Incidence Of Locoregional Failure Research Articles

High versus standard radiation dose of definitive chemoradiotherapy combined with immunotherapy for inoperable esophageal squamous cell carcinoma: A multicenter propensity score matching analysis.

e16118 Background: There is no consensus of the radiation dose for esophageal squamous cell carcinoma (ESCC) in the setting of definitive chemoradiotherapy (dCRT) combined with immunotherapy. This study aimed to compare the efficacy and safety of high-dose (HD) versus standard-dose radiotherapy (SD) for locally inoperable ESCC. Methods: Patients with locally advanced unresectable ESCC or advanced ESCC with supraclavicular lymph node metastases only who received high-dose (≥ 60Gy) or standard-dose (50-50.4Gy) radiation in dCRT combined with anti-PD-1 antibody as the first-line treatment from four academic cancer centers were enrolled. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. Results: Between March 2019 and July 2022, 328 patients were enrolled from four cancer centers in China, with 163 patients in the HD and 165 patients in the SD groups, respectively. The median follow-up time in the HD and SD groups were 28.9 and 25.9 months, respectively. There was no significant difference in overall survival (OS) (median OS: not reached in both, P = 0.080), progression-free survival (PFS) (median PFS: not reached vs. 30.3 months, P = 0.073), locoregional progression-free survival (LRPFS) and distant metastasis survival (DM) between the HD and SD groups. After 1:2 PSM, 156 patients in the HD and 78 patients in the SD groups were selected for further analyses. The results remained consistent and showed that the HD group had no significant benefits in OS (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.50-1.51, P = 0.624), PFS (HR = 0.79, 95%CI = 0.51-1.23, P = 0.300), LRPFS (HR = 0.75, 95%CI = 0.47-1.19, P = 0.228) and DM (HR = 1.05, 95%CI = 0.64-1.73, P = 0.849), compared with the SD group. In terms of failure patterns, the incidences of locoregional failure only (13.5% vs. 16.7%, P = 0.512), distant failure only (10.9% vs. 9.0%, P = 0.648) and synchronous locoregional and distant failure (2.6% vs. 6.4%, P = 0.164) were similar between two groups. No significant difference was found in the incidences of hematological toxicities, esophagitis, pneumonia (12.2% vs. 10.3%, P = 0.664) and fistula (7.1% vs 9.0%, P = 0.603) between the HD and SD groups. Conclusions: Compared with a radiation dose of 50-50.4Gy, the increase in radiation dose (≥60Gy) did not result in survival benefits for inoperable ESCC patients receiving dCRT combined with immunotherapy. Furthermore, similar failure patterns and toxicities were observed between the two treatment groups.

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

PurposeThe number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients. MethodsThe XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine‐Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs). ResultsSix hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p<0.05) and a higher incidence of LRFs (SHR=1.54 [1.00-2.38], p=.05) compared with single-agent cisplatin, whereas OS (HR=1.15 [0.80-1.65], p=.46) was comparable. There were no oncological differences between single-agent and multi-agent cisplatin regimens (all p>.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009). ConclusionsSingle-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients. Trial RegistrationXXX

MRI, FDG-PET/CT and Image-Guidance for Re-Irradiation of Locoregionally Recurrent or Second Primary Head-and-Neck Squamous Cell Carcinoma Patients – Results of a Multicenter Cohort Study

To investigate patterns of care and prognostic benefits of MRI, FDG-PET/CT and image-guidance in re-irradiation of locoregionally recurrent or second primary head-and-neck squamous cell carcinomas (r/s HNSCCs) within a multicenter cohort study. Patients receiving re-irradiation for r/s HNSCC between 2009 and 2020 at 16 tertiary cancer centers in Germany were retrospectively analyzed in terms of MRI and FDG-PET/CT usage for treatment planning and regarding image-guidance frequency during re-irradiation. Patterns of use of these modalities over time were analyzed by binary logistic regression analysis, and the association between the usage of these modalities and best locoregional treatment response was analyzed with chi-square tests. Cumulative incidence analyses of locoregional failures with death as competing event were performed. In the total cohort of 297 patients, 226 (76%) were male, median age was 62 years (IQR, 56-70), and median ECOG was 1 (IQR, 1-2). There were 260 locoregionally recurrent HNSCCs, and 37 second primary HNSCCs; 44 patients (15%) had distant metastases at the time of re-irradiation. MRI and FDG-PET/CT was used for re-irradiation planning in 117 (39%) and 71 patients (24%), respectively. In median, image guidance (IGRT) was performed twice weekly (IQR, 1-5), usually with cone beam CTs or megavolt-CTs, and 85 patients (29%) received daily IGRT during re-irradiation. Usage of MRI (OR = 0.967; 95% CI, 0.892-1.048; p = .416), FDG-PET/CT (OR = 1.053; 95% CI, 0.960-1.156; p = .274), or daily IGRT (OR = 1.057; 95% CI, 0.968-1.115; p = .218) did not increase in frequency over time within the analyzed time span but was significantly dependent on the treatment center (χ2(15), P<.001 for all modalities). Daily IGRT was associated with a higher rate of at least stable disease after re-irradiation as assessed by RECIST criteria (χ2(1) = 4.011, p<.05). There was a trend towards better RECIST-assessed treatment response for MRI (χ2(1) = 3.223, p = .073) and FDG-PET/CT (χ2(1) = 2.792, p = .095) as part of the re-irradiation planning process. Incidence of locoregional failures was not dependent on MRI (SHR = 0.94; 95% CI, 0.67-1.33; p = 0.741, Fine-Gray), FDG-PET/CT (SHR = 0.88; 95% CI, 0.59-1.33; p = 0.552) or daily IGRT (SHR = 0.76; 95% CI, 0.51-1.14, p = 0.182), There was a trend towards lower acute grade 3/4-toxicities in patients receiving daily IGRT (χ2(1) = 3.354, p = 0.067). Our data suggest that daily IGRT may increase disease control and should be regularly applied for re-irradiation of r/s HNSCCs. MRI and FDG-PET/CT usage were not associated with the incidence of locoregional failures after re-irradiation. However, prospective trials with multiparametric MRI and/or FDG-PET/CT for optimal re-irradiation planning are warranted.

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.

Effects of Tumor Mutational Burden and Gene Alterations Associated with Radiation Response on Outcomes of Postoperative Radiation Therapy in Non-Small Cell Lung Cancer

Postoperative radiation therapy (PORT) in resected non-small cell lung cancer (NSCLC) improves locoregional outcomes, but recent randomized data do not support its unselected use. We assessed if tumor mutational burden (TMB) and mutations in genes associated with radiation sensitivity can select patients for PORT. Patients with resected NSCLC treated with and without PORT who underwent tumor genomic profiling were examined. The incidence of locoregional failures (LRFs) in patients with deleterious mutations in DNA damage response and repair (DDR) genes and genes associated with radiation resistance (KEAP1/NFE2L2/STK11/PIK3CA) were investigated. Cox modeling and receiver operating characteristic curve (ROC) analysis assessed the relationship between TMB and locoregional control (LRC). Eighty-nine patients with NSCLC treated with PORT were analyzed, with a 2-year LRF rate of 19% (95% confidence interval, 10%-27%). Among patients treated with PORT, those with mutations in radiation resistance genes (n=16 [18%]) had significantly more LRFs than patients without mutations (2-year LRF rate: 60% vs 11%; P < .001). On multivariate analysis, radiation-resistance mutations were associated with LRF after PORT (hazard ratio, 7.42; P < .001). Patients with mutations identified in DDR genes (n=15 [17%]) had significantly improved LRC (P=.048) and no LRF events after PORT. On multivariate analysis, a higher TMB was associated with improved LRC after PORT (hazard ratio, 0.86; P=.01), and TMB was associated with PORT outcomes (area under ROC curve, 0.67-0.77). These genomic markers were not similarly associated with LRF in patients not treated with PORT. The data suggest that patients with radiation-resistance gene alterations may derive minimal benefit from PORT, whereas patients with high TMB and/or alterations in DDR genes may benefit from PORT and be suited for future precision-RT strategies. Prospective studies are necessary to validate these findings.

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome.

ObjectiveThe main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population.MethodsPatients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome.ResultsIn total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease.ConclusionWe present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.

Omitting surgery in esophageal cancer patients with complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by surgery is a standard treatment modality for locally-advanced esophageal cancer. However, patients who achieve clinical complete response (cCR) after nCRT have been reported to have better prognosis. Further, the role of surgery in these patients is controversial. Thus, this meta-analysis aimed to evaluate whether surgery is still useful in patients with cCR after nCRT.MethodsWe systematically reviewed the MEDLINE, PubMed, Embase, Cochrane library, and Scopus databases for studies on surgical efficacy in complete responders after concurrent chemoradiotherapy for esophageal cancer. The publication date was set to January 1, 2010–January 31, 2020. The hazard ratio (HR) and risk ratio were used to compare the 2-year overall survival (OS), disease-free survival (DFS), incidence of locoregional failure, distant metastasis, and treatment mortality between the nCRT and nCRT plus surgery groups.ResultsSix articles involving 609 patients were included. There was a significant benefit of nCRT for OS (HR = 0.80, 95% confidence interval [CI] 0.64–0.99, p = 0.04), but not for DFS (HR = 1.55, 95% CI 0.35–6.86, p = 0.56). The nCRT group tended to have lower mortality than the nCRT plus surgery group (risk ratio = 0.15, 95% CI 0.02–1.18, p = 0.07).ConclusionOmitting surgery provides better OS in complete responders after nCRT. Adding surgery could increase the morbidity and mortality and decrease the quality of life. Thus, nCRT alone could be a feasible approach for patients with cCR.

Nasal vestibule squamous cell carcinoma: a population-based cohort study from DAHANCA

Background Cancer of the nasal vestibule is a rare type of malignancy dominated by squamous cell carcinoma (SCC), and with poor survival. The treatment is either radiotherapy, surgery or a combination of both. Previous studies have shown a 5-year disease-specific survival of 74% and overall survival (OS) of 50%. Our objective was to describe the consecutive cohort of patients diagnosed with SCC of the nasal vestibule in Denmark from 2008 until 2018 and evaluate prognostic factors and treatment outcome using locoregional failure (LRF), disease-specific mortality (DSM), and OS as endpoints. Methods All patients diagnosed with SCC of the nasal vestibule from 2008 until 2018 were identified in the nationwide clinical database, DAHANCA and were followed for LRF and death (DSM and OS) until March 2021. OS was analysed using Kaplan–Meier estimator, and cumulative incidence of LRF and DSM were analysed using the Aalen–Johansen estimator. Analysis of prognostic factors was performed using Cox proportional hazard models. Results A total of 162 patients were identified. The median age was 71 years and 54% were male. Disease stage at the time of diagnosis were stage I (70%), II (17%), III (2%) and IV (11%). Curatively intended treatment was performed in 146 patients (90%), of which treatment failure occurred in 42 patients (29%). Most failures occurred at the primary tumour site (64%). Cancer Patient Pathways recommended time to treatment was fulfilled in 71% of patients. The 5-year OS and DSM in patients treated with curative intent were 65% and 11%, respectively. Stage was a significant independent prognostic factor. No difference in LRF, DSM or OS were shown between the applied treatments. Conclusions Stage is the main independent prognostic factor, and failure most commonly appear at the primary tumour site.

Pathologic Response and Locoregional Control After Preoperative Pancreatic Stereotactic Body Radiation Therapy

In light of ALLIANCE02150, the role of preoperative stereotactic body radiotherapy (SBRT) for pancreatic cancer is controversial. We studied patients who had surgery after preoperative SBRT to assess pathologic and clinical outcomes, and evaluate if elective nodal irradiation (ENI) decreases locoregional failure (LRF).Patients with pancreatic cancer who received SBRT at one center from 2007 to 2020 followed by oncologic surgery were reviewed. Local (primary tumor), regional (peripancreatic or perivascular per RTOG consensus), and distant failures were coded. Pathologic treatment response per College of American Pathologists was reviewed. Incidence of LRF with death as competing risk was assessed. Time to overall (OS) and progression-free survival (PFS) from date of pathologic diagnosis was assessed via Kaplan-Meier. Association testing via Cox analysis for OS/PFS and Gray test for LRF was performed.Twenty-eight patients were evaluable. Median (range) ECOG was 1 (0-2). Tumor stage was cT4 in 19 (67.9%) patients. Nodal stage was cN1 in 10 (35.7 %) patients. There were 7 and 21 patients with initially unresectable and borderline resectable disease respectively. Chemotherapy (CT) was given prior to SBRT in 27 (96.4%) patients, with FOLFIRINOX and gemcitabine-paclitaxel in 21 and 4 patients, respectively. Median (range) duration of CT was 5 (0-12) cycles. Median (range) dose, BED10, and fractionation were 40 Gy (25 - 50 Gy), 72 Gy (54.78 - 100 Gy), and 5 (1-5) respectively. The median (range) time between SBRT and surgery was 6.7 (2.6 - 21.9) weeks. Whipple, Appleby, and distal pancreatectomy was performed in 22, 4, and 2 patients respectively. The R0 rate was 23/28 (82.1%). Pathologic complete, near complete, partial, and poor/no treatment response was seen in 1 (3.6%), 10 (35.7%), 15 (53.6%), and 2 (7.1%) patients, respectively. The pN1 rate was 12/28 (42.3%). Median (range) follow up was 21.5 months (6.9 - 67.2 months). The 18-month (95% CI) overall survival (OS) and LRF were 66.6% (50.0 - 88.6%), and 7.8% (0.0 - 48.4%) respectively. Complete or near complete pathologic response was associated with improved OS (HR = 0.21, P = 0.022) and PFS (HR = 0.25, P = 0.021), but not LRC (P = 0.780). Longer (≥8 weeks) time between end of SBRT and surgery was associated with improved complete or near complete response rate (P = 0.024) but not OS, PFS, or LRF. BED10 did not predict for pathologic treatment response or margin status. Sixteen patients received ENI. There were no other statistically significant differences in the above baseline characteristics, OS, PFS, or pathology outcomes, with vs without ENI. The 18-month (95% CI) LRF with vs without ENI was 0.0% (0.0 - 0.0%) vs 12.8% (0.0 - 38.8%), P = 0.29.Our cohort of patients with pancreatic cancer treated with preoperative SBRT and surgery showed good pathologic response and R0 rate. ENI was associated with numerically lower LRF. Increased BED10 was not associated with improved pathologic treatment response.

Abstract PD8-11: Distribution of locoregional breast cancer recurrences in relation to previous radiotherapy and biological subtype

Abstract Background: Adjuvant locoregional radiotherapy (LRRT) reduces risk of locoregional failures (LRF) and improves survival for node positive breast cancer (BC) patients. However, LRRT increases the risk for toxicity as edema in the arm, lung cancer and cardiac mortality. Modern radiotherapy allows a more conform therapy which makes knowledge of LRF-patterns very important, in order not to underdose volumes with high risk for microscopic disease and simultaneously restrict dose to risk organs. In addition, BC-subtype may affect radiosensitivity and could possibly be used to individualize LRRT in the future. Methods: We investigated outcome for BC-patients receiving LRRT in the Southwest Sweden (2004-2008) in order to identify LRFs. During this period patients with &amp;gt;3 positive lymph nodes were given LRRT (50Gy in 2Gy fractions) to the breast/thoracic wall, axilla level II+III, supra- and infraclavicular lymph nodes according to a target definition atlas introduced in 2002. Patients with LRF as first event were identified, with distant failures and death considered as competing risks. The anatomical distribution of LRF was compared with the contouring atlas, radiotherapy given, and biological subtype based on immunohistochemistry. Results: 904 patients received LRRT. Median follow-up time was 9.8 years (0.2-14.6) for patients without an event. 59 patients (6,5%) developed a LRF, 30 of which were local failures (LF) and 31 regional failures (RF) (2 simultaneous LF/RF). Median time to LRF was 2.8 years. 37 of the 59 (63%) LRF-patients developed generalized disease within 3 months from the LRF. Of the 845 patients without LRF 316 developed distant metastases as first recurrence, 1 an isolated RF in the contralateral axilla, 64 died from other causes, and for 5 patients recurrence-status was unclear. 459 were alive at end of follow-up. Of the LF 19 developed after mastectomy (MRM) and 11 after breast conserving surgery (BCS). LF-location after MRM: 9 in-field, 6 at field margin, 2 both in/out of field, 1 out of field, and for 1 not yet determined. After BCS: 8 in-field, 1 at field margin, and for 2 not yet determined. Of the RF 28 developed after MRM and 3 after BCS. Location of RF after MRM: 11 in-field, 6 at field margin, 1 both in/out of field, 2 out of field, and for 8 not yet determined. After BCS: 1 in-field, 1 at field margin, and 1 not yet determined. The most common location for RF close to /out of field was superior to the treated area in fossa supraclavicularis. Biological approximate subtype was available for 885 of the primary tumours; luminal (ER+ and/or PR+ HER2-/?) 67% (589/885), HER2+ 19% (169/885), triple negative (ER- and PR- HER2-/?) (TN) 14% (127/885). Subtype distribution of BC later causing LRF despite LRRT was: luminal 44% (26/59), HER2+ 27% (16/59), TN 29% (17/59). Among primary tumours causing a LRF within irradiated volume 77% (24/31) were HER2+ or TN. Conclusion: In this high risk cohort of BC-patients, we found a low incidence of LRFs. The majority of LRFs developed within irradiated volume. BCs of the HER2+ and TN-subtype may be more radioresistant and have a higher risk of LRF. Updated information as well as figures mapping all recurrences in relation to previous LRRT will be presented at the symposium. Citation Format: Adra J, Karlsson P, Killander F, Lundstedt D, Alkner S. Distribution of locoregional breast cancer recurrences in relation to previous radiotherapy and biological subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD8-11.

Patterns of Failure After Postoperative Intensity Modulated Radiation Therapy for Locally-Advanced Buccal Cancer

Purpose/Objective(s): Squamous cell carcinoma (SCC) of buccal mucosa has a high incidence of locoregional failure. Its aggressive behavior and the change of lymphatic and vascular drainage after surgery make the design of the radiation treatment field difficult. We retrospectively analyzed our treatment results of locally advanced buccal cancer and intended to define the patterns of failure and provide information for the design of a better radiation treatment. Materials/Methods: Between January 2007 and December 2010, 51 patients with histologically confirmed SCC of buccal mucosa underwent surgery followed by postoperative intensity modulated radiation therapy (IMRT). All patients with locally advanced buccal cancer (AJCC stage III, 26 patients, 51%; stage IV, 25 patients, 49%). The high-risk clinical target volume (CTV) covered the surgical tumor bed and ipsilateral or bilateral upper neck. The low-risk CTV was ipsilateral or contralateral lower neck. The median prescribed radiation dose to high-risk CTV was 60 Gy and the median dose to low-risk CTV was 54 Gy. The 29 (57%) patient received bilateral neck irradiation. Ten patients (20%) also received concurrent postoperative chemotherapy with IMRT. Results: The median follow-up was 42 months (range, 6-77 months). Treatment failure occurred in 19 cases as follows: local in 13, ipsilateral neck in 9, contralateral neck in 3, and distant metastasis in 7. Most (90%) of the patients with contralateral neck recurrence or distant metastasis were accompanied with other locoregional recurrences. The median time from treatment completion to first locoregional recurrence was 7.3 months (range, 4.1-34.2 months). Of the 13 patients with local recurrence, 4 presented with perineural spreading into intracranial region and 4 patients with retromolar trigone recurrence. A total of 61.5% local recurrences were involved with infratemporal fossa or masticator space. The estimated 4-year local failure-free survival, locoregional failure-free survival, distant metastasis-free survival, and overall survival rates were 72%, 63.3%, 85.9%, and 68.8%, respectively. Conclusions: SCC of buccal mucosa is a highly aggressive form of oral cavity cancer with a high locoregional failure rate and most locoregional recurrences led to lethal events. Improvement of high-risk CTV definition especially in infratemporal fossa, masticator space, and retromolar trigone might transfer into better locoregional control. Author Disclosure: Y. Lin: None. L. Li-Ching: None.

Competing Causes of Death and Medical Comorbidities among Patients With Human Papillomavirus-Positive Versus -Negative Oropharyngeal Carcinoma and Its Impact on Compliance to Radiation Therapy

differences in outcomes in LA-HNSCC between C225 and CDDP were influenced by HPV Status. Materials/Methods: We reviewed the records of 147 consecutive patients with LA-HNSCC treated with definitive chemo-RT at one of our 3 institutions with known HPV status. Patients with nasopharyngeal carcinoma, oral cavity carcinoma, or distant metastasis at time of presentation were excluded. Further, patients who received induction chemotherapy or additional concurrent systemic agents were excluded. At institution 1, HPV Status was determined by p16 or HPV ISH; at institute 2 by PCR or p16; and at institute 3 by p16 or non-keratinizing histology. Smoking status was divided between those with a 10 pack-yr history or greater vs those without. Actuarial curves were created with the Kaplan-Meier method and multivariate Analysis (MVA) was performed with a Cox-regression model. Results: Median follow-up in surviving patients was 43 months. Ninetytwo (63%) patients were treated with CDDP and 55 (37%) with C225. T-stage, N-stage, smoking, and alcohol consumption were well balanced between the two groups. There were more patients greater than 70 yrs of age in the C225 group (22% vs 6%, p < 0.001) and more HPVpatients (44% vs 25%, p Z 0.03). The 2-year cumulative incidence of locoregional failure (LRF) was significantly higher with C225 compared to CDDP (41.9% vs 12.6%, p < 0.001). Subgroup analysis of patients by HPV status revealed increased 2-yr LRF with C225 in HPV+ patients (33.6% vs 10.4%, p Z 0.02) and in HPVpatients (52.6% vs 20.3%, p Z 0.02). MVA of LRF adjusting for HPV, T Stage, and N Stage continued to show improved outcomes with CDDP (HR Z 0.26, p Z 0.002). The 2-year DFS was also significantly worse with C225 compared to CDDP (38.6% vs 82.6%, p < 0.001). Subgroup analysis by HPV again revealed worse 2-yr DFS with C225 in HPV+ (46.4% vs 84.8%, p < 0.001) and HPVpatients (29.2 vs 74.9%, p < 0.001). MVA of DFS adjusting for HPV, Age, T stage, N Stage, and smoking demonstrated improved DFS with CDDP (HR Z 0.31, p < 0.001). Results for OS were similar. Conclusions: Loco-regional control and DFS are significantly improved with concurrent cisplatin as compared to cetuximab in definitive RT for HNSCC. Both HPV+ and HPV patients benefit from CDDP-based concurrent therapy in LA-HNSCC. Author Disclosure: N. Riaz: None. A. Baschnagel: None. D. Adkins: E. Research Grant; Lilly. S. Rao: None. J. Huang: None. P. Chen: None. J. Ley: None. D. Krauss: None. W. Thorstad: None. N. Lee: None.

Clinical Outcomes of Extensive Stage Small Cell Lung Carcinoma Patients Treated With Consolidative Thoracic Radiotherapy

ObjectivesTo determine the rates of loco-regional (LR) failure and toxicity in extensive-stage small cell lung carcinoma (ES-SCLC) patients treated with consolidative thoracic radiotherapy (TRT). MethodsA retrospective review was conducted on SCLC patients treated from January 2005 to July 2009. Patients with ES-SCLC who received consolidative TRT ≥30Gy were identified. Sites of disease failure, toxicity Common Terminology Criteria for Adverse Events version 3.0, incidence, and cause of treatment delays and vital status were determined. The cumulative LR and distant failure rates were calculated. Progression-free and overall survivals (OS) were determined by the Kaplan-Meier method. ResultsThree hundred thirty-six patients were identified with a diagnosis of SCLC and 215 patients had ES-SCLC. Nineteen (9%) patients were identified as receiving ≥30Gy consolidative TRT. Of this subgroup, the median age was 60 years (range 47 years to 82 years) and the median follow-up was 13 months (range 8 months to 32 months). Consolidative TRT was 40Gy/15 fractions (n = 16), 45Gy/30 fractions delivered twice daily (n = 2) and 36Gy/12 fractions (n = 1). Chemotherapy was sequential (n = 11) or concurrent (n = 8) with consolidative TRT. The incidence of LR failure was 26% and 39% at 1 and 2 years, respectively. The incidence of distant failure was 58% and 74% at 1 and 2 years, respectively. The median OS was 14 months. The 1-year and 2-year OS was 58% and 14%, respectively. No patients experienced clinical pneumonitis requiring treatment. ConclusionsConsolidative TRT controlled LR disease in most patients with minimal acute toxicity, though distant failure remained a significant problem.

Increased Incidence of Loco-Regional Recurrences among African American Women with Terminal Stage Breast Cancer

A prospective analysis of women with terminal breast cancer admitted to CHNE from November 2006-August 2007 evaluated anecdotal observations that African American (AA) women are likelier than Caucasian women to evidence loco-regional recurrences (LRR). Women with terminal breast cancer who were admitted to CHNE, a not-for-profit hospice serving over 90% of Northeast Florida hospice patients, were eligible for participation. 134 terminal breast cancer patients were assessed by hospice nurses for LRR presence via chest wall examination. 80% of them (107) were Caucasian, 17% (23) were AA and 3% (4) were of other ethnicities. Evidence of LRR were noted in 13% of the women (17/134). The proportion of patients with LRR was higher in AA women than Caucasian women (26% vs. 10%, 6/23 vs. 11/107, respectively), although this difference was not statistically significant (p = 0.08). The majority of Caucasian women with LRR consented to a medical record review, but a minority of AA women consented (8/11 vs. 2/6, respectively, p = 0.16). Evaluating disparities in breast cancer care outcomes is possible by reviewing data from patients served by hospice programs that aid a majority of patients within a community. This pilot data suggests that AA women with breast cancer have a higher incidence of loco-regional failure as a component of their terminal breast cancer disease than Caucasian women. A smaller proportion of AA patients and families agreed to participate in a medical record review study than Caucasians. Larger studies are necessary to confirm these findings, to elucidate factors contributing to disparities and to develop potential solutions.

Long-Term Survival After Cisplatin-Based Induction Chemotherapy and Radiotherapy for Nasopharyngeal Carcinoma: A Pooled Data Analysis of Two Phase III Trials

To evaluate the long-term outcome in patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and radiotherapy (CRT) versus radiotherapy alone (RT). The data from two phase III studies comparing CRT with RT in NPC were updated and pooled together for analysis. A total of 784 patients were included for analysis, with an equal number of patients in both arms. Induction chemotherapy consisted of two to three cycles of cisplatin, bleomycin, and fluorouracil, or cisplatin and epirubicin. RT was given to the nasopharynx and neck using megavoltage radiation (median dose, 70 Gy). The median follow-up time for surviving patients was 67 months. Analysis was based on intention to treat. The addition of induction chemotherapy to RT was associated with a decrease in relapse by 14.3% and cancer-related deaths by 12.9% at 5 years. The 5-year relapse-free survival rate was 50.9% and 42.7% in the CRT and RT arm, respectively (P = .014), and the 5-year disease-specific survival rate was 63.5% and 58.1% in the CRT and RT arm, respectively (P = .029). The 5-year overall survival rate was 61.9% and 58.1% in CRT and RT arm, respectively (P = .092). The incidence of locoregional failure and distant metastases was reduced by 18.3% and 13.3% at 5 years, respectively, with induction chemotherapy. There was no significant difference in the treatment failure patterns between the two arms. The addition of cisplatin-based induction chemotherapy to RT was associated with a modest but significant decrease in relapse and improvement in disease-specific survival in advanced-stage NPC. However, there was no improvement in overall survival.

Does post-operative radiotherapy (P-RXT) after radical prostatectomy (Px) improve progression-free survival (PFS) in pT3N0 prostate cancer (PC)? (EORTC 22911)

4504 Background:In 1992, as radical prostatectomy was more frequently applied to clinical T1–2N0M0 prostate cancer, the EORTC has undertaken a randomized trial of immediate post-operative treatment versus wait-and-see policy, for patients with high risk factors of local relapse on pathological specimen. We present the first efficacy results of this study. Methods: Eligible patients were ≤75 years old, WHO performance status (PS) 0–1, had T0–3N0M0 PC preoperatively and ≥1 pathological risk factor of: capsule invasion, positive surgical margins, invasion of seminal vesicles. P-XRT was 60Gy conventional external radiation delivered over 6 weeks. The trial was powered to detect a hazard ratio (HR) of 0.77 with 80% power with two-sided α=0.05 with regard to clinical or biological progression-free survival. Results: 1005 pts were accrued by end 2001 (P-XRT: 503, Px: 502). Median age was 65.4 years, PS 0 in 93.8%, median pre- and post-operative PSA 12.3 and 0.2 ng/ml, respectively. All but 41pts on P-XRT were irradiated with median dose 60Gy (range: 50–74). The trial was reviewed by an IDMC in December 2003, after a median follow-up of 5 years and early disclosure of the trial results was recommended. Biochemical PFS (time to twice confirmed PSA increase over nadir or first clinical failure or death) at 5 years was 72.2% (CI: 67.7–76.8) on P-XRT and 51.8% (CI: 46.8–56.8), HR=0.52 (CI: 0.42–0.64), P<0.0001. Clinical PFS was improved from 74.8% to 83.3% at 5 years (HR=0.68, CI: 0.52–0.89, P=0.004). The incidence of loco-regional failure was significantly decreased (P<0.0001). Further follow-up is needed to assess the impact on distant metastases and overall survival. P-XRT is associated with an increased risk of immediate and late grade 1–2 side effects. Grade 3 side effect rates so far were less than 5% in both groups. Conclusions: Post-operative radiotherapy results in improved biochemical and clinical PFS. This benefit is to be weighed against the treatment side effects. Further follow-up is needed to assess the impact on overall survival. No significant financial relationships to disclose.

Does post-operative radiotherapy (P-RXT) after radical prostatectomy (Px) improve progression-free survival (PFS) in pT3N0 prostate cancer (PC)? (EORTC 22911)

4504 Background:In 1992, as radical prostatectomy was more frequently applied to clinical T1–2N0M0 prostate cancer, the EORTC has undertaken a randomized trial of immediate post-operative treatment versus wait-and-see policy, for patients with high risk factors of local relapse on pathological specimen. We present the first efficacy results of this study. Methods: Eligible patients were ≤75 years old, WHO performance status (PS) 0–1, had T0–3N0M0 PC preoperatively and ≥1 pathological risk factor of: capsule invasion, positive surgical margins, invasion of seminal vesicles. P-XRT was 60Gy conventional external radiation delivered over 6 weeks. The trial was powered to detect a hazard ratio (HR) of 0.77 with 80% power with two-sided α=0.05 with regard to clinical or biological progression-free survival. Results: 1005 pts were accrued by end 2001 (P-XRT: 503, Px: 502). Median age was 65.4 years, PS 0 in 93.8%, median pre- and post-operative PSA 12.3 and 0.2 ng/ml, respectively. All but 41pts on P-XRT were irradiated with median dose 60Gy (range: 50–74). The trial was reviewed by an IDMC in December 2003, after a median follow-up of 5 years and early disclosure of the trial results was recommended. Biochemical PFS (time to twice confirmed PSA increase over nadir or first clinical failure or death) at 5 years was 72.2% (CI: 67.7–76.8) on P-XRT and 51.8% (CI: 46.8–56.8), HR=0.52 (CI: 0.42–0.64), P<0.0001. Clinical PFS was improved from 74.8% to 83.3% at 5 years (HR=0.68, CI: 0.52–0.89, P=0.004). The incidence of loco-regional failure was significantly decreased (P<0.0001). Further follow-up is needed to assess the impact on distant metastases and overall survival. P-XRT is associated with an increased risk of immediate and late grade 1–2 side effects. Grade 3 side effect rates so far were less than 5% in both groups. Conclusions: Post-operative radiotherapy results in improved biochemical and clinical PFS. This benefit is to be weighed against the treatment side effects. Further follow-up is needed to assess the impact on overall survival. No significant financial relationships to disclose.

Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: A pooled data analysis of two phase III trials

5524 Background: To evaluate the long-term treatment outcome in patients with advanced stage nasopharyngeal carcinoma (NPC) treated by cisplatin-based induction chemotherapy and radiotherapy (CRT) versus radiotherapy alone (RT). Methods: The updated records of two previously reported phase III studies (the Asian-Oceania Clinical Oncology Association trial and the Guangzhou trial). testing the benefit of adding induction chemotherapy to radiotherapy in NPC were reviewed and the data were pooled together for analysis. A total of 784 patients were included for analysis, with equal number of patients in both the CRT and RT arms. The induction chemotherapy consisting of 2–3 cycles of cisplatin 100 mg/m2 day 1, bleomycin 10 mg/m2 day 1 & 5, and fluorouracil 800 mg/m2 day 1–5, or cisplatin 60 mg/m2 day 1 and epirubicin 110 mg/m2 day 1. Radiotherapy was given to the nasopharynx and neck using megavoltage radiation, with a median dose of 70 Gy. Treatment compliance was 92.6% in the CRT arm and 98% in the RT arm. The median follow-up time for surviving patients was 67 months. Analysis was done by intention to treat. Results: The addition of induction chemotherapy to radiotherapy was associated with a decrease in relapse by 14.3% and cancer deaths by 12.9% at 5 years. The 5-year relapse-free survival rate was 50.9% in the CRT arm and 42.7% in the RT arm (p=0.014), and the 5-year disease-specific survival rate was 63.5% in the CRT arm and 58.1% in the RT arm (p=0.029). The median disease-specific survival was not yet reached in the CRT arm and it was 82 months in the RT arm. The incidence of loco-regional failure and distant metastases were reduced by 18.3% and 13.3% at 5 years respectively with induction chemotherapy. There was no significant difference in the failure patterns between the 2 arms. Conclusions: The addition of cisplatin-based induction chemotherapy to radiotherapy was associated with a modest but significant improvement in survival in advanced stage NPC. No significant financial relationships to disclose.

Atypical bronchial carcinoid tumors have a high incidence of loco-regional failure

Atypical bronchial carcinoid tumors have a high incidence of loco-regional failure

Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma

Purpose: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. Methods and Materials: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. Results: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group ( p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group ( p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group ( p = 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) Conclusion: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma.