Hui-Ling Ko

ANGIOGENIC BLOCKADE AND RADIOTHERAPY IN HEPATOCELLULAR CARCINOMA

PURPOSE We report our preliminary experience of combining sunitinib and helical tomotherapy in patients with advanced HCC. METHODS AND MATERIALS Records of patients with advanced hepatocellular carcinoma (HCC) treated with helical tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August 2008 were retrospectively reviewed. We report acute toxicities, radiologic response, serial alpha-fetoprotein (AFP) kinetics, and survival. RESULTS Of 23 evaluable patients, 60% had >or=2 hepatic lesions, extrahepatic disease was present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1 week before, during, and 2 weeks after RT. Thirteen patients continued maintenance sunitinib after RT until disease progression. Hypofractionated RT with a median target dose of 52.5 Gy/15 fractions was delivered. An objective response was achieved in 74% of patients. The 1-year survival rate was 70%, with median survival of 16 months. Multivariate analysis showed that maintenance sunitinib was the most significant factor for survival. The time to progression was 10 months in the maintenance group compared with 4 months in the control group. Eighteen out of 21 patients with elevated AFP (85.7%) had >or=50% decline of AFP within 2 months after RT. There were three episodes of upper gastrointestinal bleeding and one episode of pancreatitis; 10 patients had >or=Grade 2 elevation of liver enzymes, and 15 had >or=Grade 2 thrombocytopenia. CONCLUSIONS These preliminary results suggest that sunitinib and helical tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and AFP response rates in advanced HCC with an acceptable safety profile. Maintenance sunitinib after RT potentially prolongs survival. A randomized trial is warranted.

Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for lung cancer: A marker phase I trial

Tumor cells continuously evolve over time in response to host pressures. However, explanations as to how tumor cells are influenced by the inflammatory tumor microenvironment over time are, to date, poorly defined. We hypothesized that prognostic biomarkers could be obtained by exploring the expression of inflammation‐associated genes between early and late stage lung cancer tumor samples.

Trimodality bladder-sparing approach without neoadjuvant chemotherapy for node-negative localized muscle-invasive urinary bladder cancer resulted in comparable cystectomy-free survival

BackgroundTo retrospectively review the efficacy and organ preservation experience for muscle-invasive bladder cancer by trimodality therapy at our institution.MethodsBetween July 2004 and February 2012, seventy patients (M/F = 55/15; median age = 69 years) of lymph node negative localized muscle-invasive bladder cancer were treated primarily with trimodality approach including transurethral resection of bladder tumor (TURBT) prior to combined chemotherapy and radiotherapy (CCRT). Radiotherapy consisted of initial large field size irradiation with 3D conformal technique (3D-CRT), followed by cone-down tumor bed boost with intensity modulated radiotherapy (IMRT) technique. The median total doses delivered to bladder tumor bed and whole bladder were 59.4Gy and 40.0Gy, respectively. No patient received neoadjuvant chemotherapy (NAC). Weekly cisplatin was administered during radiotherapy. Toxicity was scored according to the RTOG criteria. Tumor response was evaluated both cystoscopically and radiographically 3 months after treatment.ResultsThe numbers of patients with T2, T3 and T4 lesions were 41, 16 and 13, respectively. Overall survival (OS) and progression-free survival (PFS) at 2 and 5 year were 65.7%, 51.9% and 50.8%, 39.9%, respectively, after a median follow-up time of 24 months. Local-regional control and distant metastasis free survival at 2 year were 69.8% and 73.5%, respectively. Complete response (CR) rate assessed three month after CCRT was 78.1%. Ten patients (20%) had local recurrence after initial CR (n = 50), 3 of them were superficial recurrence. One patient underwent radical cystectomy after recurrence. The overall 5-year bladder intact survival was 49.0% (95% CI, 35.5% to 62.5%). Acute toxicities were limited to grade 1-2. One patient developed late grade 3 GU toxicity.ConclusionsOur result suggested that trimodality bladder-sparing approach without NAC or dose-intensification could be well-tolerated with a high CR rate and bladder preserving rate for muscle-invasive bladder cancer.

Cutaneous Metastases from Squamous Cell Carcinoma of the Ureter

Objective: To present an extremely rare case of squamous cell carcinoma of the ureter with cutaneous metastases. Clinical Presentation and Intervention: A case is presented involving a 67-year-old woman presenting with a clinical history of squamous cell carcinoma of the ureter and who had undergone a nephro-ureterectomy with a bladder cuff excision in May 2004. The pathologic report showed squamous differentiation, as well as keratin pearl formation. A large regional cutaneous lesion on the chest wall was found in January 2006, and a biopsy showed metastatic malignant urothelial tumors consisting of squamous cell carcinomas. Conclusion: This report describes a case of cutaneous metastasis from a squamous cell carcinoma of the ureter that is extremely rare with a generally dismal prognosis.

Double autophagy modulators reduce 2-deoxyglucose uptake in sarcoma patients

Rationale According to the metabolic symbiosis model, cancer stromal fibroblasts could be hijacked by surrounding cancer cells into a state of autophagy with aerobic glycolysis to help provide recycled nutrients. The purpose of this study was to investigate whether combined treatment with the autophagy inhibitor: hydroxychloroquine (HCQ) and the autophagy inducer: sirolimus (rapamycin, Rapa) would reduce glucose utilization in sarcoma patients. Methods Ten sarcoma patients who failed first-line treatment were enrolled in this study. They were treated with 1 mg of Rapa and 200 mg of HCQ twice daily for two weeks. The standardized uptake values (SUV) from pretreatment and posttreatment [18F]-fluorodeoxyglucose positron emission tomography (FDG PET) scans were reviewed, and changes from the baseline SUVmax were evaluated. Results Based on FDG PET response criteria, six patients had a partial response; three had stable disease, and one had progressive disease. Nevertheless, none of them showed a reduction in tumor volume. The mean SUVmax reduction in the 34 lesions evaluated was − 19.6% (95% CI = −30.1% to −9.1%), while the mean volume change was +16.4% (95% CI = +5.8% to + 27%). Only grade 1 toxicities were observed. Elevated serum levels of lactate dehydrogenase were detected after treatment in most metabolic responders. Conclusions The results of reduced SUVmax without tumor volume reduction after two weeks of Rapa and HCQ treatment may indicate that non-proliferative glycolysis occurred mainly in the cancer associated fibroblast compartment, and decreased glycolytic activity was evident from Rapa + HCQ double autophagy modulator treatment.

Serum amyloid a as a predictive marker for radiation pneumonitis in lung cancer patients.

PURPOSE To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy. METHODS AND MATERIALS Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared. RESULTS Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively. CONCLUSIONS Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA.

REPEAT IRRADIATION OF RECURRENT HEPATOCELLULAR CARCINOMA - A SINGLE INSTITUTE EXPERIENCE

Purpose: Radiotherapy is recognized as an effective local treatment for hepatocellular carcinoma, but limited evidence exists for its efficacy in repeat liver irradiation. When other treatment modalities have been exhausted, repeat irradiation may be the only option. A single institution experience of repeat irradiation of hepatocellular carcinoma is reported here. Materials and Methods: Between 2003 and 2013, 19 patients (M/F = 17/2; median age = 64.4 years) with recurrent hepatocellular carcinoma (8 in-field and 11 out-field) and having had previous radiotherapy, were treated with repeat irradiation. The primary eligibility criteria for selecting these patients for repeat liver irradiation was normal liver volume greater than 700 mL. The median equivalent dose in 2 Gy (EQD2) delivered to tumors was 47.5 Gy (range: 30-71 Gy). A proportion of patients had concurrent and maintenance angiogenic blockades. Univariate analyses were used to identify statistically significant prognostic factors. Results: Among the 19 patients, complete response was achieved in 4 patients, and partial response in 6. The median overall survival for the entire series was 10.3 months. Overall survival rates at 1 and 2 years were 47% and 26% respectively. The presence of either longer treatment intervals between radiotherapies (＞ 6.2 months) or use of angiogenic blockades was associated with longer overall survival on univariate analysis. The incidence of radiation induced liver injury was 11%. Conclusions: Repeat hepatic irradiation is possible where the necessary dosimetric parameters can be met. Patients with longer intervals between radiotherapies may achieve longer survival rates in comparison to those without. Survival benefit is attainable with concomitant and maintenance angiogenic blockades.

Outcome of Gemcitabine Based Chemoradiation for Loco-Regional Cholangiocarcinoma

Purpose: Surgery remains the primary treatment of cholangiocarcinoma, with concurrent chemoradiation (CCRT) reserved for adjuvant treatment or as primary treatment for unresectable disease. However, the experience has been limited to flourauracilbased chemoradiation. A retrospective analysis of gemcitabine based CCRT as primary treatment for loco-regional cholangiocarcinoma in our institute was performed. Materials and Methods: Between April, 2004 and December, 2012, 26 patients (M/F=17/9; median age=66years) with cholangiocarcinoma (14 intrahepatic primary and 12 perihilar or extrahepatic primary) were treated with curative intent at our department. Baseline performance status based on Eastern Cooperative Oncology Group (ECOG) was 0-1 in 22 patients and 2 in 4 patients. Nine had regional extension of the diseases (defined as metastasis in either regional or para-aortic lymph nodes), whereas 17 had localized (T1-4N0M0) disease. The median equivalent dose in 2 Gy (EQD2) was 52.0 Gy (range: 40-72.1 Gy). Concurrent chemotherapy was low dose gemcitabine at 400 mg/m2 given weekly to biweekly. Both univariateand multivariate analyses were used to identify statistically significant prognostic factors. Results: The median survival of the entire cohort was 13.2 months. Survival rates at 1 and 2 year were 53% and 8% respectively. Patients of better performance status (ECOG 0-1) had improved median survival in comparison to those who of poorer baseline performance status (ECOG 2) (16.9 months vs. 1.5 months, p=0.045) on univariate analysis. Younger age (＜ 66 years) trended towards improved median survival (28.0 months vs. 4.8 months, p=0.055). There was eight local failures, two of which were isolated local failures. There were two treatment-related deaths. Conclusions: Outcome of low dose gemcitabine CCRT for cholangiocarcinoma seems promising. Those with better baseline performance status are most likely to benefit from this treatment. Definitive gemcitabine based CCRT for loco-regional cholangiocarcinoma may be an alternative to primary surgery.