bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of intensity-modulated radiation therapy (IMRT) with PET-defined simultaneous integrated boost (SIB) for distal rectal adenocarcinoma (DRA).
Authors: Valakh V. , Kirichenko A. V. , Betler J. , Leicher B. , Werts E. D. , Medich D. , Parda D. S. 
Published: February 2017

550 Background: PET/CT guided preoperative IMRT is being used with increasing frequency in standard practice but reports of methods, efficacy, and toxicity are limited. We report the AGH experience from 2007-2010 of IMRT with SIB for DRA. Methods: 22 pts with stage IB–IV DRA (8 with anal canal involvement) were treated with preoperative concurrent IMRT with SIB, 5FU-based chemotherapy. 15 received weekly oxaliplatin. All had PET/CT simulation. The planned target volume included PET-avid primary tumor and LNs with median margins of 3mm (range, 0–13), in a median of 24 fx (range, 20–28), a median dose of 2.25 Gy/fx (range, 1.9–2.4 Gy) to a median total dose of 53.3 Gy (range, 50.6–57.2 Gy). Clinical target volume included non PET-avid 1st echelon LNs with a median dose of 2.0 Gy/fx (range, 1.6–2.3 Gy) to a total median dose of 47 Gy (range, 40.7–54.04 Gy). Median follow-up was 18 mos (range, 4–35). Late toxicities were scored using CTCAE v. 3.0. Results: 17 of 22 patients (TNM stages IB (3), IIA (3), IIB (1), IIIA (2), IIIB (7), IV (1)) were treated curatively. The remaining 5 pts were treated palliatively. The median length of time from completion of radiation to surgery was 81 days (range, 48–398). 5 pts did not have surgery due to advanced metastatic disease (3), death (1) or biopsy proven complete response (CR) (1). R0 resection was accomplished in 15 of 17 surgical pts including 13/14 curative and 2/3 palliative cases. R1 resection occurred in 2 pts; 1 with stage IIIB and 1 with stage IV. No pts had R2 resection. 6 pts (5 with T2 lesions and 1 with a T4 lesion) had a pathologic CR. 2 of 3 non-surgical pts with metastatic disease had LRF at 5 and 11 mos. 9/22 pts had no late toxicity, 9/22 ≤ grade 2 and 4/22 had grade 3 late toxicity. No patients with T2 tumors had grade 3 late toxicity, and this appeared to be related to lower GTV. Kaplan-Meier freedom from grade 3late toxicity was 85% at 18 mos. Conclusions: IMRT with SIB is an accurate targeting technique in pts with DRA that showed a pathologic CR in 100% of T2 lesions. Advanced T stage and larger GTV were possible risk factors for grade 3 late toxicity. [Table: see text] No significant financial relationships to disclose.
Efficacy of darbepoetin alfa in colorectal cancer patients: Data from the CHOICE study.
Authors: Van Belle S. , Urbanski K. , Orfeuvre H. , Foucher P. , Wheeler T. , Pujol B. 
Published: February 2017

552 Background: To evaluate adherence to hemoglobin (Hb) values recommended by the updated European (EU) product label for darbepoetin alfa (DA) and describe hematological response in patients (pts) receiving DA for the treatment of chemotherapy-induced anemia in clinical practice. Data of colorectal cancer (CRC) pts are reported. Methods: A prospective, multicenter, observational study assessed DA use in CRC, breast, ovarian and lung cancer pts in 11 EU countries. Data (such as Hb levels and need for red blood cell (RBC) transfusions) were extracted from medical records on an electronic case report form. Results: This interim analysis included 1,290 pts. 192 pts had CRC: 1% had stage I, 6% stage II, 18% stage III and 75% stage IV cancer. The most-used chemotherapy regimens were 5-fluoruracil or capecitabine (33%), ironotecan- (27%) and oxaliplatin-based (24%). Baseline (BL) Hb values were available for 189 pts; the mean (standard deviation, SD) Hb value at BL was 9.8 (0.8) g/dL; 60% of CRC pts had BL Hb values of <10 g/dL and 90% values of <11 g/dL. Of the 119 pts still on study at week (wk) 9, 60% (95% CI: 51, 68) achieved a Hb level of 10-12 g/dL at wk 9 (primary outcome measure). With increasing BL Hb values, more pts achieved Hb ≥10 g/dL (see table). The mean (SD) Hb at the end of treatment period (EOTP) was 11.0 (1.5) g/dL. The Kaplan-Meier (K-M) % of pts with Hb levels ≥10 g/dL at EOTP was 91% (only pts with BL Hb <10 g/dL included). The K-M % of pts with Hb levels >13 g/dL at EOTP was 10% for pts with BL Hb <10 g/dL. Of pts in the study for ≥29 days after start of DA, the K-M % of pts needing RBC transfusions after wk 5 was 21% at EOTP. No treatment-related adverse drug reactions were reported. Conclusions: Most CRC pts were treated in accordance with the EU product label. The high K-M % of pts with Hb values ≥10 g/dL suggests DA is effective. Hb levels >13 g/dL were rare for pts with BL Hb <10 g/dL. Sponsored by Amgen (Europe) GmbH. [Table: see text] [Table: see text]
Safety and efficacy of first-line XELIRI with or without bevacizumab in patients with metastatic colorectal cancer: Analysis of two phase II studies.
Authors: Garcia-Alfonso P. , Alvarez S. , Munoz A. , Lopez P. , Riesco C. , Adeva J. , Martin M. 
Published: February 2017

560 Background: The safety and efficacy of first-line XELIRI (capecitabine in combination with irinotecan) and XELIRI plus bevacizumab (BEV) have been evaluated in patients with metastatic colorectal cancer (mCRC). To date, however, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy and safety data for the two regimens from separate phase II studies performed at a single institution. Methods: Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease received irinotecan 175 mg/m2 on day 1 and oral capecitabine 1,000 mg/m2 twice daily on days 2-8 every 2 weeks (XELIRI study). For patients age ≥65 years, the starting doses of irinotecan and capecitabine were reduced to 140 mg/m2 and 750 mg/m2, respectively. In the second study, patients received the same regimen plus BEV 5 mg/kg on day 1 (XELIRI + BEV study). Results: A total of 53 and 46 patients were entered into the XELIRI and XELIRI + BEV studies, respectively. Patient characteristics were generally similar in both groups. Efficacy results for the ITT populations are summarized in the Table. Patients treated with XELIRI + BEV had a significantly higher ORR and longer median TTP vs. XELIRI alone and a numerically longer median OS was observed (p=NS). The overall incidence of adverse events (all grades or grade 3/4) was similar in the two groups, although alopecia, mucositis, hand–foot syndrome, and haemorrhage were more common with XELIRI + BEV vs. XELIRI alone (all p<0.05). Conclusions: In this retrospective comparison of two studies, the addition of BEV to XELIRI appeared to improve outcome relative to XELIRI alone in the first-line treatment of patients with mCRC. The overall incidence of adverse events was similar in the two groups. [Table: see text] No significant financial relationships to disclose.
Pelvic malignancies undergoing exenteration.
Authors: Chokshi R. J. , Arrese D. , Kuhrt M. P. , Routt M. , Kocak E. , Martin E. W. 
Published: February 2017

579 Background: Pelvic exenteration is reserved for patients with locally invasive and recurrent pelvic malignancies. The literature demonstrates a high morbidity and mortality associated with this operation. At our institution, a high volume of pelvic exenterations are undertaken and their outcomes have been studied. Methods: The medical records of 53 patients with varying pelvic pathologies who underwent pelvic exenteration between 2004 and 2010 were reviewed. Demographics, histologies, periprocedural events, and outcomes were analyzed. Results: Patients were divided into a colorectal (n = 37) and noncolorectal (n = 16) group for analysis based on histology. The two groups were similar in demographics, perioperative events, and length of stay. Resection status, chemotherapy use, and intraoperative radiation therapy showed no statistical difference. Complications showed a difference in perineal abscesses in the colorectal group. The colorectal group showed a survival difference when comparing R0 resection versus R1/R2, however no difference was seen in primary versus recurrent tumors. The median survival was 20.3 months in the colorectal group and 4.8 months in the noncolorectal group. Conclusions: Patients undergoing exenteration for colorectal histology have improved survival when compared to pelvic malignancies of other origins. The greatest effect on long term survival is seen in the colorectal group undergoing a R0 resection. Despite pelvic exenterations carrying a high morbidity and mortality, careful patient selection can optimize outcomes. [Table: see text] No significant financial relationships to disclose.
Intensity-modulated radiation therapy (IMRT): Differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma.
Authors: Mok H. , Crane C. H. , Briere T. , Beddar S. , Delclos M. E. , Krishnan S. , Das P. 
Published: February 2017

586 Background: In the treatment of rectal cancer, a strong dose-volume relationship exists between the amount of small bowel receiving low- to intermediate-doses of radiation and the rates of acute, severe gastrointestinal toxicity. Highly conformal treatment approaches, such as intensity-modulated radiation therapy (IMRT), may reduce dose to adjacent organs-at-risk (OAR). We performed a dosimetric evaluation of IMRT compared to 3-dimensional conformal radiation therapy (3DCRT) in standard, preoperative treatment for rectal cancer. Methods: Using RTOG consensus contouring atlas, treatment volumes were generated for ten patients treated preoperatively, with IMRT plans compared to 3DCRT plans derived from classic anatomic landmarks, as well as modified 3DCRT plans treating the RTOG consensus volume. The patients were all T3, were node-negative (N=1) or node–positive (N=9), and were planned to a total dose of 45-Gy. Bowel displacement was achieved using a carbon-fiber bellyboard apparatus with prone positioning. Results: IMRT plans had superior PTV coverage, dose homogeneity, and conformality in treatment of the gross disease and at-risk nodal volume, in comparison to 3DCRT. Additionally, in comparison to the modified 3DCRT plans, IMRT achieved a concomitant reduction in doses to the bowel, bladder, pelvic bones, and femoral heads, with an improvement in absolute volumes of small bowel receiving dose levels known to induce clinically-relevant acute toxicity. In the six patients with the highest volume of small bowel (range: 209-537-cc), the volume of bowel receiving 15-Gy was reduced from a median of 224-cc in the modified 3DCRT plans to 185-cc with IMRT. Also, the IMRT volumes were typically larger than that covered by classic 3DCRT fields, without incurring penalty with respect to adjacent OAR. Conclusions: For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans with superior target coverage, homogeneity, and conformality, while lowering dose to adjacent OAR. This is despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus. No significant financial relationships to disclose.
Effect of PSK on FOLFOX4-induced peripheral neuropathy and bone marrow suppression in patients with metastatic colorectal cancer.
Authors: Shibata M. , Shimura T. , Gonda K. , Nakamura I. , Ohki S. , Takenoshita S. 
Published: February 2017

596 Background: FOLFOX4 has been confirmed as an effective treatment for metastatic colorectal cancer and is used as a postoperative adjuvant therapy. However adverse effects such as cold-sensitive paresthesia and bone marrow suppression are common and may necessitate changes in chemotherapy regimen despite FOLFOX effectiveness. PSK, a polysaccharide derived from a species of mushroom, has been developed in Japan as an immune-enhancing agent and is widely used in patients with gastric, colorectal and pulmonary cancer. PSK has also been reported to decrease some adverse effects of chemotherapy. Methods: FOLFOX4 combined with PSK was administered to patients with metastatic colorectal cancer and the results were evaluated. Eight cycles of FOLFOX4 and PSK (3.0 g/day, p.o.) were given to 25 patients with metastatic colorectal cancer (19 hepatic, 3 pulmonary and 3 peritoneal). Results: No patients showed CR (complete response, 0%) while PR (partial response), SD (stable disease) and PD (progressive disease) were seen in 48%, 36% and 16% of patients, respectively. Response rate was 48% and disease control rate was 84%. Frequency of adverse effects was significantly lower than described in the published data. Grades 1 and 3 neutropenia occurred in 48% and 24% of patients, respectively; grades 1 and 3 nausea in 48% and 4%, respectively; and grades 1, 2 and 3 sensory neurotoxicity in 52%, 4% and 0%, respectively. No patient dropped out due to adverse effects in this study. Conclusions: PSK plus FOLFOX4 seems as effective as FOLFOX4 monotherapy, and significantly less toxic. These results suggest that this combination therapy may be more effective when given for a longer period, with lower incidence of adverse effects. No significant financial relationships to disclose.
Application of Western patients-based Adjuvant! Online (AOL) model on Korean colon cancer patients.
Authors: Jung M. , Kim G. , Ahn J. , Kim N. , Chang H. , Rha S. Y. , Chung H. C. , Roh J. K. , Shin S. 
Published: February 2017

599 Background: Adjuvant! Online (AOL) is a web-accessible risk-assessment model that predicts the mortality and the benefits of adjuvant therapy ( www.adjuvantonline.org ). AOL has never been validated for Asian colon cancer patients. Methods: Using the Yonsei Tumor Registry (YTR) database, we calculated the survival for the patients with T1-4, N0-2, M0 colon cancer who were treated at the Yonsei Cancer Center between 1990 and 2005. Observed and predicted 5-year survival was compared for each patient. Results: The median age of the study population was 60 years (range, 15-87 years) and the median follow-up duration was 7.9 years (range, 0.06-19.8 years) for all 1,431 patients. While AOL underestimate overall survival (OS) (predicted-observed=-1.02%, P=0.008), it overestimate colon cancer-specific survival (CCSS) (predicted-observed=3.8%, P<0.001) in Korean patients. Especially, AOL underestimated OS and CCSS in younger patients than age 50 years (predicted-observed=-4.3%, P<0.001 and predicted-observed=-3.5%, P<0.001, respectively). We conducted an internal model validation by using a Korean version of AOL (KAOL), which was a new model for prognosis based on AOL's parameters. 5-year OS and CCSS between the observed and the KAOL predicted survival were not different (77.25 vs. 77.15, P=0.873 and 77.4% vs. 77.6%, P=0.78, respectively). The concordance indexes about OS and CCSS were 0.75 and 0.74, respectively. Conclusions: KAOL model for Korean colon cancer patients is more suitable to predict 5-year outcomes compared to ALO model for Western patients. No significant financial relationships to disclose.
Radiation oncologist density and colorectal cancer mortality.
Authors: Aneja S. , Yu J. B. 
Published: February 2017

605 Background: Although the use of radiation therapy is increasing, there exists geographic variation among the distribution of radiation oncologists. The impact of this variation on colorectal cancer (CRC) outcomes remains unexplored. The goal of this study was to determine the effect of radiation oncologist density on CRC mortality. Methods: Using county-level data from the 2008 Area Resource File, National Program for Cancer Registries, and US Centers for Disease Control, a regression model was constructed for CRC mortality, controlling for county-level categorized radiation oncologists density, demographics, socioeconomic status and existing healthcare facilities. Results: There was a statistically significant reduction in CRC mortality (reduction in mortality ranging from 12% to 47%, p<0.001) associated with counties that possessed at least one radiation oncologist. However, increasing the county density to greater than two radiation oncologists per 100,000 people had no statistically significant reduction in CRC mortality. Conclusions: The presence of a radiation oncologist is associated with lowered mortality for CRC within that county, but increasing radiation oncologist density does not yield further improvements. Therefore, as the use of radiation therapy to treat CRC increases, a detailed understanding of distribution of the radiation oncologists is essential for providing the greatest improvement in cancer mortality outcomes. [Table: see text] No significant financial relationships to disclose.
Neoadjuvant bevacizumab treatment for colorectal liver metastasis: A retrospective study.
Authors: García P. , Alvarez S. , Muñoz A. , Lopez P. , Riesco M. , Adeva Alfonso J. , Martin M. 
Published: February 2017

613 Background: Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis and may benefit from perioperative chemotherapy and disease resection. Bevacizumab is proven to improve outcomes in patients with metastatic CRC. Methods: This is a retrospective chart review performed in colorectal patients with liver metastases. All the patients were > 18 years old and have undergone bevacizumab therapy as neoadjuvant treatment. Results: 20 patients were analyzed. Baseline characteristics: median age 54.8 (49.2-65.8) years; male 45%; ECOG 0/1 40%/60%, 13 patients had metastatic disease at the time of their initial diagnosis. Median time from diagnosis of metastasis to surgery was 7.1 (5.4-9.6) months. Primary tumour locations were rectum (21.4%), colon (64.3%) and colon and rectum (14.3%). 80% and 20% of the patients received one and two lines of treatment before surgery, respectively. Mean cycles were 7.3±3.4 and 3.5±1.8 in first and second line, respectively. In 95% of the patients resection was curative. Mean number of resected metastasis was 3.4±2.8. 90%·of the patients achieved complete resection (R0) and 10% incomplete resection (R1). All the synchronous primary tumours (15) were resected. Among 16 valuable patients for pathological response, 1 (6.3%) experienced a pCR, 11 (68.8%) major response and 4 (25%) minor response. The median DFS was 12.2 months. The median OS was 48.9 months. Only one patient experienced grade 3-4 toxicity (rectal haemorraghe). Most frequent surgical complications were anastomotic filtration (8.7%) and wound infection (8.7%). Most frequent hepatic toxicities after surgery were steatohepatitis (25%) and sinusoidal dilatation (20%). Conclusions: These data provide evidence that neoadjuvant chemotherapy including bevacizumab can be safely administered in patients with mCRC. No significant financial relationships to disclose.
Optimal use of antihypertensive agents in management of bevacizumab-associated hypertension.
Authors: Suenaga M. , Imada H. , Nakamoto E. , Matsusaka S. , Watanabe T. , Kawazoe Y. , Shinozaki E. , Chin K. , Mizunuma N. , Hatake K. 
Published: February 2017

614 Background: Hypertension (HT) is the most common toxicity associated with bevacizumab (BV). Angiotensin converting enzyme inhibitors, calcium channel blockers (CCB), beta-blockers or diuretics are frequently chosen to control BV-associated HT. However, optimal use of these antihypertensive (AHT) agents for each grade of HT remains to be determined. Furthermore, the AHT agent to be used must be carefully chosen to avoid increasing risk for BV-associated cardiovascular adverse events. Methods: Seventy-five consecutive patients with metastatic colorectal cancer who received first-line FOLFOX4 plus BV 5 mg/kg were included in the study. Treatment continued until progression of disease or unmanageable toxicity occurred. Blood pressure was measured prior to treatment in each cycle and graded using the NCI–CTC, version 3.0. The management protocol was as follows: 8-12 mg candesartan cilexetil (an angiotensin II receptor antagonist) as the first choice for grade 2 HT; 2.5 mg ≤ additional amlodipine besylate (a CCB) when grade 3 HT occurred; BV was discontinued if HT remained uncontrolled with use of both these agents. Stable blood pressure < 150/100mmHg during treatment was defined as manageable. Results: Twenty patients (26.7%) had a history of HT. Grades 2-3 HT developed in 53 patients (70.7%) and grade 3 in 24 (32%). Median number of treatment cycles until onset of grades 2 and 3 HT was 3 and 4.5, respectively. Comparing patients with a history of HT to those without, the incidence of grade 3 was greater in the former (85 vs. 12.7%, respectively), and the median number of treatment cycles until onset of grade 3 was shorter (4 vs. 12 cycles, respectively); blood pressure was considered manageable in both groups (90 vs. 91%, respectively), and no difference in total duration of chemotherapy was observed. No AHT approach-related severe adverse events were observed. Conclusions: Grade 3 HT was manageable during BV treatment, regardless of prior hypertensive history. However, to ensure improved survival, especially in patients with a history of HT, appropriate management is needed in BV-associated grade 3 HT. These data suggest that use of AHT agents is an effective and safe strategy in the management of BV-associated HT. No significant financial relationships to disclose.
Predictors of oxaliplatin-induced peripheral neuropathy in patients with advanced colorectal cancer (CRC).
Authors: Lin A. Y. , Kouzminova N. B. 
Published: February 2017

619 Background: Chemotherapy-induced neuropathy (CINP) is one of the major dose-limiting toxicities of oxaliplatin. The purpose of this study was to identify early predictors of CIPN and investigate the feasibility of using nerve conduction studies (NCS) to monitor CINP. Methods: Under IRB-approved protocol, we systematically examined patient-reported symptoms, neurological tests and bilateral NCS of the peroneal, superficial peroneal and sural nerves every 3 weeks before each dose of oxaliplatin (75-130 mg/m2) in 12 CRC patients receiving 8 to 13 cycles of XELOX. The severity of neuropathy was graded by the NCI Common Toxicity Criteria (CTC v.4.0) and the Oxaliplatin-Specific Neurotoxicity Scale (OSNS). Results: At the end of chemotherapy three of 12 patients developed peripheral sensory neuropathy CTC grade 3, five had grade 2, and four had grade 1 (3 of them had no self-reported symptoms with loss of Achilles tendon reflexes). At the eighth cycle test only 4 patients experienced CTC grade 2 criteria, but 7 of 12 patients had paresthesias persisting between the cycles of chemotherapy (OSNS grade 2 or higher). Development of grade 2 CINP by CTC or OSNS criteria by the eights cycle of chemotherapy was not associated with the total dose of oxaliplatin received (ANOVA p = 0.86 and 0.78 accordingly), but was significantly associated with administration of concomitant medication (Spearman correlation = 0.62, p = 0.03 for OSNS and 0.6, p = 0.04 for CTC grade 2 CINP). Presence of grade 2 or higher sensory neuropathy before the 8th cycle of oxaliplatin was significantly associated with development of grade 3 CINP by the time of chemotherapy completion (Spearman correlation = 0.8, p = 0.001). The maximal CINP grade that patients have reached during chemotherapy was also significantly associated with concomitant medication use (Spearman correlation = 0.76, p = 0.004). Conclusions: Concomitant administration of medications was the only factor significantly associated with severity of CINP in our study cohort. Further study is needed to verify if it is associated with altered bioavailability of oxaliplatin. No significant financial relationships to disclose.