Cholangiocarcinomas: A study of patient and disease characteristics and the potential use of tumor molecular profiling.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 270-270
Author(s):  
Petra Prins ◽  
Jeff Riskin ◽  
Karina Charipova ◽  
Michelle Dea ◽  
Ben Furlong ◽  
...  

270 Background: There are approximately 12,000 new cases of cholangiocarcinoma in the US annually and, as for most GI cancers, the incidence is rising each year. Unfortunately treatment options are limited and surgery is only a possible curative option if the disease is diagnosed at an early stage (5 yr. survival, 20-30 %). Molecular profiling may play a crucial role in the discovery of new (early) biomarkers and treatment options for cholangiocarcinoma. Methods: Clinical records 104 cholangiocarcinoma patients (pts) at the Lombardi Comprehensive Cancer Center were reviewed. Only pts that had received surgical therapy were eligible for study. Variables collected included pt demographics, initial disease stage, tumor differentiation, and clinical (pre-existing) conditions. Tumor recurrence and pt survival from time of surgery was evaluated. Molecular profiling data was analyzed when present. Results: In our cohort we identified 41 pts with cholangiocarcinoma who underwent surgery at LCCC. Clinical data was as follows: 20 males and 21 females. Average BMI at diagnosis was 25.8 kg/m2. Twelve pts had extrahepatic cancer, 20 intrahepatic, 5 gallbladder, 3 Hilar and 1 combined hepatocellular and bile duct cancer. Most tumors were stage T2 or T3 (61%), and were moderately (71%) to poorly differentiated (22%). Vascular or perineural invasion was identified in 46% of cases. Thirty-four percent and 37% had diabetes and hyperlipidemia, respectively. Tumor recurrence had occurred in 13 cases (32%), and median time to recurrence was 8.5 months (m). Median OS from surgery was 10.5 m (to date, 4 pts > 36 m). Molecular profiles were obtained in 5 cases. Most frequently observed genetic mutations were related to tumor suppression (PTEN, 4 cases) and DNA synthesis, repair, and regulation (TOP2A [3x], TOPO1 [2x], TP53 [2x]). Conclusions: Five-year survival rates for cholangiocarcinomas are low. To improve outcomes, improved early detection methods and better treatment options are urgently needed. Increasing the frequency of molecular profiling can result in new prognostic biomarkers as well as the potential for new treatment ideas.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Roman Rüdiger ◽  
Franziska Geiser ◽  
Manuel Ritter ◽  
Peter Brossart ◽  
Mignon-Denise Keyver-Paik ◽  
...  

Abstract Background Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany. Methods Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002–December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression). Results Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar’s test, P = 0.346) between both collectives. Conclusion Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.


2012 ◽  
Vol 21 (2) ◽  
pp. 97-105 ◽  
Author(s):  
Kathleen A Griffith ◽  
Renee Royak-Schaler ◽  
Kim Nesbitt ◽  
Min Zhan ◽  
Adriane Kozlovsky ◽  
...  

Breast cancer survival rates are lower in African Americans (AAs) than in Caucasians, owing in part to a higher prevalence of obesity in the former, which increases the risk of recurrence and mortality. The Women’s Intervention Nutrition Study (WINS) found that Caucasian women who followed a low-fat eating plan experienced a lower rate of cancer recurrence than women who maintained their usual diets. The purpose of this study was to test the feasibility of a WINS plan tailored to the cultural needs of AA breast cancer survivors. This feasibility pilot study was conducted at a university National Cancer Institute-designated comprehensive cancer center outpatient clinic with AA breast cancer survivors. The culturally specific WINS (WINS-c) plan included eight individual counseling sessions, five educational group meetings, and follow-up telephone calls over a 1-year period. Outcome measures included dietary fat, triglyceride, insulin and glucose levels, and fruit and vegetable intake. Participants ( n = 8) had a mean age of 61.1 years (standard error of the mean (SEM) 3.1 years) and a mean BMI of 32 kg/m2 (SEM 4.25 kg/m)2. Baseline daily fat consumption decreased from 64.6 g (range 36.8–119.6g) to 44.0 g (21.6–73.4g) at 52 weeks ( p = 0.07). Mean daily consumption of fruits and vegetables increased by 36% and 15%, respectively. Mean triglyceride levels decreased at 12 months ( p < 0.05). Sustained hyperinsulinemia was noted in most participants, including those without diabetes. Mean calcium and vitamin D consumption decreased over the 1-year study period. In AA breast cancer survivors, the WINS-c program resulted in a trend toward reduced fat consumption and may represent a sustainable approach in this population for improvement of diet quality after breast cancer.


2000 ◽  
Vol 18 (11) ◽  
pp. 2219-2225 ◽  
Author(s):  
William M. Mendenhall ◽  
Robert J. Amdur ◽  
Scott P. Stringer ◽  
Douglas B. Villaret ◽  
Nicholas J. Cassisi

PURPOSE: There are no definitive randomized studies that compare radiotherapy (RT) with surgery for tonsillar cancer. The purpose of this study was to evaluate the results of RT alone and RT combined with a planned neck dissection for carcinoma of the tonsillar area and to compare these data with the results of treatment with primary surgery.PATIENTS AND METHODS: Four hundred patients were treated between October 1964 and December 1997 and observed for at least 2 years. One hundred forty-one patients underwent planned neck dissection, and 18 patients received induction (17 patients) or concomitant (one patient) chemotherapy.RESULTS: Five-year local control rates, by tumor stage, were as follows: T1, 83%; T2, 81%; T3, 74%; and T4, 60%. Multivariate analysis revealed that local control was significantly influenced by tumor stage (P = .0001), fractionation schedule (P = .0038), and external beam dose (P = .0227). Local control after RT for early-stage cancers was higher for tonsillar fossa/posterior pillar cancers than for those arising from the anterior tonsillar pillar. Five-year cause-specific survival rates, by disease stage, were as follows: I, 100%; II, 86%; III, 82%; IVa, 63%; and IVb, 22%. Multivariate analysis revealed that cause-specific survival was significantly influenced by overall stage (P = .0001), planned neck dissection (P = .0074), and histologic differentiation (P = .0307). The incidence of severe late complications after treatment was 5%.CONCLUSION: RT alone or combined with a planned neck dissection provides cure rates that are as good as those after surgery and is associated with a lower rate of severe complications.


2019 ◽  
Vol 29 (2) ◽  
pp. 398-403 ◽  
Author(s):  
Beijiao Qin ◽  
Wenyan Xu ◽  
Yanfang Li

ObjectiveTo evaluate the role of omentectomy and lymphadenectomy in the treatment of clinically apparent early-stage malignant ovarian germ cell tumors.MethodsWe retrospectively reviewed 245 patients with malignant ovarian germ cell tumors (yolk sac tumor, dysgerminoma, and immature teratoma) and with clinically early-stage disease, who were treated at Sun Yat-sen University Cancer Center between January 1, 1970 and December 31, 2017. The survival of patients who underwent either omentectomy or lymphadenectomy, or both (omentectomy/lymphadenectomy group) was compared with that of patients who did not undergo omentectomy or lymphadenectomy (non-omentectomy/lymphadenectomy group).ResultsSixty patients were diagnosed with yolk sac tumor, 74 with dysgerminoma, and 111 with immature teratoma. Of these 245 patients, 216 patients had stage I disease, 28 patients had stage II, and 1 patient had stage IIIA. There were 190 patients who underwent omentectomy and/or lymphadenectomy and 55 patients in the non-omentectomy/lymphadenectomy group, respectively. In the omentectomy/lymphadenectomy group, 112 patients underwent both omentectomy and lymphadenectomy, 71 underwent omentectomy only, and 7 underwent lymphadenectomy only. Two hundred and fourteen of 245 patients (87.3%) received post-operative chemotherapy. Median follow-up was 73 months (range 1–388). The 10-year overall survival rates in the omentectomy/lymphadenectomy group and non-omentectomy/lymphadenectomy groups were 96.8% and 100%, respectively (p=0.340). Multivariate analysis evaluating all potential prognostic factors showed that omentectomy and lymphadenectomy are not prognostic factors for survival.ConclusionsOmentectomy and lymphadenectomy do not appear to improve survival and may be omitted in patients with clinically apparent early-stage malignant ovarian germ cell tumors.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8548-8548
Author(s):  
P. Jiang ◽  
M. Choi ◽  
D. Smith ◽  
L. Heilbrun ◽  
S. M. Gadgeel

8548 Background: The percentage of cancer patients ≥ 80 years old is expected to rise in the United States. However data are limited on use of chemotherapy in this group of patients. Methods: Retrospective identification of patients who received systemic chemotherapy at our cancer center between 1/1/2000 to 12/31/2004 was performed using the computer generated pharmacy data and medical records. Patients who had diagnosis of cancer and ≥ 80 years were included in the study; patients receiving only supportive care, hormonal therapy, or oral chemotherapy were excluded. The protocol for this study was approved by the Wayne State University IRB. Results: A total of 133 patients ≥ 80 years who received chemotherapy was analyzed. The median age was 83 and 31% of the patients were ≥ 85 years. There were more females (61%) than males (39%). The gender distribution was more even (47% v. 53%) after excluding gender specific tumors. The racial distribution was diverse- Whites 65 (49%); Blacks 41 (31%); Other 18 (13%); Unknown 9 (7%). 16% of the patients had hematologic malignancy and 84% had solid tumors. Gynecological cancers (32%) followed by aerodigestive cancers (26%) were the most common solid tumors. Solid tumor patients primarily had regional (48%) or distant (45%) disease. During the first regimen, 512 cycles of chemotherapy was delivered with a median of 3 cycles per patient (range 1–24 cycles); 40% of patients received only 2 cycles of chemotherapy. 64% of patients were able to receive chemotherapy without 2nd cycle delay. The distribution of single or multidrug regimens was fairly similar; Solid tumors 52% v. 48%; Hematologic cancers 43% v. 57%. Carboplatin and paclitaxel (22%) was the most common regimen among solid tumor patients. 26% of all patients received a second regimen. The 1 year survival rates among hematologic cancer and solid tumor patients were 65% and 48%, respectively. Stage of disease was the only statistically significant factor predicting survival. Conclusions: In this diverse group of cancer patients ≥ 80 years old and selected for chemotherapy, the treatment was feasible. The survival outcomes in this elderly population were comparable to those of a younger patient population suggesting that the treatment is beneficial. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4004-4004 ◽  
Author(s):  
G. Lurje ◽  
A. M. Schultheis ◽  
A. E. Hendifar ◽  
S. Ashouri ◽  
W. Zhang ◽  
...  

4004 Background: Despite recent advances in the treatment of metastatic colorectal cancer, tailoring adjuvant treatment of stage II and III colon cancer patients remains controversial. Identifying a reliable panel of prognostic and predictive markers for tumor recurrence is critical in selecting an individualized and tailored chemotherapy. Tumor angiogenesis plays an important role in tumor development, progression and metastasis. In this retrospective study, we tested whether a specific pattern of 40 functionally significant polymorphisms in 37 genes involved in angiogenesis and tumor microenvironment will predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1999 and 2006 blood specimens from 140 patients (69 females and 71 males with a median age of 59 years; range=28–86) were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC). Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR based RFLP. Results: Polymorphisms in VEGF (C936T; p=0.009, log-rank) and VEGFR2 (+4422 AC- repeat; p=0.04, log-rank and +1416 T/A; p=0.0009, log-rank) were associated with risk of tumor recurrence in stage III colon cancer patients (n=77). VEGFR2 AC-repeat polymorphisms were additionally associated with risk of recurrence in Stage II colon cancer patients (n=63, p=0.02, log-rank). Conclusion: VEGF C936T and VEGFR2 (+4422 AC-repeat and +1416 T/A) polymorphisms may help to identify Stage II and III colon cancer patients who are at increased risk for developing tumor recurrence. Angiogenesis seems to play a crucial role in tumor recurrence, thus targeting VEGF and VEGFR2 may be of clinical benefit for stage II and stage III colon cancer patients. Large prospective trials are needed to validate these preliminary data. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7086-7086
Author(s):  
K. Naqvi ◽  
J. Oh ◽  
G. Garcia-Manero ◽  
S. Pierce ◽  
M. E. Suarez-Almazor

7086 Background: Cancer patients often experience comorbidities that may affect their therapeutic plan, prognosis, and outcome. Few studies have evaluated comorbidities in myelodysplastic syndromes (MDS). The aim of our study was to determine the effect of comorbidity on the survival of patients with MDS. Methods: We reviewed the medical records of consecutive adult MDS patients who presented to our comprehensive cancer center in 2002. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients, was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the International Prognostic Scoring System (IPSS). We also collected information on bone marrow transplantation (BMT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Results: Of the 55 patients included in this preliminary report, 41 (74.5%) were male, and 47 (85.5%) were white; mean age was 66.4 years; mean follow-up 22.2 months. The three most common comorbidities were hypertension, diabetes mellitus, and coronary artery disease. A total of 90.9% of patients had an IPSS risk of intermediate or higher. The ACE-27 comorbidity scores were as follows: none, 18 patients (32.7%); mild, 17 (30.9%); moderate, 9 (16.4%); and severe, 11 (20.0%). Fifty patients (90.9%) died, whereas 9 (16.4%) underwent BMT. Median survival according to ACE-27 scores was: 22 months for patients with no comorbidity, 11 months for patients with mild or moderate comorbidity, and 8 months for those with severe comorbidity; this trend did not reach statistical significance (p = 0.42). A linear trend was observed between the severity of comorbidity and having received BMT: half of the patients with no comorbidities received BMT compared to none in the group with a severe score (p = 0.02). Conclusions: A small trend was observed between survival and comorbidity. Most of our patients had an advanced IPSS stage which may have decreased the strength of this association. Patients with comorbid conditions received BMT less often than those without comorbidity. Further studies are needed to evaluate the effects of comorbidities on the prognosis and therapeutic options of patients with early-stage MDS. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 242-242
Author(s):  
Tara M. Breslin ◽  
James Kubus ◽  
Haythem Y. Ali ◽  
T. Trevor Singh ◽  
Paul T. Adams ◽  
...  

242 Background: In 2012, ASCO identified five opportunities to improve the quality of cancer care and reduce costs. Two of these recommendations focused on limiting use of advanced diagnostic imaging with computed tomography (CT), Positron Emission Tomography (PET), and radionuclide bone scans (BS) at diagnosis and during surveillance for women with early stage breast cancer with a low risk of metastasis. We describe the use of diagnostic imaging among patients with early stage breast cancer treated at hospitals in Michigan. Methods: The Michigan Breast Oncology Quality Initiative is a collaboration between Michigan hospitals, the University of Michigan Comprehensive Cancer Center, and the National Comprehensive Cancer Network (NCCN). This collaborative collects longitudinal demographic, staging, treatment, and follow up data using the NCCN Breast Outcomes Database platform. We analyzed use of advanced diagnostic testing with CT, PET, BS and contrast it with use of traditional imaging (mammography/ultrasound) at diagnosis and during follow up in patients with stage 0, I, II breast cancer between 1998 to 2009. Patients who died or recurred were excluded. Results: The cohort included 7,632 patients (19.6% stage 0, 48.1% stage I, 32.3% stage II) treated at 17 hospitals. Use of traditional imaging was documented in nearly 100% of patients at diagnosis and throughout the follow up period. With respect to advanced diagnostic imaging, 20.3 % underwent CT, 4.7% underwent PET, and 11.6% underwent BS at diagnosis. Advanced testing use decreased over time (Table). Conclusions: Despite published guidelines, which recommend against their routine use, advanced diagnostic imaging use was prevalent among patients treated for early breast cancer at MiBOQI hospitals. Education efforts should target physicians and patients on the lack of proven benefit and potential risks of using advanced diagnostic imaging in this population. [Table: see text]


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 546-546
Author(s):  
Julia Marie Cunningham ◽  
Petra Prins ◽  
Brian Conkright ◽  
Simina Boca ◽  
Shruti Rao ◽  
...  

546 Background: Front-line chemotherapy for metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine backbone plus either oxaliplatin (FOLFOX or XELOX) or irinotecan (FOLFIRI or XELIRI). Large, prospective trials enrolling chemotherapy-naïve patients (pts) show FOLFOX and FOLFIRI treatment to be equivalent with similar response rates. Methods: Irinotecan inhibits TOPO1, which is now a candidate marker for irinotecan treatment benefit. Thus, we retrospectively analyzed TOPO1 expression level in 49 pts with mCRC who were treated with irinotecan-containing regimens at the Lombardi Comprehensive Cancer Center between 2009 and 2014. Patient characteristics and outcomes were compiled through chart review and the effect of TOPO1 expression on clinical outcomes was assessed. TOPO1 expression in tumor tissue from each pt was analyzed using a commercially available molecular profiling (MP) service (Caris Life Sciences). Results: The median overall survival (OS) for all pts was 33.9 months (mo), defined as the time from metastasis to death or censorship. When grouped by “high” or “low” TOPO1 expression, as defined by Caris at the time of the testing, 29 pts were high-expressers and 20 were low-expressers. High TOPO1 expressers receiving irinotecan (n = 22) had a median OS of 27.2 mo, compared with median 41.5 mo for low-expressers (n = 14) (p = 0.27). Irinotecan is conventionally given as second-line therapy. The median OS of pts receiving second-line irinotecan was 38.2 mo for high-expressers [n = 11] vs. 68.5 mo for low-expressers [n = 5]) (p = 0.32). Conclusions: Our limited data do not support the use of TOPO1 expression levels as a predictive marker for irinotecan therapy in mCRC. However, our conclusions are limited by small sample size, lack of a control group to distinguish prognostic from predictive markers, and timing of TOPO1 measurement, which in many cases was after irinotecan therapy. Physicians currently lack an evidence-based way to choose between potentially efficacious regimens for mCRC. More rigorous studies are needed to assess the benefit of MP in mCRC care. We are currently planning a prospective study with the hope of validating the use of TOPO1 expression as a predictive marker for treatment of this disease.


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