bluuebunny/crossref_metadata_2025 huggingface dataset:
The differences in the stage classification for node-positive colorectal cancer between the United States and Japan: A single institution experience.
Authors: Sugimoto Kiichi , Sato Koichi , Orita Hajime , Maekawa Hiroshi , Sakurada Mutsumi , Ito Tomoaki , Sakamoto Kazuhiro
Published: March 2020

e14139

Background: In the United States, the stage classification by the number of lymph node metastasis (LNM) is adopted in TNM classification 7th edition. In Japan, the stage classification by the distribution of LNM was modified to that by the number of LNM in order to integrate with TNM classification in Japanese classification of colorectal carcinoma second English edition. We retrospectively examined the possibility of predicting prognosis by the number of LNM and considered the differences between TNM classification and Japanese classification. Methods: Two hundred and seventy-five patients with LNM who underwent curative surgery for colorectal cancer at our department between January 1992 and December 2004 were enrolled in this study. All patients were followed for 5 years after the operation. At first, we calculated cancer-specific survivals according to the number of LNM in order to examine whether the stratifications of prognosis by the number of LNM is appropriate or not. Secondary, clinicopathological factors and survival data were analyzed to determine prognostic factors. Finally, we considered the differences between TNM classification and Japanese classification. Results: When comparing cancer-specific survivals between the patients with the number of LNM of 1 and 2-3 and 4 or more, cancer-specific survivals were well stratified (both; p=0.006). According to the multivariate analysis using clinicopathological factors, invasion depth (T4) (p=0.007, odds ratio=2.230), venous invasion (moderate-severe) (p=0.003, odds ratio=2.577) and the number of LNM (p=0.0002, odds ratio=1.201) were significantly independent prognostic factors. In Japanese classification, there was a significant difference in cancer-specific survivals between Stage IIIa and IIIb (p<0.0001). On the other hand, in TNM classification, cancer-specific survivals in Stage IIIA, IIIB and IIIC were stratified into three groups with significant differences (IIIA vs IIIB; P=0.01, IIIB vs IIIC; p<0.0001). Conclusions: In comparison of Japanese classification and TNM classification, TNM classification seems to be superior to Japanese classification.
FOLFOX as adjuvant chemotherapy after curative resection of distant metastatic lesions in patients with colorectal cancer.
Authors: Kitayama Joji , Nozawa Hiroaki , Watanabe Toshiaki , Sunami Eiji
Published: March 2020

e14142

Background: Although FOLFOX regimen is shown to be effective to suppress the recurrence of stage III colorectal cancer (CRC) who received curative resection, the prophylactic effect of has not fully been investigated in adjuvant setting of stage IV CRC cases, namely, after curative resection of distant metastases. Methods: This is a retrospective study including 116 CRC patients with synchronous metastases and 91 with metachronous metastases who received curative resection in our hospital between 2000 and 2009. Pathological parameters of primary CRC, postoperative chemotherapeutic regimen, relapse-free survival (RFS) were analyzed retrospectively. Results: After resection of CRC and synchronous metastases, 53 (84%) out of 63 patients without chemotherapy, and 38 (83%) out of 46 that received oral or intravenous 5-fluorouracil (5-FU) alone or with leucovorin (LV) developed recurrent tumors. By contrast, only single patient (17%) among 6 who underwent FOLFOX showed recurrence. With a median follow-up period of 775 days, the FOLFOX group exhibited a significantly improved RFS as compared to the 5-FU(+LV) or surgery alone group (p=0.03, p=0.007, respectively). The 5-year OS rates of the surgery alone, 5-FU(+LV), and FOLFOX group were 67%, 75%, and 100%. In CRC cases with metachronous metastases, on the other hand, the recurrence rate of the group without chemotherapy was 63%, and that of the 5-FU (+LV) group 55%. In 7 patients who underwent FOLFOX chemotherapy (5 cases of FOLFOX4 and 2 cases of mFOLFOX6, no antibody therapy) after metastasectomy, 71% (5 patients) relapsed afterward. Thus, the tumor-relapse rate after metastasectomy was similar among patients who received no postoperative chemotherapy. The median RFSs of the surgery alone, 5-FU(+LV), and FOLFOX groups were 323, 917, and 322 days, respectively. Conclusions: Adjuvant FOLFOX is certainly beneficial for stage IV CRC patients with synchronous metastasis who received curative resection. In contrast, the prophylactic effect of FOLFOX is not superior to other follow-up strategies in patients who received complete resection of metachronous metastases.
Use and findings of K-ras in colorectal cancer (CRC) testing in administrative and electronic medical records (EMR) data from 2005 through 2010.
Authors: Valluri Satish , Sullivan Sean D , Ramsey Scott David , Kreilick Charles , Foltz Boklage Susan H , Haislip Sally , Gilmore James W. , Szabo Stephen , Sarma Syam , Asche Carl V , Seal Brian S.
Published: March 2020

e14146

Background: The use of K-ras testing in clinical decision-making has grown over the past few years. The objective of this study was to evaluate, in a real world context, the trends and diagnostic findings of K-ras testing using managed care and EMR data. Methods: The Georgia Cancer Specialists Database EMR (2005-2010) and administrative data from the MarketScan and IMPACT database(s) was used to select patients with newly diagnosed colorectal cancer (CRC). We looked for trends in use of K-ras in relation to timing of chemotherapy administration. The EMR data provided information on k-ras mutation type. Results: In MarketScan, of the 23,548 patients with a diagnosis of CRC, 1,730 (7.3%) patients had a test ordered for K-ras between 2005 and 2010. The number of patients receiving K-ras increased with line of therapy: first line 336 patients (8.2%) of 4,098 treated, second line 455 patients (15.2%) of 2,984 treated, and third line 529 patients (33%) of 1,603 treated. We found similar results using the IMPACT database: 2,256 (7.8%) CRC patients had a test ordered for K-ras between 2005 and 2010. K-ras testing increased with line of therapy: first line 244 patients (7.8%), second line 510 (14.6%), and third line 650 patients (33.1%). EMR lab results from stage IV disease (n=349) consisted of 15% mutated type, 60% unknown and 25% wild type. For confirmed test results wild type represented 62.5% and mutated type 37.5%. Conclusions: Over the last six years, use of K-ras testing has increased in use in patients with CRC. The increase has occurred in later lines of therapy. The timing occurring late in therapy may limit the use of agents specific for this test.
Prevalence of low-penetrance KRAS (codons 12/13 and 61) and BRAF mutations in metastatic colorectal carcinoma.
Authors: Rojo Federico , Caldes Trinidad , Zazo Sandra , de la Hoya Miguel , Carames Cristina , Romero Atocha , Serrano Gloria , Bando Inmaculada , Leon Ana , Sastre Javier , Martin-Valades Jose Ignacio , Cillero Lourdes , Campos Angel , Gavina Belen , Lendinez Alberto , Bausela Cristina , Ferrandez Dolores , Ramos Teresa , Garcia-Foncillas Jesus , Diaz-Rubio Eduardo
Published: March 2020

e14147

Background: In patients with metastatic colorectal cancer (mCRC), activating mutations within KRAS, which result in EGFR-independent intracellular signal transduction activation, are found in approximately 35-40% of patients with mCRC have been significantly associated with lack of response to cetuximab or panitumumab therapy. Although current guidelines recommend testing for frequent KRAS codons 12/13 mutations, emerging data indicate that additional KRAS and BRAF mutations are also predictive of non-responsiveness to anti-EGFR antibodies in mCRC. This study is aimed to analyze the prevalence of low-penetrance KRAS and BRAF V600 mutations in caucasian mCRC population. Methods: A two-institution retrospective cohort of 1,238 consecutive KRAS wild type mCRC patients previously studied for 7 mutations in codons 12/13 (G12D, G12A, G12V, G12S, G12R, G12C and G13D) by the CE-IVD marked ARMS-scorpion real-time polymerase chain reaction PCR (Therascreen, Qiagen) was assayed by the diagnostic TaqMelt PCR assay cobas KRAS mutation and cobas BRAF V600 mutation tests (Roche), which are designed to detect 19 mutations in KRAS codons 12, 13 and 61 (including G12F, G13C, G13R, G13S, G13A, G13V, G13I, Q61H, Q61K, Q61R, Q61L, Q61E and Q61P) and BRAF V600 (V600E, V600K and V600D) mutations. An additional cohort of 146 KRAS mutated patients by ARMS-scorpion PCR was studied. DNA was obtained by cobas DNA preparation kit from one single 5µm formalin-fixed paraffin-embedded tissue section. Results: In all samples, sufficient DNA was obtained for KRAS and BRAF mutational studies. Among 1238 KRAS codons 12/13 wild-type patients by ARMS-scorpion PCR,166 (13.4%) showed KRAS mutations, 117 (9.5%) in codons 12/13, and 49 (4%) in codon 61. BRAF V600 mutations were detected in 9% cases. In ARMS-scorpion PCR KRAS mutated patients, mutations were confirmed by cobas in all cases. Conclusions: The cobas mutation tests are robust and reproducible assays that, 1) detects a higher incidence (13.4%) of mutations in codons 12, 13, and 61 of the KRAS gene in wild-type mCRC population, 2) a relevant rate of BRAF mutations is present in the same population, and 3) requires a very small amount of tissue.
Incidence of colorectal premalignant and malignant neoplasm on colonoscopy in an in-patient setting.
Authors: Khan Manji Samira , Feinberg Zachery , Manji Gulam Abbas
Published: March 2020

e14185

Background: Colorectal cancer (CRC) continues to be a leading cause of death and the third most common cancer in both genders. Numerous studies have shown that routine screening for colon cancer reduces CRC incidence and mortality by detecting premalignant lesions early. Hence screening colonoscopy in the outpatient setting has been the standard of care. In contrast, the incidence of pre-malignant (PMN) and malignant neoplasms (MN) identified during a colonoscopy due to an acute presentation in an in-patient setting is currently unknown. We evaluate the incidence of PMN and MN lesions identified in patients that underwent in-patient colonoscopy for anemia, gastrointestinal bleed (GIB), and or abdominal pain. Methods: A retrospective review of all gastrointestinal consultations (GIC) from January 1st, 2009 until December 31st, 2009 at a single institution. GIC as determined by the requesting provider for anemia, abdominal pain, and/or gastrointestinal bleed (GIB) were included. Results: There were 291 GICs for anemia, abdominal pain, GIB, or a combination thereof resulting in 218 colonoscopies. A total of 15 (6.9%) PMN and MN lesions were identified. Pathological evaluation reveled 13 (86.7%) of these lesions to be consistent with that of adenocarcinoma. The remaining 2 showed squamous cell cancer morphology. PMN/MNs were identified in patients with GIB and anemia (46.7%), anemia alone (20%), GIB and abdominal pain (20%), and GIB alone (13.3%). There was no significant difference in lesions found between genders (46.7% male). Conclusions: Routine outpatient screening colonoscopy is the standard of care with the goal of resecting early stage cancerous lesions resulting in cure. However, there is paucity of data on the incidence of these lesions being identified in an in-patient setting where colonoscopy is performed for GI bleed, anemia, abdominal pain, or a combination thereof. We demonstrate that colonoscopy resulted in identification of PMN/MNs in a significant proportion of patients with afore mentioned specific complaints. Interestingly, most lesions were identified in patients with GIB and anemia, suggesting that a thorough evaluation be undertaken as it may herald an underlying neoplasm.
Phase Ib study of gemcitabine and oxaliplatin with erlotinib in patients with advanced biliary tract cancer.
Authors: Ciombor Kristen Keon , Cardin Dana Backlund , Chan Emily , McClanahan Pamela , Fan Kang-Hsien , Flynn Jayme , Young Ruth T. , DeMers April , Smith Stephen James , Berlin Jordan , Goff Laura Williams
Published: March 2020

e14503

Background: Gemcitabine (GEM) with a platinum agent such as oxaliplatin (OX) is standard therapy for advanced biliary tract cancers (ABTC). The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has also shown modest benefit in ABTC. Erlotinib (E) induces G1/S cell cycle arrest and may exhibit sequence-specific synergy with GEM. Given continuously, it may antagonize the action of chemotherapy against cycling tumor cells but intermittent pulsatile dosing of EGFR TKIs in combination with chemotherapy may lead to maximum efficacy. The purpose of this study is to assess the tolerability of E when pulsed with GEM and OX (GEMOX). Methods: This investigator initiated, single institution phase Ib study (NCT00987766) used a standard 3+3 dose-escalation model in patients with ABTC, pancreas cancer or duodenal cancer. The primary endpoint was to evaluate the maximum tolerated dose (MTD) of pulsatile E in combination with GEMOX. Patients received escalating doses of E starting at 50 mg daily (given on D3-8) with GEM on D1 (dose rate 10 mg/m2/min) and OX on D2 every two weeks. Dose-limiting toxicity was defined as any treatment-related, first course (28 days) non-hematologic ≥Gr3 toxicity, except nausea/vomiting or Gr4 hematologic toxicity. Results: Nineteen patients have been enrolled and 4 dose levels have been explored. Two of two patients experienced DLT [Gr3 diarrhea (n=1), Gr4 anemia (n=1)] at a dose of 150 mg E + 1000 mg/m2 GEM + 85 mg/m2 OX, exceeding the MTD. Most frequent toxicities were nausea (68%), neuropathy (68%), fatigue (63%) diarrhea (52%) and rash (52%), most Gr1 or 2. Disease stabilization occurred in 12/17 (71%) evaluable patients (5/9 ABTC, 7/8 pancreas), and partial responses were seen in 4/17 evaluable patients (24%), all with ABTC (4/9). The rate of progression-free survival at 6 months was 75% in ABTC. Conclusions: The MTD and recommended phase 2 dose of E in combination with GEMOX was E 150 mg given on days 3-8 with GEM 800 mg/m2 and OX 85 mg/m2 in this population. Clinical activity of this combination was seen in the majority of patients. An expansion cohort of an additional ten patients with ABTC at the MTD is ongoing, and correlative studies on available tissue will be performed.
Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of primary gastric cancer.
Authors: Kim Kyung Min , Cheong Jae-Ho , Hwang Seong-Geun , Kim Yu Min , Kim Hyoung-Il , Ahn Ji Yeong , Hyung Woo Jin , Noh Sung Hoon
Published: March 2020

e14504

Background: Thrombocytosis has been associated with malignancies and poor prognostic implications in cancer patients. In the present study the prognostic significance of pretreatment platelet (PLT) level was assessed with regard to recurrence and survival in patients with primary gastric adenocarcinoma. Methods: The authors reviewed the prospective data of 1,593 gastric cancer patients who received curative gastrectomy with extended lymphadenectomy. The correlations of PLT level with recurrence and overall survival were evaluated by both univariate and multivariate analyses. Results: Thrombocytosis (≥ 40 x 104/μL) was present in 6.4% of the patients prior to curative surgery. Thrombocytosis was more frequently associated with advanced T and N stage, larger tumor size, anemia, and old age (p<0.05). The 5-year survival rate of patients with thrombocytosis was significantly worse than that of patients without thrombocytosis (56.9% vs. 65.5%; p=0.043). The recurrence rate was higher, mainly attributed to the frequent hematogenous spread, in patients with thrombocytosis than in those without thrombocytosis (51.0% vs. 34.5%; p<0.001). Furthermore, thrombocytosis was an independent risk factor of recurrence (Odds ratio 1.649 [95% CI 1.074 – 2.531], p=0.022), along with serosa invasion and nodal metastasis. Conclusions: Pretreatment thrombocytosis correlated significantly with poor prognosis and can be used as an independent predictor of recurrence by blood-borne metastasis in gastric cancer.
Novel methods of analyzing long-term trends in incidence and survival applied to gastroesophageal cancers.
Authors: Wang Zhensheng , Goodman Michael , Mahaseth Hemchandra , El-Rayes Bassel F
Published: March 2020

e14512

Background: The incidence of esophageal squamous cell (ESC) carcinoma has been decreasing, while incidence of esophageal adenocarcinoma (EA) keeps increasing. The specific time periods during which incidence trends changed have not been examined. Secular trends in survival and changes of those trends need to be investigated. Methods: Incidence and survival were analyzed using joinpoint regression models, which are designed to examine long-term longitudinal data for a change in trend. We identified 75,497 patients with esophageal cancer and adenocarcinoma of the gastric cardia (GCA) in the Surveillance, Epidemiology, and End Results database between 1973 and 2008. Incidence and one-year survival rates for ESC, EA, and GCA were compared by race, gender and stage. Results were expressed in terms of identifiable inflexion points (joinpoints) with before-and-after estimates of annual percent changes (APC) with 95% confidence intervals (CI). Results: Incidence of ESC has demonstrated a clear inflexion point in the mid 1980s with accelerated decrease across race and gender categories. While incidence of EA has been increasing, the increase slowed down in mid 90s in all groups except blacks. For GCA, there was a clear increase in incidence up until early 80s followed by a plateau although in men there was a significant post-87 decrease. One-year survival of ESC patients has been improving; for local/regional disease the trend became less pronounced in late 80s whereas for distant disease the improvement appears to continue without identifiable inflexion points. The patterns of one-year survival for EA and GCA were similar. Local/regional diseases demonstrated a significant improvement in survival without changes in trend while survival of distant diseases showed an inflexion point in the mid 90s followed by a marked improvement. Conclusions: Joinpoint regression analysis is a valuable tool in assessing long-term trends of incidence and survival. The survival of ESC, EA, and GCA demonstrated significant improvement over the last 35 years. The inflexion points reflected introduction of combined modality therapy for regional disease and availability of newer chemotherapy agents for distant disease.
Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: Initial results of a multiinstitutional cancer registry.
Authors: Hörsch Dieter ,   AG PRRT of the DGN Germany
Published: March 2020

e14513

Background: Peptide receptor radionuclide therapy is an effective treatment option for patients with well differentiated somatostatin receptor expressing neuroendocrine tumors. However, published data results mainly from retrospective monocentric studies. Methods: We initiated a multi-institutional, prospective and board reviewed registry for patients treated with Peptide receptor radionuclide therapy in Germany in 2009. Results: In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297), small intestine (80/297) whereas 56 were of unknown primary. Most tumors were well differentiated with a median Ki67 proliferation rate of 5% (range 0.9 to 70). Peptide receptor radionuclide therapy was performed using mainly Yttrium-90 and/or Lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with a follow up between 1 and 230 months after initial diagnosis and 87 months with a follow up between 1 and 92 months after start of Peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with a proliferation rate below 20%. Conclusions: Our results indicate that Peptide receptor radionuclide therapy is an effective treatment well and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded a one of the primary treatment options for patients with neuroendocrine tumors.
Effect of three-dimensional collagen I and global histone acetylation on gemcitabine resistance in pancreatic cancer cells.
Authors: Dangi-Garimella Surabhi , Sahai Vaibhav , Shields Mario A. , Munshi Hidayatullah G.
Published: March 2020

e14515

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. PDAC is also associated with epigenetic changes. We have previously shown that PDAC cells are resistant to gemcitabine in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2) and increased ERK1/2 signaling. Methods: Pancreatic tissue microarrays were stained with trichrome and for histone H3K9, H3K27 acetylation (Ac), and histone acetyltransferase (HATs) expression. PDAC cells were plated onto tissue culture plastic or in 3D collagen gels and protein expression was assessed by Western blotting. DNA damage response was assessed by comet and clonogenic assays. Results: Human PDAC tumors display in areas of fibrosis higher histone H3K9Ac and H3K27Ac. Moreover, PDAC cells upregulate H3K9Ac and H3K27Ac along with GCN5, PCAF and p300 HATs when grown in 3D collagen. Inhibiting ERK1/2 activity and/or decreasing HMGA2 expression attenuates the effect of collagen on H3Ac and HAT expression. Human PDAC tumors with HMGA2 also demonstrate H3Ac and HAT expression. Additionally, cells in 3D collagen demonstrate reduced tailing with the comet assay, increased clonogenic potential and increased γH2AX following gemcitabine treatment, suggesting an increased repair response to damaged DNA in the collagen microenvironment. Significantly, downregulation of HATs along with inhibition of ERK1/2 activity attenuates gemcitabine-induced γH2AX detected in 3D collagen. Conclusions: Collagen microenvironment limits the effectiveness of gemcitabine through ERK1/2 and HMGA2-dependent HAT expression. HMGA2 expression is associated with histone acetylation and HAT expression in human PDAC tumors, particularly in area of fibrosis, suggesting that fibrosis may contribute to chemo-resistance through increased HMGA2-HAT signaling. Given that very little progress has been made in the treatment of pancreatic cancer, targeting HATs could be a novel approach to sensitize pancreatic tumors to chemotherapy.
F-box and WD repeat domain-containing 7 (FBXW7) mRNA and outcome in biliary tract cancer.
Authors: Arroyo Gerardo F. , Kaen Diego , Salvatierra Alejandro , Rojo Sandra Viviana , Kowalyszyn Ruben Dario , Ortiz Marcos , Carballido Marcela , Kaen Luis Alberto , Zarba Juan Jose , Roca Enrique Luis , Costa Carlota , Molina-Vila Miguel Angel , Bertran-Alamillo Jordi , Mayo Clara , Gimenez Capitan Ana , Sanchez Jose Javier , Benlloch Susana , Lemoine Antoinette , Taron Miquel , Rosell Rafael
Published: March 2020

e14521

Background: Thestandard treatment for biliary tract cancer is gemcitabine plus platinum, but median progression-free survival (PFS) is only 5-8 months (m) (Valle et al, NEJM 2010). Gene expression or somatic mutations may influence the clinical phenotype, which will affect decisions on individualized treatment. Methods: We retrospectively analyzed tissue blocks from 54 advanced or metastatic cholangiocarcinoma, gallbladder or ampulllary cancer patients (p) treated with single-agent gemcitabine or gemcitabine plus carboplatin or cisplatin. Using RT-PCR, we analyzed the mRNA expression levels of oncogenes, tumor suppressors and DNA repair genes (BRCA1, RRM1, AEG-1, RAP80, SPINK1 and FBXW7) and correlated results with PFS, overall survival (OS) and response. In addition, FBXW7 hotspot mutations were assessed. Results: p characteristics: 72% females; median age, 60 (40-87). Only FBXW7 expression correlated with PFS and OS. When FBXW7 levels were dichotomized at the median value, PFS was 4.2 m for p with low levels vs 12.6 m for p with high levels (p=0.02). When FBXW7 expression was divided by terciles, PFS was 4.9 m for p in the lowest tercile, 7.6 for p in the intermediate tercile, and 26.9 m for p in the highest tercile (p=0.08). OS was 6.2 m for p in the lowest tercile, 8 m for p in the intermediate tercile, and not reached for p in the highest tercile. No other significant correlation was observed between expression levels of the other genes examined and PFS or OS. Only AEG-1 expression correlated with response (p=0.05). No FBXW7 hotspot mutations were detected. Conclusions: Although we did not find the FBXW7 hotspot mutations previously described in biliary tract cancer, FBXW7 mRNA expression significantly influenced PFS and OS. A separate cohort of p is being analyzed to validate the prognostic role of FBXW7.
Prognostic analysis of the patients with operable gastric cancer and the importance of tolerability of therapy: Study of Anatolian Society of Medical Oncology.
Authors: Kucukoner Mehmet , Arpaci Erkan , Isikdogan Abdurrahman , Bilici Mehmet , Uncu Dogan , Cetin Bulent , Dane Faysal , Cayir Kerim , Inanc Mevlude , Ekinci Ahmet Siyar , Inal Ali , Yetisyigit Tarkan , Ozdemir Nuriye , Kaplan Muhammed Ali , Aksoy Sercan , Alkis Necati , Tekin Salim Basol , Eroglu Celalettin , Turhal Serdar , Buyukberber Suleyman
Published: March 2020

e14526

Background: The aims of this study were to evaluate the tolerability and toxicity with adjuvant chemoradiotherapy (CRT) and prognostic analysis of patients with operable gastric cancer. Methods: The retrospective analysis included 723 patients with operable gastric cancer, stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. Patients’ age, sex, tumor localization, Lauren classification, grade, stage, type of dissection, toxicity and tolerability status were analyzed. Results: 73.9% of the patients were with stage III- IVM0. 61.0% of the patients were in the intestinal type, 51.1% of the patients were with the distal type of gastric cancer and 61.4% of the patients had undergone D2 dissection. 545 (75.4%) of patients completed the entire of adjuvant CRT. The median follow-up period was 20.8 months. Overall Survival (OS) rates were 80% and 52% while relapse free survival (RFS) rates were 75% and 48%, at 1, 3 years, respectively. In univariate analysis of groups, according to the group under the age of 65 and above (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), toxicity (p=0.062 / p=0.077), tolerability of therapy (p=0.002 / p=0.001) were significantly different in both RFS and OS. In multivariate analysis, three independent prognostic factors were identified on RFS / OS; stage (ods ratio (OR)=3.0, 95% confidence interval (CI):1.8-5.0, / OR=3.2, CI=1.8-5.4), for Lauren classification (OR=1.5, CI=0.9-2.2 / OR=1.5, CI= 1.1-2.2), for tolerability of therapy (OR=2.0, CI=1.0-3.8 / OR=1.9, CI=1.0-3.6). Conclusions: We found a new independent prognostic factor whether or not tolerate adjuvant CRT because of toxicity, except for the known prognostic factors like tumor stage and Lauren classification. We suggest that the treatment of the patients with intolerable to adjuvant CRT, is to change with less toxic adjuvant therapies.
A phase I/II study (TaxXel) on the treatment with docetaxel in combination with capecitabin in patients with metastatic esophageal cancer or cancer in the cardia region.
Authors: Friesland Signe , Wickart-Johansson Gun , Kadar Lianna , Bratthall Charlotte , Letocha Henry , Franzen Lars , Jacobsen Anne-Birgitte , Weber Hauge Petra , Wagenius Gunnar , Hatlevoll Ingunn , Glenjen Nils
Published: March 2020

e14531

Background: This is an open label, non-randomized, multicenter phase I-II study with Docetaxel (Doc) given in combination with capecitabine (Cap) in patients (pts) with metastatic oesophageal cancer (mEC) or cancer in the cardia region (mCCR). Methods: In phase I, pts were treated with Cap day 1-14, 22-36 and Doc day 1, 8, 15, 22, 29. Cap was dose escalated from 1300 mg up to 1650mg/m2 per day according to modified Fibonacci design. The dose of Doc was fixed to 30mg/m2 in both Phase I-II. In Phase II 1650mg/m2 Cap was given. The primary objective in phase I was to define a dose of Cap recommended for the Phase II and to determine the feasibility and safety of this treatment. The primary objective in the phase II was to determine the response rate (RR), safety profile, quality of life and survival.The median age was 64.8 years, PS was 0 in 23 pts, I in 57 and II in 13 pts. The histology was as follows: 58 adenoca, 33 squamous cell ca and 2 poorly diff ca. Forty-three pts had previously been treated with chemotherapy, 41 with radiotherapy, 50 were chemotherapy-naive and 31 had underwent surgery. Results: From March 2006 to Oct 2010, 93 eligible pts with measurable disease were enrolled in the study. Fourteen were treated in phase I and 79 in phase II. Four pts (1 in ph I and 3 in ph II) did not receive any study treatment. Twenty-seven pts of 93 (29%) were not evaluable according to study protocol which included CT after 6 w of treatment due to rapid tumour progression and deterioration of general condition. RR was 29%, 2 CR and 25 PR, 15 pts (16%) had SD and 24 pts (26%) had PD. Median OS was 7.3 months (5.76-8.9) and median PFS was 4.2 months (2.3-4.7 months).Treatment related grad 3 or 4 toxicity was as follows: 60% of pts experienced any grade 3 or 4 toxicity, 30% related to infections, 24% had nausea, diarrhea, vomiting, mucositis, <10% had cardiac related symptoms, <1% had an allergic reaction to Doc. Conclusions: Cap together with Doc appears tolerable and has a RR of 29% in selected group of patients with mET and mCCR. Majority of treatment courses were given on out-patient bases. However, there is un urgent need to define an optimal therapy regime and further studies are warranted.
Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).
Authors: Gunturu Krishna Soujanya , Thumar Jaykumar Ranchodbhai , Hochster Howard S. , Stein Stacey , Yao Xiaopan , Cong Xiangyu , Lacy Jill
Published: March 2020

e14534

Background: FOLFIRINOX significantly increases survival in metastatic PC compared to gemcitabine (Conroy. New Engl J Med 2011;364). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in advanced PC pts. Methods: We performed a retrospective review of dose, toxicity, and efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 07/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and RR were compared to Conroy’s data using one sample proportion test. Overall survival (OS) and progress free survival (PFS) were estimated by Kaplan-Meier method. Results: 35 pts with ECOG PS 0/1 were treated. Pt characteristics: LAPC 16; MPC 19; median age 61 yrs (range 48-77); male 13; prior chemotherapy 5. Median (med) number of cycles was 10 (range 1-26). FOLFIRINOX was dose attenuated with the first cycle in 29 pts: IRI reduced in 27 and omitted in 1, OX reduced in 10, bFU reduced in 9 and omitted in 7, LV decreased in 11, FU infusion reduced in 3. Med doses of OX, IRI, bFU, and infusion FU were 90%, 68%, 68%, and 100%, respectively, compared to 78%, 81%, 82%, and 82%, respectively, in Conroy’s FOFIRINOX arm (control). We are following pts for PFS and OS. RRs were 50% and 47% in pts with LAPC and MPC. RR in MPC didnot differ significantly from the control (p=0.19). We observed significantly less grade 3/4 fatigue (p=0.008) and neutropenia (p<0.0001) compared to the control group. Conclusions: Our findings suggest that dose attenuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent RR compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.
BDNF expression and systemic dissemination via anoikis resistance in gastric cancer.
Authors: Okugawa Yoshinaga , Inoue Yasuhiro , Tanaka Koji , Kawamura Mikio , Saigusa Susumu , Hiro Junichiro , Toiyama Yuji , Ohi Masaki , Mohri Yasuhiko , Uchida Keiichi , Yanagi Hidenori , Kusunoki Masato
Published: March 2020

e14541

Background: Anoikis (apoptosis resulting from loss of cell-matrix interaction) has been suggested to act as a physiological barrier to metastasis, and resistance to anoikis is necessary for cancer cell survival during systemic dissemination and metastasis. Brain-derived neurotrophic factor (BDNF) is one of the member of neurotropin family known to activate the high affinity tyrosine kinase (Trk)B receptor as a specific suppressor of anoikis. TrkB activation by BDNF has been shown to facilitate the progression of several cancers, however no reports have shown the clinical and biological effects of BDNF/TrkB axis in gastric cancer. Methods: BDNF expression in gastric cancer tissue and clinicopathological data from 153 consective patients were analyzed by real-time PCR and immunohistochemistry. The extent of target gene expression was calculated from the standard curve, with quantitative normalization of the cDNA in each sample performed using GAPDH gene as an internal control. Recombinant human BDNF and Trk antagonist K252a were used for in vitro assays to evaluate the biological role of the BDNF/TrkB axis in gastric cancer cell lines. Results: The mean BDNF level in gastric cancer tissue was 284.5 (0-2834). One hundred eighteen (77.1%) of 153 patients showed detectable BDNF levels, whereas the remainder had no detectable. BDNF positive expression was significantly associated with histological diffuse type (p=0.019), lymph node metastasis (p<0.001), peritoneal dissemination (p=0.028) and poor prognosis (p=0.022). In addition, BDNF expression is an independent risk factor for lymph node metastasis and peritoneal dissemination. Immunohistochemical analysis indicated intense BDNF expression in the cytoplasm of cancer cells, and intense TrkB expression in the nuclei of cancer cells, respectively. In vitro, administration of recombinant human BDNF promoted proliferation, anoikis resistance, and partial migration. In addition, these effects were generally inhibited by Trk antagonist K252a. Conclusions: BDNF appears to play an important role in gastric cancer progression, and blocking BDNF/TrkB axis might be clinically useful in developing therapies for patients with gastric cancer.
Outcomes after treatment of resectable, node-negative esophageal cancer: A risk-adjusted analysis of the Surveillance, Epidemiology, and End Results registry.
Authors: Martin Jeremiah Thomas , Worni Mathias , Zwischenberger Joseph Bertram , Pietrobon Ricardo , D'Amico Thomas A. , Berry Mark Francis
Published: March 2020

e14562

Background: Esophageal cancer has poor prognosis even in early stages. We examined survival for patients with resectable tumors in the absence of nodal disease in order to assess the benefits of surgery and radiation. Methods: Patients with T1-T3N0M0 squamous cell or adenocarcinoma of the mid or distal esophagus were identified using the SEER database from 1998-2008. The Kaplan-Meier approach and risk-adjusted Cox proportional-hazard models were used to assess 5-year overall survival. Survival risk among treatment modality subgroups (surgery only (SO), radiotherapy only (RO), combined surgery and radiotherapy (CT), and local tumor resection (LR)) was evaluated for the overall patient cohort and stratified among T-stage. SEER does not record chemotherapy use, which therefore wasn’t analyzed. Results: Overall 5-year survival for 4,251 patients identified (mean age 67.7±11.4 years, 966 (22.7%) female) was 37.6% (95% CI: 35.8-39.4). Survival correlated with T-stage: T1N0 48.0% (45.4-50.6); T2N0 29.8% (26.1-33.5); and T3N0 25.8% (22.9-28.7), p<0.001. For T1N0 patients, risk-adjusted survival was better with SO compared to CT (HR: 0.84, CI: 0.74-0.96, p=0.01) while LR and SO were not significantly different (p=0.24) (Table). Treatment with SO or CT had better survival compared to RO for T2N0 and T3N0 patients. The addition of radiation to surgery (CT vs. SO) improved survival for T3N0 patients (HR 0.79, CI 0.65-0.97, p=0.03) but not T2N0 patients (HR: 1.05, CI: 0.81-1.37, p=0.71). Conclusions: Surgical resection without radiation therapy is adequate for T1N0 esophageal cancer, but combined radiation and surgery has the best outcomes for T3N0 patients. Prognoses of T2N0 cancers are more similar to T3N0 cancers than T1N0 cancers, but no survival benefit to adding radiation to surgery for T2N0 patients was seen in this study. [Table: see text]
Sorafenib as bridging therapy in patients with intermediate hepatocellular carcinoma.
Authors: Vitale Alessandro , Lombardi Giuseppe , Ramirez Morales Rafael , Lonardi Sara , Zanus Giacomo , Zagonel Vittorina , Cillo Umberto
Published: March 2020

e14563

Background: Patients with intermediate stage hepatocellular carcinoma (HCC) obtaining an unsatisfactory response after loco regional (LR) therapies are at high risk of drop-out from a new chance of LR treatment or progression to advanced-terminal stages of disease. We prospectively used Sorafenib in this particular category of patients as a bridge therapy. The aim was to decrease the risk of tumour progression and to make them again eligible for loco regional therapies. Methods: Primary endpoint: disease control (DC) with Sorafenib, defined as complete/partial response or stable disease as by the modified RECIST criteria, maintained for ≥ 28 days from the first indications of response. Secondary endpoints: proportion of patients progression free at 2 months; median overall and progression free survivals. Patients obtaining DC with Sorafenib were again considered eligible for LR therapy. Inclusion criteria: a) intermediate stage; b) Child Pugh class A; c) performance status 0; d) unsatisfactory response to LR therapies (resection, ablation, chemoembolization), defined as incomplete response after at least 2 LR therapies. Study period: 01/04/2008–31/10/2011. End of follow-up: 31/01/2012. Results: Forty one patients were enrolled according to the study design. Thirty seven patients (90%) were progression free at the 2 months evaluation. A persistent DC was obtained in 29 patients (71%). According to the study hypothesis these patients were considered again eligible for loco regional therapies: 19 patients (65%) had ablation ± chemoembolization; 6 had liver transplantation (22%); 3 had liver resection (13%); 1 had radioembolization. Median duration of therapy with Sorafenib was 5 months (1–22). Sixteen patients (55%) had Sorafenib therapy both before and after LR therapy. Fourteen patients (48%) had more than one LR procedure. Median survival was 21 months (range, 1–39) in the whole group, while it was 25 months (range, 2–39) in the DC subgroup (median time to progression = 21 months, range 2–39). Conclusions: Sorafenib achieves high DC rates in BCLC B HCC patients with unsatisfactory response to LR therapies making them again eligible for LR therapies.
Multicenter randomized phase II study of weekly docetaxel alone versus weekly docetaxel plus oxaliplatin as a second-line chemotherapy in patients with advanced gastric cancer: Preliminary response and safety results.
Authors: Kim Jin Young , Do Young Rok , Park Keon Uk , Ryoo Hun-Mo , Bae Sung Hwa , Chae Yee Soo , Kim Min Kyoung , Lee Kyung Hee , Lee Sun Ah , Kim Jong Gwang , Song Hong-Suk ,   Daegu-Gyeongbuk Oncology Group
Published: March 2020

e14570

Background: Gastric cancer is a frequent malignancy with worldwide estimated incidence of 990,000 cases, representing 7.8% of all cancers in 2008. There are limited data suggesting a benefit for doublet second-line chemotherapy in advanced gastric cancer. Methods: The eligibility criteria were patients 1) with prior exposure to cisplatin based chemotherapy and advanced or recurrent stomach cancer 2) with pathologically proven gastric adenocarcinoma, 3) with an ECOG performance status 0 to 2, 4) with measurable lesions. Each treatment cycle was consisted of docetaxel 36 mg/m2 in docetaxel mono therapy group and docetaxel 36 mg/m2, oxaliplatin 80 mg/m2 in docetaxel/oxaliplatin doublet therapy group on days 1, 8. The primary end point of this study was response rate, and secondary end points included toxicity, progression free and overall survival. Results: Fifty two patients were enrolled; median age was 63 years; male (n=42) and female (n=10); docetaxel mono therapy (n=27) and docetaxel/oxalliplatin doublet therapy (n=25). The median number of cycles administered was 2.5 (range,1-9). Fourty eight patients were assessable for efficacy. Four partial responses, 7 stable diseases in mono therapy group (RR; 4/27, 14.8%) and 1 complete remission, 4 partial responses, 13 stable diseases in double therapy group (RR; 5/25, 20.0%) were confirmed (p=0.198). Median progression free survival was 1.97 months in the mono therapy group and 4.93 months in doublet therapy group (p=0.007). Median overall survival was 11.57 months in the mono therapy group and 8.13 months in doublet therapy group (p=0.650). Grade 3 or 4 adverse events were reported in 11 of 52 patients; G3 pain were in 2 patients and G3 pneumonia was in 1 patient in mono group, G3/4 neutropenia were 5 patients in the combination group, G3 nausea, vomiting, general weakness was 1 patient each group in combination group. Conclusions: Weekly docetaxel/oxaliplatin doublet therapy showed superior progression free survival to monotherapy group as second line therapy in cisplatin pretreated advanced gastric cancer patients.
Gastric tube cancer after esophagectomy for esophageal cancer: A single-center experience with meta-analysis of 145 cases.
Authors: Lee Geun Dong , Kim Yong-Hee , Park Seung-Il , Kim Dong Kwan , Kim Hyeong Ryul
Published: March 2020

e14573

Background: Gastric tube cancer (GTC) defined as carcinoma arising in the gastric conduit after esophagectomy, is often crucial in long-term survivors of esophageal cancer. The aim of this study was to determine the optimal approach to manage GTC. Methods: We reviewed data of 863 patients who underwent esophagectomy and reconstruction with the gastric conduit for esophageal cancer at Asan Medical Center from 1993 to 2011 and identified 28 cases of GTC. We also searched through the PubMed database and included additional 117 cases of GTC from 13 studies to conduct meta-analysis. Results: In our cases, the incidence rate of GTC was 3.2%. The median interval between esophagectomy and GTC detection was 3.1 (0.6-15.2) years. Twelve (42.9%) patients were asymptomatic and diagnosed by periodic endoscopy. The Most common histologic type of GTC was adenocarcinoma (57.1%) and fifteen (53.6%) were located on the lower third of gastric tube. Chemotherapy, total gastrectomy or palliative treatment was performed in 10, 5, 2 patients, respectively. Eleven (39.3%) patients refused the further treatment for GTC. Mean survival duration of 28 patients after the diagnosis of GTC was 29.1 months. In meta-analysis, The cumulative occurrence of 5, 8 years was 59.5%, 87.8%, respectively. Two-year survival rate of the patients who underwent endoscopic resection, surgical resection or palliative treatment was 100%, 61.6%, 5.2%, respectively. The patients who underwent endoscopic resection had a better prognosis than those who underwent surgical resection or those who received palliative treatment (p=0.047, p=0.000, respectively). Conclusions: After esophagectomy for esophageal cancer, patients had a constant risk of GTC occurrence up to 8 years approximately. The patients who diagnosed as advanced-state GTC had a poor prognosis. However, endoscopic resection as a minimally invasive treatment for early-GTC represented a feasible prognosis compared with those of operative resection or palliative treatment. Therefore, a long-term follow-up including detailed endoscopy is essential for the better outcomes in patients who underwent esophagectomy for esophageal cancer.
Prognostic factors for survival in gastric cancer after radical resection: A retrospective study of 1,594 patients in Shanghai.
Authors: Sun Yihong , Wang Cong , Shen Zhenbin , Zhao Naiqing , Chen Weidong , Wang Xuefei , Wang Hongshan , Fang Yong , Liu Fenlin , Tang Zhaoqing , Li Haojie , Lv Chentao , Qin Jing , Wang Yanna , Piao Yongzhe , Wang Lisa , Chu Laura , Dong Wei , Qin Xinyu
Published: March 2020

e14575

Background: Gastric Cancer (GC) is the second leading cause of cancer death in Shanghai,and the overall treatment response remains poor. This study aimed to describe overall survival and identify prognostic factors for survival among GC patients (pts) after radical resection. Methods: Clinical data of 1594 GC pts (Shanghai residents) who had undergone R0 or R1 resection in Zhongshan hospital, January 2003 to June 2010, were analyzed. Potential prognostic factors including demographic and tumor characteristics were collected. Survival was calculated by the Kaplan-Meier method and Log-rank test was used to determine statistical significance. Prognostic factors were analyzed using Cox regression multivariate analysis. Results: Overall 5-year cumulative survival for all pts was 55.8%. The 5-year cumulative survival by TNM stage I, II, III, and IV (classified using AJCC 7th edition staging system) were 93.8%, 72.7%, 33.3%, and 12.7%, respectively. The distribution of pts by AJCC stage I-IV was 22.5%, 23.1%, 51.7% and 2.8% respectively. In univariate analyses, gender and the number of lymph nodes removed was not associated with survival (p>0.05). However, age, tumor differentiation, tumor site, lympahtic/venous invasion, depth of infiltration, presence of lymph node metastasis, and presence of distant metastasis were related to survival (p<0.05). In multivariate Cox regression model analysis, age (p<0.001), tumor site (p=0.004), lymphatic/venous invasion (p<0.001), TNM stage(p<0.001) were independent prognosticators. Among pts with TNM stage III , number of lymph nodes removed was also an independent prognostic factor (p<0.001). Conclusions: Age, tumor site, lymphatic/venous invasion, TNM stage in all patients, and the number of lymph nodes removed in TNM stage III patients, were independent prognostic factors. GC remains a significant unmet medical need in China and effective therapies are urgently needed.