No abstract

Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. Materials/Methods: A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. Results: Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for < 10 mm resection margins). Median follow-up was 6.5 years (0.8-28.6 years). Local failure occurred in 1/39 negative, 2/16 micro+, and 4/4 gross+ resection margin groups. Five-year LC, DC and OS for negative vs micro+ vs gross+ resection margin groups were: 97% vs 93% vs 25% (P < 0.001, micro+ vs negative: P = 0.083); 78% vs 75% vs 75% (P = 0.97), 83% vs 87% vs 25% (P < 0.001). No patient developed significant toxicity (e.g., blindness) related to RT. Conclusion: HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

There was no statistical difference between sham RT, PRT, and SRT. Preliminary H&E and CD34 staining (an endothelial cell marker) did not demonstrate a difference in cellularity between groups 14 days post-RT, but a possible decrease in vascularity for SFX was noted. However, histological analyses are ongoing. Conclusion: These findings demonstrate the potential use of ferumoxytol and T2*-weighted MRI to assess tumor vascularity post-RT. Using this technique, a difference in contrast agent delivery was detected in tumors receiving a single high dose of radiation, presumably due to disruption of tumor vasculature. Non-invasive imaging techniques to assess short-term RT-induced tumor vascularity changes can provide additional insight regarding RT delivery approaches in preclinical and clinical studies.

Background: Molecular profiling of tumor DNA has changed the management of many cancers. For example, differences in mutations have been observed in lung adenocarcinoma between smokers and non-smokers, with the latter harboring more EGFR mutations. However, there is a paucity of information the influence of mutagen exposure on molecular profile in other cancers. This is a pilot analysis to determine if smoking history or prior adjuvant radiation has an influence on the molecular profiles of women with breast cancer. Methods: Moffitt's Clinical Genomic Action Committee (CGAC) database was used to assess 62 patients with breast cancer treated at Moffitt with targeted deep sequencing of 315 genes as part of clinical care between 4/1/2013 and 12/31/2015. Smoking history was determined by self-report and history of adjuvant radiation therapy was abstracted from the medical record. Tumor sequencing results were analyzed for differential mutational burden (any alteration other than amplifications) and the presence of differentially altered genes between the groups of interest. The groups were similar with regards to percentage of triple negative patients (35.3% vs. 33.3%) between active/prior smokers and never smokers respectively. Results: The most frequently mutated genes across the cohort were TP53 (54.2%), PIK3CA (40.7%), MLL3 (25.4%), CDH1, PTEN, and MLL2 (18.6%), BRCA2 and NF1 (15.3%), BARD1, ESR1, CDKN2A/B, and SPEN (13.6%). There was no difference in the mutational burden between 17 smokers (mean 10.2 alterations; range 1-21) and 42 never smokers (mean 11.5 alterations; range 4-30); p=0.35, with a trend towards more mutations in never smokers. Amongst genes with at least for total alterations, breast cancers of smokers contained a higher frequency of alterations in APC, BLM, and RAD50 (17.6% vs. 2.4%), PIK3CA (58.8% vs. 33.3%), MAP3K1 (23.5% vs. 7.1%), GPR124 (17.6% vs. 4.8%), and TP53 (70.6% vs. 47.6%); although none met statistical significance for multiple comparisons. On the other hand, non-smokers contained increased alterations in MLL2 (5.9% vs. 23.8%), ATM (0.0% vs. 14.3%), as well as FAT1, ATR, AR, and KDM5C (0.0% vs. 11.9%); but also did not differ to a statistically significant degree. There was no difference in the mutational burden between 26 patients without prior radiation and the 34 with prior radiation, each group had a mean of 11.1 alterations. Conclusions: There was no difference in the mutational burden between smokers and never smokers in breast cancer or between breast cancer patients who received prior radiation therapy and those who did not. Smoking StatusMean # of AlterationsRangeAssociated Molecular AlterationsCurrent/Former (n = 17)10.21-21APC, BLM, RAD50, PIK3CA, MAP3K1, GPR124, TP53Never (n=42)11.54-30MLL2, ATM, FAT1, AR, KDM5C Citation Format: Knepper TC, Grabska J, Teer JK, McLeod HL, Solliman HH. Influence of mutagen exposure on molecular profile in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-03-08.