bluuebunny/crossref_metadata_2025 huggingface dataset:
Does expected survival influence palliative radiotherapy treatment recommendations?
Authors: Ma David L , Debenham Brock J , LeGuerrier Bronwen , Paulson Kim , Ghosh Sunita , Huang Fleur , Chu Karen P , Severin Diane , Amanie John , Nijjar Tirath , Patel Samir , Rose Jim , Wiebe Ericka , Danielson Brita Lavender , Fairchild Alysa
Published: February 2017

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Background: Survival is often overestimated, yet physicians rely on such predictions to recommend appropriate therapy and assist with end-of-life planning. Administration of radiotherapy (RT) within the last 30 days of life has been suggested as an indicator of poor quality care, since acute side effects reduce quality of life with insufficient time for symptomatic benefit. We investigated whether life expectancy predicted at the time of consultation correlates with palliative RT recommendations. Methods: Radiation oncologists from a dedicated palliative Radiation Oncology outpatient clinic anonymously completed survival estimations after clinical assessment, and recorded factors upon which each estimate was based. Demographics, primary histology, RT details, and date of death were abstracted. Summary statistics and Kaplan-Meier estimates of actual survival (AS) were obtained. Correlations between AS and clinical predictions of survival (CPS) were calculated using Spearman’s correlation coefficient (r). Multivariate logistic regression analysis explored factors associated with RT recommendations. Results: 476 survival predictions were made for 420 unique patients (06/2010-01/2014). Median age was 67.7 years, 61.9% were male and 44.0% had lung cancer. Karnofsky Performance Status (KPS) was > 70 at 23.9% of clinic visits. At 84.5% of consultations, RT was prescribed to 538 separate volumes (29.2% receiving 8Gy, 54.8% 20Gy, 6.3% 30Gy, 9.7% other). Mean AS was 179 days (SD 187d), moderately correlating with mean CPS of 242 days (SD 261d) with r = 0.38 (p < 0.0001). Factors most frequently cited as influencing CPS were KPS and extent of disease. At the time of 30/476 visits, CPS was < 30 days; at 19 of these visits, RT was prescribed to 26 volumes (21 bone, 3 whole brain, 2 chest), 2/3 as single fractions, finishing a median of 17 days before death. Expected survival was predictive of prescribed RT dose on univariate logistic regression, but did not retain significance on multivariate analysis. Conclusions: Despite international surveys in which prognosis has been cited as the main factor affecting treatment decisions, in this cohort, other aspects appear to have more strongly influenced palliative RT recommendations.
“Ask me, do you want to know the big picture?” Gynecologic oncology patient and provider perspectives on discussing prognosis.
Authors: Lefkowits Carolyn , Kavalieratos Dio , Arida Janet , Teuteberg Winifred , Donovan Heidi , Courtney-Brooks Madeleine , Arnold Robert , Kelley Joseph L
Published: February 2017

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Background: Prognosis affects decision making by providers and patients and accurate understanding of prognosis may help avoid futile end-of-life care. Gynecologic oncology (GO) patient and provider perspectives on discussing prognosis have not been described. We sought to analyze patient and provider preferences regarding timing, amount and type of information included in discussions of prognosis. Methods: Semi-structured qualitative interviews regarding palliative care with 19 GO providers (7 physicians, 7 advanced practice providers, 5 nurses) and 29 patients with advanced or recurrent gynecologic cancer at an academic medical center. Communication about prognosis was one interview domain. Two coders independently and iteratively analyzed transcripts using qualitative analysis. Results: Median patient age was 61, the most common cancer was ovary (59%) and 90% had recurrent disease. Providers were 74% female with median 15 years in practice. Themes included patients wanting frank discussions about prognosis, not limited to life expectancy. Further preferences regarding timing and content were individualized. All categories of providers reported having prognosis conversations. Providers saw these conversations as part of their clinical role, though they often found them difficult. Providers commonly equated prognosis purely with life expectancy. Providers recognized variation among patients in preferences regarding these conversations, but did not discuss asking patients directly about their preferences. Conclusions: GO patients want frank discussions about what the future might hold, often including but not limited to life expectancy. Providers see these discussions as being within their scope of practice but often find them difficult. Opportunities exist for provider education regarding communication skills for assessing patient preferences and conducting patient centered prognosis discussions. Education should include GO physicians, advanced practice providers and nurses. Collaboration with specialty palliative care providers could facilitate that education and provide assistance with challenging cases.
Qualitative study of patients’ and family caregivers’ (FC) perceptions and information preferences about hospice.
Authors: El-Jawahri Areej , Shin Jennifer Adrienne , Traeger Lara , Knight Helen , Mirabeau-Beale Kristina , Fishbein Joel , VanDusen Harry , Keenan Tanya , Jackson Vicki A. , Volandes Angelo E. , Temel Jennifer S.
Published: February 2017

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Background: Despite the benefits of hospice for patients with advanced cancer and their FC, many patients are referred late or not at all. To assess potential patient and FC barriers to enrollment, we assessed their perceptions, knowledge, and information preferences about hospice. Methods: We conducted qualitative interviews with 16 adult patients with metastatic cancer and a prognosis ≤ 12 months and 8 of their FC. We used a semi-structured interview guide to elicit their perceptions (including perceived barriers to utilization), knowledge, and information preferences about hospice. Two raters coded interviews independently and reached acceptable inter-rater reliability (κ > 0.85). We used content analysis to identify themes. Results: We found similar themes between patients and FC interviews. Participants had mixed views about which patients need hospice with some stating it is for patients only at the end-of-life and others perceiving it as important for patients who need care their family cannot provide. Notably, most patients perceived themselves as not needing hospice in the near future. While the majority perceived the role of hospice to enhance quality of life and provide comfort, some viewed it as providing practical support, including 24-hour care. 50% of participants had positive feelings about hospice, while others were more ambivalent. All participants felt they needed more information about hospice, yet they were mixed regarding the optimal timing of this information. Many thought it would be helpful to have information about hospice through pamphlets, websites, or videos, prior to a discussion with their oncologist. Most viewed denial and hope as the main barriers to early hospice enrollment. Conclusions: Study participants had misunderstandings about which patients were appropriate for hospice and regarding the services offered. Participants expressed strong desires for more information about hospice with educational tools, although were mixed about the optimal timing for reviewing these tools. These findings suggest that patients and FC would benefit from interventions to enhance their understanding of hospice and to facilitate a discussion with their oncologists.
Meta-analysis: Risk of congestive heart failure (CHF) in selected targeted agents.
Authors: Escalante Carmelita P. , Elting Linda S. , Halm Josiah , Zalpour Ali , Bossi Paolo , Yusuf SWamique , Brito-Dellan Norman , Sahai Sunil , Bhadriraju Satish , Rouleau Tanya , Chang Yuchia
Published: February 2017

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Background: Congestive heart failure (CHF) is among the most serious cardiovascular side effects of targeted agents (TA) impacting the clinical outcomes (including survival) of cancer patients on this therapy. Although clinical trials have reported this toxicity, often sample sizes are small and systemic evaluations are lacking. The objective of this study is to estimate risk and severity of CHF due to selected TAs. Methods: We identified 110 English language studies of 26 TA’s approved by the Food and Drug Administration as of November 2013 via MEDLINE. Of those, 8 studies including nearly 8000 patients provided TA-related data on the incidence and severity of CHF. Using meta-analytic methods, we calculated the relative risks of CHF, adjusting for sample size using the inverse variance technique. For each TA, we also determined the number needed to harm. Results: See table. Conclusions: In 5 studies including more than 7,000 patients, trastuzumab showed significantly greater risk of CHF. For every 9 patients treated with trastuzumab, there was 1 additional case of CHF compared to control regimens. A careful patient selection before therapy and early detection of CHF by judicious monitoring of patients on this therapy may prevent serious complications and allow maintenance of cancer treatment. [Table: see text]
Inclusion criteria for cancer cachexia clinical trials: CT-defined skeletal muscle loss versus body weight loss.
Authors: Roeland Eric , Nelson Sandahl H , Campillo Ashleigh , Heavey Sean , Ma Joseph D. , Revta Carolyn , Gallivan Andrea , Baracos Vickie E
Published: February 2017

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Background: Cancer cachexia is defined by skeletal muscle loss, with or without fat loss (Fearon et al 2011); however, inclusion criteria for cachexia clinical trials requires a defined weight loss over time rather than muscle loss. We hypothesized that cross sectional imaging may reveal the presence of cachexia otherwise obscured by fat mass changes. Methods: A retrospective analysis of longitudinal CT scans was performed in metastatic colorectal cancer (mCRC) patients screened for a cancer cachexia trial, which required ≥5% weight loss in the prior 6 mos. De-identified CT images were analyzed for total muscle, subcutaneous, and visceral fat cross-sectional areas (cm2) at the 3rd lumbar vertebra at baseline and up to 12 mos prior (Lieffers et al 2009). Logistic regression was used to test differences between patients with <5% vs ≥5% weight loss. Random intercept regression was used to evaluate significant trends in CT measures over time. Results: 42 mCRC patients were screened and 3(7%) enrolled. Patients were excluded for comorbidity/contraindication 14 (33%), excessive [>20%] weight loss 4 (9.5%), and insufficient [<5%] weight loss 19 (45%). For the <5% weight loss subset, there was a mean of 6.7 CT scans (SD=2.67) and of 9% (SD=5.4, min=0%, 25th percentile=4.9%) mean max muscle loss. Notably this group was simultaneously losing muscle (p=0.002) and gaining visceral adipose (p=0.007). For the ≥5% weight loss subset, there was a mean of 7.5 CT scans (SD=4.5) and 20% (SD=10.0, min=5.2%, 25th percentile =10.6) mean max muscle loss. Greater max muscle loss increased the odds of being in the ≥5% weight loss subset (OR=1.19, 95% CI: 1.06,1.33). This group also had a significant decrease in visceral adipose over time (p<0.001). Redefined inclusion criteria of ≥5% muscle loss would have included 14 of the 19 patients excluded because of <5% weight loss. Conclusions: Defining cancer cachexia as weight loss over time may be limited as it does not capture body composition changes and hinders trial accrual. Cross-sectional CT body composition analysis may improve early detection of muscle loss and improve trial accrual.
Occurrence, severity, and impact of cancer-related fatigue in Taiwanese patients with cancer: A national survey.
Authors: Hsieh Ruey Kuen , Shun Shiow-Ching , Rau Kun-Ming , Chiou Tzeon-Jye , Sung Yung-Chuan , Yeh Su-Peng
Published: February 2017

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Background: Cancer-related fatigue (CRF) is common symptom in cancer patients. However, there is no study related to occurrence, severity and impact of CRF in Taiwan. The aim of this study was to report the occurrence and severity of CRF, and its impact on quality of life in cancer inpatients and outpatients in Taiwan. Methods: A national survey with cross-sectional study design was used. Patients were recruited from 20 hospitals with inpatients unit (n = 574) and outpatients clinics (n = 633) in Taiwan. The structured questionnaire was used to assess patients’ demographic, clinical, and CRF characteristics among Taiwanese cancer patients. The CRF were assessed by International Classification of Diseases 10th Revision (ICD-10) and Brief Fatigue Inventory–Taiwan Form (BFI-T). Quality of life (QOL) was assessed by FACT-general. Descriptive statistics and bivariate correlations were used to compare the occurrence, severity, and impacts on quality of life of CRF between cancer inpatients and outpatients. Results: Overall, the occurrence was 23.36% based on ICD-10 CRF criteria and 31.9% and 15.6 for inpatients and outpatients, respectively. About94.4% of inpatients and 89.7% of outpatients experienced fatigue. Inpatients had significant higher fatigue severity (current fatigue, general fatigue, and worst fatigue) during the past 24 hours compared to the outpatients. Enjoyment of life was the most interfered by fatigue in both inpatients and outpatients. The mean levels of current fatigue, general fatigue and worst fatigue were moderate in inpatients, and they were mild to moderate in outpatients. The mean score of FACT-general was 17.57 in overall with the lowest level of functional well-being, and 15.68 and 19.29 in inpatients and outpatients. Conclusions: The occurrence based on the ICD-10 CRF criteria was relative low compared to self-report. Fatigue interfered patients’ enjoyment of life and the patients had the lowest level of quality of life in functional well-being. Healthcare providers should pay attention on how to decrease cancer patients’ fatigue in order to improve their QOL, especially in inpatients.
Comparison of prevalence of pain symptoms and completion rates using a patient-reported outcomes (PRO) tool of pain in palliative and curative patients.
Authors: Yeung Sabrina , Brown Catherine , Perez Cosio Andrea , Leung Yvonne , Liang Mindy , Gill Gursharan , Sarabia Samantha , Liu Aixin , Wong Lauren , Howell Doris , Liu Geoffrey
Published: February 2017

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Background: Regular self-reporting of symptoms using validated computerized assessment tools can improve individualized symptom management. Yet there are concerns that palliative patients who may benefit most from such self-reporting may be reluctant to adopt such approaches or have barriers to proper reporting. We compared actual prevalence and completion rates of a PRO-tool between patients being managed with a palliative (PAL) or curative intent (CUR). Methods: A pain PRO-tool was administered cross-sectionally using tablet technology across outpatient clinics in a comprehensive cancer centre. Questions were adapted from the Brief Pain Inventory (BPI) and Edmonton Symptom Assessment System (ESAS), recording responses on pain severity and interference in life. PRO-tool completion rates and prevalence of pain symptoms were compared between CUR and PAL. Results: Of 200 patients, 82 were PAL and 118 were CUR; median age was 60 (21-86) years; 48% were female. A greater proportion of PAL were found with gastrointestinal, gynecological and lung cancers than CUR (p = 0.04). Each question had greater than 95% completion rates for both groups, capturing a wide range of scores. 16% of PAL reported no pain as their worst pain in the last 24 hours as opposed to 31% of CUR (p = 0.02). 82% (PAL) and 68% (CUR) reported their average pain as being at least “some pain” (p = 0.03), and there were no differences in the proportion of patients reporting interference with their general activity between PAL and CUR (p > 0.05). Presence of current pain was equivocal when assessed via the ESAS adapted question (76% PAL vs 66% CUR, p = 0.16), but was significantly different when assessed using the BPI adapted question (72% PAL vs 56% CUR; p = 0.02). Conclusions: A Pain PRO-tool was completed with similarly high rates in PAL and CUR patients. As expected, prevalence of recent and current pain was high in both groups, and in some instances, higher in PAL than CUR patients. These results suggest that a Pain PRO-tool could be implemented with ease in the palliative setting, and would capture pain comprehensively.
Are palliative patients less accepting to self-report symptom measures for clinical management than curative patients?
Authors: Sarabia Samantha , Perez Cosio Andrea , Brown Catherine , Leung Yvonne , Gill Gursharan , Liang Mindy , Yeung Sabrina , Liu Aixin , Wong Lauren , Liu Geoffrey , Howell Doris
Published: February 2017

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Background: Patient reported outcome measures (PROMs) are a tool used for collecting patient symptom data in the clinic, prior to the patient’s appointment. Patients being treated with a palliative intent are often assumed to find completing PROM surveys more burdensome than patients being treated with a curative intent. We compared patient acceptability of palliative versus curative patients to complete PROM surveys. Methods: 202 cancer out-patients (120 curative and 82 palliative) at the Princess Margaret Cancer Centre completed a PROM survey using a touchscreen tablet regarding their symptoms of pain. Ten questions assessed patient acceptance of completing PROM surveys. Results: The median age was 60 (range 21-86) and 48% were female. There were no clinically relevant demographic differences between the palliative and curative patients; however there were a higher proportion of palliative patients than curative patients with gynecological (8.3% palliative, 16% curative), lung (5.8% palliative, 10% curative), and gastrointestinal (14% palliative, 28% curative) cancers. There were no significant differences in acceptability between palliative and curative patients (p>0.05, all 10 comparisons). Only 3.6% of palliative patients and 3.3% of curative patients reported that completing the survey made their clinic visit more difficult; 16% of palliative patients and 11% of curative patients found the survey to be time consuming; no palliative patients and only 0.83% of curative patients found the questions upsetting or distressful. 93% of palliative patients and 92% of curative patients were happy to complete the surveys on a touchscreen tablet. Overall 62% of patients surveyed were willing to complete surveys at every visit (56% palliative and 67% curative, p>0.05). Conclusions: Palliative and curative patients appear to have an equally high level of acceptance of PROM surveys, though a significant minority would have problems with completing them at every visit. Further research using mixed-methods analysis will be done to better understand the factors limiting the overall willingness of both palliative and curative patients to complete the survey on a regular basis.
Patient- versus physician-reported outcomes in patients enrolled in a prospective study involving stereotactic body radiation therapy in unresectable or recurrent pancreatic cancer.
Authors: Rosati Lauren M. , Cheng Zhi , Robertson Scott P. , Kummerlowe Megan N. , Hacker-Prietz Amy , Pawlik Timothy M. , Wolfgang Christopher Lee , Le Dung T , Zheng Lei , Laheru Dan , Herman Joseph M.
Published: February 2017

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Background: Prospective evaluation of correlations between patient- (PROs) and physician-reported outcomes (PhROs) was conducted among a group of patients receiving stereotactic body radiation therapy (SBRT) for recurrent or locally advanced pancreatic cancer (PCA). Methods: Forty-two patients were treated with 25-33 Gy using SBRT in 5 fractions on a single-institution study. Eight outcomes (performance status, fatigue, pain, anorexia, nausea, vomiting, constipation, and diarrhea) were consistently evaluated by patients and providers prior to SBRT and 4-6 weeks post-SBRT. Patient-reported quality of life (QOL) metrics were assessed using the EORTC QLQ-C30 and QLQ-PAN26, while physician-reported toxicities were graded using the NCI CTCAE v4.0.A Pearson’s correlation was used to determine the relationship between PROs and PhROs. Results: Of the 42 enrolled patients, 36 had both PROs and PhROs collected before (median, 2.9 weeks) SBRT. Physician-reported pain, nausea, constipation, and diarrhea did not show a correlation with patient-reported overall health or QOL. Physician-reported fatigue showed a correlation with patient-reported pain (r > 0.5, p < 0.001) and QOL (r > -0.5, p < 0.001) but not fatigue (r < 0.3, p > 0.05). Nausea and constipation were the only PROs that did not correlate with their respective PhROs (nausea, r < 0.3, p > 0.05; constipation, r < 0.5, p = 0.07) or any of the other 7 PhROs. Only 24 had both PROs and PhROs collected 4-6 weeks after (median, 5.1 weeks) SBRT. Vomiting, constipation, and diarrhea were PhROs that demonstrated no correlation with patient-reported overall health or QOL. Physician-reported vomiting did not correlate with patient-reported vomiting (r < 0.3, p > 0.05) or any of the 7 other PROs. The correlation between patient- and physician-reported pain increased from pre- (r > 0.3, p = 0.03) to post- (r > 0.7, p < 0.0001) SBRT. Conclusions: Discrepancies among PROs and PhROs appear to exist in pancreatic-specific outcomes of interest such as constipation and diarrhea. Future health care teams may find it helpful to consider PROs to better manage symptoms and deliver more personalized care. Clinical trial information: NCT01781728.
Correlations between functional Interleukin-1 and changes in fatigue and quality of life in children and adolescents with cancer.
Authors: Bomfim Emiliana de Omena , Anatriello Elen , Nunes Michelle Darezzo Rodrigues , Moraes Jordana Carvalhes , Cintra Michel Marcossi , Lopes-Junior Luis Carlos , Miyauti Michele , Nascimento Lucila Castanheira , de Lima Regina Aparecida Garcia , Floria-Santos Milena
Published: February 2017

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Background: Several studies have explored the hypothesis of involvement of the immune system in the cancer-related fatigue (CRF) and quality of life in adults with cancer via release of cytokines. However, how the immune system may produce these outcomes remains a largely unanswered question. Furthermore, research on fatigue in children and adolescents with cancer has included primarily self-reports of this symptom, with scarce although increasing data exploring biologic variables related to this symptom. Methods: To comprehensively examine the influence of cytokines in the fatigue and health related quality of life (HRQOL) in children and adolescents with cancer, we investigated the plasma levels of pro and anti-inflamatory cytokines and its correlation with fatigue and HRQOL in children and adolescents with cancer. Plasma levels of 6 cytokines were measured via flow cytometry. Results: The final sample consisted of 33 hospitalized children and adolescents aged between 8 and 18 years. We found a correlation between general fatigue and IL-1β (r = –0.361, p = 0.039) and correlation with quality of life was noted with IL-1β (r = –0.382, p = 0.028). The results of this research indicate that there may be a relationship between cytokines and fatigue, and HRQOL in children and adolescents with cancer. When analyzed the correlation between fatigue and some confounding variables found the link between general fatigue and neutrophils (r = –0.360, p = 0.040). This correlation is a novel found in this population under cancer condition, implicating a possible interleukin-hematological pathway for CRF in oncology. Conclusions: Our study confirms the potential role of cytokines in developing cancer-related symptoms, thus supporting the utility of the neuroimmunological approach to the discovery of biomarkers linked to the clusters of cancer-related symptoms.
A cross-sectional analysis of symptom burden among adult cancer patients in a Filipino tertiary care cancer center.
Authors: Bacorro Warren Ramos , Que Jocelyn C , Sy Ortin Teresa Tan , Feeley Thomas W. , Reyes-Gibby Cielito C.
Published: February 2017

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Background: Palliative and supportive care has been shown to improve quality of life (QOL) and survival and reduce caregiver burden and costs, but remains poorly integrated into cancer care in the Philippines. Understanding symptom burden profile among patients will guide policy-making in a limited/moderate resource setting. Methods: This cross-sectional study was conducted among adult Filipino cancer patients. Demographic and clinical data were collected from medical records and patient interviews. Symptom severity and interference were assessed using the M.D. Anderson Symptom Inventory. Symptom prevalence and mean severity scores were determined. Pearson correlation analysis was used to examine relationships between symptom severity and interference. Results: Participants (n = 251)were aged 18-80 years; the majority were aged < 60, females, or with good performance status (PS). Breast, head-and-neck and gastrointestinal primaries were most common; 45% had advanced disease. Moderate and severe symptoms were prevalent across stages. Fatigue (65%), pain (62%), sadness (62%), and anxiety/distress (58%) were the most prevalent, most severe and most interfering. In metastatic disease, sadness was most prevalent, and fatigue, most serious; among those with poor PS, disturbed sleep was most prevalent and most serious. Pain was more disabling among females, and fatigue and sadness, among the elderly. Conclusions: This is the first study to describe symptom burden among adult Filipino cancer patients. The clinical impact of symptoms is determined by their concurrence and the patient’s demographic and clinical profile. Symptom burden is highest for fatigue, pain, sadness, and anxiety/distress. Comprehensive symptom evaluation and tailored approach to care is necessary for optimal management. While a clinical practice guideline (CPG) has been adopted for use at our institute, effective CPGs for the screening, assessment and management of fatigue, depression and anxiety/distress have yet to be identified and implemented.
Could methylated reprimo cell-free DNA serve as a novel tumor marker to assess response in locally advanced gastric cancer treated with preoperative chemotherapy?
Authors: Muller Bettina Gabriele , Alarcon Alejandra , Arancibia Jorge M , Alfaro Francisca , Sola Jose Antonio , Maturana Maria J. , Ascui Rodrigo Andres , Fernandez Wanda , Corvalan Alejandro
Published: February 2017

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Background: Gastric cancer (GC) is one of the leading causes of cancer death. Perioperative chemotherapy (CT) for locally advanced GC improves curative resection rates and survival compared to surgery alone. Response assessment is challenging and no tumor markers have been validated for this purpose. We conducted a pilot study to investigate the role of methylated Reprimo (RPRM) cell-free DNA (cfDNA) as tumor marker for assessment of response to preoperative CT in patients enrolled in the study GOCCHI 2009-01 (NCT01633203). Methods: Patients with locally advanced GC referred to receive preoperative CT with Epirubicin + Cisplatin + Capecitabine for 3 cycles were offered to enter the study. Patients had to have operable GC, with baseline CT showing a transmural tumor and/or regional lymphnode metastasis with no distant spread assessed by a multidisciplinary tumor board. After the approval of the amendment of the protocol to allow blood sampling for tumor marker measurement and only if informed consent had been given, blood samples were taken at day one of each cycle of preoperative CT. The status of methylated RPRM cfDNA was assessed by Methylight and the number of copies per mL was determined. Patients with at least 2 samples were analyzed. Results: Thirteen patients signed the informed consent form for this substudy, and 11 patients had blood samples available for analysis. Of these, 8 patients had detectable methylated RPRM cfDNA on Day 1 of the first cycle (i.e. baseline). Five patients showed decrease in methylated RPRM cfDNA, while 5 patients had increased levels of the tumor marker in subsequent measurements. In one patient, methylated RPRM cfDNA was not detected in either of two assessments. One patient with a marked increase in methylated RPRM cfDNA after two cycles of CT had metastatic disease at laparotomy. Correlation between pathological findings and changes in methylated RPRM cfDNA will be presented. Conclusions: Our findings suggest that methylated RPRM cfDNA could serve as a novel tumor marker to assess response in locally advanced GC treated with preoperative chemotherapy. Further validation of these preliminary results is warranted.
Perioperative chemotherapy with ECX +/- panitumumab in locally advanced gastroesophageal adenocarcinomas (GEA): A randomized study of the Arbeitsgemeinschaft Internistische Onkologie and the Chirurgische Arbeitsgemeinschaft Onkologie of the German Cancer Society.
Authors: Stahl Michael , Mihaljevic Andre L. , Moehler Markus , Kanzler Stephan , Hoehler Thomas , Thuss-Patience Peter C. , Moenig Stefan Paul , Kunzmann Volker , Schroll Sebastian , Lordick Florian , Meyer Hans-Joachim , Sandermann Andreas , Schumacher Christoph , Wilke Hansjochen
Published: February 2017

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Background: Perioperative chemotherapy represents the European standard of care in locally advanced GEA. Efficacy may be improved by combining chemotherapy and molecular targeted drugs. Due to overexpression of epidermal growth factor receptor (EGFR) in most GEA EGFR-inhibitors may be candidates for such improvement. Methods: To evaluate the role of EGFR-antibodies in the perioperative treatment we performed a multicenter randomized phase II study. Patients with locally advanced (cT3-4 N0-3 M0) adenocarcinomas of the stomach or gastro-esophageal junction (GEJ) were eligible. Patients were treated with ECX with (arm 1 ) or without (arm 2) panitumumab (P, 9 mg/kg body weight iv, q 3 weeks). Three cycles were planned prior to and after surgery. The primary endpoint was to prove a reduction in ypT3-4 categories by adding P to ECX. Results: From 11/2010 to 7/2013 a total of 171 pts. were randomized, and 163 pts. (83 arm 1, 80 arm 2) were eligible. Prior to therapy 29% of the pts. in both arms had T4 tumors (CT scan and EUS) and 82% vs. 78% showed lymph node involvement. In 42% vs. 45% the primary tumour was located in the GEJ. 68 pts. (82%) vs. 68 pts. (85%) completed 3 preoperative cycles. The mean total dose of preoperative chemotherapy related to the planned dose reached 90% for panitumumab (arm 1 only), 91% vs. 92% for cisplatin, and 81% vs. 85% for capecitabine. R0-resection was achieved in 90% vs. 89% of the patients. The rate of pts. without downstaging (ypT3-4 at surgery) was statistically not significant higher in the experimental arm (73% vs. 66%, p=0.23), as was the overall treatment failure in the ITT analysis (odds ratio 1.37 (0.65-2.86)). The PCR-rate (ypT0N0) was comparable (3% vs. 5%, p=0.43). One toxic death was observed during chemotherapy (arm 2) and 1 pt. of both arms died due to complications after surgery. Conclusions: The study failed to reach its primary endpoint. The addition of P to ECX was not able to improve downstaging of locally advanced GEA. Survival data and results of translational research will be available during the course of 2015. Clinical trial information: NCT01234324.
Multicenter phase II study of trastuzumab with S-1 alone in elderly patients with HER-2 positive advanced gastric cancer (JACCRO GC-06).
Authors: Masuishi Toshiki , Kawase Tomono , Nishikawa Kazuhiro , Kunisaki Chikara , Matsusaka Satoshi , Segawa Yoshihiko , Nakamura Masato , Sasaki Kinro , Nagao Narutoshi , Tsuji Akihito , Yuasa Yasuhiro , Asami Shinya , Takeuchi Masahiro , Furukawa Hiroshi , Fujii Masashi , Nakajima Toshifusa
Published: February 2017

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Background: S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. In patients with HER2-positive AGC, ToGA trial showed survival benefit with the addition of trastuzumab to capecitabine plus cisplatin or fluorouracil plus cisplatin and HERBIS-1 trial demonstrated promising antitumor activity with the addition of trastuzumab to SP. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. And these disadvantages of cisplatin are noticeable in elderly patients. We evaluated the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC. Methods: Patients, 65 years or older, with HER2-positive AGC received S-1 (80–120mg per day) orally on days 1–28 of a 42-day cycle and trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg /kg) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary endpoints were overall survival (OS), progression free survival (PFS), time to treatment failure (TTF) and adverse events. The sample size was 40 to 60 patients estimated on the basis of threshold RR=20%, expected RR=35%, alpha=0.1 (one-sided) and power=80 to 90%. Results: A total of 51 patients were enrolled. One patient was ineligible, therefore in the full analysis set of 50 patients (actual statistical power = 87.5%), the median age was 71 years (range=65-85), male: female was 37:13 and ECOG PS was 0/1/2= 33/14/3. The confirmed RR (CR/PR/SD/PD=3/17/23/7) was 40.0% (80% confidence interval (CI); 31.1-48.9%, 95% CI; 26.4-53.6%), and the null hypothesis was rejected. The disease control rate was 86.0% (95% CI; 76.4-95.6%). Median OS, PFS, and TTF were immature. Major grade 3 or 4 adverse events included neutropenia (10.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death. Conclusions: The primary end point was met. Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects in elderly patients with HER2-positive AGC. Clinical trial information: UMIN000007368.
The prognostic value of preoperative helicobacter pylori infection in resected gastric cancer.
Authors: Postlewait Lauren McLendon , Squires Malcolm Hart , Kooby David A. , Poultsides George A. , Weber Sharon M. , Bloomston Mark , Fields Ryan C. , Pawlik Timothy M. , Votanopoulos Konstantinos Ioannis , Schmidt Carl Richard , Ejaz Aslam , Acher Alexandra W. , Worhunsky David J. , Saunders Neil , Swords Doug S. , Jin Linda X. , Cho Clifford Suhyun , Cardona Kenneth , Staley Charles A. , Maithel Shishir Kumar
Published: February 2017

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Background: Limited data exist on the prognostic implication of pre-operative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC). Our aim was to assess the association of H. pyloriwith recurrence and survival in patients undergoing resection of GAC. Methods: All patients who underwent curative intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the US Gastric Cancer Collaborative were included. 30-day mortalities were excluded. Survival analyses were conducted with Kaplan Meier log rank and multivariate Cox regression. Primary endpoints were recurrence-free survival (RFS) and overall survival (OS). Results: Of 965 patients, 559 met inclusion criteria and had documented pre-operative H. pylori testing. 18.6% (n=104) of patients tested positive for H. pylori pre-operatively. Data regarding treatment of H. pylori was not available. H. pylori infection was associated with younger age (62.1 vs 65.1 years; p=0.041), distal tumor location (82.7% vs 71.9%; p=0.033), and receipt of adjuvant radiation therapy (47.0% vs 34.9%; p=0.032). There were no significant differences in ASA class, margin status, Grade, PNI, LVI, or nodal metastases. The distribution of TNM stage I-III was similar between the two groups. H. pylori status was not associated with tumor recurrence. However, pre-operative H. pylori infection was associated with longer OS (84.3 mo vs 44.2 mo; p=0.008). When accounting for differences in age, tumor location, and delivery of radiation therapy, H. pylori infection persisted as a positive prognostic factor for OS (HR 0.60; CI 0.40-0.91; p = 0.016). Conclusions: Patients with and without preoperative H. pylori infection had no significant differences in adverse pathologic factors including positive margin, high grade, lymph node metastases, or advanced TNM stage. Despite similar disease presentation, pre-operative H. pylori infection was independently associated with improved overall survival. Further studies examining the interaction between H. pylori and tumor immunology and genetics are needed to better understand the relationship between H. pylori and survival in gastric cancer.
Intra-arterial, abdominal chemoperfusion with chemofiltration in the treatment of progressive stage IV gastric cancer.
Authors: Sendler Andreas , Aigner Karl R.
Published: February 2017

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Background: Treatment of patients (pts.) with progeressive stage IV gastric cancer remains a therapeutical problem. Survival of the pretreated pts. is low and the therapeutic options are sparse. In this situation, locoregional therapeutic strategies could be an option. Methods: 28 pretreated pts. (17 male, 11 female, mean age 59 y.) after resection and at least second line systemic chemotherapy were included in a phase II study of isolated abdominal perfusion and subsequent chemofiltration. All pts. had liver metastases (mets.), 50% (n = 14) had peritoneal carcinomatosis with malignant ascites. No pat. had cerebral, pulmonal or bone mets.. After insertion of a venous and arterial 21 ch. stop flow catheter via a femoral access, the v. cava was blocked beneath the right atrium, the arterial catheter was blocked above the celiac trunk. The thighs were blocked by pneumatic cuffs. Chemotherapy consisted of 35 mg/m2 cisplatinum, 20 mg/m2 adriamycin and 12 mg/m2 mitomycin q 3 weeks till progress or dead. The agents were administered via the arterial access, followed by 15 min of hypoxic abdominal perfusion via an external pump, followed by chemofiltration for 45 min. The procedure was done under general anaesthesia. Primary endpoint of the study were overall survival, secondary endpoint was control of the ascites. Results: A total of 92 cycles (mean 3.25) were administered. Toxicity was low with leucopenia CTC grad I in 9 pts., gastrointestinal disorders grad II in 8 pts. and surgical complications grad II in 40 % of the pat. (lymphatic fistula). In 9/14 (65%) of pts. with ascites, the ascites was at least controlled or vanished. One year survival was 28.6% (Kaplan-Meier), 2 year survival was 11.4%. Median survival was 6 months. Conclusions: Intra-arterial, isolated abdominal chemoperfusion with consecutive chemofiltration in heavily pretreated patients with gastric cancer metastasized to the abdominal cavity is a valuable option for palliative treatment with low side effects. In 65% of the affected pts., malignant ascites was controlled sufficiently, ameliorating the quality of life.
Comparison of long-term outcome between endoscopic submucosal dissection and surgical resection for early gastric cancer.
Authors: Kim Boo Gyeong , Kim Byung-Wook , Kim Joon Sung , Park Sung Min , Lim Keun Joon , Kim Jin Il , Park Jae Myung , Oh Jung-Hwan
Published: February 2017

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Background: The aim of this study is to evaluate the long-term clinical and oncologic outcome of ESD for differentiated EGC of an expanded indication compared to surgical resection. Methods: Retrospective analyses were performed in patients who underwent ESD or surgical resection for EGC of an expanded indication from 2006 and 2008 in Incheon St. Mary’s Hospital, Seoul St. Mary’s Hospital, Yeouido St. Mary’s Hospital, and St. Paul’s Hospital. First arm study was performed according to pre-ESD diagnosis including pathologic diagnosis and endoscopic findings. Second arm study was obtained from post-ESD final pathologic result. All the patients were checked with endoscopy and stomach CT regularly at least 5 years. Clinical outcomes, disease free survival and overall survival were compared between the ESD group and surgical resection group in each arm. Results: In first arm study, 41 patients who received ESD and 106 patients who received surgical resection were enrolled. Metachronous recur was found in 4 patients among ESD group and in 2 patients among surgical resection group during the follow up period. There was no local recurrence in both groups. The disease free survival was not different between the two groups (ESD vs surgical resection; 87.8 vs 95.3%, p=0.291). The 5-year overall survival rate was 100% in both groups. In second arm study, 74 patients who received ESD and 165 patients who received surgical resection were enrolled. Metachronous recur was found in 5 patients among ESD group and in 2 patients among surgical resection group during the follow up period. Local recurrence did not occur in both groups. Surgical resection group was superior to ESD group in disease free survival (97.6% vs 87.6%, p=0.002). The 5-year overall survival rate was 100% in both groups. Conclusions: ESD for EGC might be acceptable considering the overall survival rates. However, intensive surveillance should be performed to find the metachronous recur after ESD.
Comparison of transthoracic esophagectomy with definitive chemoradiotherapy as initial treatment for esophageal squamous cell carcinoma in patients who could tolerate transthoracic esophagectomy.
Authors: Matsuda Satoru , Tsubosa Yasuhiro , Niihara Masahiro , Takebayashi Katsushi , Kawamorita Keisuke , Mori Keita , Tsushima Takahiro , Yokota Tomoya , Ogawa Hirofumi , Onozawa Yusuke , Yasui Hirofumi
Published: February 2017

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Background: Transthoracic esophagectomy (TTE) and definitive chemoradiotherapy (dCRT) have been recognized as initial curative treatments for esophageal squamous cell carcinoma (ESCC). We aimed to compare TTE with dCRT as initial treatments in patients who had potentially curable ESCC and could tolerate TTE. Methods: Consecutive patients who were histologically diagnosed as ESCC with stage I/II/III (excluding cT4 or cN3) or stage IV due to supraclavicular lymph node metastasis and were planned to undergo surgery or chemoradiotherapy as an initial treatment were eligible for this retrospective study. In order to select patients who could tolerate TTE, respiratory function, ECOG PS and preoperative complications were additionally considered in patients’ selection. Patient characteristics, recurrence free survival (RFS), 3-year and 5-year overall survival (3yOS, 5yOS) and the treatments after failure of initial treatments were investigated. Results: 112 patients were included in TTE, 65 in dCRT. No significant differences were observed in age, sex and clinical stage between TTE and dCRT (stage I/II/III/IIV of 29/47/46/10 in TTE, 23/15/20/7 in dCRT). R0 resection rate was 87% in TTE and CR rate was 68% in dCRT. In intension to treat analysis, there was no significant difference in RFS of non-stage IA patients. In contrast, 3yOS was significantly longer in TTE than dCRT (TTE, 66.3%; dCRT, 51.0%; P=0.029).In non-stage IA patients, after initial treatment failure, significantly more patients could undergo local treatment (radiotherapy or surgery in TTE, surgery or endoscopic resection or photodynamic therapy in dCRT) in TTE than dCRT (TTE 74%, dCRT 40%, P=0.003). Conclusions: In patients with locally advanced ESCC who could tolerate TTE, TTE could extend short term survival, which might be encouraged by utilizing local treatment after initial treatment failure.
Phase I/II docetaxel, oxaliplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.
Authors: Kim Sung Rok , Park Sung-En , Yuh Young Jin , Sohn Byeong Seok , Lee Hye Ran , Song Hong-Suk , Lee Kyung-Hee
Published: February 2017

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Background: The results of recent studies with duo- or triple regimen for the advanced gastric cancer are still not satisfactory and the optimal doses of combinations with taxanes, fluorouracil and platinum analogues were not determined yet. The aim of this study is to determine the optimal dose of docetaxel and oxaliplatin in combination with 5-fluorouracil(FU) [DOF], with the efficacy and toxicity in patients (pts) with advanced gastric cancer. Methods: The pts with unresectable, metastatic, or relapsed gastric cancer were enrolled for a phase I/II study. The dose of docetaxel and oxliplatin was escalated from 50 mg/m2 and 80 mg/m2 day 1, respectively by traditional 3+3 design, and 5-FU was fixed at 850 mg/m2/day 24 hour continuous infusion day 1-4, all every 3 weeks. All pts had measurable disease and were assessable for toxicity. Results: A total of 50 pts including 12 patients from phase I study were enrolled. The recommended phase II dose of docetaxel and oxaliplatin were 60mg/m2 and 100mg/m2 on day 1 (cohort 2), respectively. A total of 335 cycles of chemotherapy was administrated (median: 6, range 1–24) and the dose intensity of docetaxel, oxaliplatin, and 5-FU were 96.3%, 96.2% and 98.5%, respectively. Twenty two (44.0%) of 50 patients showed partial response, 22 (44.0%) stable disease, and 1 (2.0%) complete response. The overall response rate was 46.0% (95% confidence interval [CI]: 32.2–60.0%) and the disease control rate 90.0% (95% CI: 81.7–98.3%). The median progression free survival was 6.5 months (95% CI, 3.3–9.8) and the overall survival 10.7 month (95% CI, 7.0–14.3). Grade 3/4 neutropenia and thrombocytopenia occurred in 81 (24.1%) and 3 cycles (0.9%), respectively [27 (56%) and 3 (6%) in 50 pts, respectively]. Grade 3/4 stomatitis, diarrhea and neuropathy occurred in 2 (0.6%), 6 (1.8%) and 6 cycles (5.7%), respectively. Conclusions: The recommended phase II dose of docetaxel and oxaliplatin was 60mg/m2 and 100mg/m2, respectively. This DOF combination chemotherapy has no better efficacy than reference regimen. The toxicities were substantial in some pts, but generally manageable.
The relationship between pathologic nodal disease and residual tumor viability (RV) in patients with locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastroesophageal junction (E/GEJ) receiving induction chemotherapy, surgery, and postoperative chemoradiotherapy (CRT).
Authors: McNamara Michael J. , Rybicki Lisa A. , Rodriguez Cristina P. , Videtic Gregory M.M. , Stephans Kevin L. , Greskovich John , Sohal Davendra , Murthy Sudish C. , Raja Siva , Ives Denise I. , Bodmann Joanna , Adelstein David J.
Published: February 2017

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Background: A complete pathologic response to induction CRT has been identified as a favorable prognostic factor for patients with LRA ACA of the E/GEJ. Less is known, however, about the impact of pathologic regression after induction chemotherapy. Methods: Between 2/08 and 1/12, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3 or N1 or M1a (AJCC 6th). Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and fluorouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy @ 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) over 4 days during weeks 1 and 4 of radiotherapy. RV was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring. Results: Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier (KM) projected 3 year OS for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (p<0.001). The KM projected 3 year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) RV was 67%, 42%, and 17% respectively (p=0.004). On multivariable analysis, both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3yr OS 85% (0-25% viable) v 51% (>25% viable), p=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3yr OS 20% (0-25% viable) v 21% (>25% viable), p=0.55]. Conclusions: RV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of viability. Clinical trial information: NCT00601705.