bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of macroscopic features in relation to tumor response to neoadjuvant chemoradiation therapy in rectal cancer.
Authors: Arrington Amanda Kathleen , Garcia-Aguilar Julio , Duldulao Marjun Philip , Luu Carrie , Sanchez Julian , Kim Joseph , Choy Kristi 
Published: February 2017

507 Background: Several studies show locally advanced rectal cancer patients with clinical complete response (cCR) have comparable oncologic outcomes to pathologic complete response (pCR) to neoadjuvant chemoradiation therapy (NCRT). Thus, total mesorectal excision (TME) could potentially be avoided. Our objective was to validate macroscopic features of cCR. Methods: 164 patients with stage II/III rectal cancer were previously enrolled in a phase II trial and treated by NCRT and TME. Tumor response in the surgical specimens was assessed according to AJCC guidelines. A pCR was defined as absence of viable tumor cells. Gross macroscopic features by the pathologist were tabulated and our cohort was applied to previously published cCR criteria. Results: 25.0% (n = 41) had pCR; 75.0% (n = 123) had non-pCR. Descriptors were condensed into 14 macroscopic features by combining terms and excluding those rarely mentioned. Several reports affirm that scarring signifies cCR, while others suggest that fibrosis, edema, ulceration and nonpalpable tumor to be consistent with cCR. In our study, scarring was found in 6.1% of patients, 16.7% of which had pCR. We found that hyperemia, scarring, flat, smooth, and tan-pink mucosa were significantly associated with pCR (p < 0.05). In contrast, a firm lesion and ulceration were frequently observed in patients with non-pCR (p = 0.02 and 0.05 respectively). Conclusions: Our study suggests that macroscopic pathologic features do correlate with pCR. Although cCR has comparable oncologic outcomes as pCR with favorable outcomes, standard criteria of cCR should first be defined so NCRT patients can safely be selected for observation only. [Table: see text]
The impact of palliative resection (PR) of the primary tumor on overall survival (OS) in metastatic colorectal cancer (mCRC).
Authors: Gresham Gillian , Renouf Daniel John , Chan Matthew , Cheung Winson Y. 
Published: February 2017

509 Background: The role of PR of the primary tumor in mCRC remains unclear. Using population-based data, we explored the impact of PR on OS. Methods: Patients (pts) with mCRC who were referred to 1 of 5 regional cancer centers in British Columbia between 2006 and 2008 were reviewed (n=802). Pts with prior early stage CRC who relapsed with mCRC were excluded (n=285). We conducted survival analysis using Kaplan Meier methods and determined adjusted hazard ratios (HR) for death using Cox proportional hazards models. A secondary propensity score matched analysis was performed to control for baseline differences between pts who underwent PR and those who did not. Results: A total of 517 pts with mCRC were identified: median age was 63 years (range 23-93), 54% were men, 55% had ECOG 0-1, 76% had a colon primary, and 31% had >1 metastatic site. The majority (n=378; 73%) underwent PR of the primary tumor and a significant proportion (n=327; 63%) received palliative chemotherapy (CT). Compared to pts without PR, those with PR were more likely to be men (62 vs 51%, p=0.03), aged <65 years (63 vs 52%, p=0.03), ECOG 0-1 (61 vs 38%, p<0.0001), and receive palliative CT (68 vs 50%, p=0.0004). PR was associated with improved median OS across groups (Table). The benefit of PR on prognosis persisted in multivariate analysis (HR for death 0.56, 95%CI 0.43-0.72, p<0.0001 for entire cohort; HR 0.51, 95%CI 0.37-0.70, p<0.0001 for individuals who were treated with CT; and HR 0.54, 95%CI 0.34-0.84, p=0.007 for those who did not receive CT). In a propensity score matched analysis that considered age, gender, ECOG, and receipt of palliative CT, prognosis continued to be more favorable in the PR group (HR 0.66, 95% CI 0.50-0.86, p=0.0019). Conclusions: In this population-based analysis, PR of the primary tumor in mCRC was associated with a significant OS benefit. [Table: see text]
A randomized phase II study of neoadjuvant chemoradiotherapy with 5-FU/leucovorin or irinotecan/S1 in patients with locally advanced rectal cancer.
Authors: Jung Minkyu , Shin Sang Joon , Lim Seungtaek , Park Ji Soo , Koom Woong Sub , Keum Ki Chang , Kim Nam Kyu , Back Seung Hyuk , Min Byung Soh , Hur Hyuk , Kim Ho Geun , Lim Jun Seok , Kim Tae IL , Roh Jae Kyung , Park Young Suk , Ahn Joong Bae 
Published: February 2017

511 Background: The purpose of this study was to evaluate rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) with 5-FU/leucovorin (FL) versus Irinotecan/S-1 (IS) and surgery followed by fluoropyrimidine based adjuvant chemotherapy. Methods: Patients with resectable, locally advanced (cT3-4 and/or cN positive) adenocarcinoma of rectum were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25-28 daily fractions) and concomitant chemotherapy with bolus injections of 5-FU 400 mg/m2/day and LV 20 mg/m2/day for 3 consecutive days every 4 weeks for 2 cycles (FL group), or with irinotecan 40 mg/m2 on days 1, 8, 15, 22, 29 and S-1 35mg/m2 twice on the day of irradiation (Monday-Friday) (IS group). Curative surgery was performed for about 4-8 weeks after the completion of chemoradiotherapy. Postoperative chemotherapy regimen is FL. The primary endpoint was pCR rate. Results: 142 eligible patients were randomly assigned. Of 142, 130 patients (91.5%) underwent total mesorectal excision. The pCR was achieved 11 (17.2 %) of 64 patients in the FL group and was 16 (24.2%) of 66 patients in the IS group (p=0.1). When pCR was combined with few residual cells, the rate was significantly higher in IS group compared to FL group (57.6 % vs. 39.1 %, p-value=0.035). Preoperative rate of grade 3-4 toxicity was 1.4% with FL and 7.0 % with IS group (p=0.095). Conclusions: The results have suggested that neoadjuvant CRT using IS is feasible and effective for patients with locally advanced rectal cancer. Longer follow-up is needed to assess survival. Clinical trial information: NCT01269216.
Prediction model for ypΝ status after preoperative chemoradiotherapy in patients with rectal cancer.
Authors: Jwa Eunjin , Kim Jong Hoon , Han Seungbong , Park Jin-hong , Kim Jin Cheon , Yu Chang Sik , Lim Seok-Byung , Kim Tae Won , Hong Yong Sang 
Published: February 2017

513 Background: Pelvic lymph node status after preoperative chemoradiotherapy (CRT) is not only an important indicator for oncologic outcome but critical information to determine the type of a subsequent surgical resection (i.e. curative surgery or local excision) in patients with locally advanced rectal cancer. The purpose of this study is to develop a nomogram to predict the lymph node status after preoperative CRT in rectal cancer patients whose ypT information is available. Methods: Using logistic regression analyses, we constructed a prediction model to predict the probability of lymph node metastasis after preoperative CRT in a cohort of 1,099 patients with rectal cancer treated with preoperative CRT and total mesorectal excision (TME) from 2007 to 2011. The model was internally validated for discrimination and calibration using bootstrap resampling. Results: Pretreatment clinical nodal stage, distant metastasis, pre- and post-treatment tumor differentiation, and ypT stage were reliable predictors for lymph node metastasis after preoperative CRT. The nomogram developed using these parameters represents a valid and accurate method for predicting lymph node metastasis after preoperative CRT in rectal cancer patients. (c-index: 0.75) Patients with low pretreatment nodal stage, nonmetastatic, and well differentiated rectal adenocarcinoma downstaged to ypT0-1 after preoperative CRT will have low chance of pelvic lymph node involvement. Conclusions: Our model is expected to assist clinicians in quantifying the benefit of radical resection and finding out the patient group who can be treated with local excision after preoperative CRT for rectal cancer.
FOLFOXIRI plus bevacizumab (BEV) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC): Preliminary safety results from the OPAL study.
Authors: Stein Alexander , Atanackovic Djordje , Hildebrandt Bert , Stuebs Patrick , Steffens Claus-Christoph , Brugger Wolfram , Hapke Gunnar , Illerhaus Gerald , Bluemner Ernst , Bokemeyer Carsten 
Published: February 2017

515 Background: The addition of BEV to standard doublet chemotherapy (CT) improves outcomes vs CT alone in pts with mCRC. Use of more intensive triplet CT may prolong overall survival (OS), progression-free survival (PFS), increase response rates and improve resectability rates but at the expense of greater toxicity. The OPAL study examined the effect of BEV + FOLFOXIRI on PFS in pts with previously untreated unresectable mCRC. Here we report preliminary safety findings. Methods: Eligible pts had histologically confirmed mCRC, ECOG PS ≤1 and were 18–70 years old. Pts received ≤12 cycles of FOLFOXIRI (infusional 5-fluorouracil [FU] 3200 mg/m2, folinic acid [FA] 200 mg/m2, oxaliplatin 85 mg/m2, irinotecan 165 mg/m2) + BEV 5 mg/kg q2w (induction phase) followed by ≤40 cycles of 5-FU/FA + BEV q2w (maintenance phase). PFS was the primary endpoint; secondary endpoints included OS, proportion of pts achieving resectability and safety. Results: 96 pts were enrolled. Of these, 90 received study medication and formed the safety population: 64 male, 26 female; median age 58 (range 28–71) years; ECOG performance status 0/1 in 49/41 pts. All pts have completed induction treatment and the study is ongoing. In total, 61 serious AEs occurred in 34 pts (38%). AEs resulting in death occurred in 3 pts (3%); these were not considered treatment-related by the investigators. The incidence of AEs of special interest with BEV was low. Main AEs reported during the induction phase are summarised in the table. Conclusions: BEV + FOLFOXIRI was generally well tolerated in this mCRC pt population. The incidence of AEs was as previously reported [Falcone et al. ASCO 2010] and there were no new safety signals. Clinical trial information: NCT00940303. [Table: see text]
Randomized, controlled trial comparing S-1 with UFT/LV as adjuvant therapy for curatively resected stage III colorectal cancer (BCOG-CC02 study).
Authors: Koda Keiji , Miyauchi Hideaki , Yokoi Kimiyoshi , Kosugi Chihiro , Kaiho Takashi , Kobayashi Susumu , Ochiai Takenori , Matsubara Hisahiro 
Published: February 2017

520 Background: Oral anticancer drug, UFT/LV, has recently been reported to improve both overall survival (OS) and relapse free survival (RFS) for patients with Stage III colorectal cancer in Japan. We conducted a randomized clinical trial to compare S-1 with UFT/LV for adjuvant therapy in patients with Stage III colorectal cancer. Methods: Patients with Stage III colorectal cancer (PS, 0 to 1; age, 20 to 80 years) were randomized to take either UFT / LV (28 days per 5 weeks) for 6 months. or S-1 (28 days per 6 weeks) for 12 months started within 6 weeks following curative resection. We investigated the correlations between disease- free survival (DFS) and tissue mRNA levels of 5-FU and folate metabolism-related enzymes. In addition, we investigated overall survival (OS) and safety. Results: Between April 2008 and August 2010, a total of 145 patients were registered from 22 centers. There were no clear intergroup differences in background factors. The patients who relapsed during protocol duration of treatment were excluded, the percentages of patients who took expected dosage of medicine were 67.1% (47/70) and 87.3% (62/71) in S-1 and UFT/LV groups, respectively. Grade3 to 4 myelosuppression(4%), bilirubin(3%) and diarrhea(8%) were occurred in S-1 group whereas, grade 3 liver dysfunction (5%) and diarrhea (5%) occurred in UFT/LV group, but all of them were reversible. The median follow-up period was 934 days, 3-years’ DFS in patients of S-1 and UFT/LV groups were 65.9% and 72.7%, respectively (p=0.88). In a univariate analysis, topoisomerase-1 (TOPO-1) mRNA level was shown as a factor of the recurrences. A poor-prognosis patient population was observed in the S-1 group such as with low gamma-glutamyl hydrolase (GGH) mRNA level. Conclusions: Oral anticancer drug, S-1 showed an equivalent effect for UFT/LV in Stage III colorectal cancer as adjuvant therapy. Tissue levels of mRNA of 5-FU/ folate metabolism-related enzymes were important parameters for postoperative prognosis in patients with stage III colorectal cancer who take oral 5-FU derivatives for adjuvant therapy. Clinical trial information: UMIN000001560.
Course of calcium and magnesium serum levels in cetuximab-treated patients: Relation to concurrent chemotherapy and possible predictive value.
Authors: Stintzing Sebastian , Fischhaber Doris , Modest Dominik Paul , Giessen Clemens Albrecht , Hendrich Saskia , Aubele Phillip , Heinemann Volker 
Published: February 2017

521 Background: Hypomagnesaemia and hypocalcaemia are well known adverse events of cetuximab treated patients. Whether these side effects are of predictive value remains unclear. Methods: Patients receiving cetuximab for antitumoral treatment in the day clinic were investigated. Calcium and magnesium serum levels were analysed weekly during therapy, and tumor response and adverse events were followed. Serum levels were noted in relation to baseline measurements. Evaluable patients should at least be treated over a period of 6 weeks. Results: Between 2008 and 2011, a total of 97 patients were treated with cetuximab and were evaluable for serum levels. 38 patients had metastatic colorectal cancer, 27 suffered from SCCHN, 14 had other neoplastic diseases. During therapy, calcium serum levels decreased to a level of about 97% of baseline measurement and stayed there for the duration of treatment. Magnesium levels, however, showed a time dependent decrease during the whole observation time. When calculating the serum levels in relation to the chemotherapeutic combination partner, serum levels of magnesium were significantly lower when cetuximab was combined to a platin-derivative (oxali-, cis- or carboplatin). After a treatment duration of 12 weeks, magnesium levels dropped to 70% in platinum-treated pts, while they decreased to only 90% of baseline in pts without platinum therapy. In patients treated for metastatic colorectal cancer (mCRC) a decline of serum magnesium below 95% of baseline levels 14 days after initiating treatment separated patients with good outcome from those with poor outcome. While, a significant correlation between lower magnesium serum levels and the occurrence of acneiform exanthema was shown, no correlation of hypomagnesemia with clinical symptoms such as e.g. muscle cramps were documented. Conclusions: Magnesium levels decline in a time dependent manner during cetuximab therapy without occurrence of clinical symptoms. Hypomagnesaemia was more prominent in patients receiving platinum agents and was associated with better outcome.
Induction chemotherapy followed by chemoradiotherapy and total mesenteric excision for locally advanced rectal cancer with resectable metastases.
Authors: Hajj Carla , Cercek Andrea , Saltz Leonard , Segal Neil Howard , Reidy Diane Lauren , Stadler Zsofia Kinga , Kemeny Nancy E. , Wu Abraham Jing-Ching , Weiser Martin R. , Paty Philip , Guillem Jose G. , Nash Garrett Michael , Temple Larissa K. F. , Garcia-Aguilar Julio , Goodman Karyn A. 
Published: February 2017

526 Background: Optimal management of patients with locally advanced rectal cancer (LARC) and synchronous, resectable metastases remains controversial and treatment decisions benefit from a multidisciplinary approach. To better characterize the role of induction chemotherapy followed by chemoradiation and surgery, we evaluated patterns of distal progression and overall survival in this subset of patients. Methods: We reviewed records of 25 LARC patients with synchronous resectable metastases treated with induction chemotherapy (ICT) followed by 5-fluorouracil-based concurrent chemoradiation (CRT) at our institution between December 2006 and December 2010. Radiation was delivered using a standardized three-field technique or IMRT. The incidence and sites of failure were analyzed. Overall survival (OS) and progression-free survival (PFS) were calculated from the completion of CRT using the Kaplan-Meier method. Results: Of the 25 patients who received ICT followed by CRT, 21 (84%) underwent total mesorectal excision and metastectomy. Eleven patients (44%) had liver metastases. The median ICT duration was 2.4 months. Twenty patients (80%) received a FOLFOX-based ICT regimen and 5 patients (20%) received irinotecan-based chemotherapy. Two patients had unresectable disease, one was medically inoperable, and surgery was aborted due to intra-operative complications in one patient. Eighteen of the 21 were NED after surgery and metastatectomy (86%) with 24% pathologic complete response rate in the primary tumor; 10 (56%) received adjuvant chemotherapy. None of the patients recurred locally. Six of the 18 (33%) progressed distally, four of whom had received adjuvant chemotherapy. Four distal recurrences were in the lungs. With a median follow-up of 29.6 months, the 3-year OS was 50.4%. Median OS and PFS were 25.1 months and 13.5 months, respectively. Conclusions: ICT prior to CRT is associated with acceptable toxicity, substantial primary tumor regression, and promising clinical outcomes in patients with high-risk LARC with synchronous, resectable metastatic disease.
Efficacy and safety of venting percutaneous endoscopic gastrostomy (VPEG) tube placement in patients with malignant obstruction.
Authors: Keswani Rajesh N. , Issaka Rachel B , Shapiro David M , Mulcahy Mary Frances , Komanduri Srinadh , Martin John A. , Parikh Neehar 
Published: February 2017

538 Background: Refractory nausea and vomiting are common in patients with advanced malignancy. A venting percutaneous endoscopic gastrostomy (VPEG) tube can be placed to eliminate the need for a nasogastric tube and palliate obstructive symptoms. The aim of this study was to determine the outcomes of VPEG placement in patients with advanced malignancy. Methods: We retrospectively reviewed all patients in whom a VPEG tube was attempted for a malignant indication over a 13-year period (1998-2010). Demographic and clinical information, procedure details, and immediate & delayed complications were recorded. Results: Endoscopic VPEG placement was attempted in 96 patients (95% inpatient) with a median age of 57y. Colorectal (27%), pancreas (18.8%), and gynecologic (17.7%) malignancies were most common. Ascites was present in 46.9% of patients with drainage performed in a minority of patients (35.6%). VPEG was successfully placed by endoscopy in 89 patients (92.7%). Relief of obstructive symptoms was observed in 91.7% of patients. Eight patients had refractory obstructive symptoms despite functioning VPEG tube. Ten post-procedural complications were noted in 9 patients, with 1 death. Patients with ascites were more likely to have infectious complications (12.2%) than those without ascites (0%, p=0.02) with a trend towards decreased infectious complication when ascites was drained prior to VPEG placement (14.8% vs. 7.1%, p=NS). We observed decreased survival when complications occurred (73 days) compared to when they did not (141 days, p = NS). Conclusions: VPEG tubes can be safely placed in patients with inoperable malignancy and obstructive symptoms with complete relief of symptoms in the majority of patients. The presence of ascites was a risk factor for post-procedural infectious complications. Drainage of ascites prior to VPEG tube placement may minimize this risk, though this warrants further study.
A multicenter phase II trial of mFOLFOX6 plus bevacizumab as treatment for liver-only metastases from colorectal cancer unsuitable for upfront resection (TRICC 0808).
Authors: Uetake Hiroyuki , Yasuno Masamichi , Ishiguro Megumi , Kameoka Shingo , Shimada Yasuhiro , Takahashi Keiichi , Watanabe Toshiaki , Muro Kei , Baba Hideo , Yamamoto Junji , Mizunuma Nobuyuki , Tamagawa Hiroshi , Mochizuki Izumi , Kinugasa Yusuke , Matsubara Yoshihiro , Sugihara Kenichi 
Published: February 2017

543 Background: Liver resection is a standard treatment for resectable liver metastases (mets) from colorectal cancer. In patients (pts) with multiple or large liver mets, liver tumors may not be resected completely or recurrence after complete resection are frequently observed. Methods: This prospective single arm phase II trial assessed R0 liver resection rate after mFOLFOX6 + bevacizumab (BV) in pts with liver mets considered unsuitable for upfront resection. Pts with liver-only mets, those were larger than 5cm in diameter or more than 4 in number, were treated with 6 cycles of mFOLFOX6 + BV (without BV in the 6th cycle). After chemotherapy, resectability of liver mets was assessed by CT or MRI. Secondary endpoints included liver resection rate, conversion rate from unresectable to resectable, safety of liver resection, recurrence rate, and survival. Results: Between May 2009 to October 2011, 46 pts were registered (one was excluded after registration due to ineligibility). Among the 19 pts with resectable mets at entry, 18, except one who refused the continuation of chemotherapy after the first cycle, underwent liver resection after 6 cycles of chemotherapy. In 16 of the 18 pts, R0 resection was performed. Among the 26 pts with unresectable mets at entry, 6 underwent liver resection and 4 had R0 resection. Overall R0 resection rate, liver resection rate and conversion rate were 44.4% (20/45), 53.3% (24/45) and 23.1% (6/26), respectively. The grade 3/4 adverse effects (AEs) by mFOLFOX6 + BV included fatigue (6.5%), stomatitis and nausea (2.2%), neutropenia (16.3%) and increase of serum total bilirubin (2.2%). As to BV related grade 3/4 AEs, hypertension (6.5%) and thromboembolism (2.2%) were observed. After liver resection, grade 3 wound infection, intra-abdominal abscess and delayed wound healing were complicated in two, in one and in one, respectively. Conclusions: In pts considered unsuitable for upfront resection of liver-only mets, mFOLFOX6 + BV was associated with high R0 resection rate, liver resection rate and conversion rate without severe toxicities and surgical complications. Updated results including survival will be presented. Clinical trial information: UMIN000002101.