Locoregional Disease-free Survival Research Articles

Pushing the envelope in breast conserving surgery − is multiple-wire localization (3 or more wires) associated with increased risk of compromised margins and long-term recurrence?

IntroductionIn the last two decades there has been a paradigm shift with breast conserving surgery (BCS) being applied to larger and more extensive breast malignancies. The aim of this study is to examine the success of BCS being performed in patients with extensive breast malignancies requiring at least 3 wires for localization, and to assess possible risk factors for failure. Materials and methodsWe performed a retrospective single center review of 232 patients who underwent BCS between 2010 and 2020 requiring at least 3 wires for localization, thus comprising the multi-wire group (MWG). The cohort included a control group of 232 single-wire BCS patients (SWG) chronologically matched with the MWG. Patients with either invasive malignancy or ductal carcinoma in situ (DCIS) were included in the study. Clinical, radiological, and pathological data was collected. Proportions of positive surgical margins, re-lumpectomies and conversion to mastectomy were calculated. Survival analysis for locoregional and distant recurrence was performed. ResultsWomen in the MWG were younger (mean age 57 vs. 63.1, P < 0.001), had larger tumor size (mean size 5.1 cm vs. 1.3 cm, p < 0.001), a higher prevalence of calcifications on mammograms (72 % vs. 17 %, P < 0.001), a higher proportion of positive lymph nodes (75 % vs. 45 %, P = 0.019), and an elevated incidence of a ductal carcinoma in situ (DCIS) component (72 % vs. 38 %, P < 0.001).Positive surgical margins were higher in the MWG (13 % vs 7 %, P = 0.03), which lead to higher proportions of re-lumpectomies or conversion to mastectomies (7 % vs 4 %, P = 0.17). On multivariate analysis of the entire cohort, patients with positive margins were more likely to have a DCIS component (77 % vs 53 %, P = 0.001), an infiltrating lobular carcinoma (ILC) component (15 % vs 9 %, P = 0.013), and positive ER hormonal status (94 % vs 85 %, p = 0.05). The number of wires was not an independent predictor of positive margins.On long-term analysis, the locoregional disease-free survival was similar between the SWG and MWG (P = 0.1). However, the MWG showed higher rates of distant metastasis (12 % vs 4 %, P = 0.006). ConclusionsBCS requiring 3 or more wires is associated with a slightly higher proportion of positive margins. The increased risk of positive margins appears to be related to the type of tumor (DCIS component, ILC component and ER status) rather than to the number of wires. The number of wires does not significantly impact locoregional disease-free survival.

A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial

BC2001 showed combining chemotherapy (5-FU+mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). invasive loco-regional control (ILRC); secondary overall survival. Hypoxia affected overall survival (HR=1.30; 95% CI 0.99-1.70; p=0.062): more uncertainty for ILRC (HR=1.29; 95% CI 0.82-2.03; p=0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n=90, HR 1.69; 95% CI 0.99-2.89 p=0.057) but not conventional (n=207, HR 0.70; 95% CI 0.28-1.80, p=0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n=51; HR 14.2; 95% CI 1.7-119; p=0.015) but not conventional (n=24, HR 1.04; 95% CI 0.07-15.5, p=0.978) radiotherapy. Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. Cancer Research UK, NIHR, MRC.

Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma.

Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies. We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response. Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells. Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

An Innovative Scoring System to Select the Optimal Surgery in Breast Cancer after Neoadjuvant Chemotherapy.

The selection of surgery post-neoadjuvant chemotherapy (NACT) is difficult and based on surgeons' expertise. The aim of this study was to create a post-NEoadjuvant Score System (pNESSy) to choose surgery, optimizing oncological and aesthetical outcomes. Patients (stage I-III) underwent surgery post-NACT (breast-conserving surgery (BCS), oncoplastic surgery (OPS), and conservative mastectomy (CMR) were included. Data selected were BRCA mutation, ptosis, breast volume, radiological response, MRI, and mammography pre- and post-NACT prediction of excised breast area. pNESSy was created using the association between these data and surgery. Area under the curve (AUC) was assessed. Patients were divided into groups according to correspondence (G1) or discrepancy (G2) between score and surgery; oncological and aesthetic outcomes were analyzed. A total of 255 patients were included (118 BCS, 49 OPS, 88 CMR). pNESSy between 6.896-8.724 was predictive for BCS, 8.725-9.375 for OPS, and 9.376-14.245 for CMR; AUC was, respectively, 0.835, 0.766, and 0.825. G1 presented a lower incidence of involved margins (5-14.7%; p = 0.010), a better locoregional disease-free survival (98.8-88.9%; p < 0.001) and a better overall survival (96.1-86.5%; p = 0.017), and a better satisfaction with breasts (39.8-27.5%; p = 0.017) and physical wellbeing (93.5-73.6%; p = 0.001). A score system based on clinical and radiological features was created to select the optimal surgery post-NACT and improve oncological and aesthetic outcomes.

Local Treatment of Triple-Negative Breast Cancer: Is Mastectomy Superior to Breast-Conserving Surgery?

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). TNBC accounts for about 15% of breast cancers and has a poorer prognosis as compared with other subtypes of breast cancer. The more rapid onset of this cancer and its aggressiveness have often convinced breast surgeons that mastectomy could provide better oncological results. However, there is no relevant clinical trial that has assessed differences between breast-conserving surgery (BCS) and mastectomy (M) in these patients. This population-based study aimed to investigate the distinct outcomes between conservative treatment and M in a case series of 289 patients with TNBC treated over a 9-year period. This monocentric study retrospectively evaluated patients with TNBC who underwent upfront surgery at Fondazione Policlinico Agostino Gemelli IRCCS, in Rome, between 1 January 2013 and 31 December 2021. First, the patients were divided in two groups according to the surgical treatment received: BCS vs. M. Then, the patients were stratified into four risk subclasses based on combined T and N pathological staging (T1N0, T1N+, T2-4N0 and T2-4N+). The primary endpoint of the study was to evaluate locoregional disease-free survival (LR-DFS), distant disease-free survival (DDFS) and overall survival (OS) in the different subclasses. We analyzed 289 patients that underwent either breast-conserving surgery (247/289, 85.5%) or mastectomy (42/289, 14.5%). After a median follow-up of 43.2 months (49.7, 22.2-74.3), 28 patients (9.6%) developed a locoregional recurrence, 27 patients (9.0%) showed systemic recurrence and 19 patients (6.5%) died. No significant differences due to type of surgical treatment were observed in the different risk subclasses in terms of locoregional disease-free survival, distant disease-free survival and overall survival. With the limits of a retrospective, single-center study, our data seem to indicate similar efficacy in terms of locoregional control, distant metastasis and overall survival with the use of upfront breast-conserving surgery as compared with radical surgery in the treatment of TNBC. Therefore, TNBC should not be considered to be a contraindication for breast conservation.

Conservative Surgery in cT4 Breast Cancer: Single-Center Experience in the Neoadjuvant Setting.

The diffusion of screening programs has resulted in a decrease of cT4 breast cancer diagnosis. The standard care for cT4 was neoadjuvant chemotherapy (NA), surgery, and locoregional or adjuvant systemic therapies. NA allows two outcomes: 1. improve survival rates, and 2. de-escalation of surgery. This de-escalation has allowed the introduction of conservative breast surgery (CBS). We evaluate the possibility of submitting cT4 patients to CBS instead of radical breast surgery (RBS) by assessing the risk of locoregional disease-free survival, (LR-DFS) distant disease-free survival (DDFS), and overall survival (OS). This monocentric, retrospective study evaluated cT4 patients submitted to NA and surgery between January 2014 and July 2021. The study population included patients undergoing CBS or RBS without immediate reconstruction. Survival curves were obtained using the Kaplan-Meyer method and compared using a Log Rank test. At a follow-up of 43.7 months, LR-DFS was 70% and 75.9%, respectively, in CBS and RBS (p = 0.420). DDFS was 67.8% and 29.7%, respectively, (p = 0.122). OS was 69.8% and 59.8%, respectively, (p = 0.311). In patients with major or complete response to NA, CBS can be considered a safe alternative to RBS in the treatment of cT4a-d stage. In patients with poor response to NA, RBS remained the best surgical choice.

PD09-02 THE IMPACT OF VARIANT HISTOLOGY ON CLINICAL OUTCOMES AFTER RADIATION-BASED THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD09-02 THE IMPACT OF VARIANT HISTOLOGY ON CLINICAL OUTCOMES AFTER RADIATION-BASED THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER Daniel Halstuch, Ronald Kool, Gautier Marcq, Rodney H Breau, Peter C Black, Bobby Shayegan, Michael Kim, Ionut Busca, Hamidreza Abdi, Mark T. Dawidek, Michael Uy, Gagan Fervaha, Fabio L. Cury, Nimira S. Alimohamed, Claudio Jeldres, Ricardo Rendon, D. Robert Siemens, Girish S. Kulkarni, Wassim Kassouf, and Jonathan I. Izawa Daniel HalstuchDaniel Halstuch More articles by this author , Ronald KoolRonald Kool More articles by this author , Gautier MarcqGautier Marcq More articles by this author , Rodney H BreauRodney H Breau More articles by this author , Peter C BlackPeter C Black More articles by this author , Bobby ShayeganBobby Shayegan More articles by this author , Michael KimMichael Kim More articles by this author , Ionut BuscaIonut Busca More articles by this author , Hamidreza AbdiHamidreza Abdi More articles by this author , Mark T. DawidekMark T. Dawidek More articles by this author , Michael UyMichael Uy More articles by this author , Gagan FervahaGagan Fervaha More articles by this author , Fabio L. CuryFabio L. Cury More articles by this author , Nimira S. AlimohamedNimira S. Alimohamed More articles by this author , Claudio JeldresClaudio Jeldres More articles by this author , Ricardo RendonRicardo Rendon More articles by this author , D. Robert SiemensD. Robert Siemens More articles by this author , Girish S. KulkarniGirish S. Kulkarni More articles by this author , Wassim KassoufWassim Kassouf More articles by this author , and Jonathan I. IzawaJonathan I. Izawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003240.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radiation-based therapy (RT) is an acceptable bladder-preserving treatment for selected patients with muscle-invasive bladder cancer (MIBC). Real-world outcomes of RT-based therapy for histologic variants are lacking. Our objective was to compare oncological outcomes between pure urothelial carcinoma (PUC) and variant urothelial carcinoma (UC-HV) patients with MIBC treated with RT-based therapy. METHODS: A collaborative Canadian multicenter retrospective study of 864 patients with MIBC who underwent curative-intent bladder-sparing RT for T2-4a N0-3 M0 MIBC between 2001-2018. Tumours were classified based on the presence of non-urothelial components as either PUC or UC-HV. A complete response (CR) was defined by a negative tumour bed biopsy and/or the combination of a negative urine cytology, negative cystoscopy and normal imaging post-RT. Loco-regional disease-free survival (LR-DFS), disease-free survival (DFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were calculated using Kaplan-Meier method. Cox regression models were used to estimate the effect of UC-VH on oncologic outcomes for patients with MIBC treated with RT-based therapy. RESULTS: Of 864 patients treated with RT-based therapy, 123 (14.2%) had UC-HV. Seventy-five (61%) had UC-HV with squamous and/or glandular differentiation and 48 (39%) had other variants. A CR after RT-based therapy was confirmed in 69.1% of patients with PUC and 63.4% with UC-HV (p=0.266). The 5-yr CSS was 62.0% in PUC vs. 66.8% in UC-HV. The 5-yr OS was 47.7% in PUC and 53.3% in UC-HV. Rates of LR-DFS, DFS and MFS at 5 years were not statistically different between the groups. Salvage cystectomy (sRC) rates were similar (p=0.781). In the univariate Cox regression analyses, UC-HV status was not associated with inferior LR-DFS, DFS, MFS, CSS, and OS. CONCLUSIONS: Variant histology of urothelial carcinoma responded to RT-based therapy with no significant difference in CR, LR-DFS, DFS, MFS, CSS, OS, or rates of salvage cystectomy compared to PUC. The presence of variant histology in MIBC does not confer resistance to RT-based therapy and these patients should not be excluded from bladder preservation treatment. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e239 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Halstuch More articles by this author Ronald Kool More articles by this author Gautier Marcq More articles by this author Rodney H Breau More articles by this author Peter C Black More articles by this author Bobby Shayegan More articles by this author Michael Kim More articles by this author Ionut Busca More articles by this author Hamidreza Abdi More articles by this author Mark T. Dawidek More articles by this author Michael Uy More articles by this author Gagan Fervaha More articles by this author Fabio L. Cury More articles by this author Nimira S. Alimohamed More articles by this author Claudio Jeldres More articles by this author Ricardo Rendon More articles by this author D. Robert Siemens More articles by this author Girish S. Kulkarni More articles by this author Wassim Kassouf More articles by this author Jonathan I. Izawa More articles by this author Expand All Advertisement PDF downloadLoading ...

The Role of a Neoadjuvant RET Inhibitor in Medullary Thyroid Cancer

The Role of a Neoadjuvant <i>RET</i> Inhibitor in Medullary Thyroid Cancer

Radiomics Approaches for the Prediction of Pathological Complete Response after Neoadjuvant Treatment in Locally Advanced Rectal Cancer: Ready for Prime Time?

In recent years, neoadjuvant therapy of locally advanced rectal cancer has seen tremendous modifications. Adding neoadjuvant chemotherapy before or after chemoradiotherapy significantly increases loco-regional disease-free survival, negative surgical margin rates, and complete response rates. The higher complete rate is particularly clinically meaningful given the possibility of organ preservation in this specific sub-population, without compromising overall survival. However, all locally advanced rectal cancer most likely does not benefit from total neoadjuvant therapy (TNT), but experiences higher toxicity rates. Diagnosis of complete response after neoadjuvant therapy is a real challenge, with a risk of false negatives and possible under-treatment. These new therapeutic approaches thus raise the need for better selection tools, enabling a personalized therapeutic approach for each patient. These tools mostly focus on the prediction of the pathological complete response given the clinical impact. In this article, we review the place of different biomarkers (clinical, biological, genomics, transcriptomics, proteomics, and radiomics) as well as their clinical implementation and discuss the most recent trends for future steps in prediction modeling in patients with locally advanced rectal cancer.

Clinical outcomes of combined cervical and transthoracic surgical approaches in patients with advanced thyroid cancer.

Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches. Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015. Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and wound infection (13%). One-year overall survival was 84%; 1-year locoregional disease-free survival was 64%. Median time to locoregional recurrence was 36 months. Only esophageal invasion was associated with worse oncologic outcomes. Combined transcervical and transthoracic surgery for advanced thyroid cancer can be performed without mortality and with acceptable morbidity.

Lymph Node Ratio as a Prognostic Factor in Neck Dissection in Oral Cancer Patients: A Systematic Review and Meta-Analysis.

Simple SummaryLymph node ratio (LNR) is a well-studied prognostic factor in colorectal and breast cancer, and it has been recently evaluated as a clinically relevant biomarker in oral squamous cell carcinoma. LNR represents the ratio of positive lymph nodes extracted in a neck dissection to the total number of nodes harvested (lymph node yield, LNY). Many single-center cohort studies and a few multicenter have assessed the significance of LNR as a prognostic factor in oral cancer. In this systematic review and meta-analysis of 32 studies and 20,994 oral cancer patients, we demonstrate that LNR is an independent prognostic indicator in patients with oral squamous cell carcinoma.Many studies have evaluated the clinical implications of lymph node ratio (LNR) as a prognostic factor in patients with oral squamous cell carcinoma (OSCC). The main purpose of this systematic review and meta-analysis was to address LNR as a prognosticator in patients with OSCC. A systematic search was conducted in the following databases: PubMed, EMBASE, Google Scholar, OpenGrey, Cochrane library, and ClinicalTrials.gov, and studies between 2009 and 2020 were sought. The pooled relative risk was calculated along with 95% confidence intervals for the following endpoints: overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), locoregional disease-free survival (LRDFS), local recurrence-free survival (LRFS), and recurrence-free survival (RFS) according to the random-effects model (Der Simonian–Laird approach). Subgroup and meta-regression analyses were performed as well. Finally, 32 cohort studies were eligible, which included 20,994 patients with OSCC. Patients were subdivided into two categories, group YES (studies that included in their analysis only patients with positive lymph nodes) and group NO (studies that did not exclude LNR = 0 patients). In the group YES, patients with high LNR had shorter OS (RR = 1.68, 95% CI: 1.47–1.91), DFS (RR = 1.68, 95% CI: 1.42–1.99), DSS (RR = 1.94, 95% CI: 1.56–2.42), DMFS (RR = 1.83, 95% CI: 1.13–2.96), LRDFS (RR = 1.55, 95% CI: 1.10–2.20), and LRFS (RR = 1.73, 95% CI: 1.41–2.13) compared to patients with low LNR. In the group NO, patients with high LNR in comparison had shorter OS (RR = 2.38, 95% CI: 1.99–2.85), DFS (RR = 2.04, 95% CI: 1.48–2.81), and DSS (RR = 2.90, 95% CI: 2.35–3.57) compared to patients with low LNR. Based on those findings, LNR might be an independent prognostic factor for OS in patients with OSCC and could be incorporated into future classification systems for better risk stratification.

A Multicenter Retrospective Cohort Series of Muscle-invasive Bladder Cancer Patients Treated with Definitive Concurrent Chemoradiotherapy in Daily Practice

BackgroundConcurrent chemoradiotherapy (CRT) as a definitive treatment option for patients with nonmetastatic muscle-invasive bladder carcinoma (MIBC) is increasingly being applied in clinical practice. ObjectiveTo assess the oncological and toxicity outcomes in a contemporary cohort of nonmetastatic MIBC patients treated with concurrent CRT in daily practice. Design, setting, and participantsPatients with nonmetastatic MIBC (cT2-4aN0M0) who had received CRT with curative intent between January 2010 and April 2020 in three centers were retrospectively identified. The CRT consisted of 66 Gy (or biologically equivalent) plus either mitomycin C and fluorouracil/capecitabine or cisplatinum. Outcome measurements and statistical analysisThe primary endpoint was the 2-yr locoregional disease-free survival (LDFS) estimate. Secondary endpoints were complete response, disease-specific survival (DSS), overall survival (OS), bladder intact event-free survival (BI-EFS), and severe adverse events (<90 d of starting CRT). Kaplan-Meier survival and Cox multivariable regression analyses were performed. Results and limitationsWe included data of 240 MIBC patients with a median age of 74 yr and a median follow-up of 27 mo (interquartile range 11–44). Complete response on first cystoscopy after CRT was seen in 209 cases (90%). The 2-yr LDFS was 76% (95% confidence interval [CI] 70–82%); the 5-yr OS and DSS were 50% (95% CI 42–59%) and 70% (95% CI 62–79%), respectively. On multivariable analysis, cT2 versus cT3–4 tumor stage was significantly associated with better DSS (hazard ratio 1.02, 95% CI 1–1.05, p = 0.024). The 2-yr BI-EFS was 75% (95% CI 69–82%). Forty-three (17%) patients experienced a severe adverse event (grade ≥3). Limitations include retrospective design and heterogeneous administration of CRT. ConclusionsConcurrent CRT is a safe and effective treatment modality for nonmetastatic MIBC. Patient summaryChemoradiotherapy for the treatment of muscle-invasive bladder carcinoma is increasingly being applied. In this study, we reviewed the outcomes of this bladder-sparing treatment using a series of patients treated in three hospitals in daily practice. We found that administration of chemoradiotherapy can be safe and effective.

Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AimsSubstantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. Materials and methodsA retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan–Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. ResultsIn 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DiscussionSubstantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Hypofractionated radiotherapy in ten fractions for postmastectomy patients: a phase II study compared with another hypofractionation schedule with sixteen fractions

BackgroundThe purpose of this phase II study was to evaluate the feasibility of hypofractionated radiotherapy (HFRT) with a dose of 36.5 Gy in 10 fractions in postmastectomy patients.MethodsFrom March 2014 to December 2015, 85 patients with locally advanced breast cancer were eligible to participate in this study with a schedule of 36.5 Gy in 10 fractions. Intensity-modulated radiation therapy (IMRT) was delivered to the chest wall with or without the supraclavicular region. The primary endpoint was radiation-related toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS) and overall survival (OS). And the outcomes were compared with our retrospective study of 72 patients with 42.5 Gy in 16 fractions.ResultsThe median follow-up was 69.0 (range 66.5-71.5) months in the 36.5 Gy group and 93.0 (range 91.9-94.1) months in the 42.5 Gy group, respectively. Radiation-related toxicities were mainly grade 1, although a few patients had grade 2 plexopathy (1.2%) and acute skin toxicity (1.2%) in the 36.5 Gy group, and grade 2 acute skin toxicity (5.6%) and lymphedema (4.2%) in the 42.5 Gy group. There were no significant differences between the groups in acute and late toxicities. For all the patients, the 5-year LRFFS, DFS and OS were 97.7 and 100.0%, 93.1 and 90.3%, 98.8 and 97.2%, respectively, without significant differences between the groups.ConclusionPostmastectomy HFRT with a schedule of 36.5 Gy in 10 fractions was feasible, with mild toxicities and excellent 5-year clinical outcome.Trial registrationTrial registration number: ChiCTR-ONRC-14004391.Date of registration: 9/3/2014.

P-99 SUCNR1 and SDHA Gene Expression in Tumoral Tissue Is Associated with Locoregional Disease-Free Survival

P-99 SUCNR1 and SDHA Gene Expression in Tumoral Tissue Is Associated with Locoregional Disease-Free Survival

Oncologic outcomes in the era of modern radiation therapy using FIGO 2018 staging system for cervical cancer

BackgroundThe recently published ASTRO cervical cancer guidelines recommend the use of modern radiotherapy. Imaging is now incorporated in the updated FIGO 2018 staging with a new stage IIIC. This study aims to evaluate the oncologic outcomes and predictors of survival using FIGO 2018 staging in a cohort of patients treated in an era of high-precision image-guided radiotherapy. MethodsWe performed a retrospective cohort study of 216 adult cervical cancer patients treated with definitive chemoradiotherapy between 2010 and 2018. Eligible patients had non-metastatic cervical cancer treated at a single academic institution. All patients had pre-treatment MRI and CT/PET. Treatment protocol consisted of external beam intensity-modulated radiotherapy and 3D image-guided brachytherapy. Kaplan-Meier curves were used for survival analysis. Multivariate cox proportional-hazards model was performed to identify potential prognostic factors. ResultsMedian age at diagnosis was 50 and median BMI was 26.4 kg/m2. Median follow-up time was 44.3 months. Five-year overall survival (OS), disease-free survival and loco-regional disease-free survival rates were 76.8%, 68.5% and 82.6%, respectively. FIGO 2018 showed better OS discrimination compared to FIGO 2009 classification. OS was increasingly worse with positive pelvic and para-aortic nodes (p < 0.001). In a multivariate prediction model, performance status (p = 0.044) and FIGO 2018 classification (stage III p = 0.016; stage IVA p = 0.010) were predictors of mortality; FIGO 2018 classification (stage III p = 0.003; stage IVA p = 0.001) was a predictor of any recurrence; MRI tumor diameter (p ≤ 0.001) and nodal metastases (p = 0.024) were predictors of loco-regional recurrence. ConclusionsIntegration of state-of-the-art imaging in cervical cancer staging and in radiotherapy planning leads to good loco-regional control rates, however distant recurrence remains an important issue. FIGO 2018 staging better reflects patient prognosis, highlighting the need for new treatment strategies for stage IIIC cervical cancer.

Succinate Pathway in Head and Neck Squamous Cell Carcinoma: Potential as a Diagnostic and Prognostic Marker.

Simple SummaryEmerging evidence points to succinate as an important oncometabolite in cancer development; however, the contribution of the succinate-SUCNR1 axis to cancer progression remains unclear. Head and neck squamous cell carcinoma (HNSCC) is associated with disease and treatment-related morbidity so there is an urgent need for innovation in treatment and diagnosis practices. Our aim was to evaluate the potential of the succinate-related pathway as a diagnostic and prognostic biomarker in HNSCC. The circulating succinate levels are increased in HNSCC, being a potential noninvasive biomarker for HNSCC diagnosis. Moreover, the succinate receptor (SUCNR1) and genes related to succinate metabolism, which are predominantly expressed in the tumoral mucosa as compared with healthy tissue, are positively associated with plasma succinate. Remarkably, we found that SUCNR1 and SDHA expression levels predict prognosis.Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77.1% [95% CI: 48.9–100.0] vs. 16.7% [95% CI: 0.0–44.4], p = 0.018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis.

Abstract OT-19-01: Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer

Abstract Background: Breast conserving therapy is an established option for early stage breast cancer. Shorter postoperative radiotherapy (RT) regimens have similar efficacy in lower risk breast cancer, including hypofractionated whole breast RT and Accelerated Partial Breast Irradiation (APBI). Despite similar efficacy results for APBI, RAPID trial showed worse cosmetic outcomes for patients receiving APBI compared to whole breast RT. Larger postoperative lumpectomy cavity volumes and the used dose regimen could have had an impact on cosmesis. There are only few published preoperative APBI pilot studies with different dosimetric schemes treating smaller RT target volumes that would potentially translate into less toxicity. Our study is designed to evaluate the safety and feasibility of preoperative ablative RT in patients with early stage breast cancer. An array of ancillary imaging, blood and tissue biomarker collection is also planned in order to study the radiation response in breast cancer. Trial Design: This phase I study uses a modification of the standard 3+3 Phase I design to identify the recommended phase 2 dose of preoperative SABER for treatment of selected breast cancer patients. Participants will be treated with assigned dose level of preoperative SABER, once a day, for 5 fractions given on non-consecutive days, over a period of 2 weeks. The tested dose levels are: Level I=35 Gy (7 Gy x 5), Level II (starting dose)= 40 Gy (8 Gy x 5), Level III=45 Gy (9 Gy x 5), Level IV=50 Gy (10 Gy x 5). Standard partial mastectomy and axillary surgery will be performed 4-6 weeks after preoperative SABER. Adjuvant systemic therapy will be per standard of care. Exploratory studies will be performed pre/post RT and postoperative, including multiparametric breast MRI, biomarkers in blood (CTC’s, SNPs, cytokines, CRP) and tissue (assessment of radiation response, expression of PD-L1, PD1, TILs). Cosmesis and QoL assessment will be performed at scheduled 1, 6, 12, 24 months follow-up. Eligibility criteria: Women, 50 or older, clinical stage T1 unifocal, N0, ER/PR+/HER2 negative, ECOG 0-1, able to undergo MRI with contrast are eligible. Specific Aims: Aim 1. To identify the recommended phase II dose of preoperative SABER; Aims 2.a) to determine the safety, tolerability, Dose Limiting Toxicity (DLT) and toxicity profile of delivering SABER; b) to determine the rate of complete pathological response after preoperative SABER; c) To assess cosmetic results (by MD and patient’s assessment) and QoL after SABER and standard partial mastectomy/axillary surgery. Exploratory aims: a) to determine biomarkers in blood and tissue, and multiparametric MRI radiographic changes and associate them with toxicity and radiation tumor response; b) to assess locoregional recurrence, disease-free survival, and overall survival; c) to assess sentinel lymph node biopsy identification rates after SABER. Statistical Methods: In this novel phase I study, escalation to the next higher dose level will occur only if 0 or only 1 out of 6 patients has DLT. Present accrual and target accrual: A total of 12 to 18 evaluable patients will be enrolled. Expected enrollment period is 3 years and time to complete the study is about 5 years. Open for accrual in 06/2020. Clinical trial information: NCT04360330 Citation Format: Cristiane Takita, Isildinha M. Reis, Radka Stoyanova, John C. Ford, Brian Marples, Jose Net, Monica Yepes, Carmen Gomez, Susan Kesmodel. Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-19-01.

Effective Radiotherapy in Tracheobronchial Adenoid Cystic Carcinoma With Positive Surgical Margin

The study aimed to evaluate the role of postoperative radiotherapy (PORT) in the treatment of trachea and main bronchus adenoid cystic carcinoma (ACC) with a positive surgical margin. Patients with pathologically confirmed trachea or main bronchus ACC operated on at Shanghai Chest Hospital were enrolled. Survival, univariate, and multivariate analyses were performed. The χ2 test was applied to analyze the failure patterns among different groups (R0/0: negative margin resection without PORT; R1/0: positive margin resection without PORT; R1/1: positive margin resection with PORT). From January 2001 to December 2014, 77 patients were deemed eligible for the study. Pairwise comparisons showed that the overall survival rate of group R1/1 was comparable to that of group R0/0 (P=.438), and significantly longer than the rate of group R1/0 (P= .032). Additionally, the local disease-free survival rate of group R1/1 was much higher than that of group R0/0 (P= .023) and R1/0 (P= .001). Cox multivariate analysis identified the radiologic feature (P= .012) and PORT (P= .006) as significantly favorable prognostic factors for locoregional disease-free survival. By contrast, for overall survival, PORT (P= .032) was the only corresponding variable identified by univariate analysis. Furthermore, PORT significantly decreased the locoregional recurrence rate (P= .002) but not distant metastases (P > .999). PORT helped patients with tracheobronchial ACC and microscopic positive surgical margins to achieve a similar outcome as patients with complete resection. R0 resection may not be necessary for tracheobronchial ACC if it is difficult to be completely resected.

Ipsilateral versus Bilateral Neck Radiation Therapy for Tonsillar Squamous Cell Carcinoma

Ipsilateral neck radiation (I-RT) has been adopted for patients with early stage, well lateralized tonsillar squamous cell carcinoma (SCC), however there are limited data on outcomes of this approach in those with N2b disease. We report locoregional disease free survival (LR-DFS) for patients with tonsillar SCC who received I-RT or bilateral neck radiation (B-RT). Patients with tonsillar SCC who underwent definitive radiation, with or without chemotherapy, at a single academic institution between 3/1/90 and 10/15/18 were identified. Patient, tumor, and treatment characteristics were recorded. Stage was assigned per AJCC 7th ed. Wilcoxon Rank Sum and Chi-Square tests were used to compare patients who underwent either B-RT or I-RT. The primary outcome was locoregional disease-free survival (LR-DFS). Secondary outcomes were freedom from distant recurrence (FFDR) and overall survival (OS). Outcomes were estimated with Kaplan Meier method and compared via log rank test. Multivariate cox proportional hazards were used to estimate the effect of variables on endpoints. 216 patients with tonsillar SCC were treated with B-RT (n = 159) or I-RT (n = 57). Median age was 56 (IQR 51 – 64). Patients who underwent I-RT had T1 (45.6%) or T2 (54.4%) disease. Those who underwent B-RT had a higher proportion of T3/T4 disease: 8.2% T1, 25.8% T2, 42.8% T3, and 23.2% T4 disease (p<0.01). Most patients had nodal disease, I-RT: 3.5% N0, 19.3% N1, 14.0% N2a, 63.2% N2b and B-RT: 15.1% N0, 13.8% N1, 7.6% N2a, 36.5% N2b, 13.2% N2c, and 13.8% N3. HPV/p16 status for patients with B-RT was positive in 31.0%, negative in 2.0%, and unknown in 67.3%; for I-RT, HPV/p16 was positive in 59.6%, negative in 3.5%, and unknown in 36.8%. Median total dose to both groups was 70 Gy at 2 Gy/fraction. Concurrent chemotherapy was used in 94% of patients with B-RT and 77% with I-RT (p<0.01). 5-year estimates for survival endpoints are given below. On multivariate analysis controlling for T/N stage, use of chemotherapy, and HPV status, LR-DFS did not differ significantly for patients receiving B-RT versus I-RT (HR 0.67, 95% CI 0.40 – 4.10, p = 0.67). Among those treated with I-RT, 2 developed local recurrence at the primary tumor site. There were no ipsilateral or contralateral neck recurrences. Of 94 patients with N2b disease, 36 received I-RT. For those with N2b disease, 5-year LR-DFS was 93% (95% CI 73% – 98%) after I-RT versus 85% (95% CI 72% – 92%) after B-RT (p = 0.18). High rates of LR-DFS were achieved with I-RT for T1-T2 N0-2b tonsillar SCC, with no ipsilateral or contralateral neck recurrences. Use of I-RT did not compromise LR-DFS compared to B-RT. For patients with N2b disease, I-RT also resulted in high rates of LR-DFS. To our knowledge, this series represents the largest single institution cohort incorporating patients with tonsillar SCC and N2b disease treated with I-RT.Abstract 3868; TableB-RTI-RTLR-DFS (95% CI)78% (70-84%)91% (78-97%)FFDR (95% CI)89% (82-93%)96% (85-99%)OS (95% CI)71% (63-78%)91% (78-97%) Open table in a new tab