bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical prognostic factors associated with survival after definitive chemoradiotherapy in advanced squamous cell carcinoma of esophagus.
Authors: Shim Hyun-Jeong , Choi Won-young , Kim Dae-Eun , Hwang Jun-Eul , Bae Woo Kyun , Cho Sang-Hee , Chung Ik-Joo
Published: March 2020

e15121

Background: Definitive chemoradiotherapy (dCRT) has been used as a standard care for treating and palliating of symptoms in advanced esophageal cancer patients even if they have metastatic disease. The purpose of this study is to identify the treatment outcomes and prognostic factors for survival in squamous cell type of esophagus. Methods: We retrospectively studied the patients who treated with dCRT using 5-FU and cisplatin, and histologically proven squamous cell esophageal carcinoma of stage III and IV between January 2004 and December 2010. Results: In total 110 patients were enrolled in analysis of whom 64 patients were stage III and Iva (localized advanced) and 46 patients were stage IVb. The ratio of male/female was 109/1 and the median age was 65 years. T-stage was cT2=8%, cT3=75, cT4=17% and N-stage was cN0=5%, cN1=95%. The most common metastatic site was distant LN (60%). The median dose of radiation was 5400 cGy (range, 4400-6600). The median OS for locally advanced and metastatic disease group was 19.0 and 12.8 months, respectively (p=0.032). The median PFS for these groups was 8.3 and 6.9 months, respectively (p=0.208). The most common pattern of failure was locoregional area. In univariate analysis, cell type (poorly differentiation), dysphagia score, PS (ECOG 1-2 vs. 0), PFS (<5months) and CRP were significantly associated with OS and cell type, PS, PFS were shown significantly poor prognostic factors for OS in multivariate analysis. Among the patients who had locally advanced disease, maintenance chemotherapy after dCRT did not influence the OS. However, “good risk” patients who had less than 2 risk factors receiving maintenance chemotherapy showed better OS than those with no maintenance chemotherapy (40.9 vs. 12.3 months; p=0.011). Conclusions: dCRT has a major role in improving survival and palliation of dysphagia in inoperable advanced esophageal cancer even in metastatic stage. Cell type and PS have been still important prognostic factors in survival. In addition, maintenance chemotherapy after dCRT may be helpful for prolongation survival in good risk patients.
The role of VEGFR-2 expression in outcomes and survival of patients with peritoneal carcinomatosis from appendiceal cancer.
Authors: Sardi Armando , Jimenez William Andres , Francis Jennifer , Macdonald Ryan , Studeman Kimberly , Nieroda Carol Ann , Falla Juan Camilo
Published: March 2020

e15123

Background: Vascular endothelial growth factor receptor 2 (VEGFR-2) is considered a prognostic factor and treatment target for metastatic colorectal and ovarian cancer. Peritoneal Carcinomatosis (PC) from appendiceal cancer is a rare malignancy, treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), for which tumor histology, completeness of cytoreduction (CC), and lymph node (LN) status are predictors of survival. We hypothesize that high VEGFR-2 expression is a negative prognostic factor for survival in patients with PC from appendiceal cancer. Methods: A retrospective study of a prospective database was conducted in 127 patients with PC from appendiceal cancer who underwent CRS/HIPEC. Surgical specimens from a total of 59 patients were tested to identify “high” vs. “low” VEGFR-2 expression. Patients were divided into 2 groups: high VEGFR-2 expressers and low VEGFR-2 expressers. Patients’ outcomes and survival were analyzed. Results: There were 26 males and 33 females. Mean age was 51 years. Mean follow up of high and low expressers was 25.1 and 26.6, respectively (p = 0.806). At follow up, 33 (70%) of high expressers were alive and 14 (30%) deceased, while 11 (92%) of low expressers were alive and 1 (8%) deceased. Overall recurrence, use of bevacizumab, CC score, PCI, and LN status showed no differences between high and low expressers and did not correlate with survival or outcome. OS for high expressers was 90.5%, 59.8, and 47.1% at 1-, 3-, 5-years (p = 0.133) respectively, while OS for low expressers was 91.7% at 1-, 3-, and 5-years. Conclusions: There is a trend toward better outcomes and survival in patients with PC from appendiceal cancer who have low expression of VEGFR-2 compared to high expression. However, follow up is short and a larger number of patients is needed to confirm this trend and possibly correlate a high expression of VEGFR-2 to poorer outcomes and decreased survival in PC of appendiceal origin.
Effect of adjuvant chemoradiotherapy on survival in primary small cell carcinoma of esophagus (SCCE) patients: An analysis of multicenter clinical outcomes.
Authors: Zou Bingwen , Tao Li , Qiang Zhou , Yuan Ma Dai , Chen Yongshun , Xie Conghua , Li Wenhui , Lu You , Xu Yong
Published: March 2020

e15125

Background: To retrospectively evaluate the therapy pattern and survival in patients with dissection of primary SCCE. Methods: This study included 119 patients from seven centers in Middle and Western China who underwent radical section of SCCE. Forty six of them were treated with postoperative chemoradiotherapy (POCRT), and 73 of them with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 44 and 52 Gy), while the cycles of platinum-based chemotherapy ranged from two to eight with a median of four. Results: The 5-year OS and DFS were 14.5% and 11.7% of all patients, respectively. The median OS and DFS of all patients were 17.0(95%CI: 13.2-20.8) and 10.0(95%CI: 7.3-12.3) months, respectively. The 5-year OS and DFS were 22.0% and 20.0%, respectively, in the POCRT group, and 9.3% and 6.4%, respectively, in the POCT group (P=0.003 for OS and P=0.007 for DFS). There was significant difference in LRFS, favoring the POCRT group (5-year LRFS 74.3% vs. 42.0%, P=0.010), while the 5-year DRFS was 34.1% for the POCRT group comparing to 15.5% for the POCT group (P=0.039).In a multivariate analysis, treatment with more than four cycles of chemotherapy was associated with significantly better OS (HR=0.553, 95% CI, 0.347 to 0.881, P=0.0128) and DFS (HR=0.594, 95% CI, 0.386 to 0.914, P=0.0177). Tumor size less than 3cm was a poor prognostic factor for both overall survival and disease-free survival. Conclusions: Compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected SCCE. Future study of treatment modality with radiotherapy and chemotherapy is warranted.
Phase I dose-escalation study of pasireotide LAR in patients with advanced neuroendocrine tumors.
Authors: Phan Alexandria T. , Wolin Edward M. , Chan Jennifer A. , Huang Jerry M. , Hudson Michelle , Hughes Gareth , Shen Guoxiang , Strosberg Jonathan R.
Published: March 2020

e15126

Background: Somastatin analogs (SSA), including octreotide and lanreotide, bind predominantly to somatostatin receptor (SSTR) 2 and form the foundation of treatment for symptomatic neuroendocrine tumors (NET). Pasireotide, a novel SSA with a broad binding affinity (SSTR 1-3 and 5), is being explored for treatment of NET. A phase 1 dose-escalation study (NCT01364415) of pasireotide long-acting release (LAR; starting dose of 80 mg) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to characterize safety, tolerability, pharmacokinetics, and efficacy in pts with advanced NET. Methods: Pts with advanced, well- or moderately differentiated NET received pasireotide LAR beginning at a dose of 80 mg q28d. Successive cohorts will receive doses (up to 220 mg) guided by a Bayesian logistic regression model until MTD/RP2D is reached. Results: To date, 15 pts have been treated at 80 mg (n=6) and 120 mg (n=9). Median age is 59 (44-76) years. Primary tumor sites include small intestine (40%), pancreas (20%), and lung (13.3%). All pts received prior antineoplastic therapy; 93% received prior SSA. Median number of cycles of pasireotide was 6.68 (2-14) (1 cycle=28 days). 10 (67%) pts remain on treatment: 3 on 80 mg and 7 on 120 mg. 5 (33%) have discontinued (disease progression, 2 pts; withdrew consent, 2 pts; adverse event [AE], 1 pt). Median plasma concentrations of pasireotide increased with dose. No dose-limiting toxicities have been reported. Most frequent AEs were similar in both dose groups and included hyperglycemia (87%), diarrhea (53%), abdominal pain (47%), nausea (40%), anemia (33%), and fatigue (33%). Most AEs were mild/moderate. 2 pts (1 in each group) had grade 3 hyperglycemia. 4 (27%) and 2 (13%) pts had HbA1C increase from <6.5% at baseline to 6.5-<8% and ≥8%, respectively. 13 (87%) pts had radiographically stable disease as best response. More pts at 120 mg (50%) vs 80 mg (33%) achieved ≥50% reduction in chromogranin A. Conclusions: Pasireotide LAR up to 120 mg appears to be well tolerated in patients with advanced NET. The study is ongoing. Pasireotide represents a promising therapy for pts with NET. Clinical trial information: NCT01364415.
A prospective study on the incidence of postoperative venous thromboembolism in Korean gastric cancer patients: An inquiry into the application of western guidelines to Asian cancer patients.
Authors: Lee Keun Wook , Kim Jin Won , Chun Eun Ju , Choi Sang Il , Park Do Joong , Bang Soo-Mee , Lee Jeong-Ok , Kim Yu Jung , Kim Jee Hyun , Lee Jong-Seok , Kim Hyung-Ho
Published: March 2020

e15129

Background: Several Western guidelines recommend the routine use of pharmacologic thromboprophylaxis for cancer surgery patients to prevent venous thromboembolism (VTE). However, the necessity of routine pharmacologic perioperative thromboprophylaxis in Asian gastric cancer (GC) patients has not been clearly determined. Methods: To determine the necessity of routine perioperative pharmacologic thromboprophylaxis in Korean gastric cancer patients, the incidence of postoperative VTE was prospectively evaluated in gastric cancer patients receiving surgery. Among 610 GC patients who had received surgery, 375 patents prospectively underwent routine duplex Doppler ultrasonography (DUS) on days 5-12 following surgery to detect VTE and then VTE-related symptoms and signs were checked at 4 weeks after surgery (cohort A). The 235 patients that declined DUS were registered to cohort B and the occurrence of postoperative VTE was retrospectively analyzed. Results: In cohort A, symptomatic or asymptomatic VTE until 4 weeks after surgery was detected in 9 patients [2.4%; 95% confidence interval (CI); 0.9-3.9]. Tumor stage was a significant factor related to VTE development [stage I, 1.4%; stage II/III, 2.4%; stage IV, 9.7% (P = 0.008)]. In multivariate analysis, patients with stage IV had a higher postoperative VTE development [odds ratio, 8.18 (95% CI, 1.54-43.42)] than those with stage I. In cohort B, a low incidence of postoperative VTE was reaffirmed; only one postoperative VTE case (0.4%) was observed. Conclusions: The incidence of postoperative VTE in Korean GC patients was only 2.4%. Risk-stratified applications of perioperative pharmacologic thromboprophylaxis are thought to be more appropriate than the routine pharmacologic thromboprophylaxis in Korean GC patients receiving surgery.
Effect of the 92-gene molecular classifier on therapeutic decision-making in cancers of uncertain primary.
Authors: Schroeder Brock , Schnabel Catherine A. , Erlander Mark G. , Kim Benjamin
Published: March 2020

e15130

Background: Patients with metastatic cancer of uncertain primary site are at risk of suboptimal therapy if tumor type and subtype cannot be determined. Gene expression-based assays for tumor classification are utilized to complement clinicopathologic evaluation in cases with unknown primary sites of tumor origin or differential diagnoses; however, few studies have evaluated their clinical utility and effectiveness in real-world practice. The objective of this study was to evaluate the influence of a 92-gene molecular classification assay on clinical diagnosis and therapeutic decision-making. Methods: Medical oncologists who ordered the 92-gene assay as part of clinical care were invited to participate in a retrospective, questionnaire-based study. To minimize selection and recall biases, recruitment was based on consecutive cases: participating physicians were instructed to review the medical record of the first patient they ordered the 92-gene assay after a specified date and subsequently complete a 61-question survey. Results: Of 1,105 physicians invited, 103 (9.4%) completed the study (82% community practice; median practice time: 10 years). The majority of respondents had not initiated oncologic treatment before ordering the 92-gene assay: 31% had begun treatment, 24% had a specific regimen chosen but were waiting to begin treatment and 45% had not begun treatment or chosen a specific regimen. The 92-gene assay prediction was concordant with the final clinical diagnosis in 84% of cases; in one-third of these, the molecular diagnosis had not been clinically considered prior to molecular testing. Eighty-one percent of study participants reported that the 92-gene assay helped with therapeutic decision-making. Of these, the assay guided initial treatment choice in 52%, changed a considered treatment in 10%, excluded a potential treatment in 6%, and confirmed a previously determined treatment in 29% of cases. Conclusions: The results of this retrospective study demonstrate the clinical utility of molecular cancer classification: the molecular diagnoses provided by the 92-gene assay influenced therapeutic decision-making in the majority of cases.
Clinical outcomes with yttrium-90 resin microsphere radioembolization for hepatocellular carcinoma in a multiethnic southeast Asian population.
Authors: Khor Andrew Yu Keat , Toh Ying , Allen John Carson , Ng David Chee Eng , Zhu Guili , Choo SuPin , Lo Richard H. G. , Tay Kiang Hiong , Goh Anthony , Chow Pierce K. H.
Published: March 2020

e15137

Background: Treatment options for unresectable hepatocellular carcinoma (HCC) are limited. Intra-arterial yttrium-90 (90Y) microsphere radioembolization is an emerging treatment option with good outcomes among Caucasian patients. We report clinical outcomes in a multi-ethnic south-east Asian population treated with 90Y microspheres. Methods: A single-centre, retrospective, observational cohort study was conducted on patients who received 90Y microsphere radioembolization at Singapore General Hospital between January 2008 and June 2012. Patients were followed from the date of treatment until January 30, 2013, or until the date of death. Disease was staged by Barcelona Clinic Liver Cancer (BCLC) and Child-Pugh class. Patient survival was estimated using the Kaplan-Meier method. Response rate was determined by RECIST criteria. Prognostic factors for survival were identified using Cox proportional hazards regression. Results: 103 patients comprising 40.8% Chinese, 30.1% Myanmar, 14.6% Indonesian, 6.8% Indochinese and 7.7% others were treated with 90Y microspheres. Hepatitis B or C was recorded as the etiology in 47.6% and 23.3% of patients, respectively. The median overall survival (OS) was 14.4 months [95% CI 11.3-22.2 months] (BCLC B, 23.8 months ; BCLC C, 13.6 months; P = 0.048); (Child-Pugh A, 21.7 months; Child-Pugh B, 10.1 months; P < 0.0001). Median OS in patients with portal vein thrombosis (PVT) was poorer than those without PVT (PVT, 11.0 months; No PVT, 18.1 months; P = 0.024). Overall disease control rate by RECIST was 64.7%, while target lesions response rate was 98.3%. Progression of disease was mainly due to new lesions (69.2%). Significant prognostic factors for survival were serum albumin levels, presence of ascites and PVT. Conclusions: Survival outcomes in south-east Asian patients treated with 90Y microsphere radioembolization for HCC are comparable to Western populations in spite of the different etiologies. While target lesions response was good, new lesions are common and suggest that concomitant systemic therapy may have a role in disease control.
Clinicopathologic significance of HER2 expression in gastric cancer: A retrospective study in Indian population.
Authors: Kataru Sudheer Reddy , Vankamamidi Venkata Sampath , Chowhan Amit Kumar , Manickavasagam Meenakshisundaram , Radhakrishna Khajjayam , Raghuvamsi Nadiminty , Bhargavi Dandugundu , Andra Vindhya Vasini
Published: March 2020

e15143

Background: Gastric cancer is the second most common cause of cancer related death worldwide. HER2 expression is an important biomarker for identifying patients who could respond to targeted therapy. The purpose of this study was to evaluate the frequency of HER2 expression and its clinicopathological significance in Indian population with gastric cancer. Methods: In this retrospective study, clinicopathological details and formalin fixed embedded tissue from patients with gastric and gastro-esophageal junction Adenocarcinoma of all stages from August 2009 to January 2012 were collected. HER2 status in the tissue was evaluated by the validated methods. IHC (Immunohistochemistry) scores of 3+ were considered positive, 2+ equivocal, 1+ and 0 negative for HER2. Equivocal staining was further evaluated with FISH (Fluorescence In-situ Hybridization) testing. The significance of HER2 expression was correlated with epidemiological, clinical, pathological and biochemical parameters using Pearson’s test. Progression free survivals (PFS) were compared using Log Rank test (Mantel-Cox). Kaplan-Meier curves were determined for PFS. SPSS version 17.0 was used for statistical analysis. Results: We studied 135 patients, of which IHC for HER2 was 3+ in 8.8%, 2+ in 10.4%, 1+ in 8.9% and zero in 71.9%. Among HER2 equivocal samples (n=14), FISH showed HER2 gene amplification in 14.2%. HER2 status was negative in 89.6% and positive in 10.4%.HER2 status significantly correlated with stage (p=0.03), smoking status (p=0.022) and not correlated with Age, Gender, Site, Lauren’s classification, Albumin, Hemoglobin. HER2 negative patients have better PFS (13.1 versus 7.1 months; p=0.005) and the levels of HER2 expression significantly influenced the PFS (p=0.006).Median PFS in patients with 3+, 2+, 1+ and zero IHC scores were 8.2, 8.8, 9.3, and 14.2 months respectively. Conclusions: The frequency of HER2 expression in gastric cancer in Indian population is comparable to the published data. HER2 in Gastric cancer serves as a prognostic marker.
The effect of delay of adjuvant chemotherapy on survival in patients with resected stage II and III gastric cancer.
Authors: Jung Minkyu , Park Hyoung Soon , Park Han Na , Lim Seungtaek , Park Ji Soo , Chon Hong Jae , Kim Hyoung-Il , Ahn Ji Yeong , Cheong Jae-Ho , Hyung Woo Jin , Noh Sung Hoon , Kim Hye Ryun , Kim Hyo Song , Rha Sun Young , Chung Hyun Cheol
Published: March 2020

e15144

Background: Adjuvant chemotherapy improved survival in patients with gastric cancer. However, the association between the timing of adjuvant chemotherapy and survival has not been investigated. Methods: Patients with stage II and III gastric cancer who received adjuvant chemotherapy at Yonsei University Health System were included in this study. Time to adjuvant chemotherapy, relapse free survival (RFS), and overall survival (OS) were calculated from the day of surgery. RFS and OS were compared using log-rank test and multivariate analysis by the Cox proportional hazards model. Results: Among 675 patients, 226 patients (33.5%) began adjuvant chemotherapy within 1 month, 421 patients (60.1%) began adjuvant chemotherapy in 1 to 2 months, and 28 patients (4.1%) began adjuvant chemotherapy > 2 months after surgery. Intervals > 2 months between chemotherapy and surgery was associated with worse RFS and OS in both univariate analysis (RFS, p=0.039; OS, p=0.022, respectively) and a Cox proportional hazards model (RFS, hazard ratio [HR] =1.81, 95% confidential interval [CI] =1.05-3.12; OS, HR=1.96, 95% CI=1.11-3.47, respectively). Conclusions: Only 4.1% of patients initiated adjuvant chemotherapy >2 months after the date of curative surgery. Adjuvant chemotherapy delay > 2 months after surgical resection is associated with worse survival among patients with resected stage II and III gastric cancer.
The use of AFP and DCP as serum biomarkers to differentiate between hepatocellular carcinoma and intrahepatic cholangiocarcinoma in non-cirrhotic livers.
Authors: Nathavitharana Ravindhi Lakmalee , Teng Mabel Joey , Johnson Philip James , Berhane Sarah , Skowronska Anna , Morse Janet
Published: March 2020

e15162

Background: Differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) can be challenging in patients without evidence of liver cirrhosis. Definitive diagnosis is based on tissue biopsy. We investigated if the use of serum biomarkers could help differentiate between these two types of malignancies, thereby avoiding the risks associated with biopsy. Methods: Patients with cholangiocarcinoma and HCC were recruited from Queen Elizabeth Hospital, Birmingham, UK; blood samples were collected at time of diagnosis. Two biomarkers, alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were measured in the serum samples from 56 patients with cholangiocarcinoma and 35 patients with HCC without evidence of liver cirrhosis. Of the 56 patients with cholangiocarcinoma, 17 were intrahepatic and 39 were extrahepatic. Results: 17 ICC and 35 HCC were included in the analysis. The levels of AFP and DCP were much higher in HCC as compared to ICC. The median AFP was 64.6 (IQR 10.9, 3564.2) in HCC as compared to 3 (IQR 2.4, 3.9) in ICC. Similarly, the median DCP was 215.41 (IQR 22.46, 692.53) in HCC as compared to 0.33 (IQR 0.16, 1.08) in ICC. Stepwise logistic regression was performed using both biomarkers. Log- DCP remained significant at 95% level in predicting HCC from ICC, giving an AUC of 0.96. Conclusions: In patients with a non-cirrhotic liver and radiological evidence of cancer, measurement of serum AFP and DCP level may help differentiate between HCC and ICC. In this study, DCP is the most useful discriminator between HCC and ICC. Further prospective studies should be done with larger sample sizes to validate the use of AFP and DCP as diagnostic biomarkers in this clinical setting.
Phase II study of paclitaxel and capecitabine (PX) combination as neoadjuvant chemotherapy for unresectable locally advanced gastric cancer.
Authors: Ko Yoon Ho , Hong Sook Hee , Roh Sang Young , Song Kyo Young , Jung Eun Sun , Jeon Hae Myung , Park Cho Hyun , Hong Young Seon
Published: March 2020

e15164

Background: Unresectable locally advanced adenocarcinoma (AGC) of the stomach is associated with poor prognosis due to the lack of effective treatment. Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally AGC in the current multidisciplinary treatment model. Paclitaxel and capecitabine (PX) has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. This phase II study was performed to evaluate the efficacy and safety of neoadjuvant PX chemotherapy in patients with unresectable locally AGC. Methods: Patients with AGC, clinically unresectable because of local invasion and/ or conglomerated regional lymph nodes (station 7, 8, and 9) metastasis on based on laparoscopic staging, were enrolled. PX consisted of paclitaxel 175 mg/m2 i.v. on day 1, and capecitabine 835 mg/m2 twice daily p.o. on days 1–14 every 21 days. After three cycles of NAC, patients with clinically resectable AGC underwent surgical resection. Results: This trial was stopped for poor accrual after 18 patients were enrolled; 50% patients had tumors located in the proximal third of the stomach. Seventeen patients finished three cycles of chemotherapy. The overall response rate was 41.2% (7/17 cases), of which 71.4% (10/14 cases) metabolic response. Fourteen (77.8%) of the 18 patients enrolled underwent surgery, and 12 (85.7%) had an R0 resection. Pathological complete response was observed in one (7.1%) of patients. Toxicity was mild to moderate and there were no treatment-related deaths and no major surgical complications. With a median follow-up of 28.6 months (range 6.4-38.4 months), the 2-year survival rate for all patients was 71.1%. Subgroup analysis found R0 resection (35.7 months vs. 20.6 months, P= 0.005) and patients with pathologic N downstaging (P < 0.001) to have improved overall survival. Conclusions: Neoadjuvant chemotherapy with PX shows promising results in unresectable locally AGC patients without increased morbidity and mortality. Neoadjuvant PX may permit a larger chance of curative resection in unresectable locally AGC patients.
Frequency of BRCA1 5382insC mutations in Russian non-selected pancreatic cancer patients.
Authors: Kashintsev Alexey
Published: March 2020

e15165

Background: Pancreatic cancer (PC) is known to be associated with BRCA2 mutations, while the role of BRCA1 in the increase of PC risk is less evident. BRCA1/2-driven tumors, including pancreatic cancer, are sensitive to platinating agents and PARP inhibitors. Epidemiology of BRCA1 mutations in Russia is characterized by a pronounced founder effect, with the allele BRCA1 5382insC being detected in 70-90% of all BRCA1 mutation carriers. Methods: 237 patients with consecutive patients with pancreatic cancer were by questionnaires, and 149 have provided their normal DNA to the study and underwent genotyping for BRCA 1 5382insC mutations. Results: Among all the patients in 105/237 (44.3%) patients reported first-degree relatives with various types of cancer, including 11/237 (4.6%) cases of pancreatic cancer. 2/149 genotyped patients carried BRCA1 5382insC allele. Both mutation carriers had first-degree family history of breast cancer. Conclusions: Given the simplicity of founder mutation detection, BRCA1 5382insC allele deserves to be tested in Slavic pancreatic cancer, especially in those reporting family history of BRCA1-associated tumors.
The impact of adjuvant delayed radiotheraphy (RT) on survival in patients with resected periampullary adenocarcinomas.
Authors: Yalcin Suayib , Kertmen Neyran , Yuce Deniz , Yildiz Ferah , Hamaloglu Erhan
Published: March 2020

e15168

Background: Postoperative prognosis for ampullary carcinoma (AC) is superior to that of pancreatic cancer (PC), the former exhibiting higher complete surgical resection, lower recurrence and longer survival rates (1). Despite all the major recent advances in surgery, chemotherapy (CT) and RT, PC is still one of the most lethal malignancies, overall survival (OS) rates being as low as 5% at 5 years (2). This study was intended to evaluate survival in patients with resected periampullary cancer treated with adjuvant Gemcitabine (Gem) and cisplatin (Cis) with or without delayed RT (with Gem). Methods: This retrospective study involved 91 patients diagnosed and treated with periampullary cancer. Patients with adenocarcinoma of periampullary region with gross total tumor resection and lymph node dissection (R0 and R1 resections only) were included. Of 59 patients with PC, 38 received Gem and Cis for 3 cycles (3 months) before CRT. When delivered after Gem /RT, Gem and Cis were usually given for another 1-3 cycles. Twenty-seven patients received Gem and Cis alone over 6 cycles. Of 32 patients with non-pancreatic periampullary 23 received CT+CRT and 9 patients received CT alone. Results: Patients with non-pancreatic periampullary cancer had better OS (p:0.017) and disease free survival (DFS) ( p<0.001 ) compared to patients with PC. Median OS of patients with PC was 21 months. Both OS and DFS were superior in the RT arm compared to nonRT arm (p: 0.043 and p <0.001). In non-pancreatic periampullary cancer patients OS was 31 months in RT group and 51 months in non-RT group (p: 0.709). DFS was 29 months and 49.8 months respectively, p:0.504). Conclusions: The prognosis of PC was worse than non–pancreatic periampullary tumor. In PC adjuvant delayed RT improved patient outcome. Although OS and DFS were better in patients receiving CT alone, the difference was not statistically significant in non–pancreatic periampullary tumors.
S-1/docetaxel compared with the other standard S-1 based regimens as a first-line chemotherapy for patients with advanced gastric cancer.
Authors: Kusumoto Tetsuya , Ando Koji , Ida Satoshi , Kimura Yasue , Saeki Hiroshi , Oki Eiji , Morita Masaru , Maehara Yoshihiko
Published: March 2020

e15173

Background: S-1 monotherapy or S-1/CDDP have remained important as a standard chemotherapy regimen for patients with advanced gastric cancer (AGC), based on the randomized phase III trials. Although S-1/docetaxel has been reported highly active and well tolerated for AGC by many researchers, it could not show the superiority compared with S-1 monotherapy in the recent international randomized trial. We have also demonstrated that it might be effective for patients with Stage III AGC in both preoperative and postoperative adjuvant setting. The aim of this study was to evaluate efficacy, toxicity and validity of S-1/docetaxel retrospectively, compared with the standard regimens. Methods: We conducted a retrospective review of the data of 89 patients with AGC who received chemotherapy who were given S-1-containing regimens as the first line chemotherapy; 15 patients treated with S-1 monotherapy, 21 with S-1/CDDP, and 53 with S-1/docetaxel. The objective response, adverse event (AE), progression-free survival (PFS), and overall survival (OS) were compared between the three groups. Results: The overall response rates (ORRs) were obtained 6.7%, 38.1% and 30.2% for S-1 monotherapy, S-1/CDDP, and S-1/docetaxel, respectively. The incidence of AEs was more frequent in S-1 based combined treatments than in the S-1 monotherapy, however there was no significant difference in the severe AEs between each group. Survival data showed that the PFSs were 121 days, 199 days and 178 days, respectively, and there was the significant difference between S-1 monotherapy and S-1/docetaxel (p<0.05). The overall survival showed that the MSTs were not significantly different. The conversion rate to the subsequent treatments following S-1 monotherapy was higher than the other treatments. Conclusions: S-1/docetaxel was active and well tolerated for the patients with ARGC as the first line. Although the Japanese guideline for treatment of gastric cancer recommends S-1 monotherapy or S-1/CDDP as the standard regimens, docetaxel could be applied for patients with AGC in case of CDDP-resistant or –naïve patients.
Feasibility and potential benefits of adjuvant chemotherapy with S-1 in patients with curative resected advanced biliary tract cancer: A multicenter trial.
Authors: Toyoki Yoshikazu , Ishido Keinosuke , Kudo Daisuke , Kimura Norihisa , Wakiya Taiichi , Umehara Yutaka , Tohyama Shigeru , Endoh Masaaki , Tateoka Hiroshi , Ohishi Susumu , Hakamada Kenichi
Published: March 2020

e15179

Background: S-1 chemotherapy is reported to be effective for treating metastatic and unresectable biliary tract cancer (BTC). We assessed the safety and feasibility of adjuvant S-1 chemotherapy in patients with curative resected advanced BTC. Methods: Patients with pathological stage II, III, or IVa BTC (according to JSBS) who underwent radical resection received oral S-1 (80 mg/m2/day) for 2 consecutive weeks every 3 weeks (1 cycle). Patients were aged 20–80 years, had a performance status of <1, and provided informed consent. The treatment was repeated until 1 year after surgery. The primary endpoint was feasibility of the adjuvant chemotherapy with S-1. The secondary endpoints were safety, disease-free survival (DFS), and overall survival (OS). Results: We enrolled 40 patients, but 5 patients were excluded on the basis of eligibility criteria (4 patients) or no drug administration (1 patient). We analyzed data from 35 patients (29 men and 6 women with a median age of 68 years) between January 2009 and November 2011. The feasibilities of 6-month and 12-month administration of S-1 were 65.7% (95% confidence interval [CI]: 47.8–80.9%) and 45.7% (95% CI 28.8–63.4%), respectively. Grade 3 neutropenia and anemia were observed in 2.9% and 5.7% of cases, respectively. Grade 3 non-hematological toxicities included anorexia in 14.3%, fatigue in 8.6%, and nausea in 2.9% of cases. No grade 4 hematological or non-hematological toxicities were observed, and no treatment-related deaths occurred. The 1-year OS was 91.4% (95% CI: 76.6–97.2%), and the 1-year DFS was 68.6% (95% CI: 51.7–81.7%). Conclusions: Adjuvant chemotherapy with S-1 for curative resected advanced BTC patients was both safe and feasible. Although the follow-up period was insufficient to evaluate OS and DFS, adjuvant chemotherapy with S-1 is believed to have improved the prognosis.
Pain and other symptoms in patients with hepatocellular carcinoma (HCC): A qualitative analysis.
Authors: Butt Zeeshan , Mallick Rajiv , Mulcahy Mary Frances , Benson Al B. , Cella David , Kaiser Karen
Published: March 2020

e15187

Background: HCC is the second leading cause of cancer related deaths worldwide and incidence is increasing. Most HCC patients are diagnosed late-stage and with pain. Understanding the nature of pain experienced by HCC patients is complicated by co-morbid (including other liver) diseases and treatment related pain. The purpose of this study was to identify pain symptoms that are important and relevant to HCC patients who have received systemic therapy. Methods: We conducted semi-structured thematic interviews with 10 HCC patients who were currently on or previously had received oral systemic therapy (e.g., sorafenib) and had not received local or loco-regional therapy (e.g., surgery, radiation or chemo-embolization) within 4 weeks of the interview. Interviews included open elicitation of key symptoms, side effects and concerns. Patients also completed selected pain items from the FACT-Hep; items had previously been validated for patients with hepatobiliary cancers. Results: Mean age was 58 years (range 33-77); 2 patients had co-morbid cirrhosis, 1 had co-morbid hepatitis, and 4 patients had cirrhosis and hepatitis. When asked to describe the symptoms, side-effects or other issues that most significantly impact their quality of life, patients most often mentioned fatigue (n=5), diarrhea (n=5), skin toxicities (n=5), and loss of appetite (n=4). Nine patients reported experiencing pain over their HCC treatment course. Abdomen (N=7) and lower back (N=3) were the most common sites of pain; 2 patients reported only experiencing temporary pain from prior chemoembolization. The other 7 patients experienced ongoing pain, partly attributed to systemic therapy, ascites, or metastases. Ongoing abdominal and back pain were frequently not attributed to a specific cause. All patients indicated that FACT-Hep items adequately assessed their pain. Conclusions: Although pain was not a major driver of quality of life and for a few HCC patients it was transient and treatment-related, the majority of patients experienced some persistent pain. Abdominal pain and back pain were the most common pain sites for HCC patients. These results support the relevance of pain symptoms that have been previously identified as important in HCC.
Clinical value of FDG PET/CT in predicting local failure in patients with esophageal cancer.
Authors: Fan Bingjie , Hu Man , Kong Li , Zhang Xiaoli , Fu Zheng , Yu Jinming
Published: March 2020

e15197

Background: Local failure, including local residual tumor and local recurrence, is the most common failure patterns for patients with esophageal cancer (EC) treated with radiotherapy. The purpose of this study was to evaluate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for predicting local failure in patients with EC. Methods: Twenty-two patients with biopsy-proven EC treated definitively with RT with or without chemotherapy were enrolled from June 2010 to August 2012. Dose of 60.4 - 70.2 Gy with 1.8 - 2.0Gy /fraction were delivered with three-dimensional conformal radiation therapy (CRT). All patients underwent FDG PET/CT scan prior to therapy. The patients were followed up every 3 months after treatment completion. Patients who developed local failure were confirmed with histological evidence or follow-up. Results: The follow up time was in the range of 5-30 months. Of 22 patients, 3 patients had local residual tumor, 2 patients experienced local recurrence. The mean SUVmax for patients with local failure was higher than that for patients without local failure (15.688±3.115 vs. 14.137± 4.397, p = 0.54). The local failure regions were mostly the regions with higher metabolic activity before radiotherapy. Conclusions: Patients with higher FDG-uptake may have higher risk to experienced local failure. The local failure regions were localized mostly in the higher FDG uptake regions of pre-therapeutically FGD PET/CT scans of the patients with EC.
Safety and activity of sunitinib in elderly patients (75 years or more) with metastatic renal cell carcinoma: Results of retrospective study in Paoli-Calmettes Cancer Institute in France.
Authors: Boulaamane Lamia , Rousseau Frederique , Cecile Maud , Braticevic Cecile , Dermeche Slimane , Walz Jochen , Salem Naji , Brunelle Serge , Thomassin Jeanne , Errihani Hassan , Gravis Gwenaelle ,   National Institute of Oncology
Published: March 2020

e15506

Background: Actual tolerability of cancer treatment is still poorly documented in elderly patients. Recently some retrospective reviews have been carried out to evaluate tolerability and efficacy of Sunitinib in elderly patients (> 65 years), with metastatic renal cell carcinoma (mRCC) enrolled in clinical trials. Yet data on routine clinical practice are still lacking. Methods: Between January 2009 and May 2012, 17 patients >= 75 years treated with Sunitinib for mRCC were reviewed, to assess toxicity, cause of treatment reduction or discontinuation. Correlation of toxicity with 7 domains comprehensive geriatric assessment (CGA), tumoral response and progression-free survival (PFS) were also analysed. Results: The median age was 79 years, and patients were followed-up until September 2012. The majority of patients were in the MSKCC favourable or intermediate-risk groups. Eleven patients have received Sunitinib in first line. The median dose received was 37.5mg. Grade II-III diarrhea was observed in 6 patients and grade I-II hand-foot syndrome in 9 patients. Treatment was stopped earlier (< 50 days) for 4 pts, due to severe toxicity: hospitalization in intensive care unit, oesophageal ulceration, asthenia and malnutrition. Temporary treatment discontinuation was observed for 3 pts. All patients underwent 7 domains CGA, and were classified according to Balducci scale. Correlation was not found between impairment at CGA with severe toxicity nor with response, but correlation was found between initial dose and treatment discontinuation. Sunitinib at level of 50 mg was associated with early and permanent treatment discontinuation, and initial dose reduction was associated with an acceptable safety profile and long time treatment duration. Response rate was 41.1% for partial response and 41.1% for stable disease. Median PFS was 23.3 months. Conclusions: This is the first retrospective study performed in elderly cancer patients aged over 75 years. There is no evident correlation between CGA impairment and toxicity profile of Sunitinib. Low starting and dose escalation in the absence of severe toxicity could be suggested.
Real-world treatment patterns in U.S. mRCC patients who fail two lines of targeted therapy.
Authors: Malangone Elisabetta , Gorritz Magdaliz , Stern Lee , Coombs John H. , Turnbull James D. , Liu Zhimei , Pal Sumanta Kumar
Published: March 2020

e15511

Background: The treatment landscape for mRCC has undergone rapid growth in recent years with the approval of several targeted therapies (TTs). An analysis of real-world treatment patterns in patients who fail two lines of TT using the MarketScan database was recently presented (Pal S et al ASCO GU 2013 [Abstr 231]). The current study aimed to assess treatment patterns in mRCC patients who fail 2nd line TT using the PharMetrics database. Methods: Data were obtained from the PharMetrics database for patients with an RCC diagnosis and at least 3 lines of TT between January 1, 2004 and September 30, 2011. The PharMetrics database covers over 100 health plans across the U.S, and is plan-based, unlike MarketScan which is employer-based. Adult patients with at least 3 months of follow-up prior to initiation of 3rd line TT were included. Treatment patterns were examined for the final sample. Time to treatment discontinuation (TTD) was defined as the time from initiation of 1st line to end of 3rd line TT. Patients who did not switch to a 4th line TT were censored at end of 3rd line. Results: 377 mRCC patients initiated 3rd line therapy with sorafenib (So), sunitinib (Su), bevacizumab (Be), temsirolimus (Te), everolimus (Ev), or pazopanib (Pa). The sample was majority male (71%) with a mean age of 61 years (SD=10.5). The most common metastatic sites at any time were lung (76%) and bone (56%). The most common 1st line agent was Su (46%) and the most common 2nd line single agents were Te (26%) and Ev (17%). The most frequently used single agents in 3rd line were Te (23%), Be (17%) and Ev (15%). Third-line treatment choice differed by year; Te (49%) was most common in 2007 while Ev and Pa were most common between 2010 and 2011. The most common sequences were VEGF->mTOR->VEGF (41%), VEGF->VEGF->mTOR (22%), and VEGF->mTOR->mTOR (11%). The median TTD in months, adjusted for censoring were as follows (median (25th-75th percentile): VEGF->mTOR->VEGF: 36.9 (23.3-NA); VEGF->VEGF->mTOR: 27.7 (15.74-NA); VEGF->mTOR->mTOR: 29.9 (18.3-38.0). Conclusions: These results confirm those presented at ASCO GU. There is a growing number of TTs being prescribed in 3rd line mRCC patients. TTD results suggest an average treatment period of 32 months for the overall study sample.
Effect of sorafenib on cathepsin B-dependent BID-mediated apoptosis in cancer cells.
Authors: Santoni Giorgio , Amantini Consuelo , Santoni Matteo , Morelli Maria Beatrice , Farfariello Valerio , Nabissi Massimo , Liberati Sonia , Burattini Luciano , Bonfili Laura , Eleuteri Anna Maria , Mozzicafreddo Matteo , Berardi Rossana , Cascinu Stefano
Published: March 2020

e15515

Background: Several tyrosine kinase inhibitors (TKIs), have been developed and approved for clinical use in multi-targeted cancer therapy. Among these, sorafenib is an orally available multikinase inhibitor approved for the treatment of the advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Aim of our study was to evaluate the mechanisms responsible for the cytotoxic effects induced by in vitro use of µM doses of sorafenib in 5637 and J82 bladder cancer (BC) cell lines. Methods: The viability of BC cell lines were tested by MTT assay. Autophagy was evaluated by western blot analysis with the anti-LC3 and anti-p62 antibodies, acridine orange staining and cytofluorimetric analysis. Apoptosis, (ΔΨm) dissipation and ROS generation were determined by Annexin-V/PI, JC-1 and DCFDA staining, respectively and cytofluorimetric analysis. The cathepsin B activation was evaluated by western blot using an anti-cathepsin B antibody; the cathepsin B proteolytic activity was determined using the fluorogenic Z-Arg-Arg-AMC peptide and the fluorescence of the hydrolyzed 7-amino-4-methyl-coumarin was detected by a SpectraMax Gemini XPS microplate reader. Results: We found that sorafenib markedly reduced at µM dose the viability of BC cells. Treatment for 24h with 20µM of sorafenib, triggered “Incomplete autophagy”, that induced apoptosis of BC cells. Sorafenib by inducing an increased cathepsin B activity and pro-apoptotic protein BID activation, triggered a ROS-mediated-mitochondrial-dependent apoptosis of BC cells. Moreover, the increase of cathepsin B activity induced by sorafenib was inhibited by a specific tyrosine phosphatase inhibitor (e.g., orthovanadate) strongly suggesting for a contribute of tyrosine-phosphatases in sorafenib-induced apoptosis. Conclusions: Sorafenib by triggering incomplete autophagy, stimulates a cathepsin B-induced-BID-mediated-ROS- and mitochondrial-dependent apoptosis of BC cells, which is likely regulated by tyrosine-phosphatases.
First-line mTOR inhibition in metastatic renal cell carcinoma (mRCC): An updated analysis from the International mRCC Database Consortium (IMDC).
Authors: Harshman Lauren Christine , Kroeger Nils , Rha Sun Young , Donskov Frede , Wood Lori , Tantravahi Srinivas Kiran , Vaishampayan Ulka N. , Rini Brian I. , Knox Jennifer J. , North Scott A. , MacKenzie Mary J. , Yuasa Takeshi , Srinivas Sandy , Pal Sumanta Kumar , Heng Daniel Yick Chin , Choueiri Toni K.
Published: March 2020

e15518

Background: FDA approval of the mTOR inhibitors (mTORi) in mRCC was based on efficacy in poor risk patients (pts) in the first line setting for temsirolimus (T) and in VEGF inhibitor-refractory pts for everolimus (E). Little is known about T’s effectiveness in good and intermediate risk patients and E’s outcomes in the first line setting. Methods: We interrogated the IMDC for the outcomes of pts who received mTORi as first-line targeted therapy. Results: 127 pts received a first line mTORi; the majority received T (93 T, 34 E). The main reasons for T administration were poor risk (38%), non-clear cell histology (27%), and clinical trial (15%) whereas clinical trial (82%) and non-cc histology (6%) drove E use. Of the T and E pts, 58% and 32% were poor risk, respectively. Median age was 61 years and median KPS was 80%. 68% had prior nephrectomy (62% T vs. 82% E). Median progression-free survival (PFS) and overall survival (OS) are detailed below. In the 97 pts with response data, 5% and 53% for T and 8% and 58% for E achieved partial responses and stable disease, respectively. Progressive disease as best response occurred in 41% for T and 33% for E. Second line therapy was captured in 52 pts (41%), of whom 48 received VEGF inhibitors. Conclusions: Given the different populations in which they were administered, direct comparisons of the frontline efficacy of T vs. E cannot be made. The majority of T pts were poor risk, which their dismal PFS and OS reflect. The better outcomes in the E pts highlight that the majority were not poor risk and were healthy enough for clinical trials. While limited by small numbers, this data characterizes a real world experience of mTORi in the first line setting. [Table: see text]