac artery (CA) and/or superior mesenteric artery (SMA). It is unclear whether an alternative approach of prescribing ablative dose to gross disease plus elective coverage prevents and/or delays LRF. The study objective was to describe the incidence and anatomic distribution of LRF using this treatment approach. A single institution retrospective analysis was performed of non-metastatic PDAC patients who received ablative stereotactic MR-guided on-table adaptive radiation therapy (A-SMART) on a 0.35T MR-Linac from 2018-2022. Median prescribed dose was 50 Gy/5 fractions. Elective coverage (EC), including a margin around the primary tumor, CA, and SMA, to 33-35 Gy/5 fractions became routine in 2019 using a simultaneous integrated boost; the porta hepatis was not routinely covered. LRFs were contoured and defined as out-of-field (OOF), marginal (M), or in-field (IF) if >80%, 20-80%, or <20% of it was outside of the most peripheral prescription isodose line. One hundred four patients were evaluated (87% head tumors). 94% had induction chemotherapy (median 4 months), usually FOLFIRINOX (66%) or gemcitabine/nab-paclitaxel (27%). 88% received EC. Median GTV, CTV, PTVgrosstumor, and PTVelective volumes were 29 cc, 90 cc, 64 cc, and 127 cc, respectively. 16 patients (15%) had LRF after a median of 17 months (range: 2.4-30.8) from A-SMART; 13 had scans available for delineating LRF. Median follow-up from A-SMART for the entire cohort vs. LRF was 12 vs. 24 months. LRF involved the primary tumor (31%), retroperitoneal lymph nodes (25%), SMA (19%), porta hepatis (19%), and CA (6%). LRF was OOF, M, or IF in 30.8% (n = 4), 61.5% (n = 8), and 7.7% (n = 1). Distance from the 3 SMA failures to SMA origin was 10 cm (EC used), 9.3 cm (EC used), and 3 cm (no EC). The 1 CA failure involved the CA origin (no EC). Median mean, maximum, and minimum dose of the contoured LRF region on the original plan was 33.3 Gy (range: 9.7-50.3 Gy), 56 Gy (range: 44.2-71.4 Gy), and 11.4 Gy (range: 1.2-22.7 Gy), respectively. Median V20, V25, V30, V35, and V40 of the contoured LRF was 84.3% (range: 16.1-100%), 69.2% (range: 12.5-99.7%), 57.5% (range: 9.3-95.5%), 41.2% (range: 6.8-84.0%), and 32.7% (range: 4.8-71.8%). This study represents the first patterns of LRF analysis after ablative 5-fraction SBRT for PDAC. Although EC is not currently endorsed by published pancreas SBRT guidelines, our low LRF incidence especially involving the CA/SMA demonstrates that EC should be considered, even when delivering ablative dose. Furthermore, given that nearly all LRF were M or OOF we have considered expanding our institutional elective volumes. While the optimal EC dose is uncertain, 33-35 Gy appears effective in limiting IF LRF and therefore has been standardized within ongoing ablative SBRT trials for PDAC at our institution.

Evaluation of Metastatic Potential in Esophageal and Gastroesophageal Junction (GEJ) Cancer with Adherence to Elective Nodal Volume Guidelines: A Retrospective Analysis of Elective Nodal Irradiation

In 2015, expert guidelines on esophageal/GEJ cancer contouring for intensity-modulated radiation therapy (IMRT) were published in IJROBP, which delineate recommended elective nodal basins (celiac, para-aortic, gastrohepatic ligament, supraclavicular) to be irradiated depending on the primary tumor location. We hypothesize that incomplete coverage of these areas increases the risk of the development of distant failures. Patients treated for non-metastatic esophageal or GEJ cancer with chemoradiotherapy pre-operatively or definitively from 2012 to 2021 were retrospectively identified from a single institution database. Radiation plans of eligible patients were then analyzed by tumor location. Plans were deemed guideline-compliant if radiation dose coverage, between 41.4 to 45 Gy, encompassed nodal basins recommended by the 2015 guidelines. The primary endpoint of this study was the overall rate of distant disease. Other endpoints included locoregional failures, defined as failures within the radiation field but outside of the primary tumor, and local failures within the gross tumor volume. Summary and descriptive statistics were used to define collected variables. Differences were measured using chi-square and Fisher's exact test for categorical variables and two-sided t-tests for continuous measures. Assessment of distant, locoregional, and local failures were assessed using univariate logistic regression with statistical significance at p < 0.05. With a median follow-up of 25.0 months, 37 patients, with a median age of 66, were included in the study. Most patients were male (94.6%) with cT3 (54.1%), cN0 (43.2%), moderately differentiated (47.1%) adenocarcinoma (75.7%) located at the GEJ (56.8%). The median radiation dose used was 50.4 Gy, with the majority of patients receiving concurrent carboplatin and paclitaxel (83.8%). Four patients received induction chemotherapy and 20 (55.6%) underwent esophagectomy. When examining guideline compliance, 17 (46.0%) radiation plans demonstrated adequate ENI. The most common improperly covered nodal basin was para-aortic (65.0%), followed by gastrohepatic (30.0%). No patients with sufficient ENI coverage (0/17) developed distant failure compared to 45.0% (9/20) with insufficient coverage (p = 0.001). There were inappreciable differences in locoregional or local failure rates between those with and without complete ENI. Patients with complete ENI were more likely to be of larger craniocaudal length (p = 0.007) or have N2 disease (p = 0.003). When examining other tumor characteristics (histologic subtype, location, HER2 status, esophagectomy rate) of patients with and without complete ENI, no further differences were noted. These results suggest that proper coverage of nodal basins, when indicated by expert guidelines, could improve distant metastasis. ENI analysis of previous prospective CRT studies for esophageal cancer could validate these findings.

Abstract PR09: Detection of minimal residual disease in post-surgical drain fluid can predict locoregional recurrence in HPV-negative head and neck cancer patients

Abstract Introduction: Locoregional cancer relapse remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC), particularly for HPV-negative patients whose 3-year locoregional failure rate is 32.5%. There is a major unmet need for an accurate diagnostic test that predicts risk of locoregional recurrence prior to adjuvant therapy selection. We present a novel proximal assay for minimal residual disease (MRD) profiled in lymphatic exudate collected via surgical drains (“lymph”). Methods: Lymph, plasma, and peripheral blood were collected from 22 HPV-negative HNSCC patients postoperatively at 24 hours along with resected tumor. Cell-free DNA was extracted from lymph and plasma and sequenced using the TruSeq Oncology 500 panel to a depth of &amp;gt;100 million reads. One plasma sample failed due to inadequate coverage. Two patients were censored due to lack of clinical data, yielding 9 patients with disease recurrence (REC) and 11 with no evidence of disease (NED) with &amp;gt;1 year of follow-up. Somatic mutations were identified from exome sequencing (200x) in tumor with matched blood. Tumor-specific variants were force-called in lymph and plasma using a custom bioinformatic pipeline. Mutation calls were filtered by a base-specific error model to eliminate artifacts. Student’s t-test was used for group comparisons. The Kaplan-Meier (KM) estimator with log-rank test and Cox proportional-hazards model were used for survival analyses. Results: ctDNA allelic fraction was 1.5x higher in lymph than in plasma (lymph = 0.11% ± 0.16%; plasma = 0.076% ± 0.12%. p = 0.018, N = 100 mutations). Significantly more mutations were detected in REC lymph compared to NED (p = 0.009), but not in plasma REC vs. NED (p = 0.16). We classified patients as positive (&amp;gt;1) or negative (£1) for detected mutations in each analyte and performed a KM survival analysis, showing lymph could accurately predict recurrence (sensitivity = 89%, specificity = 82%; p &amp;lt; 0.005) while plasma could not (sensitivity = 67%, specificity = 40%; p = 0.59). The hazard ratio in lymph was 12.52 (95% CI 1.54-101.61). We stratified REC patients by locoregional or locoregional + distant relapse and observed significantly more mutations detected in lymph (p = 0.01) from locoregional relapse while lymph and plasma performed similarly for locoregional + distant relapse (p = 1.0). We compared lymph MRD outcomes to extranodal extension (ENE), a high-risk pathologic feature. Lymph was concordant with ENE in 12/20 patients and identified an additional 6 ENE-negative relapse cases. Conclusion: Postoperative ctDNA analysis of lymph from surgical drains represents a novel MRD approach in HPV-negative HNSCC. Lymph significantly outperforms plasma for prediction of recurrence, particularly in patients with locoregional relapse. Accurate MRD identification in patients with lower risk pathologic features suggests that postoperative lymph MRD testing has the potential to significantly augment traditional pathology and provide more personalized adjuvant treatment decision-making in patients with HPV-negative HNSCC. Citation Format: Aadel A. Chaudhuri, Zhuosheng Gu, Damion Whitfield, Noah Earland, Adam Harmon, Megan Long, Peter Harris, Zhongping Xu, Ricardo Ramirez, Sophie Gerndt, Maciej Pacula, Marra S. Francis, Wendy Winckler, Jose P. Zevallos. Detection of minimal residual disease in post-surgical drain fluid can predict locoregional recurrence in HPV-negative head and neck cancer patients [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR09.

Atezolizumab plus tiragolumab in combination with chemoradiotherapy in localized squamous cell carcinoma of the anal canal: TIRANUS (GEMCAD-2103) trial.

TPS3624 Background: Radical chemoradiotherapy (CRT) is the standard of care in patients with localized anal squamous cell carcinoma; however, around 30% of patients do not achieve a complete clinical response (CCR) and require savage surgery. Approximately 84% of anal carcinoma is associated with high risk types of human papilloma virus (HPV), primarily HPV 16 that generates high frequencies of tumor-infiltrating lymphocytes and inflammatory responses that have been linked with upregulation of PD-L1 (up to 74% of patients with squamous cell anal cancer). Additionally, poliovirus receptor (PVR) expression has been described in several squamous cell carcinomas, and has been correlated with PD-L1 expression and poorer prognosis, suggesting dual inhibition of PVR and PD-L1 as a potential mechanism of overcome the resistance to immune checkpoint monotherapy. Moreover, CRT induces the generation of tumor-neoantigens and could act in synergy with immunotherapy in this setting. The trial hypothesizes that the addition of atezolizumab (anti-PD-L1) and tiragolumab (anti-TIGIT) to chemoradiotherapy may lead to enhanced and more durable responses. Methods: TIRANUS is a Phase II, single-arm, open-label, non-randomized, multicenter clinical trial of atezolizumab and tiragolumab in concomitance with standard CRT as definitive therapy in treatment-naïve, localized squamous cell carcinoma of the anal canal. Patients receive atezolizumab (1200mg) plus tiragolumab (600 mg) for 2 cycles (Q3W) in concomitance with the 6 weeks of CRT (cisplatin: 60 mg/m² on days 1 and 29; 5-FU: 1000 mg/m² per day on days 1-4 and 29-32; radiotherapy: 1.8 Gy per day / total dose 54 Gy). After the concomitant phase, patients receive atezolizumab (1200mg) and tiragolumab (600 mg) Q3W for 6 additional cycles (consolidation phase). The primary endpoint is CCR rate, defined as the percentage of patients who achieve radiological complete response (CR), disappearance of all lesions according to RECIST 1.1 criteria (locally assessed) and no presence of residual disease assessed by biopsy at the end of consolidation phase (week 26). Secondary endpoints include Locoregional failure rate (LFR), Disease-free survival (DFS), Colostomy-free survival (CFS), Overall survival (OS), quality of life, safety and the determination of immune biomarkers potentially predictors of response in blood and tumor samples. Using a precision analysis by Clopper-Pearson method (asymptotic 95% confidence interval) and an expected CCR rate of 85%, a total of 45 evaluable patients are needed to obtain a precision estimation of ±10.4%. Accrual started in February 2023. EudraCT: 2021-005887-24 Clinical Trial identifier: NCT05201612. Clinical trial information: NCT05661188 .

Surgical management of oral squamous cell carcinoma of the lower gingivobuccal complex: A case report

Head and neck cancers are one of the most common cancers in India, the majority of which hare comprised of Oral squamous cell carcinoma (OSCC). Managing such tumours necessitates not only astute clinical judgement but also precise imaging and a full understanding of the biology of tumour dissemination paths. Despite the fact that radical excision with adjuvant radiotherapy is the conventional treatment, advanced gingivobuccal tumours have extremely high locoregional failure rates. The current case report describes the presentation and management of OSCC of the lower gingivobuccal complex. It would serve to guide clinicians in the decision-making aspect during the management of extensive gingivobuccal OSCC.

HYPOFRACTIONATED RADIOTHERAPY WITH CONCURRENT CHEMOTHERAPY WITH WEEKLY CISPLATIN IN LOCALLY ADVANCED RELATIVELY RADIORESISTENT SUBSITES OF HEAD AND NECK CANCERS

Background. Locoregionally advanced head and neck cancers are more aggressive and locoregional failure rate after conventional radiotherapy is high. Objective. The aim of the study is to assess the tumor response and toxicities of hypofractionated radiation therapy with concurrent chemotherapy in treatment of four relatively radioresistent tumor sites of head and neck. Methods. A prospective randomised control trial was conducted in 27 head and neck cancer patients. All patients were treated with hypofractionated radiotherapy at 250cGy/fraction once daily to a maximum of 62.5Gy in 25 fractions with concurrent cisplatin 30 mg/m2. Data were evaluated with SPSS version 21.0 for Windows with p-value &lt;0.05. Results. Complete and partial responses were achieved in 15 (57.7%) and 8 (30.8%) patients respectively with an overall response rate of 88.5% and three patients having stable disease. Grade 3 and 4 acute mucositis was experienced by 17 patients (65.4%) and seven patients (27%), respectively. Grade 3 dysphagia was found in 21 patients (80.7%) and grade 3 and 4 skin reactions – in 11 and 2 patients, respectively. Most patients had manageable acute toxicities. Most of the late complications were of grade 2 and 3. The median time to locoregional recurrence was 12 months and one year progression-free survival attained by 61.5% patients. Conclusion. Treatment with hypofractionated radiotherapy with concurrent cisplatin appears feasible and safe and is associated with a good response rate. Although grade 3 and 4 toxicities were comparatively high but it was manageable. Late toxicities were within tolerable levels.