bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early prediction of pathological complete response (pCR) of rectal cancer after 1 week of preoperative radiochemotherapy (RCT) using positron emission computererized tomography (PET-CT) imaging.
Authors: Purim O. , Goldberg N. , Kundel Y. , Brenner R. , Efremov N. , Gordon N. , Morgenstern S. , Wasserberg N. , Brenner B. 
Published: February 2017

572 Background: Preoperative radiochemotherapy (RCT) is the standard treatment of locally advanced rectal cancer (LARC), obtaining pathological complete response (pCR) in 15%-30% of cases. Post-RCT reduction of 18F-fluorodeoxyglucose (FDG) uptake within the tumor compared with the baseline, i.e. the tumor's metabolic response, correlates with pCR. However, an earlier prediction of pCR could enable tailored modifications of the treatment. We hence evaluated the correlation between the metabolic response after only one week of RCT for LARC and the actual pCR at the post-RCT surgery. Methods: Patients (pts) were eligible for this prospective study if they had LARC, defined as T3-4NX or TxN+ tumors by pre-treatment PET-CT and endoscopic ultrasound. Pts received standard RCT regimen, consisting of 50.4Gy radiotherapy concurrently with a fluoropyrimidine-based chemotherapy, followed by surgery. Pts underwent baseline FDG-PET-CT imaging within 2 weeks prior to the initiation of RCT and a second one on day 8 of RCT. Maximum standardized uptake value (SUV-max) was measured in both scans and changes in FDG- uptake were recorded. Man-Whitney test was used to evaluate differences in the SUV-max between baseline and day 8 in pts obtaining pCR and those who did not. Results: Twenty pts participated in the study. Half were males and the median age was 64 years. Ten pts had T3N0 tumors and 10 had T3N+ disease. Radical surgery was done in 19 pts and local excision in one. Considering the entire group, there was a borderline-significant difference between the metabolic response of pts with pCR and those without pCR (Chi-square = 3.429, p = 0.064). Yet, the changes in FGD-uptake were able to identify pts who achieved pCR and those who did not: only pts with a decrease of more than 33% in SUV-max had pCR while none of the pts who had less than 8.9% decrease in SUV-max had pCR. Conclusions: A decrease in SUV-max between baseline-PET-CT scans and scans done after only one week of RCT for LARC may be able to predict the achievement of pCR in the post-RCT surgical specimen. Validation in a larger independent cohort is planned. No significant financial relationships to disclose.
Patient (Pt)-reported symptoms of chemotherapy (chemo) and VEGFR/EGFR antibody therapies for the treatment of metastatic colorectal cancer (MCRC) in a U.S. community-based oncology practice network.
Authors: Feinberg B. A. , Gilmore A. , Lunacsek O. , Haislip S. , Yu E. , Yim Y. , Gilmore J. W. 
Published: February 2017

575 Background: Targeted therapies for MCRC have increased treatment (Tx) options in multiple therapy lines. Symptoms associated with MCRC Tx have not been well studied from the Pt perspective. Objective: To characterize symptoms reported by MCRC Pts treated with chemotherapy and/or targeted drugs at a large US oncology network. Methods: Pt reported symptom data were linked to electronic medical records and Pt charts from Georgia Cancer Specialists in Southeast US. MCRC Pts aged ≥18 years with ≥1 administration of chemo or targeted therapy between 1/2007-3/2009 were included. Pt reports captured 13 symptoms, onset, and severity. Due to small sample sizes, no statistical comparisons were conducted. Results: 332 MCRC Pts were included (median age 62 years, 47% male, median weight 74 kg, 48% ECOG PS 0 or 1). Amongst Pts receiving 1L Tx (n=299), 78% received bevacizumab (BV) +/- chemo, 4% cetuximab (CX) +/- chemo, 15% chemo only, and 2% other. 162 Pts received 2L Tx: 49% BV +/- chemo, 17% chemo only, 28% CX +/- chemo, and 6% other. The 5 most common symptoms in 1L Tx for all severity ratings were 36% fatigue, 20% nausea, 17% weight (wt) loss, 15% diarrhea, and 9% constipation. The 5 most common symptoms in all 2L Tx groups were 44% fatigue, 27% nausea, 19% diarrhea, 16% wt loss, and 11% abdomen pain. 2L moderate, severe, or disabling symptoms reported in >10% Pts receiving BV +/- chemo, CX +/- chemo, and chemo only Tx are shown in the table. Conclusions: The most commonly reported symptoms by 1L and 2L MCRC Pts were fatigue, nausea, diarrhea, and weight loss. Overall, a numerically higher % of 2L Pts treated with CX +/- chemo reported moderate, severe, and disabling symptoms than Pts receiving BV +/- chemo and chemo alone. Rash was not observed in the BV +/- chemo group. Further research of MCRC Pt reported symptoms in a larger sample size are warranted. [Table: see text] [Table: see text]
The final report of post-marketing surveillance for cetuximab in colorectal cancer in Japan.
Authors: Yamaguchi K. , Satoh T. , Watanabe T. , Ishiguro M. , Maruyama K. , Seriu T. , Miki T. , Ito H. , Sugihara K. , Sakata Y. ,   Advisory Board for Proper Use of Cetuximab
Published: February 2017

590 Background: Cetuximab (ERBITUX) was approved in Jul 2008 in Japan with indication for EGFR-positive and unresectable metastatic or refractory colorectal cancer. Post-marketing surveillance is required by Japanese Health Authority to collect, obtain, verify or validate information on the safety, efficacy and quality of medicines. We conducted this surveillance in all patients treated with cetuximab to access in practical use since clinical data on Japanese patients are limited. Methods: The target number of patients was 1,800. Following adverse drug reactions were investigated: infusion reaction, skin disorders, interstitial lung diseases, electrolyte abnormalities (including hypomagnesemia), heart toxicities, gastrointestinal disorders, thrombosis/embolism, delayed wound healing, and eye disorders. Results: Between Sep 2008 until Jan 2010, 2,126 pts registered, 2,006 pts were evaluable for safety (safety population), 1,687 pts for efficacy (efficacy population). Of the 2,006 pts, 1,975 pts (98.5%) were EGFR-positive. Patients characteristics: male/female; 1,234/772 (61.5%/38.5%), median age; 64 (range 18-87), site of primary tumor; colon/rectal/others (multiple selection); 1,235/775/3 (61.6%/38.6%/0.2%), PS0/PS1; 1,370/630 (68.3%/31.4%), combination chemotherapy; cetuximab monotherapy/CPT-11/FOLFIRI: 460/1,255/256 (22.9%/62.56%/12.8%). Of the 2,006 pts, 133 pts (6.6%) and 1,869 pts (93.2%) were treated in second-line and in third-line or later treatment, respectively. The adverse drug reactions incidence was 89.9%. Incidence of skin disorders, gastrointestinal disorders, electrolyte abnormality including hypomagnesaemia, and infusion reaction were 83.7%, 23.1%, 11.5%, and 5.7%, respectively. Efficacy result: Of the 1,687 pts, 658 pts (39.0%) were evaluated to be effective. Of the 658 pts, 614 pts (93.3%) experienced skin adverse reactions. Conclusions: This post-marketing surveillance confirms the safety and efficacy of cetuximab in the Japanese population treated in clinical practice. The outcome of this surveillance with Japanese 2,006 pts would be useful for clinical use of cetuximab. [Table: see text]
Increased incidence of adverse events after concomitant hepatic arterial infusion plus systemic chemotherapy and bevacizumab for colorectal cancer with liver metastasis.
Authors: Sadahiro S. , Suzuki T. , Maeda Y. , Tanaka A. , Okada K. , Ogoshi K. , Kamijo A. 
Published: February 2017

591 Background: FOLFOX+bevacizumab (BEV) is the standard systemic chemotherapy for metastatic colorectal cancer (CRC). We investigated the combination of FOLFOX4 and hepatic arterial infusion (HAI) in patients who had isolated liver metastasis from CRC. We also compared efficacy and safety between this combination therapy and its concomitant use with BEV. Methods: Twenty-five patients entered a phase I/II trial of HAI (5-FU 250 mg/d, leucovorin 25 mg/d; d1-7, q2w) combined with FOLFOX4. Fourteen other patients with a similar background received HAI + FOLFOX4 combined with BEV and the two regimens were compared. Results: In the phase I/II study, the recommended doses for FOLFOX were as follows: L-OHP, 85 mg/m2; l-LV, 100 mg/m2; 5-FU (bolus), 400 mg/m2; and 5-FU (infusion), 600 mg/m2. Sixteen patients who received this regimen showed a response rate of 93.8% (2 CR and 13 PR), a median progression-free survival of 323 days, and a one-year survival rate of 93.7%. In the subsequent phase II trial of HAI + FOLFOX4 with BEV, 14 patients were enrolled and the response rate was 78.6% (2 CR and 9 PR). The outcome was inferior when BEV was used concomitantly. The median numbers of doses were 10 (range: 1-27) for FOLFOX4 and 9 (1-27) for HAI without BEV, whereas the corresponding numbers with BEV were 8 (1-12) and 2 (0-9), respectively. There was a marked decrease in the number of HAI procedures when BEV was used. Thrombosis occurred in 8 patients who received concomitant BEV, which was the most common reason for cessation of HAI. Other adverse events (≥Grade 3) were neutropenia (n=7; 43.8%) and thrombocytopenia (n=2; 12.5%) without BEV or neutropenia (n=7; 43.8%) and diarrhea (n=1; 7.1%) with BEV, and no marked difference was seen between the two regimens. Both regimens were well tolerated. Severe neuropathy was only observed in 1 patient (6.3%; Grade 3) who received concomitant BEV. Conclusions: In the present study, HAI + FOLFOX combined with BEV caused thrombosis and disturbance of wound healing, thereby increasing the incidence of complications and making it difficult to continue treatment. These findings suggest that BEV should not be administered with HAI therapy. No significant financial relationships to disclose.
A phase II trial of high-dose cetuximab (cmab) plus irinotecan in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (MCRC) who progressed on standard-dose cmab plus irinotecan.
Authors: Patta A. M. , McMahon J. A. , Samborski C. , Fakih M. 
Published: February 2017

598 Background: Prior clinical data suggest a dose-related response to cmab when combined with irinotecan in pts with KRAS WT tumors who do not develop grade 2 and above rash with standard cmab dosing. However, the investigation of higher doses of cmab in the setting of acquired or innate resistance to standard dose cmab has not been previously investigated. We conducted a phase II clinical trial of high-dose cmab plus irinotecan in KRAS WT pts with standard-dose cmab plus irinotecan – refractory disease to address this question. Methods: Pts with KRAS WT MCRC progressing on standard dose of cmab with irinotecan were eligible for study. Pts should have received a minimum of 6 weeks of prior standard dose cmab plus irinotecan and progressed within 4 weeks from the last dose. Cmab was administered at 500 mg/m2/week and irinotecan was administered at the same dose/schedule on which the patient previously progressed. 12-week PFS rate was the primary endpoint. Results: 8 pts were treated on study: median age 68 yrs (45-85), 5 pts were males, ECOG performance status was 1 in all 8 pts. Grade ≥ 3 toxicities consisted of hypomagnesaemia (4 pts), anemia (1 pt), leucopenia (1 pt), fatigue (1 pt), and diarrhea (1 pt). 6 pts achieved stable disease (with regression in target lesions noted in 3 pts). 12 week PFS rate is 5/8 and 18 week PFS is 4/8. 3 pts remain on study at 4.5, 5, and 8 months from enrollment. Conclusions: High-dose cmab/irinotecan is well tolerated except for hypomagnesemia. Encouraging prolonged disease stabilizations warrant further investigation of this approach in pts in KRAS WT population. Accrual is ongoing. [Table: see text]
Prophylactic administration of epinephrine in oxaliplatin-related hypersensitivity reaction.
Authors: Iwasa S. , Hamaguchi T. , Tada K. , Yanai T. , Hashimoto H. , Nakajima T. E. , Kato K. , Yamada Y. , Shimada Y. 
Published: February 2017

610 Background: Alongside disease progression or neurotoxicity, oxaliplatin-related hypersensitivity reaction is a common reason for treatment discontinuation and remains a critical issue. It is unclear whether prophylactic administration of epinephrine to patients with this severe hypersensitivity reaction is effective and safe. Methods: We retrospectively reviewed 839 consecutive colorectal cancer patients treated with oxaliplatin-containing regimens at our hospital between April 2005 and March 2010. The medical records of those patients who had received prophylactic epinephrine (1:1000 solution) were examined. Hypersensitivity reaction was graded according to CTCAE version 3.0. Results: Twelve patients (8 male and 4 female; median age, 66 years) had received prophylactic epinephrine. The hypersensitivity reaction, even though the patients were receiving prophylactic corticosteroid and antihistamine drugs, was grade 0/1/2/3 = 0/0/10/2. The median number of epinephrine doses administered was 6 (range, 1 to 21). The worst grade of hypersensitivity for rechallenge with oxaliplatin under prophylactic administration of epinephrine was grade 0/1/2/3 = 4/3/4/1. Reasons for treatment discontinuation were disease progression in 10 patients and neurotoxicity in one patient. The remaining one patient developed grade 3 hypersensitivity reaction during 4 cycles of treatment under prophylactic administration of epinephrine, but the reaction subsided after additional administration of epinephrine and corticosteroid. Common adverse events with administration of epinephrine were hypertension (4 patients), palpitation (3 patients) and headache, dizziness, fatigue, and bladder pain (1 patient each). Conclusions: Prophylactic administration of epinephrine may be effective and tolerated in patients with moderate to severe oxaliplatin-related hypersensitivity reaction. No significant financial relationships to disclose.
Clinical experience with neuroendocrine rectal tumors.
Authors: Derbel O. , Limem S. , Tassy L. , Desseigne F. , Rivoire M. , Meeus P. , Peyrat P. , Stella M. , Martel-Lafay I. , De La Fouchardiere C. 
Published: February 2017

611 Background: Carcinoids are heterogeneous neuroendocrine tumors with malignant potential. The rectum is the third most common location for gastrointestinal carcinoids after small bowel and colon. Due to their rarity, the characteristics and behavior of this unusual malignancy remain unclear. Methods: Retrospective review of the clinicopathologic features of patients treated for carcinoid tumors of the rectum. Results: A single institute's tumor registry was retrospectively queried, identifying nine patients with rectal carcinoid tumors over a 10-year period. The mean age at diagnosis was 57.6 years. Four of the nine patients were female. Presenting symptoms included abdominal pain in five patients, rectal bleeding in two patients and a change in bowel habits in one patient. As previously reported, no patient had symptoms consistent with carcinoid syndrome. The rectal tumor size was > 2 cm in five patients. The rectal tumor was located in the lower third of the rectum in three cases (< 5 cm from anal verge) whereas three were in the middle third (6-11 cm) and two in the upper third (11-15 cm). Four of the tumors were well differentiated tumors (grade 1), 1 was atypical carcinoid or moderately differentiated tumors (grade 2), and 4 were poorly differentiated tumors (grade 3) according to the SEER. Initially, 5/9 patients had distant metastasis. As an initial site of metastasis, the liver was the most common site (4/5 patients, 80%). Five patients underwent surgical treatment of their rectal tumor, two with endoscopic transanal resection whereas 3 patients had a low anterior resection (LAR). Three patients received chemotherapy treatment only in the metastatic setting and one patient received chemotherapy and radiotherapy as palliative treatment. Of the nine patients, five had progressive disease after initial treatment. With a median follow-up of 14 months, the overall survival of the entire population was 13.4 months. Conclusions: Neuroendocrine carcinomas of rectum are uncommon. Only small rectal carcinoids can be safely managed and surgery represents the treatment that can offer a greater chance of survival to these patients. Larger primary tumors have a high tendency to spread early. They are associated with aggressive behavior, resistance to chemotherapy and poor prognosis. No significant financial relationships to disclose.
Characteristics of treatment-related dermatological toxicity in colorectal carcinoma.
Authors: O'Reilly A. M. , Bird B. R. , O' Keeffe J. 
Published: February 2017

617 Background: The use of novel targeted therapies is becoming increasingly prevalent. This study aimed to determine how novel- targeted therapies have changed the profile of dermatological toxicity in patients being treated for colorectal carcinoma. Methods: Retrospective analysis was performed in a single institution for all patients presenting over a period of 4 weeks. Participants were followed up for the remainder of the study period. Patient charts were reviewed for previou incidences of dermatological toxicity. Toxicity was graded using the Common Toxicity Criteria version 3. Statistical analysis was performed using SPSS version 19. Results: A total of 45 patients receiving treatment for colorectal carcinoma were included in the final analyses. Twenty-nine of these received novel targeted therapy (NTT) including bevacizumab, cetuximab, capecitabine, and panitumumab. Sixteen participants received traditional chemotherapy. In total 79 toxicities were evaluated. Participants receiving NTT experienced a higher mean number of toxicities (2.2 [95%CI 1.9-3.7]) then those receiving traditional chemotherapy (0.9 [95%CI 0.6-1.2]), p < 0.01. Those receiving NTT experienced significantly more HFS (p < 0.01) and rash (p < 0.01) Participants receiving NTT experienced significantly more grade 2 or above dermatological toxicity (p < 0.01) Those receiving NTT underwent more alterations in chemotherapy then those receiving traditional chemotherapy (p < 0.05). HFS affected 14 (31%) participants, 4 of these were grade 2 or above. Twenty (44%) participants experienced rash, 4 of these were grade 2 or above. All patients (9) receiving cetuximab experienced acneiform rash, 3 were grade 2 or above, 5 patients required dose reduction/dose delay. Fifteen (33%) participants experienced stomatitis. Additional toxicities evaluated include alopecia (13%), nail dystrophy, and xerosis. Conclusions: Those receiving novel targeted therapy for the treatment of colorectal carcinoma may be at increased risk of developing dermatological toxicity. Dermatological toxicity in this group may be of higher grade and greater complexity. Treatment of dermatological toxicity in this group may require more dose modifications. No significant financial relationships to disclose.
A retrospective study of first-line combination chemotherapy in advanced colorectal cancer: A Korean single-center experience.
Authors: Lee S. , Park J. , Park S. , Kang W. , Lim H. , Park Y. , Park K. , Lee J. 
Published: February 2017

623 Background: Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, have demonstrated efficacy and tolerability against advanced colorectal cancer (ACC). Methods: Between Jan 2006 and Dec 2007, 478 ACC patients were treated with combination chemotherapy in first-line setting: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until disease progression or unacceptable toxicity occurred or until a patient chose to discontinue treatment. Results: The median age was 58 years (range, 19-84 years) and the median chemotherapy duration for FOLFOX, FOLFIRI, XELOX and XELIRI were 4.9, 4.5, 5.7 and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median PFS for all patients was 6.8 months (95% confidence interval, 6.3-7.3 months). No statistically significant difference in PFS was found each regimen used as first-line chemotherapy. Sixty-percent (n=290) of patients received second or further lines of therapy after failure. Conclusions: Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC. No significant financial relationships to disclose.
Analysis of pO2 in malignant ascites of patients with peritoneal dissemination of gastric cancer.
Authors: Emoto S. , Kitayama J. , Ishigami H. , Yamaguchi H. , Yamashita H. , Kaisaki S. , Nagawa H. 
Published: February 2017

63 Background: Peritoneal metastasis is considered to develop from carcinoma cells detached from the serosal surface of the primary site and dispersed in the peritoneal cavity. And oxygen is one of the most important environmental factors for tumor development. To investigate the oxygenation condition in the abdominal cavity, that is largely unknown, we collected ascitic fluid from patients with peritoneal dissemination of gastric cancer and measured pO2 of it. Methods: In 19 patients with peritoneal dissemination of gastric cancer, who had a considerable amount of ascites and was receiving systemic and/or intraperitoneal chemotherapy, ascitic fluid was collected at the bedside in room air, and its pH, pCO2 and pO2 were measured using a blood gas analyzer immediately. Results: In 19 patients, pH of malignant ascites was significantly lower than that of arterial blood (7.39 ± 0.069 vs 7.44 ± 0.025 mmHg, p < 0.05). pCO2 tended to be higher in ascites than in arterial blood. Unexpectedly, pO2 in malignant ascites showed relatively high values (85.47 ± 23.31 mmHg), which were mostly the same as that of arterial blood (97.19 ± 10.40 mmHg, p = 0.149), and appeared to be higher than that in solid tumor tissue. Conclusions: Malignant ascites in gastric cancer patients showed an unexpectedly high oxygen tension, which was almost the same as that of arterial blood. The hyperpermeability condition may enable efficient oxygen delivery to peritoneal fluid via the microvessels lining the peritoneal cavity. Since the oxygen level critically affects the sensitivity of tumor cells to chemotherapeutic agents through metabolic transformation, aerobic conditions may be beneficial for the progression of peritoneal metastasis and also clinically important in considering the efficacy of chemotherapy. No significant financial relationships to disclose.