Citations

289 Background: Cholangiocarcinoma (CC), hepatocellular carcinoma (HCC), and pancreatic ductal adenocarcinoma (PDAC) are all devastating malignancies. Limited data exists about PD-1 and PDL1 expression in these cancers. We assessed expression of PD1/PDL1 in a large cohort of patients with hepato-pancreatico-biliary (HPB) cancers and explored the existence of accompanying genomic mutations associated with expression of PD-1/PD-L1. Methods: 524 patients with HPB cancers (354 PDAC, 58 HCC, 54 intrahepatic (ICC), 18 extrahepatic (ECC), and 40 gallbladder (GBC)) were included in the study and tumors tested centrally at a CLIA lab (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (next generation sequencing, Illumina TruSeq), protein expression (immunohistochemistry [IHC]) and gene amplification). PD-1 (SP142 antibody) and PD-L1 (MRQ-22 antibody) status was tested in all samples. Two-tailed Fisher's exact test was performed to test where proportions of positive results were different by subgroup (p²0.05). Results: Among those with PDAC, HCC, ICC, ECC, and GBC, rates of PD1 expression on tumor infiltrating lymphocytes (TILs) and PD-L1 expression on tumor cells is detailed in the Table. In PD-1+, compared with PD-1- HPB cancers, mutations in the following were more prevalent, though not statistically significant: BRCA2, ATM, CTNNB1, and PIK3CA. Among all theranostic biomarkers tested, TOP2A expression (IHC) was significantly increased in PD-L1+ versus PD-L1- tumors (82% vs 60%; p=0.0083). Conclusions: HPB tumors express PD-L1 at a frequency of 4-18%, and PD-1 at a frequency of 29-45%. A statistically significant association of mutations with PD-1+ or PD-L1+ tumors was not identified in this group of tumors. PD-L1 expression associates with TOP2a expression, a marker of proliferation and also anthracycline sensitivity. Further evaluation of this correlation and PDL1/PD-1 + anthracycline combination therapy may be warranted. [Table: see text]

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA < 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.

96 Background: In the last decade there has been an increase in the incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. Although many factors have been proposed to explain this trend, the impact of breast reconstruction on the decision to undergo CPM has not been extensively studied. Methods: A retrospective review of breast cancer patients from Surveillance, Epidemiology and End Results (SEER) registry data (2004-2008) was conducted. Characteristics of patients undergoing CPM were evaluated. Results: 71,176 patients with a diagnosis of stage I-III infiltrating ductal or lobular breast cancer underwent mastectomy for their primary lesion. Among these, 10,558 patients (15%) underwent a CPM. A significantly higher proportion of women undergoing CPM had reconstruction performed (44%) than those patients not undergoing CPM (13%), p<0.001. On multivariate analysis (Table), significant variables predicting CPM included age <50 years (OR 10.12), breast reconstruction (OR 3.58), and lobular histology (OR 1.41), all p<0.001. Of the 12,466 patients (18%) who underwent reconstruction, 4,636 (37%) had implant reconstruction, 4,498 (36%) had tissue reconstruction, and 1,122 (9%) had combined tissue/implant reconstruction (no data for 18%). On multivariate analysis, predictors of reconstruction included age <50 years (OR 20.5; CI 18.5-22.7), year of surgery (2008 vs. 2004; OR 1.60; CI 1.49-1.71), low tumor grade (OR 1.19; CI 1.13-1.25) and ER+ status (OR 1.16; 95% CI 1.10-1.23). The use of radiation therapy was associated with a lower likelihood of pursuing reconstruction (OR 0.61; CI 0.58-0.65). Conclusions: Apart from age, the factor most strongly associated with CPM is the decision to have reconstructive surgery performed. This suggests that CPM may not be purely associated with risk-reduction but also with treatment factors such as cosmesis. [Table: see text]

Merkel cell carcinoma (MCC) is a rare and biologically aggressive neuroendocrine tumour of the skin. Recent analysis of a surveillance, epidemiology and end results program has shown a statistically significant increase of 8% per year in the age-adjusted rates for MCC of the skin over the past 15 years. MCC commonly presents as a painless, rapidly growing, single red or purple cutaneous nodule. Diagnosis is often delayed until histopathological examination due to the relative rarity of the disease. MCC-specific immunohistochemical markers are available for definitive diagnosis, including anticytokeratin-20-positive stain and thyroid transcription factor-1-negative stains. Because there are no phase III trials to guide management, treatment is often tailored to the individual patient by integrating surgery, radiation and chemotherapy.

Successful dialysis access necessitates superficial arteriovenous fistula (AVF) placement to facilitate identification of anatomical landmarks for safe cannulation. Suction-assisted lipectomy (SAL) may be an alternative to traditional surgical AVF revision procedures for placing fistulas more superficially. Three patients with an average body mass index of 45.2 kg/m 2 , with inaccessible AVFs due to obesity, underwent ultrasound-guided SAL of their upper extremities. Successful cannulation was achieved within two weeks. A clinically insignificant hematoma and arm swelling occurred in one patient. SAL provides a safe and effective alternative for salvaging deep AVFs for dialysis access in the upper extremities of obese patients.

INTRODUCTION Acellular dermal matrices have been used with increasing frequency in both reconstructive and cosmetic surgery. While many studies have described the safety and morbidity profiles of these materials, little is known about the relative mechanical properties of individual sheets of allograft harvested from distinct donors. METHODS Sixty-two individual sheets of an acellular dermal matrix from distinct lot numbers (signifying different donors of the dermis) were prospectively analyzed before use. Distribution of thickness according to manufacturer specifications in the dry state were as follows: 0.009 inches to 0.013 inches (1 [1.6%]); 0.79 mm to 1.78 mm (3 [4.8%]); 0.79 mm to 2.03 mm (5 [8%]); 0.8 mm to 3.3 mm (1 [1.6%]); 1.8 mm to 3.3 mm (10 [16.1%]) and 28 mm (6 [9.7%]). The size of the matrix was recorded while dry, after hydration and following stretch. The percentage change in surface area was recorded for each lot. RESULTS The 62 reconstructive cases included breast implant reconstruction (2 [3.2%]); ventral hernia repair (11 [17.7%]); abdominal closure following autologous tissue harvest (6 [9.6%]); autologous breast reconstruction (37 [59.6%]); extremity wound closures (3 [4.8%]) and reinforcement of vertical rectus abdominis muscle closure (3 [4.8%]). The mean percentage change in the size of the acellular dermal matrix to the hydrated state was 58% (36 of 62; thickness 0.06 mm to 3.30 mm); the mean percentage change in size from dry state was 7.14% (range 0% to 18.7%). The mean percentage change in the size of the hydrated matrix to the stretched state was 25.7% (range 0.25% to 70.6%). The variability in elasticity among the individual sheets was significant (P<0.0005). CONCLUSION The acellular dermal matrix displayed highly variable elastic properties among distinct donors. This may be significant in procedures in which symmetry is critical.

The deep inferior epigastric artery perforator flap is an option for women desiring autologous tissue breast reconstruction. If this reconstruction fails, other autologous tissue flaps, including the gluteal artery perforator and latis-simus dorsi flaps, may be used for salvage. The anterolateral thigh (ALT) flap offers adequate tissue volume for breast reconstruction, acceptable fat quality and a long vascular pedicle. Other advantages include obviating the need for intraoperative position changes and harvesting tissue outside of the radiation field. Two cases involving ALT flaps used in the setting of deep inferior epigastric artery perforator failure are presented with favourable results. A review of the anatomy of the ALT flap is included.