bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of prognostic factors and survival outcome between gastrointestinal tract and cutaneous invasive malignant melanoma.
Authors: Lin Chi , Brown Christopher K , Enke Charles Arthur , Loberiza Fausto R. 
Published: February 2017

618 Background: Gastrointestinal melanoma (GIM) is a rare disease. The objective of this study is to compare the overall survival (OS), cancer specific survival (CSS) and prognostic factors of GIM to those of skin melanoma (SKM) using the Surveillance, Epidemiology, and End Results (SEER) registry. Methods: Patients diagnosed with invasive GIM (406) and SKM (173,622) between 1973 and 2008 were identified from the SEER database. Factors analyzed included age (18-40/41-60/61-100), gender, race (White/nonwhite), marital status, stage (localized/regional/distant), year of diagnosis (1973-87/1988-97/1998-2008), and type of treatment (radiotherapy (RT)/surgery). OS and CSS were evaluated using the Kaplan-Meier method. Cox proportional hazards regression analysis examined what factors were prognostic of survival. Results: The median age was 69 and 57 for patients with GIM and SKM, respectively. The GIM group was older with more advanced-stage cancer than the SKM group. Surgery was performed on 85% and 95%, while RT was received by 18% and 2% of GIM and SKM patients, respectively. The GIM group had a median OS and CSS of 15 and 16 months, respectively, while the SKM group had a median OS of 283 months and did not reach a median CSS. Cox analysis showed that SKM had significantly lower risk of total and cancer-specific mortality compared to GIM (Hazard Ratio (HR) 0.40, p<0.0001) and (HR 0.34, p<0.0001). Factors associated with improved OS and CSS in SKM included: age ≤60, female gender, non-white race, early stage, being married, more recent diagnosis, undergoing surgery and not receiving RT. Factors associated with improved OS and CSS in GIM included: age ≤60, early stage, non-white race and undergoing surgery. Subgroup analysis on patients who underwent surgery showed that lymph node status was the only prognostic factor for GIM, while all of the previously identified prognostic factors except for race were associated with OS and CSS for SKM. Conclusions: Outcomes of patients with GIM are inferior to those with SKM. The melanomas in these two sites also have different prognostic factors. Future studies should explore the reasons behind these differences to improve treatment outcomes.
Physical function and quality of life in frail and/or elderly metastatic colorectal cancer patients treated with bevacizumab and capecitabine: An exploratory analysis.
Authors: Ward Peter Richard , Liem Andre K. D. , Wang He-jing , Patel Ravi , Hu Eddie Hong-Lung , Tchekmedyian Nerses Simon , Wainberg Zev A. , Hecht J. Randolph , Naeim Arash 
Published: February 2017

627 Background: Optimal treatment strategies in frail and/or elderly patients with metastatic colorectal cancer have not been well defined. Although the safety and efficacy of bevacizumab and capecitabine in this population has been reported, the impact on functional measures and quality of life has not been well described. In a prospective, phase II study of elderly metastatic colorectal patients with ECOG performance status (PS) 1 or 2 treated with first-line bevacizumab and capecitabine, we collected data on geriatric functional status and quality of life. The primary aim of this analysis was to explore the differences in geriatric health measures between patients with ECOG status 1 and 2. Methods: Functional status was measured by patient-reported limitations in ADLs and IADLs and ECOG PS was assessed. A “Get up and Go” test, hearing test, and 3-item recall exam was also performed. Quality of life (QoL) was assessed by means of the FACT-C questionnaire and patient-rated health status was measured by the EQ-5D questionnaire. The prognostic impact of baseline characteristics on survival was studied using univariate Cox-regression analysis. Results: The majority (62%) of the 45 participants treated were ECOG 2. This group had more limitations in IADLs, lower baseline QoL, and a lower patient-rated health score. For all participants, QoL significantly improved from baseline to the start of cycle 2 (FACT-C: 99.9 vs. 105.4, p=0.01) and did not deteriorate when baseline scores were compared to when participants went off study. (FACT-C: 99.9 vs. 98.6, p=0.59). In the Cox-regression analysis, the participant’s ability to perform the “Get up and Go” test was the only baseline characteristic that was prognostic for improved survival (HR = 0.31, p = 0.01). Conclusions: Our analysis shows that in this study of frail and/or elderly patients with metastatic colorectal cancer treated with bevacizumab and capecitabine, there is a significant amount of heterogeneity between the ECOG 1 and 2 groups in both functional measures and quality of life. We also showed that the “Get up and Go” test may be a useful prognostic indicator for survival in this population.
Evaluating the agreement between the empirical volumes of tumor lesions and the estimated volumes of tumor lesions based on the longest diameter.
Authors: Laubender Ruediger P. , Schlichting Michael , Sartorius Ute , Modest Dominik Paul , Mansmann Ulrich Robert , Heinemann Volker , Graser Anno 
Published: February 2017

635 Background: Tumor lesions are commonly evaluated by RECIST or WHO criteria, which involves reducing the development of a three-dimensional tumor to a two-dimensional process. However, volume measurements might reflect the clinical impact of the disease process more precisely. Therefore, we investigated if the volume of a tumor lesion can be reconstructed from RECIST- or WHO-based measurements. Methods: 20 colorectal cancer patients underwent routine staging MDCT examinations as part of the multicenter phase II CIOX trial comparing cetuximab + XELOX versus cetuximab + XELIRI. Two hepatic target lesions per patient were defined at baseline and measured using 1) semi-automated volumetry (Siemens Syngo Via Oncology, Siemens Healthcare) with manual correction and 2) semi-automated measurement of the longest diameter (LD) according to RECIST 1.1 and the corresponding longest orthogonal diameter (LOD). Patient lesions were followed over time using the same measurement strategies. An algorithm was developed for reconstructing the volume of a lesion based on the LD and the corresponding LOD. Agreement of the volume data generated by both methods was analyzed by a Bland-Altman plot. The limits of agreements were calculated using a variance components model considering repeated tumor assessments based on the log-transformed sum over the volume of a patient’s lesions. Results: 151 lesions from the 20 patients were measured at 73 tumor assessments. Volume was slightly overestimated by the algorithm compared to the volumetric measurements (p = 0.07). The Bland-Altman plot showed good agreement (mean difference −0.05, limits of agreement [−0.40, 0.30]). As expected, three out of the 73 measurements fell outside the limits of agreement. Conclusions: The proposed algorithm for the WHO-based reconstruction of the tumor volume provides a good approximation to the true sum of the volumes of the lesions. In future studies, volumetric tumor information can be included even if not all centers have full volumetric software available. This enables further research on the impact of changes in tumor volume on disease prognosis and/or prediction of treatment efficacy.
A novel approach to manage skin toxicity caused by therapeutic agents targeting epidermal growth factor receptor.
Authors: Berardi Rossana , Campanati Anna , Onofri Azzurra , Pierantoni Chiara , Conte Irene , Giuliodori Katia , Molinelli E , Marcucci Fabiana , Offidani Annamaria , Cascinu Stefano 
Published: February 2017

636 Background: Inhibition of EGFR represents an important field in cancer therapy.Skin rash is a common adverse reaction in patients receiving EGFR inhibitors. Nicotinamide has been shown to be an effective treatment for skin inflammation in various conditions, since nicotinamide inhibits IL-8 production through the NF-kB and MAPK pathways in an in vitro keratinocytes/P. acnes model of inflammation. Furthermore green tea polyphenols could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans.In this study we evaluated the effect of nicotinamide and green tea polyphenols on skin toxicity EGFRI related. Methods: Patients with skin toxicity induced by EGFRI were enrolled. They underwent a skin biopsy and skin samples for microbiological analyses at first presentation of skin toxicity (T0). Skin toxicity was assessed with NCI-CTACE,EGFR index and Dermatology Life Quality Index (DLQI) test. Therapy protocol consisted in topical application of moisturizing cream containing green tea polyphenols plus oral administration of nicotinamide 200 mg/die for 12 weeks. Topical application of 1% clindamycin gel and/or systemic administration of minocicline were provided in case of superbacterial infection. All treated patients were monitored for at least 12 weeks (T12), across three time points (T0,T6,T12). Results: 24 colorectal cancer patients receiving anti-EGFR monoclonal antibodies (cetuximab or panitumumab) and developing skin toxicity were treated by a multidisciplinary team including oncologists, dermatologists, a pathologist and a nurse. All the patients experienced a significant reduction of skin toxicity according to the NCI-CTACE and EGFR index (p<0.05). Papulo-pustular eruption and itching significantly improved after 6 weeks of treatment and erythema decreased after 12 weeks. A significative improvement of the global score and of DLQI was evident. No toxicity related to the treatment of skin toxicity was observed. Conclusions: Treatment with nicotinamide and green tea polyphenols represent a novel effective approach to manage skin toxicity caused by EGFRI.
Effect of lymphadenectomy on survival in patients with esophageal cancer.
Authors: Almhanna Khaldoun , Weber Jill M. , Shridhar Ravi , Hoffe Sarah E. , Karl Richard C. , Meredith Kenneth 
Published: February 2017

65 Background: The number of resected lymph nodes is associated with overall and disease-free survival in some gastrointestinal malignancies. The impact of nodal harvest during esophagectomy remains to be determined. We examined the influence of lymphadenectomy on overall survival in patients with esophageal cancer. Methods: Utilizing a prospectively maintained comprehensive esophageal cancer database we identified patients who underwent esophagectomy with between 1994 and 2011. The association between disease free survival (DFS), overall survival (OS) and nodal harvest was evaluated using multivariable Cox regression models. The number of harvested nodes was examined as a categorical variable based on strata(S): 1) ≤8, 2) 9-12, 3) 13-20, and 4) >20. Results: We identified 635 patients, 541 males and 94 females with a median age of 65 years (28-86) and median follow-up of 22 months (0-168). Adenocarcinoma 559 (88 %) was the predominant histology where as squamous cell carcinoma represented 76 (12%) of the cases. The 5-year OS and DFS rate for S1-S4 was (43%, 42%, 55%, and 36%, p=0.1836) and (44%, 37%, 46%, and 36%, p=0.5166) respectively. There were 209 patients with metastatic disease in 1 or more lymph nodes. The 5-year OS and DFS for S1-S4 was (17%, 31%, 21%, and 27%, p=0.4372) and (17%, 23%, 16%, and 25%, p=0.2726). There were 418 node negative patients. The 5-year OS and DFS rates by S1-S4 was (54%, 51%, 79%, and 26%, p=0.0538) and (55%, 48%, 64%, and 27%, p=0.3703). Multivariate analysis revealed that patients within S3 exhibited a survival benefit adjusted odds ratio (AOR) 0.57 (CI 0.360-0.916, p=0.020). However patients within S1 were more likely to die, AOR 1.74 (CI 1.09-2.78, p=0.020). No survival benefit was demonstrated for patients within (S4) AOR 1.11 (CI 0.60-2.09, p=0.731). There were 171 (27.5%) recurrences with a median time to recurrence of 12.2 (1-101) months. There were no differences in recurrences between strata p=0.129. Conclusions: We demonstrated that patients with ≤8 lymph nodes resected were more likely to die of their disease compared to those with 13-20 nodes resected. Additionally, extended lymphadenectomy (>20 nodes) does not increase the likelihood of proper staging and does not improve patient outcome.
Use of anti-EGFR agents among elderly patients with metastatic colorectal cancer (mCRC).
Authors: D'Silva Ashley James , Dotan Efrat , Kloth Dwight D. , Beck Andrew , Cohen Steven J. , Denlinger Crystal Shereen 
Published: February 2017

657 Background: Limited data are available regarding the tolerance of older mCRC patients to anti-EGFR therapy. To evaluate the treatment patterns and tolerability of cetuximab/panitumumab in this patient population, we conducted a retrospective review of elderly patients treated with these agents at Fox Chase Cancer Center between 2004-2010. Methods: Patients ≥ age 65 with mCRC treated with cetuximab/panitumumab were included in the analysis. Patient demographics, disease characteristics, treatment drugs and duration, KRAS status and overall survival were recorded. Toxicity evaluation included review of common hematologic and non-hematologic toxicities seen with these agents. Results: 118 patients were included; 100 received cetuximab and 18 received panitumumab therapy. The majority of patients were male (59.3%) with colon cancer (82.2%) and stage IV disease at presentation (50.8%). The median age at treatment initiation was 73 yrs (range: 65-90). Median overall survival was 510 days, and the median time on treatment 73 days. Most patients were treated prior to the incorporation of routine KRAS testing thus, KRAS status was available for 35 patients (29.7%) with 14.2% KRAS mutant tumors. 66% of cetuximab and 45% of panitumumab treatments were given in combination with another agent. The overall incidence of any grade 3/4 non-hematologic toxicity was 36% (34% for single agent; 37.8% for combination therapy). Common grade 3/4 non-heme toxicities were: hypomagnesemia-16.9%, diarrhea-10.2%, and rash-9.3%. Diarrhea and hypomagnesemia were more common among patients receiving combination therapy. The overall incidence of any grade 3/4 hematologic toxicity was 15.2% (6.8% for single agent ; 20.3% for combination therapy). Anemia was the most common heme toxicity in both single and combination therapy. Advanced age at treatment initiation was associated with higher incidence of single agent therapy (p=0.0005, ANOVA statistics). Conclusions: Our data demonstrate that elderly patients with mCRC tolerate anti-EGFR therapy, with toxicity rates similar to those reported in large clinical trials with younger patient populations. Older mCRC patients can safely receive anti-EGFR treatment as part of their therapy.
Phase II study of capecitabine in substitution of 5-FU in the chemoradiotherapy regimen for patients with squamous cell carcinoma of the anal canal.
Authors: Ribeiro Suilane Coelho , Venchiarutti Camila , Riechelmann Rachel , Gil Erlon , Nahas Caio , Coudry Renata , Freitas Daniela , Saragiotto Daniel F. , Arruda Fernando , Azambuja Rodrigo , Hoff Paulo 
Published: February 2017

659 Background: Squamous cell carcinoma (SCC) of the anal canal is an uncommon malignancy accounting for 1-5% of intestinal tumors; however, its incidence has been increasing. The standard treatment of anal canal SCC stage II-III consists of infusional 5-fluorouracil associated with mitomycin and radiotherapy. This scheme was proposed by Nigro in 1974, and since then no other effective treatment was developed. Methods: Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status, normal blood and renal function were treated with capecitabine 825 mg/m2 12/12hs during radiotherapy associated with a single dose of mitomycin 15 mg/m2 on Day 1. Primary objective is determine local control rate in 6 months with capecitabine, mitomycin and radiotherapy in patients with SCC of the anal canal. After the end of the treatment patients were reassessed for clinical and radiological response. Sample size was calculated using Fleming's single stage. Considering 85% of expected events (rate of local control in 6 months), standard deviation and a 5% error, sample size calculated was 51 patients. Results: 13 patients have been included, 9 patients have finished, 3 patients are still in treatment and 1 patient was excluded because of poor compliance with oral medications. Regarding the staging, 5 patients (38,4%) with stage II, 4 patients ( 30,8%) with stage IIIA and 4 patients (30,8%) with stage IIIB. Among patients who finished the treatment and were reevaluated 1 patient ( 16,7%) presented partial clinical response, 6 patients (83,3%) had clinical complete response. Three patients are waiting for clinical and radiologic reassessement. The main toxicities observed were grade I diarrhea ( 30,7%), grade II (38,5%) and III (30,7%) radiodermitis, nausea ( 38,5%), grade I-II plaquetopenia( 30,7%). Grade I hand–foot syndrome was observed in 1 patient and hemorrhagic cystitis related to radiotherapy was observed in 1 patient. No serious adverse event was observed. Colostomy was required in 1 patient before the beginning of the treatment. Conclusions: The study is ongoing but capecitabine and mytomicin with radiotherapy seem to be a safe treatment for SCC of the anal cancer.
Propensity score–based comparison of outcomes with 3D conformal radiotherapy (3D-CRT) versus intensity-modulated radiation therapy (IMRT) in treatment of esophageal cancer.
Authors: Lin Steven H. , Myles Bevan H , Wang Lu , Thall Peter F. , Vaporciyan Ara A. , Mehran Reza J. , Swisher Stephen , Lee Jeffrey H , Bhutani Manoop S. , Maru Dipen , Ajani Jaffer A. , Cox James D. , Komaki Ritsuko , Liao Zhongxing X. 
Published: February 2017

66 Background: Although 3D-CRT is the current standard for treatment of esophageal cancers, IMRT improves dose conformality and reduces radiation exposure to normal tissue. There is no assessment of long term clinical outcomes comparing these two modalities. Methods: Between 1998-2008, 676 patients (3D-CRT=413, IMRT=263) with stage Ib-IVa (AJCC 2002 edition) esophageal cancers were treated with chemoradiation with or without surgery. To correct for potential bias inherent in observational studies, we employed inverse probability of treatment weighted (IPW) methods based on propensity scores. IPW survival plots and IPW log rank tests were used to adjust for potential bias in treatment selection. Treatment probabilities (propensity scores) were estimated using logistic regression. Results: IMRT patients were less likely to receive induction chemotherapy (35.7% vs 46.7%, p<0.01) and had poorer performance status (KPS≤80: 66.5% vs 50.0%, p<0.01). A fitted multivariate IPW-adjusted Cox model showed that overall survival was significantly associated with age (HR 1.10 for 10 years older, p=0.02), KPS (≤70 vs 90-100, HR 1.5, p=0.0002), having surgery (HR 0.56, p<0.0001), lower vs upper esophagus (HR 1.4, p=0.009), stage (3-4a vs 1-2, HR 2.6, p<0.01), and radiation modality (IMRT vs 3D-CRT, HR 0.68, p<0.0001). 3D-CRT patients had a greater risk of dying at 5 years compared to IMRT (72.6% vs 52.9%, p<0.0001) without a difference in cancer-specific mortality (Gray’s test p=0.86), time to local recurrence (p=0.27) or distant metastasis (p=0.13). Cumulative incidence of documented cardiac deaths trended higher in the 3D-CRT group (p=0.16), but most deaths were due to unknown causes (5 year estimate: 13.4% in 3D-CRT vs 4.2% in IMRT, Gray’s test p<0.0001). Analyses using propensity score as a covariate gave very similar results. Conclusions: There was a substantially higher risk of non-cancer related deaths in 3D-CRT versus IMRT. While the true cause of death cannot be determined for many 3D-CRT patients, our results suggest that improvements in radiation technology may improve treatment-related mortality in management of esophageal cancer.
5-flourouracil (5FU) shortage: Clinical implications and costs in a single month.
Authors: Gupta Shweta , Jain Prantesh , Gupta Saurabh , Yim Barbara , Mullane Michael Russell 
Published: February 2017

663 Background: Capecitabine (XELODA) is an orally active fluoropyrimidine that is absorbed intact through the gastrointestinal tract and converted in to 5FU. Standard chemotherapy for advanced colon cancers includes infusional 5FU with leucovorin in combination of oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). With the national shortage of 5FU we had to switch our FOLFOX and FOLFIRI regimens to XELOX or XELIRI. Although in trials the xeloda regimens were non-inferior, the PFS (progression free survival) and OS (overall survival), survival curves tailed behind the infusional 5FU regimens. Methods: At our institution over one month period from August 18th 2011 to September 18th 2011, all patients who were switched from 5FU to xeloda due to national shortage were identified. All charts were retrospectively reviewed identifying patients with colon cancer. Patients with other cancer histologies, were excluded. The charts were reviewed for number of cycles, clinical toxicity, admission to hospital. Results: A total of 90 patients were switched form 5FU to xeloda. 51 had colon cancer. Out of which, 6 (11.7%) patients had the drug discontinued due to toxicity and 4 out of the 6 required hospitalization due to adverse effects of xeloda, mainly diarrhea and vomiting. 80% of these had left sided colon cancer and 50% each received oxaliplatin and irinotecan respectively. The total number of hospitalization days was 20. The average wholesale price (AWP) of one cycle of xeloda for body surface area range from 1.5m2 to 2m2 ranges from 2605.68$ to 3474.24$ for every 3 week cycle. In comparison the corresponding AWP for 2 cycles of 5FU over a month is 51.81$ to 69.08$. This would become a net higher price of 2553.87$ to 3405.16$ for BSA of 1.5 to 2m2 per month for the switch to xeloda. There were 51 patients who received xeloda at least one cycle which costed about 151,954.50$ if we average the body surface area. Additionally there were 20 admission days costing about 50,000$, making the net costs of switching to xeloda more than 200,000$ in a single month. Conclusions: Although xeloda is non-inferior to 5FU and can be a substitute, left sided colon cancers tend to do have more adverse effects. Additionally Xeloda is associated with higher administration costs.
Use of calcium and magnesium to prevent oxaliplatin-related neurotoxicity.
Authors: Brady Bernadette , Cogan Grainne , Grogan William , Hennessy Bryan 
Published: February 2017

672 Background: Sensory neurotoxicity is a dose limiting side effect of oxaliplatin. The postulated cause is interference with ionic channels. Calcium and magnesium pre and post oxaliplatin infusion have been suggested to prevent this as they act as chelators. Methods: We performed a review of all patients who were treated with oxaliplatin over a 2 year period. 25 patients received oxaliplatin with calcium gluconate 1g and magnesium sulphate 1g (Ca/Mg group) and 33 did not (no Ca/Mg group). 49 (84%) patients received oxaliplatin as part of the FOLFOX regimen. Other regimens included XELOX, EOX and FLOX. Peripheral neuropathy was defined and graded by the Common Terminology Criteria for Adverse Events v3.0 and was assessed by a clinical nurse specialist (CG). Results: 55 (95%) patients had peripheral neuropathy. There was no significant difference in overall neuropathy and the grade of neuropathy between the Ca/Mg group and no Ca/Mg group. 4 patients required discontinuation of oxaliplatin. One patient (Ca/Mg group) required dose reduction. Patients requiring medical treatment were treated with pregabalin. Conclusions: Oxaliplatin-induced neuropathy is a drug limiting adverse effect. We found that the addition of calcium gluconate and magnesium sulphate did not reduce the incidence or severity of peripheral neuropathy experienced in our cohort. It has been suggested (Park S.B. et al. The Oncologist. 2011;16:708-716) that oxaliplatin induced peripheral neuropathy may not be reversible. This emphasises the importance of managing this difficult symptom appropriately. [Table: see text]