bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal residual local disease predicts improved survival after chemoradiotherapy in patients with squamous cell carcinoma of the esophagus
Authors: Rizk N. P. , Tang L. , Park B. J. , Flores R. , Venkatraman E. , Bains M. S. , Ilson D. , Minsky B. , Rusch V. W.
Published: March 2020

15070

Background: Our recent analyses (JCO, in press) showed that residual nodal disease but not T-stage predicted survival after chemo-radiotherapy (CRT) and surgery for esophageal adenocarcinoma (AC). In this study, we investigated prognostic factors for esophageal squamous cell carcinoma (SCC) after CRT. Methods: Retrospective review of patients with esophageal SCC who had CRT and esophagectomy. Data collected: demographics, CRT details, pathologic findings, and survival. Statistical methods included recursive partitioning (RP) and Kaplan-Meier (KM) analyses. Results: Patients included in the study were treated between 1/1996 and 2/2006. Follow up was thru 5/06. 91 patients were appropriate for analysis. There were 56 men (61.5%) and 35 women (38.5%). 72 (79.1%) patients had clinical regional disease prior to treatment, while the rest had locally advanced disease. Median radiation dose was 5040 cGy, and 78 (85.7%) patients received cisplatin based chemotherapy. 49 (53.8%) patients had a complete local pathologic response (pCR), including 10/91 (10.9%) who had a pCR with residual nodal disease. 42 (46.2%) patients had residual local disease. RP analysis identified 3 prognostic groups: a) Group 1 (n=52), patients with minimal residual local disease (pCR & T1- regardless of nodal status), b) Group 2 (n=28), patients with residual T2 disease (N0 and N1) as well as patients with T3–4N0 disease, and c) Group 3 (n=11), patients with residual T3–4N1 disease. 3-year survival by KM analysis was 68.4% in group 1, 45.6% in group 2, and 0 % in group 3 (p<0.001). Conclusions: Unlike adenocarcinoma of the esophagus where residual nodal disease after CRT is the most significant predictor of survival, in SCC of the esophagus, the presence of minimal residual local disease after CRT, regardless of nodal status, predicts the best survival. The implications of these findings might include establishing different endpoints to assess response to treatment and prognostic criteria.

No significant financial relationships to disclose.
Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma
Authors: Lind P. A. , Isaksson B. , Almström M. , Johnsson A. , Albiin N. , Byström P. , Permert J.
Published: March 2020

15073

Background: The optimal care for patients with irresectable, non-metastatic pancreatic carcinoma (PAC) is debated. We treated 17 consecutive cases with preop radiochemotherapy (RCT) as a means for downstaging their tumors and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period. Methods: The patients had biopsy proven, irresectable, non-metastatic PAC which engaged >50% of the circumference of a patent mesenteric/portal vein for a distance >2 cm and/or <50% of the circumference of a regional artery for <2 cm. The preop therapy included 2 courses of Xelox (oxaliplatin 130mg/m2 d1; capecitabine 1000mg/m2 X 2 d1–14 q 3 w) followed by 3-D conformal radiotherapy (50.4 Gy; 1.8 Gy fractions) with reduced Xelox (d1–5 q 1 w X 6). Results: 6 cases of RCT-related CTC Grade 3–4 non-hematologic side-effects were diagnosed. Sixteen patients completed the RCT and were rescanned with CT/reevaluated for surgery 4 weeks post-RCT. Five cases were diagnosed with new metastases to the liver. Eleven patients were accepted for surgery and 8 underwent a curative R0-resection. The median overall survival for the latter group was 29 mos, which compared favorably with our control group of patients undergoing direct surgery for primarily resectable PAC (median OS: 16 mos (P=0.02). RO- rate: 75%). Periop morbidity was similar in the two cohorts but the duration of surgery was longer (576 vs 477 min; P<0.05) and the op blood loss was greater (3288 vs 1460 ml; P<0.05) in the RCT-cohort. The 30-day mortality was zero in both cohorts. Conclusions: Preop RCT in fit patients with locally advanced PAC resulted in a high rate of curative resections and promising median survival in our treatment series. This trimodality approach merits further exploration in new studies, which are currently underway at our Department.

No significant financial relationships to disclose.
Predictive value of chemotherapy-induced neutropenia for drug efficacy in advanced gastric carcinoma: Analysis of prospective nationwide survey
Authors: Yamanaka T. , Matsumoto S. , Teramukai S. , Ishiwata R. , Nagai Y. , Fukushima M.
Published: March 2020

15075

Background: Myelosuppression that occurs during chemotherapy has been reported to be a predictor of better survival in patients with breast or lung carcinomas. We evaluated the prognostic implications of chemotherapy-induced neutropenia in advanced gastric cancer. Methods: Data obtained from a prospective nationwide survey of oral fluoropyrimidine S-1, performed in Japan between 1999 and 2000, were reviewed. Advanced gastric cancer patients with both adequate bone marrow function and no prior history of chemotherapy within 6 months before starting S-1 therapy were analyzed (N=1055). Chemotherapy-induced neutropenia was treated as a time-dependent covariate, and the hazard ratios [HRs] of death for experiencing neutropenia, compared with no such toxicity, were estimated using Cox regression model. Results: During treatment with S-1, a total of 293 (28%) patients had grade 1 or higher neutropenia. The adjusted HRs from a multivariate Cox model were 0.72 for patients with grade 1 neutropenia (95% confidence interval [CI] 0.54–0.95; P=0.0189), 0.63 for those with grade 2 neutropenia (95% CI 0.50–0.78; P<0.0001), and 0.71 for those with grade 3–4 neutropenia (95% CI 0.51–0.98; P=0.0388). Conclusions: The results of this study suggest that occurrence of neutropenia during chemotherapy is an independent predictor of better survival for advanced gastric cancer, while the absence of such toxicity indicates that the dosages of drugs are pharmacologically inadequate. Monitoring of neutropenia in patients who receive chemotherapy may contribute to improved drug efficacy and patient survival.

No significant financial relationships to disclose.
Hyperfractionated radiotherapy and biliary stenting for unresectable biliary tract cancers: Useful baseline data adding chemotherapy
Authors: Nakazawa M. , Shibayama C. , Nakamura M. , Akahane K. , Tamada K.
Published: March 2020

15079

Background: The morbidity and survival advantage treated with the combination of hyperfractionated radiotherapy (HF) and biliary stenting has not yet established for patients with unresectable biliary tract cancers. A prospective study was carried out using HF and metallic stent in consecutive patients over 10 years in a single institution. Methods: From 1993 to 2003, consecutive 162 pts (radical 74, postoperative 83, postoperative relapse 5) were treated with HF. Out of 74 radical cases, 71 pts (36 male/35 female; median age 70yrs, range 35–88) were analyzed except 3 cases (manifestation of liver metastasis 1, ascites 1, rejection of treatment 1). Primary sites were; extrahepatic bile duct 56, gall bladder 15. Bile cytology showed adenocarcinoma in every case. HF was administered twice daily by 10MV photon, using 2 portals (ant-post), 3 portals (ant-post-right lateral) or wedged pairs (ant-lateral) with relatively small radiation fields (PTV was CTV +1∼1.5cm). Fractional dose was 1.4Gy with the interfractional interval of 4.5 hrs to a total median dose of 59.8Gy. Endpoints were overall survival and acute and late complications. Results: 1) Obstructive jaundice was relieved before HF through endoscopic biliary drainage in 92.9% (66/71). Metallic stent was applied in 66.2%(47/71), before HF in 35.2% (25/71) and after HF in 31.0% (22/71). 2) Median survival was 8 months (1–90) and 5-year survival was 28%. Multivariate analysis showed total HF dose as a sole significant prognostic factor (p=0.0347). 3) Acute complication was observed mainly in digestive tract, i.e., Grade 1–2 symptoms (anorexia, nausea) in 50.7% (36/71). Late complications were Grade 1–2 gastritis in 9.9% (7/71), Grade 3 gastric ulcer in 2.8% (2/71) and cholangitis in 1.4% (1/71). Conclusions: HF combined with meticulous biliary drainage and stenting by G-I specialists for advanced biliary tract cancers demonstrated excellent pt’s quality of life with less serious morbidities. This modality would offer useful baseline data further with appropriate systemic chemotherapy.

No significant financial relationships to disclose.
Cell-based breast cancer risk stratification based on DNA methylation in fine needle aspiration samples
Authors: Euhus D. , Bu D. , Milchgrub S. , Leitch A. M. , Lewis C. M.
Published: March 2020

1508

Background: Tumor suppressor gene (TSG) methylation is identified in nearly all breast cancers, but rarely in histologically normal breast tissue from wonen unaffected with breast cancer. Its occurrence in high risk preneoplasia and in benign breast tissue adjacent to breast cancer suggests that it may represent a high risk field change that could be exploited for cell-based breast cancer risk stratification. Methods: TSG methylation was measured by quantitative methylation-specific real time PCR in 53 breast tumor fine needle aspiration (FNA) biopsies, 84 cellular random periareolar FNAs (RP-FNA) ipsilateral or contralateral to these cancers, 36 cellular RP- FNAs from unaffected women at high risk for breast cancer by the Gail model, and 95 cellular RP-FNAs from unaffected women at lower risk by the Gail model. Results: The breast tumors showed a high frequency of TSG methylation: RASSF1A 80%, HIN-1 65%, Cyclin D2 60%, RAR-β2 53%, and APC 47%. In general, RP-FNA samples from cancer patients and Gail high risk patients showed a greater frequency of methylation than samples from Gail lower risk patients: RASSF1A 43% vs. 21%, P = 0.001, HIN-1 32% vs. 20%, P = 0.05; Cyclin D2 18% vs. 9%, P = 0.10; RAR-β2 21% vs. 18%, P = 0.68; and APC 25% vs. 16%, P = 0.17. Twelve of 215 RP-FNA samples (5%) showed very high levels of methylation (>10% methylation for two or more genes). Only two of these samples were from women classified as lower risk by the Gail model. Methylation frequencies were entirely independent of cell yields but the frequency of RASSF1A methylation increased with increasing Masood scores (P = 0.05). Methylation of RASSF1A in one breast was highly predictive of RASSF1A methylation in the opposite breast (P < 0.0001). Conclusions: TSG methylation appears to be a breast cancer risk-associated field change that can be quantified in RP-FNA samples. RASSF1A methylation occurs frequently in benign breast epithelium, provides reasonable discrimination between high and lower risk breasts (O.R. = 2.0), is related to cytological atypia, and may be an early marker of a methylator phenotype. Quantification of TSG methylation in RP-FNA samples may provide a valuable surrogate endpoint biomarker for Phase II prevention trials.

No significant financial relationships to disclose.
Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer: A single-center study
Authors: Boeck S. H. , Wilkowski R. , Bruns C. J. , Issels R. D. , Schulz C. , Moosmann N. , Laessig D. , Golf A. , Heinemann V.
Published: March 2020

15085

Background: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem)-failure is defined in patients with advanced pancreatic cancer (PC). Methods: Within this study we prospectively collected clinical data of 37 patients (pts) with advanced PC who were treated with capecitabine (Cape) at our center. Cape was offered to patients who already had received at least one previous treatment regimen containing full-dose Gem (either as single- or combination chemotherapy or sequentially within a radio- chemotherapy (RCT) protocol), who presented with a KPS = 70% and had adequate organ function. Cape was administrated orally at a daily dose of 2 x 1250 mg/m2 for 14 consecutive days followed by 7 days of rest (in pts > 65 years: 2 x 1000 mg/m2/d). Treatment cycles were repeated every 3 weeks and continued until disease progression or unacceptable toxicity. Results: A median number of 3 treatment cycles (range 1–36) was given to 37 pts (54% male, median age 63 yrs, 97% with metastatic disease); 15 pts previously underwent RCT, 20 pts had received one previous treatment regimen and 17 pts 2 or more previous regimens. After a median follow- up of 6.1 months, 10 pts are still alive including 4 pts still on Cape. Currently, 35 pts are evaluable for response: no complete or partial response was observed, but 13 pts (37%) had stable disease (SD). A CA19–9 reduction > 20% after 8 weeks of Cape was determined in 6 pts (16%), all of them had SD. Median TTP was 2.2 months, median overall survival (since start of Cape treatment) was 7.5 months. Predominant grade 2 and 3 toxicities (per patient analysis) were: hand-foot-syndrome 30%, anemia 24%, diarrhea 14%, nausea/vomiting and leukopenia 11% each. One pt had a grade 3 infection, 1 pt experienced grade 4 cerebral ischemia during treatment with Cape. Conclusion: Single-agent Cape is a safe treatment option for Gem-pretreated pts with advanced PC. The disease control rate of 37% and a median TTP of 2.2 months appear interesting in this patient population. Further evaluation of Cape in controlled clinical trails is recommended in Gem-refractory pts with advanced PC.

No significant financial relationships to disclose.
Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese
Authors: Okuno T. , Tamura T. , Yamamori M. , Chayahara N. , Miki I. , Shirasaka D. , Nakamura T. , Kasuga M. , Azuma T. , Sakaeda T.
Published: March 2020

15088

Background: A 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT) was proposed for esophageal cancer patients. Currently, there is an urgent need to establish a methodology to decide which is preferable for a patient, i.e., surgical treatment or CRT, especially for Stage II to III tumors defined as resectable. This study was performed to find the genetic factors predictive of clinical outcome to a 5-FU/ CDDP-based CRT in Japanese patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Thirty-one patients with Stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One course of treatment consisted of protracted venous infusions of 5-FU (400 mg/m2/24 h for day 1–5 and 8–12), CDDP (40 mg/m2/3 h on day 1 and 8) and radiation (2 Gy/day on day 1–5, 8–12 and 15–19), and a 2nd course was successively repeated after a 2-week interval. A total of 8 measurements of the plasma concentration of 5-FU were made using high performance liquid chromatography. Genetic polymorphisms examined herein included those in the genes coding thymidylate synthase (TS), glutathione S-transferase P1 (GSTP1) and multi-drug resistant transporter MDR1/P-glycoprotein. Results: The complete response rate depended on Stage (p = 0.001), but the analysis was not sufficiently powered to reach a level of statistical significance for the 2-year survival rate (p = 0.061). For Stage II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5’-TSER, a 6bp of 3’-TSUTR, and GSTP1-Leu105Val resulted in an extensively longer survival (p =0.0197), although no difference was found between 2 groups, with respect to the plasma concentrations of 5-FU and clinical or pathological characteristics. Conclusions: The genetic prognostic index may allow predictions of the clinical outcome of a 5- FU/CDDP-based CRT in Stage II/III ESCC patients. Now, we are analyzing the contribution of genetic polymorphisms of cytokines, including tumor necrosis factor a.

No significant financial relationships to disclose.
Serial ductal lavage for biomarker assessment in a phase 2 prevention study with tamoxifen
Authors: Khan S. , Lankes H. A. , Patil D. , Bryk M. , Nayar R. , Hou N. , Krontiras H. , Rademaker A.
Published: March 2020

1509

Background: Effective methods of epithelial sampling to measure breast-specific biomarkers will aid the rapid evaluation of new preventive interventions. We report a proof-of-principle Phase 2 study to assess the utility of ductal lavage (DL) to measure biomarkers using tamoxifen (TAM) as the gold standard prevention agent. Methods: We enrolled women with a 5-year Gail risk >1.6 or the unaffected breast of women with breast cancer =1 cm. After entry DL, participants chose TAM or observation (OBS), and underwent repeat DL 6 months later. Samples were processed for cytology and immunohistochemistry for ER and Ki-67 labeling indices (LIs). If =1 duct showed atypia, the sample was called atypical. LI data were analyzed by duct (comparing the same duct at 2 time points) and by woman (comparing the mean of all ducts at 2 time points). Results: Of 168 women recruited, 135 (80%) underwent entry and repeat DL; 82 (49%) had sufficient cells for analysis at both time points (mean age 50 years, mean Gail 3.0). 44 chose observation and 38 chose TAM. Cytologic findings, by woman and by duct, showed significantly greater net improvement (from atypical to benign) in the TAM than in the OBS group (see table ). The repeat ER and Ki-67 LIs showed a significant reduction from entry within the TAM group (p=0.01 and 0.0001, respectively), but not in the OBS group when analysed by duct. Similarly, in analyses by woman, the ER and Ki-67 LIs decreased from entry to repeat DL within the TAM group (p=0.046 and 0.004 respectively), with minimal changes in the observation group. Between-group data are shown in the table and are similar to the within- group differences. Conclusions: Using DL, we saw the expected changes in TAM-related biomarkers, with stronger reductions in duct-to- duct comparisons than when findings were averaged across ducts in individual women. However, the 51% attrition rate of subjects from recruitment to biomarker analyses, along with the expense of DL, raises questions regarding the efficiency of this procedure in biomarker assessment over time.

[Table: see text]

No significant financial relationships to disclose.
A phase II study of capecitabine-gemcitabine(CapGem) as a first line therapy in Bangladeshi patients with locally advanced or metastatic pancreatic adenocarcinoma
Authors: Reza M. S. , Hai M. A. , Chowdhury Q.
Published: March 2020

15100

Background: Pancreatic cancer is one of the cancers with very poor prognosis because of its diagnosis at an advanced or metastatic stages. There is no consensus on the optimal management of locally advanced or metastatic pancreatic cancer. This phase II study was designed to evaluate the efficacy and safety of CapGem in patients (Pts.) with pancreatic adenocarcinoma. Methods: From January 2001 to December 2004, 30 pts with; histologically / cytologically proven, bidimensionally measurable locally advanced or metastatic pancreatic adenocarcinoma, age 18∼75 years with ECOG performance status 0∼3, no prior chemotherapy, life expectancy >3 months, adequate bone marrow, renal, hepatic and haematological values were enrolled. It was an open - labeled, non-randomized, single - centered and prospective study. The pts received Capecitabine 750mg/m2 twice dailly,days 1–14,orally and Gemcitabine 1000mg/m2 days 1 & 8, intravenous infusion at an interval of 21 days.The efficacy was measured by response rates, CA-19.9 & pain status and safety was measured by adverse events and laboratory blood values. Results: This study consisted of 16 (53.33%) male and 14 (46.67%) female pts. Median age was 52 years. 18 (60%) pts were inoperable locally advanced and the remaining 12 (40%) were metastatic diseases where 8 hepatic and 4 pulmonary. In total, 152 cycles chemotherapy were administered with a median of 5.06 cycles per pt and 28/30 pts were evaluated for responses. The overall response was 9 ( 32.14%) with 2 complete and 7 partial responses. 14 pts (50%) had stable diseases and 5 (17.86%) had progressive diseases. There was 55% decrease in CA-19.9 and pain reduction was 60%. Overall survival was10 months. Grade 3 haematological toxicities were observed as follows: neutropenia 30% and anaemia 18%. Some non- haematological toxicities including nausea & vomiting 30%, diarrhoea 20% and hand foot syndrome 10% were observed. Conclusions: This phase II study supports the use of CapGem combination in chemo naive locally advanced or metastatic pancreatic adenocarcinoma due to its promising anti-tumor activity with well-tolerated toxicities in Bangladeshi pts.

No significant financial relationships to disclose.
Palliative treatment of unresectable pancreatico-biliary cancer by either gemcitabine or octreotide/imatinib: Impact on biomarkers of angiogenesis
Authors: Treiber G. , Wex T. , Malfertheiner P.
Published: March 2020

15101

Background: Gemcitabine represents standard Tx for unresectable cancers of the pancreas / distal biliary tract. Recent interest has focused on antiangiogenic properties in a mouse model of pancreatic cancer (JCI 2003); either VEGF or PDGF inhibition alone were less effective than the combination of both in terms of angiogenesis. In humans, imatinib (targeting PDGF) alone has been shown to be equivalent to gemcitabine in terms of survival (Cancer Lett. 2006;233:328–37), while most trials for octreotide (targeting IGF-1, VEGF) were disappointing. In HCC pts. we recently evaluated the impact of biomarkers on disease progression and survival (Cancer Res Clin Oncol 2006; 132:699–708). Methods: To investigate in a phase I/II trial the feasability of a combination (group I, n=11) of octreotide (30 mg im every 4 weeks, targeting VEGF-A) plus imatinib (400 mg po daily, targeting PDGF-B) vs gemcitable (group II, n=11, 1000mg/m2 weekly for 7/8 wks, then for 3/4 wks). Pts had either unresectable pancreatic cancer (n=18) or ampullary cancer (n=4). Primary outcome measure were changes in biomarkers (VEGF-A, PDGF-BB, soluble E-selectin, Ca19–9, CEA). Secondary outcome measures were TTP and OS. Results: 19/22 pts. had biomarker data available within the first 12 wks, changes over time are shwon in table . Median TTP was 109 vs 166 days (p<0.05) and median OS was 163 vs 325 days (p=NS) for group I vs II. Baseline Ca19–9 levels correlated with prognosis independent of Tx (p=0.05). In group I, high levels of PDGF-BB and VEGF-A levels at wk 12 but in group II, low levels of VEGF-A and s-E-selectin correlated with a better OS (p<0.05 each). TTP showed no correlations with biomarkers. Conclusions: The combination of octreotide plus imatinib is clinically less effective compared to gemcitabine. Although the absolute changes of angiogenesis markers are comparable between groups, chemotherapy compared to targeted therapy has a different impact on these in terms of survival.

[Table: see text]

No significant financial relationships to disclose.
Can 1H-Nuclear magnetic resonance (NMR) be used for early detection of hepatocellular cancer (HCC)?
Authors: Iyer R. V. , Tennant B. , Ruiz M. , Szyperski T. , Trump D. , Odunsi K. , Wollman R.
Published: March 2020

15107

Background: HCC is a common and rapidly fatal cancer. Current screening tools are inadequate for identification of potentially curable cases. Our aim was to determine whether H-NMR can identify HCC compared to controls in the woodchuck (WC) model of hepatitis related HCC. Methods: Eastern WCs were bred and inoculated at birth with dilute sera from WCs that are chronic carriers of Woodchuck Hepatitis B Virus (WHV). This resulted in chronic hepatitis in ∼60% animals and all carriers developed HCC by 24–36 months. Serum from 10 chronic WHV carriers with HCC (group 1), 5 WHV carriers with no HCC (group 2) and 15 matched non-infected controls (group 3) was obtained. 45uL serum was diluted with 5uL of D2O containing 27mM formic acid + 0.9% saline. Spectra were collected on a 600 MHz INOVA spectrometer using a CapNMR flow probe with 10uL flow cell at 298K without knowledge of group assignments. The resulting 1D spectra were processed using Nuts from AcornNMR. Results: Principle component analysis and supervised PLS-DA was performed using Simca P+ from Umetrics. Despite general separation of groups, the Q2 value of this model was relatively low (0.20). We trained a Support Vector Machine (SVM) algorithm, a supervised machine-learning algorithm, to learn to identify the groups. Evaluation of the performance of the algorithm using 10-fold validation on the data set achieved a Kappa value of 0.43. This algorithm learnt to identify HCC [0.765 ROC, 0.8 sensitivity, and 0.727 positive predictive value (PPV)] and controls (0.75 ROC, 0.69 sensitivity and 0.73 PPV) but not the WHV carrier group, likely due to the small numbers. In a second analysis of 10 HCC and 15 controls, PLS-DA showed clear separation using three components (Q2= 0.5). The corresponding SVM model showed a kappa value of 0.52 and ROC values of 0.767 for both classes. Conclusions: Our preliminary results indicate that H-NMR spectra alone can be used to distinguish HCC from healthy controls using the machine-learning algorithm for classification. Further validation in a larger cohort of woodchucks is ongoing and confirmation of these preliminary findings would support investigation of this technique as a screening tool in patients at risk for developing HCC.

No significant financial relationships to disclose.
Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer
Authors: Park Y. , Yi S. , Kim H. , Lee S. , Hwang I. , Park S. , Park B. , Park J. , Lim H. , Kang W.
Published: March 2020

15111

Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine.

No significant financial relationships to disclose.
Efficacy of recent chemotherapy regimen in advanced small bowel carcinoma
Authors: Aparicio T. , Costes L. , Moulin V. , Locher C. , Bidault A. , Lecomte T. , Mitry E. , Taieb J. , Landi B. , Malka D.
Published: March 2020

15112

Background: Small bowel carcinoma (SBC) is a rare tumour. Very few data concerning the chemotherapy efficacy are published. The overall survivals previously reported were 8 to 14 months. The aim of the study was to evaluate the efficacy of recent chemotherapy regimen in advanced SBC. Methods: All the consecutive patients treated recently by first line chemotherapy for advanced SBC were included retrospectively in a multicentric study. Clinical and radiological evaluations were performed every 2 or 3 months according to WHO criteria. Chemotherapy was stopped in case of progression, severe toxicity or patient willing. Results: Fifty seven patients (33 men, 24 women), median age 56 years [32–83] treated from 1994 to 2006 in 10 institutions were included. Primary tumours were: duodenum n=35 (61%), jejunum n=14 (25%) and ileum n=8 (14%). Three patients had Crohn disease and one HNPCC syndrome. The tumour were locally advanced in 6 patients (10%), or with metastasis in 51 (90%), synchronous n=35 or metachronous n=16. The mains metastasis sites were peritoneal carcinomatosis in 29, liver in 19 and nodes in 13 patients. Sixteen patients have had an initial R0 surgery and 8 had received, before inclusion, adjuvant chemotherapy. The regimens used in first line were: FOLFOX n=21 (37%), LV5FU2-cisplatine n=13 (23%), LV5FU2 n=12 (21%), FOLFIRI n=10 (17%). Twenty five (44%) patients have had grade 3 or 4 toxicity. A toxic death occurred after a cure of FOLFOX. Chemotherapy was stopped in relation to toxicity in 7 (12%) patients. A dose reduction was done in 15 (26%) patients for a total of 16% of the cures. Tumor was measurable in 42 (73%) pts. A partial response was observed in 13 patients (31%), stabilisation in 14 (33%) and progression in 15 (36%). Thirty six (63%) pts had a second line chemotherapy. Time to treatment failure was 6 [1–21] months in all patients and 7 [2–19], 7 [2–20], 5 [1–21] and 4 [1–10] months according to treatment by FOLFOX, LV5FU2, FOLFIRI or LV5FU2-cisplatine respectively. Overall survival was 11 months [1–36]. Overall survival according to the primary localization were: duodenum: 9 [1–34], jejunum: 18 [3–32], ileum: 15 [4- 36]. Conclusions: Advanced SBC have a bad prognosis. The chemotherapy regimen used in colon cancer did not reach the same efficacy in SBC.

No significant financial relationships to disclose.
Doubling time of preoperative serum alpha-fetoprotein level can predict recurrence and prognosis after hepatic resection of hepatocellular carcinoma
Authors: Masuda T. , Beppu T. , Ishiko T. , Mizumoto T. , Hayashi H. , Horrart H. , Takamori H. , Kanemitsu K. , Hirota M. , Baba H.
Published: March 2020

15118

Background: It is quite important to predict postoperative recurrence or prognosis in the patients with hepatocellular carcinoma (HCC) before surgery. There have been few reports about the value of doubling time of preoperative serum a-fetoprotein (AFP) or protein induced by vitamin K absence (PIVKA-II) levels. Methods: Between January 2000 to December 2005, 160 consecutive HCC patients underwent hepatic resections in our institution. Serum AFP and PIVKA-II level was prospectively measured at least two points before surgery to calculate a doubling time. Clinical factors such as age, gender, BMI, etiology of hepatitis, degree of liver damage, gross tumor type, tumor size, tumor numbers, portal vein tumor thrombosis (PVTT), and AFP-L3 were concurrently investigated. Univariate and multivariate analyses were done to clarify predictive factors of postoperative recurrence and survival. Results: There were no relationship between preoperative levels and doubling time of both tumor markers. In univariate analysis, significant predictors of postoperative recurrence were AFP > 200 ng / ml, PIVKA-II > 200 mAU / ml, AFP-L3 > 10%, non-simple nodular type tumor, tumor size > 3 cm, multiple tumors, PVTT positive, and doubling time of AFP < 40 days. The significant prognostic factors were AFP > 200 ng / ml, HBs antigen positive, non-simple nodular type tumor, multiple tumors, PVTT positive, and doubling time of AFP < 40 days. In multivariate analysis, multiple tumors (odds ratio: 1.48), and doubling time of AFP < 40 days (odds ratio: 2.17) were significant predictors of recurrence. The significant prognostic factors were non-simple nodular type tumor (odds ratio: 6.41), multiple tumors (odds ratio: 7.62), and doubling time of AFP < 40 days (odds ratio: 6.49). Postoperative mean recurrence free survival time of HCC patients with doubling time of AFP < 40 days was only 2.8 months and mean survival time was 34 months. Conclusions: In HCC patients, doubling time of preoperative serum AFP level is useful to predict early recurrence and poor prognosis. Perioperative adjuvant therapy should be considered for such high risk patients.

No significant financial relationships to disclose.
Ki67 labelling index and performance status are predictive factors of response to concomitant radiochemotherapy (RCT) in esophageal cancer
Authors: Seitz J. F. , Dahan L. , Ressiot E. , Liprandi A. , Giorgi R. , D’journo X. B. , Padovani L. , Alibert S. , Ries P. , Thomas P. A.
Published: March 2020

15119

Background: In oesophageal cancer, preoperative RCT allows a prolonged survival for patients achieving a complete pathological response at time of surgery. However, predictive factors for complete response to RCT are not well known. The aim of this retrospective study was to identify clinical and histopathological factors predictive of complete endoscopic response (CER) in patients treated by RCT before surgery or as exclusive treatment for esophagus cancer. Methods: from 2000 september to 2006 march, 56 patients with esophagus cancer (35 squamous cell carcinoma (SCC), 20 adenocarcinoma (ADK), 1 undifferentiated) were treated by RCT (45–50 grays /25 fractions / 5 weeks and 2 courses of 5FU-CDDP at weeks 1 and 5). 16 patients subsequently underwent oesophageal resection. Endoscopy with biopsies was performed 3 weeks after the end of RCT. Clinical, biological, radiological and pathological (including EGFR, p53 and Ki67 immunostaining) parameters were included in univariate and multivariate analysis to determine predictive factors for CER. Results: CER was observed in 31 out of 54 appraisable patients (57.4%). In both univariate and multivariate analysis, 2 factors were predictive of complete endoscopic response: good performance status (PS 0 vs 1–2: OR = 15.75 - p=0.01) and higher expression of Ki67 (>=18 vs <18: OR = 4.46 - p=0.04).A pCR was seen in 7 (44%) of the 16 operated patients. Positive predictive value of endoscopy for pCR was 87.5% (IC95%: 47.4–99.7%), and negative predictive value was 100% (IC95%: 68.7–100%). Predictive factors of pCR were: a complete endoscopic response (p<0.01), a complete CT-scan response (p=0.03) and a good performance status (p=0.04). Median survival in all 56 patients was 40 months. Pejorative prognostic variables for survival in multivariate analysis were adenocarcinoma histology (RR=3.11; p=0.03), and performance status (RR=4.79; p=0.04). Conclusions: In our study, a good performance status and surexpression of Ki67 were independent predictive factors for complete endoscopic response after RCT. The 2 prognostic factors for survival are histologic type and performance status.

No significant financial relationships to disclose.
Phase II study of induction chemotherapy with fixed dose rate (FDR) gemcitabine and cisplatin followed by concurrent chemoradiation with capecitabine for locally advanced pancreatic cancer (LAPC)
Authors: Kim J. , Im S. , Park H. , Chie E. , Hwang J. , Kim J. , Kim T. , Bang Y. , Ha S. , Yoon Y.
Published: March 2020

15122

Background: Despite the use of 5-FU based chemoradiotherapy (CRT) over the past decades, prognosis of patients with LAPC remains dismal. To deliver more efficient systemic treatment earlier and reduce toxicity of CRT, we designed a treatment protocol consisting of induction (IND) chemotherapy with FDR gemcitabine (GEM) and cisplatin (CDDP), followed by CRT with capecitabine (CAP) in LAPC. Methods: Eligible patients had unresectable, histologically confirmed adenocarcinoma of pancreas, ECOG PS of 0–2, and no prior chemo- or radiotherapy for this phase II study. Patients received FDR GEM 1000 mg/m2 (D1,8) and CDDP 60 mg/m2 (D1) every 3 weeks for 3 cycles. Patients without disease progression subsequently received CRT of 55.8 Gy in 31 fractions concurrently with CAP, 650 mg/m2 given twice daily without drug holidays. Four weeks after CRT, FDR GEM 1000 mg/m2 was given on day 1, 8 every 3 weeks for 3 cycles. Time to progression was the primary endpoint. Results: Between Jan 2005 and Nov 2006, 21 patients were enrolled (median age 59, M/F: 13/8, ECOG PS 0/1: 3/18). Two patients withdrew consent after 1st and 2nd cycle and remaining 19 patients completed all three cycles of IND chemotherapy, with three (15.8%) out of 19 evaluable patients achieving partial response (0 CR, 3 PR, 14 SD, 2 PD). All 17 patients completed CRT with mean radiation dose of 55.4 Gy. Further four patients progressed during CRT, while one additional patient achieved partial response. As of Jan 2007, 5 patients died and 12 patients showed tumor progression. Median TTP was 12.5 mo (95% CI: 4.2–20.8) and median survival was not reached with median follow up duration of 9.7 months. Grade III/IV toxicities included neutropenia (38.1%/9.5%), thrombocytopenia (4.8%/0%), and anemia (14.3%/0%) during IND phase. Toxicites were generally mild during CRT phase with grade III neutropenia and diarrhea occurring in one and two patients, respectively. One patient died of neutropenic sepsis after 3rd cycle of IND chemotherapy. Conclusions: FDR GEM-CDDP induction chemotherapy followed by CAP-RT and maintenance FDR GEM is feasible and active with promising TTP of 12.5 months. Enrollment continues till reaching target accrual of 37 patients.

No significant financial relationships to disclose.
What caused the decline in breast cancer incidence rates?
Authors: Chagpar A. B. , McMasters K. M.
Published: March 2020

1513

Background: Recently, a sharp 7% decline in breast cancer incidence rates among women over the age of 50 was noted in 2003. It has been speculated that this may be due to changes in mammographic screening or in the use of hormone replacement therapy (HRT). The purpose of this study is to elucidate the cause of the decline in breast cancer incidence rate. Methods: The National Health Interview Survey (NHIS) is a population-based personal interview survey conducted annually by the Centers of Disease Control. In 2000 and 2005, a cancer supplement was administered containing information regarding behaviors which may affect breast cancer incidence. These data were analyzed using SAS-callable SUDAAN software to determine trends in the use of mammography, HRT use, and chemoprevention over this period of time in women older than 50. Results: 7147 and 7396 women over 50 were surveyed in 2000 and 2005 respectively. There was a significant drop in the proportion of women reporting current use of HRT between 2000 and 2005 (27.66% vs. 12.09%, p<0.0001). While there was also a drop in the proportion of women reporting current use of tamoxifen (1.34% vs. 0.74%, p<0.0001), there was an increase in the proportion of women reporting current use of raloxifene (0.92% vs. 1.27%, p<0.0001). Overall, there was a slight decrease in the use of chemoprevention between 2000 and 2005 (2.18% vs. 1.99%, p<0.0001). There was a reduction in the proportion of women over the age of 50 reporting ever having had a mammogram (83.85% vs. 82.76%, p<0.0001) or clinical breast examination (81.63% vs. 75.34%, p<0.0001) between 2000 and 2005. Fewer women over the age of 50 reported that their last mammogram was within the preceding 2 years (87.33% vs. 84.68%, p=0.0002). Similar results were seen for clinical breast examination within the preceding 2 years (88.98% vs. 86.22%, p<0.0001). Conclusions: The decline in breast cancer incidence rate is multifactorial, due in part to declining rates of early detection and chemoprevention. The principal etiologic factor, however, is likely the dramatic reduction in the use of HRT.

No significant financial relationships to disclose.
A phase II study of chemoradiotherapy in patients with stage II, III esophageal squamous cell carcinoma (ESCC): (JCOG 9906)
Authors: Muro K. , Ohtsu A. , Ishikura S. , Boku N. , Takiuchi H. , Saito H. , Kaneko K. , Miyata Y. , Komatsu Y. , Shirao K.
Published: March 2020

15137

Background: The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin and 5- fluorouracil (5FU) in patients with stage II, III ESCC. Methods: Patients with clinical stage II or III (T1N1 or T2–3N0–1 and M0) thoracic ESCC, age of 70 or younger, preserved organ functions were eligible. Treatment consisted of two courses of cisplatin 40 mg/m2 (day 1, 8) and 5FU 400 mg/m2/day (days 1–5, 8–12), q5w combined with concurrent radiotherapy of 60 Gy in 30 fractions over 8 weeks with 2-week break. For responders, two courses of chemotherapy of cisplatin 80 mg/m2 (day 1) and 5FU 800 mg/m2/day (days 1–5) q4w were added. The primary endpoint was overall survival and the secondary endpoints were response, toxicity, and progression-free survival. Results: From April 2000 to March 2002, 76 patients were accrued from 12 institutions. Characteristics of all patients were as follows: median age of 61 (range 39–70), male/female; 68/8, PS 0/1; 59/17, stage IIA/IIB/III; 26/12/38. There were two ineligible cases with inadequate liver function and T4 disease. Grade 4 neutropenia, leukopenia, and anemia occurred in 1.3%, 1.3% and 2.6%. Grade 3/4 esophagitis, stomatitis and infection occurred in 17%, 8% and 17%. Grade 3/4 late toxicities occurred in the following incidences; esophagus (dysphagia, mucositis, stenosis, and fistula) in 13%, pericardial effusion in 17%, pleural effusion in 8%, and radiation pneumonitis in 4%. There were 4 treatment related deaths due to late toxicities such as esophageal fistula, radiation pneumonitis, and the other cardiopulmonary diseases. Of eligible 74 patients, there were 50 complete responses (CRs) with a CR rate of 68% (95% Confidence Interval (CI): 56–78%). Median survival time was 31 months and the 2, 3-year survival rates were 55% (95% CI: 43–67%), 47% (95% CI: 36–59%), respectively. Conclusion: CRT for stage II, III ESCC is effective with acceptable acute toxicities, however, careful follow up is necessary for late toxicities.

No significant financial relationships to disclose.
Phase II study of weekly docetaxel in combination with capecitabine (C) in advanced gastric (AGA) and gastro-esophageal adenocarcionma (AGEA)
Authors: Hantel A. , Lo S. , Khorana A. , Javle M. , Hwang J. , Wang H. , Simon S. , Crandall T. , Shayne M. , Ramanathan R. K.
Published: March 2020

15139

Background: Chemotherapy regimens for AGA and AGEA have shown considerable toxicity and most require continuous IV administration. Both D and C are active agents in AGA. D upregulates thymidine phosphorylase, the enzyme which catalyzes the conversion of C to 5-FU, with preclinical evidence of synergy for the combination. A phase I study of D and C showed acceptable tolerability and activity in patients (pts) with AGA (Ramanathan et al., 2005). This multi-institutional phase II trial evaluates the combination of D and C in 1st or 2nd line treatment of AGA and AGEA. Methods: Pts with AGA/AGEA who received ≤ 1 prior chemotherapy regimen were eligible. D 30 mg/m2 on d 1, 8 and C 825 mg/ m2 BID were administered on days 1–14 of a 21 day cycle. The one stage study design had an accrual goal of 40 pts. The primary endpoint was to detect a 50% improvement in median survival in previously untreated pts to 10 months (mo), by one-sided log-rank test at level a = 0.05. Results: Enrollment is complete with 40 pts, all are evaluable for response and toxicity. Pt characteristics: 79% male; 94% with ECOG performance status 0/1; median age 60 yrs (34–84), 32 pts (80%) were previously untreated. Overall response rate is 25% with 1CR and 9 PR. The projected median time to progression (TTP) and survival are 6.2 and 7.8 mo respectively. Dose modifications were required in 9%. Median cycles administered 4 (range 1–10). Grade 3/4 adverse events include: diarrhea (13%), hand-foot syndrome (13%), dehydration (6%), abd pain, anorexia, fatigue, febrile neutropenia, gastric ulcer, hyperglycemia, vertigo, and vomiting (3% each). Conclusion: The combination of D and C is well tolerated and active. The preliminary TTP (6.2 mo) and survival (7.8 mo) compare favorably with published regimens for 1st line therapy, but did not meet study endpoint. The combination of D and C is an easily administered outpatient regimen for AGA and AGEA and may be worthy of further investigation with a targeted agent. (Funded by Sanofi-Aventis and Roche Pharmaceuticals).

No significant financial relationships to disclose.
Effect of complementary alternative medical (CAM) therapy on pain and fatigue in pancreatic cancer patients
Authors: Birdsall T. C. , Levin R. D. , Alschuler L. , Daehler M. , Birdsall S. M. , Martin J. , Dounaevskaia L. , Lis C. G. , Braun D. P.
Published: March 2020

15142

Background: Pain and fatigue are frequent, difficult to manage, and negatively impact quality of life (QOL) in pancreatic adenocarcinoma patients (PCpts) causing some to seek CAM therapy in place of or in conjunction with conventional analgesics. But the efficacy of CAM on pain and fatigue has not been adequately tested in controlled trials. We employed an alternative strategy by abstracting pain and fatigue scores from the EORTC-QLQ-C30 questionnaire administered to PCpts treated at Midwestern Regional Medical Center, an integrative oncology center offering conventional and CAM treatment. Methods: 50 PCpts treated with chemotherapy and/or radiation clinically appropriate for advanced PC + CAM were evaluated. The CAM group (n=36) had 70%, 11%, and 19% and the nonCAM group (n=14) 71%, 14%, and 15% Stage IV, III, and II tumors respectively. PCpts received narcotic and anti-inflammatory agents consistent with ASCO and NCCN guidelines. CAM treatments included Green Tea Extract; Melatonin; and high-potency multivitamins. Baseline, 3 month(M), and 6M data were analyzed. Results: Median baseline, 3M and 6M pain scores were: 50; 0; 33.3 and 75; 16.6; 83.3 for CAM and nonCAM respectively; not significant (NS) CAM vs nonCAM at any time point by non-parametric tests. Pain control at 3M was improved significantly vs baseline levels for each cohort; p=0.02 (CAM) and 0.03 (nonCAM) by paired 2 tail t tests. The relative numbers of PCpts with manageable pain (≤ 33) were comparable for CAM vs nonCAM at baseline (41% vs 36%) and 3 M (81% vs 90%), but not at 6M (67% vs 22% CAM vs nonCAM respectively, (p<0.05 by ?2 test). Median baseline, 3M and 6M fatigue scores were: 55.5; 33.3; 33.3 and 44.4; 33.3; 66.6 for CAM and nonCAM respectively (NS, CAM vs nonCAM at any time point). By paired 2-tail t tests, 3M (p=0.01) and 6M (p=0.02) values were improved significantly vs baseline in CAM but not nonCAM cohorts. Conclusion: This exploratory study shows that CAM treatment may improve fatigue and extend the period of effective pain control by conventional analgesics in PCpts. Given the negative impact exerted by pain and fatigue on QOL in this difficult to manage malignancy, CAM treatment appears to have efficacy for PCpts.

No significant financial relationships to disclose.