Habboush, Yacob

Introduction and aim: Combined hepatocellular-cholangiocarcinoma (HCC-CCA) is a rare liver malignancy distinct from either hepatocellular carcinoma (HCC) or cholangiocarcinoma. Liver transplantation (LT) is not recommended for HCC-CCA because of suboptimal outcomes. Because non-invasive diagnosis of HCC-CCA is extremely challenging, some HCC-CCAs are presumed as HCC on imaging and listed for LT with the correct diagnosis ultimately made on explant pathology. We compared HCC-CCA with HCC to determine the utility of response to pre-transplant loco-regional therapy (LRT) in predicting outcomes for HCC-CCA after LT as a potential means of identifying appropriate HCC-CCA patients for LT. Materials and methods: Retrospective review of 19 patients with pathologically confirmed HCC-CCA individually matched to 38 HCC patients based on age, sex, and Milan criteria at listing was performed. The modified response evaluation criteria in solid tumors was used to categorize patients as responders or non-responders to pre-transplant LRT based on imaging performed before and after LRT. Overall survival (OS) and recurrence-free survival (RFS) were examined. Results: OS at 3 years post-transplant was 74% for HCC-CCA and 87% for HCC. RFS at 3 years was 74% for HCC-CCA, and 87% for HCC. Among responders to LRT, the 3-year OS was 92% for HCC-CCA and 88% for HCC; among non-responders, 3-year OS was 43% for HCC-CCA and 83% for HCC. Higher 3-year OS was observed among HCC-CCA responders (77%) compared with HCC-CCA non-responders (23%). Conclusions: OS was similarly high among responders to pre-transplant LRT irrespective of tumor type. Radiologic response to LRT could potentially be used to select appropriate HCC-CCA patients for LT if the findings are validated in independent studies.

Abstract Background: Mixed hepatocellular cholangiocarcinoma (HCC-CCA) is a rare primary malignancy of the liver which is distinct from hepatocellular carcinoma (HCC) or cholangiocarcinoma. HCC-CCA is presumed to have a poor prognosis and is not recommended for transplantation. The clinical and radiological presentation of HCC-CCA overlaps with HCC; thus, patients with these cancers may be mis-diagnosed as HCC and undergo liver transplantation, with the precise diagnosis ultimately determined on explant pathology. Patients undergoing transplant for presumed HCC receive loco-regional therapy (LRT), such as transarterial chemoembolization and radiofrequency ablation pre-transplant. Our goals were to (1) evaluate pre-transplant response to LRT, as predictors of recurrence and survival after transplant in HCC-CCA, and to (2) compare outcomes of transplant with adjuvant LRT in HCC-CCA and HCC. Methods: A retrospective study of 57 patients with presumed HCC who underwent liver transplantation and had pre-transplant LRT was performed. The study included 19 HCC-CCA cases and 38 HCC cases diagnosed on explant pathology, and individually matched (1:2) on age, sex, and Milan criteria. Response to LRT was determined by MRI performed before and after LRT. The response evaluation criterion in solid tumors (RECIST) was used to categorize treatment responses as “responders” if a patient had a complete or partial response or “non-responders” if a patient had stable or progressive disease. Recurrence rates, recurrence-free survival (RFS), and overall survival (OS) following LRT and transplant were compared between groups using Fisher’s exact tests. Results: The overall 1- and 3-year survival rates were 84% and 74% for HCC-CCA, and 95% and 87% for HCC, respectively. RFS at 1 and 3 years was 79% and 74% for HCC-CCA, and 92% and 87% for HCC (p-values >0.05). For HCC-CCA, one-year OS and RFS in LRT responders were 92% and 83%, whereas for LRT non-responders, OS and RFS were 71% each. In contrast, for HCC, one-year OS and RFS in LRT responders were both 97%, whereas among non-responders, they were 83% and 67%, respectively. At three years, OS and RFS in responders were 92% and 75% for HCC-CCA and 88% and 90% for HCC, respectively; whereas among non-responders, OS and RFS rates were 43% and 57% for HCC-CCA and 83% and 50% for HCC, respectively (all p-value >0.05). Conclusions: Short-term, post-transplant survival was poorer for HCC-CCA than HCC. However, OS among LRT responders for both cancers was similar. Response to LRT predicts favorable RFS in both HCC-CCA and HCC. Among non-responders, recurrence rate and RFS at three years were dismal and similar for both HCC-CCA and HCC, although OS is much lower for HCC-CCA patients. Response to pre-transplant LRT can be used for identifying HCC-CCA patients at high risk of recurrence and poor survival after liver transplantation. Citation Format: Yacob Y. Habboush, Samuel O. Antwi, Lori Chase, Tushar C. Patel. Response to loco-regional therapy as predictors of outcomes after transplantation for mixed hepatocellular cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-237. doi:10.1158/1538-7445.AM2017-LB-237

IntroductionAdult prostatic sarcoma (PS) is a rare disease. While surgery is considered the standard approach, the role of other therapies is not completely established. We report results of the largest multicentric contemporary cohort of PS patients.Materials and MethodsThis study included 61 adult PS patients treated in 16 American and European Institutions. Median age was 64.4 years (range: 22‐87). Curative surgery was delivered in 48 patients (prostatectomy = 26, cystoprostatectomy = 22), usually with lymphadenectomy (n = 40). Curative radiotherapy (RT) was delivered in 32 patients, as radical (n = 5), neoadjuvant (n = 10), or postoperative treatment (n = 17). Eighteen patients received chemotherapy. None of the patients received hormonal therapy.ResultsMedian follow‐up was 72 months (95%CI: 55‐not reached). Five‐year local control (LC), overall survival (OS), cancer‐specific survival, disease‐free survival, and metastases‐free rates were 47%, 53%, 56%, 35%, and 35%, respectively. Notably, curative RT (neoadjuvant, adjuvant, or definitive) was associated with improved 5‐year LC (55% vs. 31%, P = 0.02) and OS (59% vs. 46%, P = 0.1). Surgically treated patients presenting with a cT3‐4 tumor (n = 31), who received RT (n = 24), had a significantly improved 5‐year LC (68% vs, 33%, P = 0.004) and OS (65% vs. 21%, P < 0.001) rates compared to patients not receiving RT. cT4 patients demonstrated a significantly lower 5‐year OS (43% vs. 61%, P = 0.006) and LC (29% vs. 69%, P < 0.001) rates. Histologic subtype was not associated with LC and OS, but patients with prostatic stromal sarcoma, rhabdomyosarcoma, or sarcomatoid carcinoma had worse 5‐year LC compared to other types (47% vs. 55%) and OS (49% vs. 58%).ConclusionAdult PS has a poor prognosis. Locally advanced tumors have poor LC and OS rates. Curative RT should be considered part of the multidisciplinary approach to PS.