bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of gender, age, and ethnicity with survival in patients with pancreas cancer
Authors: Ottochian M. , Yang D. , El-Khoueiry A. , Iqbal S. , Pohl A. , Zhang W. , Ning Y. , Lenz H. J.
Published: August 2020

e15587

Background: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. However little is still known about factors that influence its development and progression. Recent data suggest that PC is, at least in part, an estrogen- dependent disease; there is growing epidemiological evidence that aspects of reproductive history and hormonal exposure are associated with risk of this disease. It was shown that age at menarche of <13 is associated with less risk of PC. However no data are available whether gender is associated with outcome in patients with PC. The purpose of this study was to test whether age, gender or ethnicity influence the outcome in PC. Methods: The data of the 50,302 adults diagnosed with PC between 1988 and 2004 were extracted from the Surveillance Epidemiology and End Results public use database. These included 24,240 patients diagnosed with localized pancreatic cancer (LPC) and 26,062 patients with metastatic pancreatic cancer (MPC). Demographic, clinical variables and survival time were retrieved. The primary endpoint was overall survival. We constructed Cox proportional hazards models to evaluate association between patient characteristics and survival in LPC and MPC separately. Pair interactions were also tested. Results: On multivariate analysis gender, age, race, marital status, tumor size, grade, histology, type of treatment and lymph node involvement were found to be independent predictors of survival. Females had a significant longer survival, with an HR of 0.959 (95% CI: 0.932–0.987) among patients with LPC and an HR of 0.918 (95%CI: 0.894–0.942) among patients with MPC. Each age group displayed a significant longer survival than its correspondent older age group. When we combined age and gender in the analysis, females had a longer survival than males in each single age group in the MPC group. In the LPC group the longer survival of female patients was only observed in the youngest age group. Conclusions: This is the first and largest study to address gender and outcome in PC. Our data suggest that the estrogen pathway may play an important prognostic role in patient with this disease. These data also warrant further in vitro and in vivo investigations on the mechanisms of estrogen and pancreas progression.

No significant financial relationships to disclose.
Phase II trial of adjuvant hyperthermic intraperitoneal chemotherapy with three drugs for the prophylactic treatment of carcinomatosis after resection of advanced gastric cancer
Authors: Murata S. , Naito H. , Yamamoto H. , Mekata E. , Shimizu T. , Shiomi H. , Naka S. , Abe H. , Kurumi Y. , Tani T.
Published: August 2020

e15588

Background: This prospective study was performed to assess the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) with three drugs in patients with curative resection of T3 or T4 advanced gastric cancer. Methods: Patients with curative resection of clinically T3 or T4 advanced gastric cancer were required to be under 75 years of age and to have adequate organ function. After the curative resection of gastric cancer with D2 lymph node dissection and the reconstruction of the alimentary tract, HIPEC was carried out for 30 minutes with 50mg of CDDP, 10mg of MMC, and 1000mg of 5-FU in 5 L saline maintained at 42–43°C. Patients were given an adjuvant S-1 treatment after surgery. Primary endpoint of this study was overall survival. Results: A total of 29 patients were eligible. Pathologically, 8 patients had sub-serosal invasion (pT2(ss)), 18 patients had serosal invasion (pT3), and 3 patients had adjacent organ invasion (pT4). These patients included pT2(ss)pN0 (n=2), pT2(ss)pN1 (n=6), pT3pN0 (n=4), pT3pN1 (n=9), pT3pN2 (n=5), pT4pN0 (n=1), and pT4pN1 (n=2). Median follow-up period was 44 months (10–72 months). Overall 5- year survival rate in all eligible patients was 89.5%. Overall 5-year survival rate in patients with pT2(ss), pT3, or pT4 was 100%, 82.4%, or 100%, respectively. Three patients with pT3 had recurrence of pleural dissemination (n=1), lymph node metastases (n=1), or pulmonary metastases and peritoneal dissemination (n=1). A total of 7 patients had postoperative complications such as continuous pancreatic juice secretion (13.8%), abdominal abscess (10.3%), leakage of the anastomosis (3.4%), and pulmonary insufficiency (10.3%). Conclusions: The present study suggests that HIPEC with three drugs after curative resection of advanced gastric primary cancer is associated with improved overall survival with an acceptable morbidity.

No significant financial relationships to disclose.
Second-line pemetrexed–oxaliplatin combination for advanced pancreatic adenocarcinoma
Authors: Mazzer M. , Zanon E. , Foltran L. , De Pauli F. , Cardellino G. , Iaiza E. , Ermacora P. , Aprile G. , Fasola G.
Published: August 2020

e15597

Background: Few regimens showed efficacy in advanced pancreatic cancer patients (pts) who had failed a first-line gemcitabine-based therapy. However, there is growing evidence suggesting that second-line treatment may provide further disease control in selected pts. Both pemetrexed and oxaliplatin demonstrated activity in this setting, and their combination resulted safe and tolerable.Methods: Pancreatic cancer pts with advanced disease, PS>60, age>18 years, who progressed after a gemcitabine-based therapy were enrolled in a phase II trial, and treated with pemetrexed 500 mg/mq followed by oxaliplatin 120 mg/mq, day 1 every 3 weeks, together with adequate oral folinic acid and intramuscular vitamin B12 supplementation. Accordingly to the Simon Minimax two-stage study design, an accrual of 31 patients was planned, with a minimum response rate considered of interest of 25%, α level 0.10 and β level 0.10. Results: To date, 16 patients have been treated. Of them, 12 progressed during or shortly after gemcitabine (13) or gemcitabine-cisplatin combination (3), with a median time to progression of 186 days. 62 cycles were delivered, with a median of 4 cycles per patient (range 2–8). Overall, the regimen was well tolerated: most common adverse events were mild-to-moderate sensory neurotoxicity and gastrointestinal disturbances. We reported grade 3 anemia, grade 3 thrombocytopenia, and grade 3 fatigue in 1 patient each. Three among the treated patients died within 30 days from last delivered cycle due to progressive disease. Confirmed partial (3) or minor responses (6) were observed in 9 out of 15 evaluable pts, with a median decrease in the Ca 19.9 value of 43% among those who responded. Median progression-free survival was 99 days. At the time of analysis, 3 out of 16 patients are still on treatment.Conclusions: The preliminary results suggest that second-line pemetrexed-oxaliplatin combination is well tolerated and reasonably active, and allow the continuation of the study until the full sample of 31 pts.

No significant financial relationships to disclose.
A pilot phase I/II study of combination chemotherapy with nafamostat mesilate and gemcitabine for unresectable pancreatic cancer
Authors: Uwagawa T. , Misawa T. , Iida T. , Matsumoto M. , Gocho T. , Hirohara S. , Sadaoka S. , Yanaga K.
Published: August 2020

e15600

Background: To improve chemoresistance of gemcitabine (GEM) caused by GEM-induced nuclear factor kappa B (NF- κB) activation, we have conducted combination chemotherapy of GEM with NF-κB inhibitor, nafamostat mesilate (NAM) which is commercially approved as an effective therapeutic agent for disseminated intravascular coagulation, systemic response syndrome, or pancreatitis in Japan for patients with unresectable pancreatic cancer patients through phase 1/2 study. Methods: Study treatment consists of GEM 1,000 mg/m2 on d 8, 15 and 22 plus NAM 2.4∼4.8 mg/kg on d 8, 15 and 22. NAM was administered intra-arterially by continuous regional infusion for 24 hours via an infusion port system one hour before administration of GEM. Overall survival, response rate (RECIST), serum CA19–9 and clinical benefit response (body weight, pain alleviation) were assessed. Results: Between Feb 2007 and Oct 2008, 20 patients with unresectable pancreatic cancer were included in this study. Pts characteristics: male/female: 18/2, median age 63.5 (range 38–79) yrs, median Karnofsky PS 80% (range 70–90%), stage III/IV: 8/12, serum CA19–9 4,662 U/ml (range 88–32,100), baseline visual analogue scale 0–1/2–4/5–7/8–10; 9/4/7/0, baseline analgesic consumption (morphine-equivalent, mg/day) 0/10–100/100>; 10/7/3. The combination of NAM with GEM is well tolerated and MTD has not been reached. The recommended dose was GEM 1,000 mg/m2; NAM 4.8 mg/kg. Overall survival was 8.0 (range 4.7–17) months. CR/PR/NC/PD/not evaluated; 0/3/14/2/1. Serum CA19–9 reduction rate; 89%. Three pts. could become off and 1pt. could reduce oral morphine sulfate, and 5 pts. gained weight. Conclusions: The GEM/NAM regimen is safe, and the clinical data, including overall survival and clinical benefit response, suggest that the initial clinical outcome of this trial has been encouraging. An expanded cohort of the combination chemotherapy is underway.

No significant financial relationships to disclose.
Hepatocellular carcinoma presenting with lung metastasis: Clinical characteristics and prognostic factors
Authors: Kojima Y. , Ueno H. , Okusaka T. , Morizane C. , Kondo S. , Hagihara A. , Iwasa S.
Published: August 2020

e15604

Background: The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) has been limited, but sorafenib has changed the strategy treating for metastatic HCC. The lung is one of the most common metastatic sites for HCC. Therefore, we focused on clinical features and prognostic factors of HCC patients (pts) with lung metastasis in this study. Methods: Between January 2000 and April 2008, 1,117 HCC pts were admitted into our division. During this period, extrahepatic metastasis was detected in 286 pts, and the initial metastatic site was lung in 130 pts. The relationships between the characteristics of these pts at the time of lung metastasis detection and prognosis were examined. Results: There were 107 males and 23 females. Median age was 64 years. The Child-Pugh classification was A in 84 pts, B in 32 pts. HCV Ab was positive in 57 pts, HBs Ag was positive in 46 pts, and both were negative in 27 pts. The median survival time of all pts was 298 days. Univariate analysis revealed 12 of the 20 variables evaluated to be significantly associated with survival time: number of lung metastasis, presence of intrahepatic HCC, maximum size of intrahepatic HCC, presence of tumor thrombus, AFP, PIVKA II, albumin, prothrombin time, ALP, presence of ascites, Child-Pugh classification, and previous history of hepatic resection. Multivariate analysis using the Cox proportional hazards model demonstrated a lower number (≤5) of lung metastases (p<0.0001), the absence of intrahepatic HCC (p=0.0002), and the absence of ascites (p=0.0339) to be independent favorable prognostic factors. Conclusions: These results may provide useful reference data for determining treatment strategies and planning further clinical trials involving HCC patients with lung metastasis.

No significant financial relationships to disclose.
Locoregional therapies as a bridge to transplant in patients with hepatocellular carcinoma
Authors: Sakaria S. S. , Dhanasekaran R. , Pankonin M. , Parekh S. , Kauh J. S. , Kim H. S.
Published: August 2020

e15608

Background: Orthotopic liver transplantation (OLT) has been widely established as the definitive treatment for patients with HCC who fit within the Milan criteria. The limited availability of donor organs results in prolonged waiting periods leading to tumor progression and potential disqualification for OLT. As a result, there has been a rising interest in locoregional therapies that may stall tumor progression until a donor organ is available for transplantation. Methods: We reviewed patients with a diagnosis of HCC on the transplant list between 1998 and 2008. Of these patients, 72 patients received locoregional therapies (LRT). The various LRT consisted of transcatheter therapy alone (29 patients); combination transcatheter therapy and radiofrequency ablation (RFA) (33 patients), and RFA alone (10 patients). Kaplan Meier method with the log rank test and Cox proportional hazards method were used for survival analysis. Results: Of the 72 patients, 71% (51/72) were transplanted and 29% (21/72) dropped out. The reasons for drop-out from the transplant list included tumor progression (4.2%); condition deteriorated (11.1%); death (6.9%); refusal of transplant (2.7%); other causes (4.2%). The long term survival rates in the transplanted patients at 1 yr, 2 yrs and 5 yrs is 90%, 87% and 72%. The long term survival in the non-transplanted patients at 1 yr and 2 yrs is 47% and 33% respectively. Mean duration from the first LRT to OLT was 126 days (SD 208). In patients who dropped out, mean duration from the first LRT to the removal date was 143 days (SD 256). The mean post transplant follow-up period was 758 days (SD 527). No recurrence was found in the post transplant follow- up. Conclusions: Locoregional therapies can be effectively used as a bridging therapy to treat patients with HCC awaiting transplant. The long term recurrence-free survival in patients who received OLT after bridging therapies demonstrated 5-year survival rates of 72% and no recurrence after transplant.

No significant financial relationships to disclose.
Prognostic factors of survival in 236 advanced hepatocellular carcinoma patients enrolled in prospective clinical trials of systemic therapy
Authors: Lin Z. , Chang D. , Shao Y. , Hsu C. , Hsu C. , Yeh K. , Yang C. , Hong R. , Cheng A.
Published: August 2020

e15632

Background: Hepatocellular carcinoma (HCC) is a common malignant disease. Promising results of prospective clinical trials using systemic therapy for patients with advanced HCC are emerging. The aim of this study was to explore prognostic factors of survival in advanced HCC patients eligible for clinical trials of systemic therapy. Methods: From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into 6 phase II trials of systemic therapy using the following regimens: (1) oral etoposide + tamoxifen, (2)doxorubicin + tamoxifen, (3)IFN-α2b + doxorubicin + tamoxifen, (4)pegylated liposomal doxorubicin, (5)thalidomide, and (6)arsenic trioxide. Univariate and multivariate analyses of 23 relevant clinical characteristics/staging systems were used to identify prognostic factors of survival. Results: Baseline characteristics: median age 55; male/female: 192/44; HBsAg(+) 71%; anti-HCV(+) 30%; Okuda stage I/II/III: 42%/55%/3%; AJCC stage III/IV: 30%/61%; BCLC stage B/C/D: 1%/94%/5%; CLIP score 0–3/4–6: 70%/30%; portal vein thrombosis 53%; extrahepatic metastasis 59%; prior chemoembolization 46%. The objective response rate according to WHO criteria was 11.4%. The median overall survival was 118 days (95% CI, 103–133). In the multivariate analysis, significant predictors of a shorter overall survival were: HBsAg(+) with a hazard ratio (HR) = 1.808 (95% CI, 1.121–2.916; P= 0.015), symptomatic with HR = 1.745 (95% CI, 1.072–2.840; P= 0.025), ECOG≥2 with HR = 1.763 (95% CI, 1.040–2.988; P= 0.035), and high BCLC stage with HR = 3.282 (95% CI, 1.129–9.541; P= 0.029). Conclusions: Patients with advanced HCC who are eligible for systemic therapeutic trials have patient- and disease-related prognostic factors. Positive HBsAg, symptomatic, ECOG performance≥2, and high BCLC stage predict a shorter overall survival.

No significant financial relationships to disclose.
Multimodality salvage therapy for anal cancer failing standard chemoradiation
Authors: You Y. N. , Larson D. W. , Dozois E. J. , Nelson H. , Antpack Filho E. , Klein K. , Miller R. C.
Published: August 2020

e15635

Background: Most squamous cell carcinomas of the anal canal (SCC) respond to chemoradiation, but effective therapy for locally-invasive(T4) or recurrent disease that fails standard chemoradiation and/or salvage abdominoperineal resection (APR) has not been clearly delineated. A multimodality approach including chemoradiation, extended pelvic resection and intraoperative radiation therapy (IORT) was assessed for survival impact and treatment morbidity.morbidities. Methods: A prospective registry including 26 patients with locally-invasive or recurrent disease treated between 1993 and 2007 was reviewed. Primary endpoint was overall survival (OS), obtained from prospectively collected patient questionnaires and medical record review, and analyzed by the Kaplan-Meier method. Short (60-day postoperative) and long-term (median followup: 1.6 years; 5.3 years among survivors) complications were assessed. Results: Patients (median age: 51 years) presented with (1) locally-invasive disease that persisted despite initial standard chemoradiation (n=10, 39%), (2) disease that recurred after initial standard chemoradiation (n=10, 39%; median 1.7 years to recurrence), or (3) re-recurrence after a salvage APR (n=6, 23%; median 1.3 years since APR). All patients received chemotherapy and external beam radiation preoperatively, and 19% received additional postoperative chemoradiation. Gross pelvic disease was completely resected in all (R0 in 73%; R1 in 27%). IORT (750–3250cGy) was delivered at single (92%) or two sites (8%). Median overall survival (OS) was 1.7 years. Five-year OS were: 50%, 10%, and 22% for patients with locally-invasive, recurrent, and re-recurrent disease respectively. Short-term complications predominantly related to the perineal wound. Fifteen patients reported long-term complications (>grade3): bowel obstruction in 8 (1 requiring operation), perineal wound fistula/non-healing in 9, leg paresthesia in 5, hydronephrosis in 3. Conclusions: For select patients with locally-persistent or recurrent SCC who fail standard primary treatment, a multimodality approach involving chemoradiation, extended pelvic resection and IORT offers a chance for improved survival.

No significant financial relationships to disclose.
Prognostic impact of the NFKB1 insertion/deletion promoter polymorphism on survival in patients with surgically resected gastric cancer
Authors: Kim S. , Kim J. , Chae Y. , Sohn S. , Moon J. , Kang B. , Chung H. , Yu W. , Baek J.
Published: August 2020

e15638

Background: The present study analyzed the functional insertion/deletion polymorphism in the promoter region of NKFB1 gene and their impact on the prognosis for patients with gastric adenocarcinoma. Methods: Five hundred and three consecutive patients with surgically resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and the -94 insertion/deletion ATTG polymorphism of NFKB1 determined using a PCR- RFLP assay. Results: The NFKB1 promoter gene polymorphism was successfully amplified in 97.8% of the cases. There were no sexual differences in relation to the genotype and allele. No correlation was observed between the frequency of the genotype or allele and the T, N, or M stage. The multivariate survival analysis showed no association between the NFKB1 -94 insertion/deletion promoter polymorphism and the disease-free survival or overall survival of the patients with gastric cancer. Conclusions: The functional NFKB1 promoter polymorphism was not found to be a prognostic marker for Korean patients with surgically resected gastric adenocarcinoma.

No significant financial relationships to disclose.
Case study of a flexible bayesian design in a phase II study in patients with resected pancreas cancer
Authors: Harrell F. E. , Rodell T. , Apelian D.
Published: August 2020

e15651

Background: This presentation will describe a Bayesian flexible design for an ongoing randomized, placebo controlled phase II trial in newly diagnosed, resected pancreas cancer comparing gemcitabine plus therapeutic vaccine (GI-4000) vs. gemcitabine alone. The design allows for infinitely many looks at the data, possible study expansion, and conversion to adaptive allocation. Unlike frequentist approaches, the Bayesian procedure does not require penalizing the final analysis for earlier analyses nor does it require down-weighting of data collected before the decision to expand the study. The same analysis procedure is used for final and interim analyses, whereas there is no consensus in the frequentist approach for how to analyze an expanded study. Methods: Our primary analysis is based on a Bayesian Cox proportional hazards model using a skeptical prior distribution. The endpoint is time to recurrence or death. Evidence for efficacy is taken to be a posterior probability of efficacy ≥ 0.95 at any analysis time, where ‘efficacy’ means a true hazard ratio < 1.0. The planned rule for expanding the study is a probability of efficacy ≥ 0.7 prior to the last pre-planned analysis. Results: This ongoing study remains blinded. Results will include statistical methods (including simulations to assess study properties of the design) and experience in collaborating on the design with the FDA. Conclusions: In the frequentist approach, computing the probability of getting a result as or more impressive than that observed if there is truly no treatment effect (the P-value) requires contemplating experiments that were never carried out and analyses that were never done. The Bayesian approach offers the advantage of computing only ‘forward’ probabilities (Bayesian posterior probabilities) and conditioning only on what has been observed up to the time of analysis. There is no requirement to assume unknowable information such as the true population treatment effect. The adaptability afforded by Bayesian trial design can greatly enhance the likelihood of gaining useful clinical data from phase II trials.

[Table: see text]
Prognostic relevance of ribonucleotide reductase small subunit p53R2 in pancreatic cancer
Authors: Chung V. M. , Liu X. , Chu P. , Yen Y.
Published: August 2020

e15655

Background: Pancreatic cancer has the worst survival of any solid tumor, with most patients presenting with metastatic disease. Even after surgical resection the median survival is only 20 months suggesting micrometastatic disease. Ribonucleotide reductase is a critical enzyme in DNA synthesis and repair. Previous studies have shown that ribonucleotide reductase M2 (RRM2) subunit is associated with invasion and metastasis. Even though p53R2 has 80% homology to RRM2, its role is quite different. Here we report on the prognostic relevance of p53R2 in pancreatic cancer. Methods: Archived pathology specimens were obtained from 30 patients and immunohistochemistry for p53R2 performed on an IRB approved protocol (#06253). Clinical data was obtained by chart review and log-rank and Cox hazard proportional models were used to analyze overall and disease-free survival. Cell culture analysis was performed to further evaluate the role of p53R2. Utilizing a Matrigel chamber, invasive MiaPaCa-2 cells were collected for comparison to parental cells. Results: The median overall survival (OS) was 13.2 months (p53R2+) vs 8.5 months (p53R2-) (p=0.01). Disease free survival (DFS) was 12.4 vs 8.5 months respectively (p<0.05). By Western analysis, invasive cells have a higher protein level of RRM2 compared to parental cells. Interestingly, the protein level of p53R2 was low in the invasive cells suggesting an opposing role. To confirm this we inhibited p53R2 using siRNA which enhanced the migration ability of Mia PaCa-2 cells. Conclusions: Patients with p53R2 expression have improved disease-free and overall survival suggesting this may be used as a prognostic marker in pancreatic cancer patients.

No significant financial relationships to disclose.
Systematic meta-analysis on percutaneous ethanol injection and percutaneous acid injection for the treatment of early HCC: A Cochrane analysis
Authors: Schoppmeyer K. , Weis S. , Mossner J. , Fleig W. E.
Published: August 2020

e15657

Background: Hepatocellular carcinoma (HCC) is the fifth most common global cancer with high geographical variability. When HCC is detected early, percutaneous approaches such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), and radiofrequency thermal ablation (RFTA) have curative potential and represent low invasive alternatives to surgery. The role of percutaneous ethanol or acetic acid injection and other percutaneous interventions except RFTA has not been addressed in a systematic metaanalysis. The objective was to evaluate the effects of PEI and PAI for early HCC. Methods: A systematic search was performed in EMBASE, Cochrane Central, The Cochrane Hepato-Biliary Group Controlled Trials Register, Medline and Scopus as well as a handsearch of meeting abstracts. Only randomised controlled trials were included. RFTA studies were not considered. Primary endpoint was overall survival, secondary endpoints were cancer free survival, number and type of adverse events, duration of hospital stay, and quality of life. Results: 3 studies covering 261 patients were identified. Two studies compared PEI with PAI. 91 and 94 patients with one to three HCC-nodules ≤ 3cm underwent PEI and PAI, respectively. Overall survival (HR 1.47; 95% CI 0.68 to 3.19) and cancer free survival (HR 1.42; 95% CI 0.68 to 2.94) were not significantly different after treatment by PEI versus PAI. Both treatments were safe with no serious adverse events reported and modest pain being the most frequent adverse event. Data on the duration of hospital stay were inconclusive and data on quality of life not available. One study compared PEI with surgery. 38 patients were allocated to each treatment arm. There was no significant difference in survival (HR 1.57; 95% CI 0.53 to 4.61) and cancer free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group but 3 postoperative deaths occurred in the surgery arm. Conclusions: PEI and PAI are similarly effective and safe in patients with one to three small (≤ 3 cm) HCC nodules. Although the evidence is weaker, the beneficial effect of PEI is comparable to that of segmental liver resection and thus should be used preferentially due to its low morbidity and mortality.

No significant financial relationships to disclose.
Postoperative LV5FU2 combination chemotherapy in patients with curative resected advanced gastric cancer
Authors: Lee H. , Lee K. , Park E. , Hwang I. , Jang J. , Lee S.
Published: August 2020

e15660

Background: To illuminate the effect and toxicity of fortnightly low-dose leucovorin(LV) and fluorouracil(5FU) bolus plus continuous infusion(LV5FU2) postoperative chemotherapy(adjuvant) in patients with curative resected, advanced gastric cancer. Methods: Total 40 patients were enrolled in this study. All patients received LV 20mg/m2(bolus), 5FU 400mg/m2(bolus), 5FU 600mg/m2(24-hour continuous infusion) on day 1, 2, 15, and 16, every 4 weeks(LV5FU2), total 6 cycles. Results: Postoperative chemotherapy was initiated median 19 days after surgery. Total of 238 cycles were administered and median follow-up was 602 days. The median disease-free survival time was 728 days (95% CI, 411∼1045) and 2-year overall survival was 77%. Relapses were reported in 18 (45%) of the patients : Two of 9 patients relapsed in stage IIIA (22.2%), seven of 12 patients relapsed in stage IIIB (58.3%) and nine of 17 patients relapsed in stage IV (52.9%). They were all distant relapsed. Eight patients died. 7 patients died as a result of cancer progression and 1 patient suicided while receiving palliative chemotheraphy for cancer relapse. The grade 3∼4 toxicity of neutropenia 8.4% and anemia 0.4%, neutropenic fever 0.4% were observed. Conclusions: Postoperative LV5FU2 adjuvant chemotherapy is effective and tolerable for the patients with curative resected, advanced gastric cancer.

No significant financial relationships to disclose.
A phase I/II safety and efficacy study of intratumoral light-activated drug therapy using talaporfin sodium in patients with inoperable hepatocellular carcinoma
Authors: Wang S. , Keltner L. , Winship J. , Lee W.
Published: August 2020

e15684

Background: Light Infusion Therapy™ (Litx™) consists of the light-activated drug, talaporfin sodium (LS11®; mono-L-aspartyl chlorin e6), activated by a single-use, disposable device with an array of light-emitting diodes (LEDs). We evaluated talaporfin in combination with the light source in a phase 1/2 safety and efficacy trial in patients with hepatocellular carcinoma (HCC). To the best of our knowledge, this is the first clinical study of light-activated drug therapy in patients with HCC. Methods: Patients had confirmed primary HCC, 1–3 liver lesions, an ECOG score of 0–2, and a life expectancy of at least 16 weeks. Prior treatment failure with locally ablative techniques was allowed. The light-activated drug used in the study was talaporfin, a semi-synthesized, water-soluble chlorin e6 derivative. The LED device used in this study was a 1.5 mm diameter linear array of LEDs with a 25 mm emitting length at a wavelength of 664 nm. Patients underwent image-guided percutaneous placement of 1–4 LED device(s) using either local anesthesia or conscious sedation. The LED devices were used in single lesions or in multiple lesions. Following intratumoral placement of the LED devices, patients received talaporfin at 1 mg/kg IV bolus. Delivery of light energy commenced 15 min to 1 hr following drug administration with a total illumination time of 2.8 hrs. Results: The enrolled study group consisted of 8 patients. All 8 patients completed the week 4 assessment and were evaluated for tumor response. One (12.5%) out of 8 patients in this study was reported to have a complete response at week 4. Five patients (62.5%) were reported to have stable disease, and another 2 patients (25%) showed progressive disease. During the study, 7 patients reported a total of 16 treatment-related adverse events. There were no treatment-related adverse events that were greater than grade 2. At 1 year post treatment, all patients were alive. Conclusions: The results from this phase 2 study demonstrated that the therapy was safe for the treatment of HCC. A subsequent randomized controlled phase 3 pivotal trial is nearing completion and is designed to prove efficacy in patients with inoperable HCC.

[Table: see text]
p53 and its influence in adenocarcinoma stomach
Authors: Servarayan C. M. , Chandramohan A. , Datta D. , Manickavasagam K.
Published: August 2020

e15685

Background: Gastric cancer is the second most common cause of the malignancy in the world after lung cancer. Various pathogenesis have been given for the adenocarcinoma, like mutation in the E-catherin gene, amplification of COX-2, HGF/ SF, VEGF; deletion of FHIT, APC, p53 but none have provided a definite target for treatment. Methods: This is a immunohistochemical prospective experiment study done on 76 cases of Gastric Adenocarcinoma.The location of the tumors were recorded as in the proximal stomach (fundus and body) and distal stomach (antrum, prepylorus, and pylorus). PAb1801 clonewas obtained from the ZYMED LABORATRIES, San Franscisco. A standardised immunohistochemical method was followed in this study. Results: p53 mutations were seen 41 out of 76 cases(53.95%). And 23 out of 41(56.09%) cases of p53 expression of the total mutated cases expressed p53 100%. 20 out of 36 cases (55.55%) of age below 60 yrs and 21 out of 40 cases (52.55%) of age above 60 yrs were p53 positive. 33 out of 60 (55%)of the males and 8 out of 16 (50%) females were reported of having gastric adenocarcinoma with p53expression. The histology of the tissue samples from the gastric adenocarcinoma patients had following relationship with the p53 immunoreactivity, 20 out of 37 cases(54.05%) of the well differentiated,7 out of 17 cases (41.18% )of the moderately differentiated, and and 13 out of 21 cases(61.90%) of the poorly differentiated gastric adenocarcinoma showed positive immunoreactivity. 15 out of 33 cases (45.45%)were localized to the proximal stomach and 30 out of 52 cases (57.69%)were localized to the distal stomach. 52.63 % of the non-mucinous type of gastric adenocarcinoma showed positive p53 immunoreactivity. Conclusions: The TP53 mutation is slightly more common in males than females, with greater occurrence in the late years of life. The mutation is more marked in the poorly differentiated gastric adenocarcinoma. The antral, pylorus,and the prepyloric parts of the stomach( the distal stomach) are more prone for mutated p53 induced adenocarcinoma.

No significant financial relationships to disclose.
Carboplatin and fluoropyrimidine-based treatment for metastatic gastric and gastroesophageal junction cancer: A retrospective review of the Stanford experience
Authors: Kunz P. L. , de Bruin M. A. , Balise R. R. , Fisher G. A. , Ford J. M.
Published: August 2020

e15686

Background: There is no single standard chemotherapy regimen for the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. At Stanford Cancer Center (SCC) we regularly use a regimen of carboplatin and 5- fluorouracil (CF) or carboplatin and capecitabine (CX) for the treatment of these patients. Methods: A single institution retrospective review of patients with metastatic gastric and GEJ adenocarcinoma treated with CF or CX was conducted. Patients received carboplatin AUC 6 on day 1 and either 5-FU at 200 mg/m2/day (via continuous IV infusion) or capecitabine at 1,000 mg/m2 po BID for 14 days, repeated every 21 days. Only patients treated at SCC who received ≥ 2 cycles of chemotherapy were included. Results: Fourty-five patients were identified. The majority (62%) were male. Median age at diagnosis was 66 years. Twenty-nine (64%) had gastric and 16 (36%) had GEJ cancers. Thirty-six patients (80%) were chemotherapy-naïve. Twenty-nine (64%) had poorly differentiated and 10 (22%) had moderately differentiated adenocarcinomas; 13 (29%) had signet ring features. The average number of cycles administered was 5.4; one possible treatment-related death (2%) was identified. Median time to progression was 4.9 months and median overall survival was 7.3 months. Conclusions: CF and CX are well tolerated and yield acceptable outcomes in high-risk metastatic gastric and gastroesophageal junction cancers. The tolerability allows for the addition of novel targeted agents in future studies.

No significant financial relationships to disclose.
Stereotactic robotic radiosurgery for localized prostate cancer: Initial evaluation of acute toxicities
Authors: Ponsky L. E. , Lillibridge C. , Brindle J. , Zhang Y. , Wessels B. , Einstein D. B.
Published: August 2020

e16006

Background: We evaluated the initial acute toxicities experienced by patients treated with cyberknife fractionated radiosurgery for low and low-intermediate risk prostate cancer. Methods: Twenty-two patients with low or low-intermediate risk prostate cancer (T2a, GG 3+3=6 or 3+4=7, PSA <10) were enrolled prospectively on an IRB approved protocol and treated the planning target volume (PTV)(prostate+5mm margin) with cyberknife fractionated radiosurgery to a dose of 36.25 Gy in 5 fractions (7.25Gy/fraction). The target volume included the prostate and seminal vesicles. PSA values, AUA symptom scores (AUA SS), and NCI CTC acute toxicities were analyzed prior to radiosurgery and at 1 month (N=16), 3 months (N=12) and 6 months (N=5)post-treatment. Results: Patients treated on study included 12 with GG 3+3=6 cancer and 10 with GG 3+4=7 cancer. Mean patient age was 66 years old (range 49–79). Mean pre-treatment PSA was 5.29 (range 0.64–9.36) declining to 3.44 (range 0.00–10.43) at 1 month post treatment, 1.99 (range 0.31–3.99) at 3 months post-treatment and 2.08 (1.05–3.13) at 6 months post-treatment. Mean pre-treatment AUA SS was 7 (range 0.–18) increasing to 12 (range 2–29) at 1 month post treatment, decreasing to 8 (range 2–17) at 3 months post-treatment and 11 (3–17). There were 5 grade 1 acute toxicities including (diarrhea, fatigue, mild urinary frequency, hemorrhoid and a rash) and 7 grade 2 toxicities including (bladder spasms, painful urinary, bowel irregularity, rectal pain, urethritis and numbness in the upper thigh), all grade 1 and 2 toxicities resolved within three months of treatment. The one patient with grade 2 thigh numbness was not thought to be study related toxicity. Two patients developed grade 3 toxicity. One developed bacteremia after the transrectal ultrasound guided placement of the fiducials, the infection completely resolved after treatment with antibiotics. One patient on Coumadin developed hematuria which resolved with conservative management. Conclusions: Cyberknife fractionated radiosurgery for patients with early stage prostate cancer appears to be safe on our early initial assessment.Continued evaluation and longer follow-up ongoing.

[Table: see text]
Correlation of RRM1 expression in muscle invasive locally advanced urothelial cancer with age
Authors: Harshman L. C. , Bepler G. , Zheng Z. , Higgins J. P. , Allen G. I. , Tibshirani R. , Srinivas S.
Published: August 2020

e16021

Background: RRM1, the regulatory subunit of ribonucleotide reductase, plays a role in DNA repair after chemotherapy damage and in gemcitabine metabolism. Prior studies demonstrated a survival benefit to high expression in resected early stage lung cancer and a trend toward longer time to progression with low expression in advanced bladder cancers treated with gemcitabine and cisplatin. We hypothesized that patients with resected locally advanced (T2–4NxM0) urothelial transitional cell carcinoma (TCC) whose tumors had higher RRM1 expression would have longer overall survival (OS). Methods: 84 radical cystectomy specimens with muscle invasive TCC were identified from existing tissue microarrays (TMAs) containing 343 specimens. The medical records of these patients were retrospectively reviewed to confirm pathology and stage. Presence of muscle invasion was required. Specimens were analyzed for RRM1 expression using AQUA. The median value of RRM1 was established a priori as the cutoff for high and low expression. Results: Median age of the patients was 69.3 years. There was near equal distribution of stages: 30%, 38%, and 32% for stage II, III, and IV respectively. The majority were high grade (99%) with no nodal involvement (69%). Median OS was 2.0 years (0–13.1). Median RRM1 expression was 1493.3. Degree of RRM1 expression did not correlate with OS, but when adjusted for age, adding an interaction term, high RRM1 expression in younger patients correlated with increased OS (p = 0.0278). Median OS for high expressors age <69.3 years was 6 years compared to 2.3 years for low expressors. 35% of patients less than 70 years were high expressors. Conclusions: Our results suggest that high RRM1 expression may be a prognostic factor for improved survival in locally advanced TCC patients less than 70 years old. These results deserve further study in a larger prospective analysis with disease-specific survival assessment and correlation with other possible prognostic genes such as ERCC1.

[Table: see text]
Granulocyte macrophage: Colony stimulating factor (GM-CSF), ketoconazole, and mitoxantrone as second-line therapy in patients (Pts) with progressive hormone refractory prostate cancer (HRPC)
Authors: Doshi G. , Cen P. , Ramirez P. , Amato R.
Published: August 2020

e16033

Background: A variety of docetaxel regimens have been tested in HRPC pts, yielding response rates between 38% - 69%. Docetaxel therapy has been widely used as first line therapy. Second line therapies, which are non - taxane based with comparable activities do not exist. This trial is built on the significant body of work which has demonstrated anti-tumor activity of GM-CSF, Ketoconazole and Mitoxantrone alone and in combination in pts with HRPC. The trial is designed to assess the combination of all three agents. Methods: No more than two prior chemotherapy regimens (one which contained docetaxel), progressive disease, and adequate marrow / organ function. Treatment consisted of: Ketoconazole daily 400mg po tid, GM-CSF subcutaneous 250mcg / m2 (14 days on/ 7 days off) and Mitoxantrone 12mg / m2 every 3 weeks (maximum cumulative dose of 140mg / m2), until either the completion of Mitoxantrone or maximum anti-tumor benefit. Pts continued Ketoconazole/ GM-CSF until disease progression. PSA was evaluated every 3 weeks and radiographic studies were performed every 9 weeks. Results: 31 pts were enrolled; 4 pts with PSA only, 9 bone only, 5 soft tissue only, and 13 bone and soft tissue. 2 pts withdrew from study due to toxicity. 8 pts had a PSA response of ≥ 50%, 5 pts had a PSA response of ≥ 80%, and 7 pts had a PSA response of ≥ 90%. 9 pts progressed. The majority of pts had stabilization of their bone and soft tissue involvement and 2 pts with nodal involvement demonstrated a radiographic CR. Significant adverse events included grade III/IV neutropenia, thrombocytopenia, and nausea. Median duration of treatment was 6.22 months (range 2 months - 20.5 months). Conclusions: GM-CSF, Ketoconazole and Mitoxantrone in combination demonstrate significant anti-tumor activity and reversible toxicity in pts who have failed prior docetaxel therapy. Information regarding PSA response, radiographic outcome and adverse event data will be presented. This data warrants further investigation such as a randomized phase II study.

[Table: see text]
Prostate cancer screening practice among men age 75 and older: Results from a national survey
Authors: Hoffman K. E. , D'Amico A. V.
Published: August 2020

e16034

Background: The U.S. Preventative Services Task Force recently recommended not to screen men aged 75 and older for prostate cancer. This study evaluated the use of prostate specific antigen (PSA) screening among men age 75 and older prior to this declaration. Methods: The study cohort comprised 718 men age 75 or older without a history of prostate cancer who responded to the 2005 National Health Interview Survey, representing an estimated 4.47 million non-institutionalized men annually. Univariable and multivariable logistic regression was used to determine factors associated with PSA screening. Results: Of the 718 men, 19.2 % were age 85 or older, 42.2% reported fair or poor health, 24% had two or more significant diseases and 10.9% were dependent in at least one instrumental activity of daily living (IADL). More than half (51.6%) underwent PSA screening within the previous two years. Men who reported poor health status (42.2 vs. 55.2%, p=0.005) and men who had difficulty with at least one IADL (37.4 vs. 53.3%, p=0.010) were less likely to have a screening PSA. After adjustment for age, race, education status, and physician access, poor health status (adjusted odds (AOR): 0.70, 95% CI (CI): 0.45 to 1.10; p = 0.119), two or more significant diseases (AOR: 0.78, CI: 0.48 to 1.27; p = 0.333) and difficulty with at least one IADL (AOR: 0.71, CI: 0.42, 1.20; p = 0.202) were not associated with the use of PSA screening. Of the 104 men likely to live for five years or less because of poor health, 35.0% underwent PSA screening. Conclusions: Health status, a predictor of life expectancy, should be considered when determining which men receive PSA screening. This would reduce the use of PSA screening in men unlikely to benefit.

No significant financial relationships to disclose.
Cytokines and angiogenic factors in metastatic renal cell cancer: Association of pretreatment serum levels with survival
Authors: Montero A. J. , Diaz-Montero C. M. , Liu J. , Do K. , Millikan R. E. , Tannir N. M.
Published: August 2020

e16036

Background: To correlate serum cytokine and angiogenic factor (CAF) levels and overall survival (OS) in metastatic renal cell cancer (mRCC) treated with interferon-alpha (IFN-α). Methods: Serum CAF levels were measured in 103 patients treated on a randomized trial with IFN-α 0.5 million units (MU) twice daily or 5 MU daily. Concentrations of 17 analytes including vascular endothelial growth factor (VEGFA) and several cytokines were determined by multiplex bead immunoassays or ELISA (basic fibroblast growth factor). We used proportional hazards models to evaluate the effect of CAF levels and clinical factors on OS. Results: Pretreatment serum interleukin (IL)-5, IL-12p40, VEGFA, and IL-6 levels, and Memorial Sloan-Kettering Cancer Center risk grouping were independently correlated with OS, with hazard ratios of 2.33, 2.00, 2.07, 1.82 and 0.39, respectively (concordance index = 0.69 for the combined model versus 0.60 for the CAF model versus 0.52 for the clinical model). Based on an index derived from these five risk factors (RF), patients with 0–2 RF had a median OS time of 32 months, versus 9 months for patients with 3–5 RF (p < 0.0001). Conclusions: Serum CAF profiling contributes to prognostic evaluation in mRCC and helps to identify a subset of patients with 20% 5-year OS.

No significant financial relationships to disclose.
High response to docetaxel (D)/carboplatin (C) based chemotherapy as salvage therapy in patients with docetaxel-resistant metastastic hormone-refractory prostate cancer (HRPC)
Authors: Reuter C. , Ivanyi P. , Morgan M. , Ganser A. , Winkler T. , Fenner M. , Grünwald V.
Published: August 2020

e16041

Background: Presently, there is no standard treatment for prostate cancer (PC) patients who are resistant to docetaxel therapy. While previous reports support the use of C in combination with D in these patients (pts), the optimal regime is still unknown. Methods: Metastatic HRPC pts with clinical and/or radiographic evidence of progression while on docetaxel were included in our retrospective analysis. Between February 2005 and December 2008, 30 pts received treatment with C AUC 5 q3wks in combination with D 75 mg/m2 q3wks or D 35 mg/m2 d1, d8, d15 q4wks. All pts were assessed for PSA response and clinical outcome. Results: 27 pts were evaluable for response. Median age was 69 years (range 56–77) and median baseline performance status was ECOG 1 (range 0–2). The median number of prior therapies was 1 (range 1–3) with a median of 7 cycles of D therapy (range 3–34) administered. Median PSA at baseline was 297.15 ng/ml (range 12.33–6,446). Serum chromogranin A and neuron-specific enolase (NSE) were elevated in 24/24 and 8/25 cases, respectively. The median follow-up was 8.9 months (range: 0–38) with a median number of 6 cycles DC administered (range: 2–35). PSA declines of ≥50% (= PSA-response) was achieved in 14 of 27 pts (52%, 95% C.I. 0.32, 0.71) and PSA stabilization in 9 pts (33%). 4 pts (15%) progressed without PSA response. 6 PSA responders had a PSA reduction of >90%. The median duration of PSA response was 20.7 wks (95% C.I. 18.4, 59 wks). TTP was significantly longer in PSA responders vs. PSA non-responders (64.7 wks vs 15 wks, p<0.0001). 10 of 16 pts with measureable disease were evaluable for response. 3 of 6 PSA responders had a PR and 3 SD, while 2/4 pts with PSA non-response had PD and 2 SD. At the time of analysis, 2 PSA responders and 7 PSA non-responders have died. Median OS of all patients was 69.7 weeks with 79.9 wks for PSA responders vs. 38 wks for PSA non-responders (p=0.0034). The most common grade 3/4 toxicities were neutropenia in 42%, anemia in 23% and thrombocytopenia in 15% of pts. 17 of 30 pts had blood transfusions due to anemia. Conclusions: This retrospective analysis supports the usefulness of C plus weekly D chemotherapy as ≥second-line chemotherapy in docetaxel-resistant PC patients.

No significant financial relationships to disclose.