bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and predictors of burnout among specialty palliative care clinicians in the United States: Results of a national survey.
Authors: Kamal Arif , Bull Janet , Wolf Steven , Samsa Greg , Ast Katherine , Swetz Keith Mark , Shanafelt Tait D. , Abernethy Amy Pickar
Published: February 2017

87

Background: The increasing demand for specialist palliative care (PC) in cancer care requires an available and responsive clinical workforce. But as the volume of work expands, PC providers face an increased risk of burnout, characterized by depersonalization and work-related emotional exhaustion. The prevalence and predictors of burnout among PC providers is poorly understood. Methods: Members of the American Academy of Hospice and Palliative Medicine (e.g. advanced practice provider, registered nurses, chaplains) completed the Maslach Burnout Inventory (MBI) via electronic survey in the second half of 2013; respondents were recruited via e-mail, blog and Facebook posts, and Twitter tweets. The MBI determine burnout severity across two domains, Emotional Exhaustion (EE) and Depersonalization (DP). Severity is reported as “low”, “moderate”, or “high”; “high” is consistent with burnout. Demographic and work-related variables associated with burnout in other studies were determined via stepwise logistic regression. Results: We received surveys from 1,241 clinicians. We estimated a response rate of 30%. 68% of respondents were physicians. Most respondents were over age 50 (57%), female (65%), were married or partnered (82%) and had worked in the field for less than 10 years (67%). 42% took overnight call regularly, 30% reported working 50 hours per week or more, and 57% had at least 4 colleagues. Regarding burnout, 24% reported high DP, 59% reported high EE, and 62% of reported high burnout symptoms on either EE or DP scales. In logistic regression, younger physicians, those working more than 50 hours per work, and those with fewer colleagues within their practice were at greatest risk of burnout (p<0.02). Conclusions: PC clinicians report a burnout rate of 62%. Even with the limitations of our methods and potentially biased sampling, this prevalence is remarkable and higher than data reported in medical oncology (45%). Burnout severity is associated with working in isolation and working longer hours. Further studies on how burnout affects sustainability of the PC workforce are needed, especially since this workforce is so critical to the provision of high quality cancer care.
Perceptions of palliative care among hematologic malignancy specialists: A mixed-methods study.
Authors: LeBlanc Thomas William , O'Donnell Jonathan David , Crowley-Makota Megan , Dohan Daniel Paul , Rabow Michael W. , Smith Cardinale B. , White Douglas B , Tiver Greer A , Arnold Robert , Schenker Yael
Published: February 2017

9

Background: Patients with hematologic malignancies have unmet palliative care needs but are less likely to receive specialist palliative care services than patients with solid tumors. This difference is poorly understood. Methods: Multisite, mixed-methods study to understand and contrast perceptions of palliative care among hematologic oncologists and solid tumor oncologists. Between February and October 2012, oncologists at 3 academic medical centers with well-established palliative care services completed surveys assessing referral practices and in-depth, semi-structured interviews about their views of palliative care. We compared referral patterns using standard statistical methods. We then analyzed qualitative interview data using constant comparative methods to explore reasons for observed differences. Results: Among 66 interviewees, 23 oncologists cared exclusively for patients with hematologic malignancies, and 43 treated only patients with solid tumors. Seven of 23 hematologic oncologists (30%) reported never referring a patient to palliative care; all solid tumor oncologists had previously referred (p<0.001). In qualitative analyses, most hematologic oncologists viewed palliative care as end-of-life care, while most solid tumor oncologists viewed palliative care as a subspecialty that could assist with complex cases and/or offload burden in a busy clinic. Solid tumor oncologists emphasized practical barriers to palliative care referral, such as appointment availability and reimbursement issues. Hematologic oncologists emphasized philosophical concerns about palliative care referrals, including different treatment goals, responsiveness to chemotherapy, and a preference to control palliative aspects of patient care. Conclusions: Most hematologic oncologists view palliative care as end-of-life care, while solid tumor oncologists more often view palliative care as a subspecialty for co-managing complex patients. Efforts to integrate palliative care into hematologic malignancy practices will require solutions that address unique barriers to palliative care referral experienced by hematologic oncologists.
Early adulthood body mass index, cumulative smoking, and esophageal adenocarcinoma survival.
Authors: Spreafico Anna , Coate Linda E. , Shen Xiaowei , Zhai Rihong , Xu Wei , Chen Zhen-Fei , Chen Zhuo , Patel Devalben , Brown Catherine , Kuang Qin , Boyd Kevin , Kulke Matthew , Su Li , Mackay Helen , Knox Jennifer J. , Wong Rebecca , Darling Gail , Christiani David C. , Liu Geoffrey
Published: February 2017

10

Background: Little is known about the individual and combined effect of early-adulthood obesity and cumulative smoking on the survival of esophageal adenocarcinoma (EAC) patients. Methods: We analyzed two independent cohorts of EAC patients: 235 patients from Toronto, Canada (TO, 2006-2011) and 329 patients from Boston, USA (BO,1999-2004). Associations between early adulthood body mass index (EA-BMI) and smoking with overall survival (OS) were assessed using Cox proportional hazard models, adjusted for stage, treatment, and other relevant covariates. Results: Median age (range) for TO dataset was 64(29-88)yrs; for BO dataset, 64(21-91)yrs. Males comprised 86% of TO and 89% of BO datasets. 90% of TO and 98% of BO patients were Caucasians. The Median (range) for packyears was 34 (0.2-118; TO) and 34 (0.2-212; BO). The Median (range) for EA-BMI was 24(15-44; TO) and 24(15-47; BO). Median BMI 1 yr prior to diagnosis was 25(16-43; TO) and 25(20-49; BO). 92% of TO and 88% of BO patients had ECOG 0 or 1. Disease stage distribution (early/locally-advanced/metastatic) was 11%/64%/25% (TO) and 30%/52%/18% (BO). For TO, the aHR for smoking was 1.03 (95%CI: 1.02-1.04; p=8E-08) per packyear, while for BO, smoking also independently conferred worse OS, with aHR of 1.007 (95%CI: 1.002-1.01; p=0.003) for each packyear increase. The aHRs for being underweight (EA-BMI<18.5), overweight (EA-BMI 25-30), and obese (EA-BMI>30) in early adulthood were 2.19 (95%CI: 1.0-4.6), 1.89 (95%CI:1.2-3.0), and 2.49 (95%CI:1.5-4.2), respectively for the TO dataset (global p=0.003 for EA-BMI). In BO, the corresponding values were 1.30 (95%CI: 0.8-2.2), 1.45 (95%CI: 1.0-2.5), and 2.39 (95%CI:1.5-3.8), respectively (global p=0.002). In contrast, BMI at one year prior to diagnosis had no association with OS in either study. Conclusions: Elevated BMI in early adulthood and heavy cumulative smoking history are independently associated with increased mortality risk in two North American EAC populations. These survival differences may reflect comorbidity differences, biological differences or both, and offer insight into how key modifiable behaviors in prevention can also affect cancer prognoses. AS, LC, DCC and GL contributed equally.
Effect of body mass index on operative complications after robotic-assisted Ivor-Lewis esophagogastrostomy: Retrospective analysis of 133 cases at a single high-volume tertiary care center.
Authors: Thau Matthew R. , Strom Tobin Joel Crill , Almhanna Khaldoun , Saeed Nadia , Hoffe Sarah E. , Shridhar Ravi , Karl Richard C. , Meredith Kenneth L.
Published: February 2017

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Background: The impact of body weight on robotic-assisted surgical morbidity has not been studied in esophageal cancer. We thus examined operative outcomes in patients according to their body mass index (BMI) following robotic-assisted Ivor-Lewis Esophagogastrostomy (RAIL) at a high-volume tertiary-care referral cancer center and evaluated the safety of robotic surgery in patients with an elevated BMI. Methods: We retrospectively studied patients who underwent RAIL for pathologically confirmed malignancy in the distal esophagus and assessed morbidity and intraoperative outcomes relative to BMI. We evaluated operative complications from surgery to discharge, including average operating time, estimated blood loss (EBL), pneumonia, atrial fibrillation, pulmonary embolism, deep vein thrombosis, wound infection, and surgical leaks. Median ICU days after surgery and 30 day operative mortality was assessed. Wilcoxon Rank-Sum and Spearman Coefficient were used. Results: Of 134 total patients, 106 were male and 28 were female, with an average age of 67 years. Among patients, 76% (N=102) received neoadjuvant therapy. According to BMI, 3 patients were underweight, 35 were normal weight, 62 were overweight, and 34 were obese. All patients had R0 resection, with a median of 19 lymph nodes removed. Among evaluated surgical complications, anastomotic leak rate was significantly higher in patients with high BMI (p=0.01). Median operating time was 407 mins and EBL was 150cc. High BMI was significantly associated with increased operation time and EBL (p=0.01 & p=0.05, respectively). Conclusions: This retrospective study shows that patients with distal esophageal cancer and an elevated BMI undergoing RAIL have increased operative times and EBL during the procedure. An elevated postoperative risk for anastomotic leak also exists and must be carefully monitored. However, BMI does not affect the quality of oncological resection as determined by the number of harvested lymph nodes and rates of R0 resection, suggesting similar outcomes irrespective of BMI among all patients undergoing RAIL at a high volume tertiary center.
Phase II trial of S-1 plus split cisplatin (SSP) in patients with advanced gastric cancer (HGCSG0702): Final report.
Authors: Yuki Satoshi , Komatsu Yoshito , Fukushima Hiraku , Sasaki Takahide , Kobayashi Yoshimitsu , Harada Kazuaki , Dazai Masayoshi , Sogabe Susumu , Miyagishima Takuto , Ishiguro Atsushi , Takahata Takenori , Sato Atsushi , Kudo Mineo , Kato Sosuke , Kato Kanji , Iwanaga Ichiro , Ehira Nobuyuki , Uebayashi Minoru , Sakata Yuh
Published: February 2017

113

Background: On the basis of SPIRITS trial, S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with advanced gastric cancer (AGC) in Japan (Koizumi W, et al. Lancet Oncol, 2008). However, conventional S-1 plus cisplatin (60mg/m2) regimen requires hospitalization for hydration. Therefore, we conducted phase II trial of S-1 plus split Cisplatin (SSP) for outpatient chemotherapy. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 75, ECOG performance status (PS) of 0 to 1; adequate organ function; and written informed consent. S-1 (40 mg/m2) was given orally, twice daily for 21 days, and cisplatin (30 mg/m2) was given intravenously on day 1 and 15, followed by 2-week rest period, within a 5-week cycle. Primary endpoint was the response rate (RR), and secondary endpoints were progression-free survival, overall survival, safety profile, and non-hospitalized survival. Results: Between Mar 2008 and Mar 2012, 40 pts were enrolled. Patients characteristics were as follows: median age 63 years (range 41-75), Male: female 30:10, PS 0:1 33:7, diffuse: intestinal 23:17. Median number of cycles was 3. The main grade 3-4 AE were neutropenia (37.5%), anemia (30%), anorexia (30%) and fatigue (15%). These toxicities were safely managed. The median relative dose intensity of S-1 was 0.782, and cisplatin was 0.824. Response rate was 57.5% (95%CI 42.2-72.8%) and disease control rate was 90.0%. Median progression-free survival was 6.1 months (95%C.I. 3.0-9.1 months) and median survival time was 15.8 months (95%C.I. 12.7-18.8 months). Conclusions: SSP showed comparable tolerability and efficacy to SPIRITS trial. In addition, most patients underwent the treatment without hospitalization. SSP may be one of practical alternatives for AGC.
Evaluation of PET response to neoadjuvant therapy for patients with gastric and GEJ adenocarcinoma.
Authors: Hernandez Jonathan M. , Beylergil Volkan , Goldman Debora , Schöder Heiko , Gonen Mithat , Tang Laura H. , Downey Robert J. , Shah Manish A. , Strong Vivian E. , Coit Daniel G.
Published: February 2017

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Background: The implications of response to neoadjuvant treatment as measured by PET remain poorly defined for patients with gastric and gastro-esophageal junction (GEJ) adenocarcinoma. Our aims are to determine if changes in PET avidity correlate with histologic response, and to determine the best predictor(s) of disease-free survival (DFS) and overall survival (OS). Methods: We reviewed a prospective database to identify patients with gastric and GEJ adenocarcinoma who were evaluated with PET imaging prior to andfollowing neoadjuvant treatment. Spearman correlation and Cox proportional hazards were utilized. Results: Since 2002, 216 patients of median age 63 years met our criteria. At last follow-up (median 22 months, range: 0 - 119), 118 patients recurred or died. The median DFS and OS for expired patients were 7.5 months (range: 0-62) and 14 months (range: 0 - 69), respectively. Between baseline and follow-up PET imaging (median 63 days, range: 15 - 454), 170 patients were treated with chemotherapy and 46 patients with chemoradiotherapy. The median change in SUV was 43% (range: -300 - 100.0%) and the median histologic tumor response was 50% (range: 0 - 100%). No association was identified with the use of chemoradiation (as compared to chemotherapy alone) and change in SUV (p=0.8). We identified a significant relationship between change in SUV and histologic response (r=0.32, p<0.01). Furthermore, the change in SUV was related to both DFS and OS on univariate analysis, as was tumor response and pathologic stage (Table). On multivariate analysis only pathologic stage, and specifically the presence of lymph node metastases, was related to DFS (p<0.01) or OS (p<0.01). Conclusions: Following neoadjuvant therapy for gastric and GEJ adenocarcinoma, PET response is prognostic, although pathologic nodal status is the best predictor of outcome. [Table: see text]
Implications for the American Joint Committee on Cancer staging systems on esophageal squamous cell cancer patients receiving multimodality therapy.
Authors: Nomura Motoo , Abe Tetsuya , Komori Azusa , Narita Yukiya , Uegaki Shiori , Nitta Sohei , Yamaguchi Kazuhisa , Taniguchi Hiroya , Kawai Ryosuke , Uemura Norihisa , Kadowaki Shigenori , Takahari Daisuke , Ura Takashi , Andoh Masashi , Niwa Yasumasa , Shinoda Masayuki , Muro Kei
Published: February 2017

123

Background: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system is based on pathologic data from esophageal cancers treated by surgery alone. The objective of this study was to evaluate the prognostic impact of the pretreatment clinical stage (cTNM) and posttreatment pathologic stage (ypTNM) on esophageal cancer patients undergoing neoadjuvant chemotherapy followed by surgery (NAC-S). Methods: Information on 245 consecutive esophageal squamous cell carcinoma patients undergoing NAC-S was reviewed. Data collected included demographics, cTNM, ypTNM, and survival. Statistical methods included the Cox regression model, Akaike information criterion (AIC) within the Cox proportional hazard regression model, and Kaplan-Meier analyses. Results: The overall three-year survival rate was 67.6%. There were significant differences between stages II and III in cTNM and ypTNM stage, respectively (P < 0.01, respectively). There were no significant survival differences between stages I and II, between stages III and IV in each TNM stage. For all patients, cN stage (cN0 vs. cN1-3), ypT stage (ypT0-2 vs. ypT3-4), ypN stage (N0 vs. N1-3), and ypM stage were independent prognostic factors by multivariate analysis (P< 0.05). Compared with cTNM stage, ypTNM stage has a smaller AIC value, which described the optimum prognostic stratification. Conclusions: Our study indicates that the ypTNM stage of the 7th edition of AJCC staging system has better performance than the cTNM stage in patients undergoing NAC-S.
Impact of Hispanic ethnicity on the clinical presentation and survival of esophageal and gastric cancer in south Florida.
Authors: Palacio Sofia , Sussman Daniel A. , Ardalan Bach , Rocha Lima Caio Max S. , Hosein Peter Joel
Published: February 2017

125

Background: Race and ethnicity are associated with differences in survival among patients with esophageal and gastric cancer (EGC); outcomes are better in Asian patients but worse for African-Americans compared to Caucasians and Asians. Limited data exist for Hispanics (Hisp) compared to non-Hispanic whites (NHW) or African-Americans (AA). Because of the large Hisp population in South Florida, we compared the clinical presentation and survival of patients with EGC by race and ethnicity. Methods: Using a cross-sectional study design, this IRB-approved analysis of the Florida Cancer Data System database identified all patients diagnosed at the University of Miami and Jackson Memorial Hospital between January 2000 and December 2012 with squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus, and adenocarcinomas of the gastro-esophageal junction (GEJ) or stomach (STO). Demographic, treatment and survival data were extracted from the registry. Survival was analyzed using the Kaplan-Meier method and variables associated with survival were analyzed using a Cox proportional hazards model. Results: Data from 2,170 patients were available; 44% were Hisp, 19% AA and 38% NHW. Compared to NHW's and AA's, Hisp's were more likely to have the following features: male gender, advanced age at cancer diagnosis, esophageal site of malignancy, adenocarcinoma histology, earlier stage at presentation, history of smoking and alcohol use, private insurance, surgical resection and receipt of chemotherapy (p < 0.001 in each case). Hisp were less likely to have STO (p<0.001). In a multivariate model, race and ethnicity were not independently associated with survival but age, stage, surgical resection and chemotherapy administration were all independently associated with survival (p < 0.01 in each case). Country of birth did not influence results among Hispanic patients. Conclusions: Race and ethnicity were not independently associated with survival in this large registry study. However, significant differences in the tumor location, histology and stage of presentation exist, and further studies to elucidate the biological or environmental reasons for these disparities are warranted.
Freedom from recurrence after induction cisplatin/5-FU/RT versus carboplatin/paclitaxel/RT in patients with esophageal cancer.
Authors: Thomay Alan Adolph , Su Stacey , Friedant Adam J. , Ruth Karen J. , Astsaturov Igor A. , Burtness Barbara , Denlinger Crystal Shereen , Dotan Efrat , Hall Michael J. , Meyer Joshua E. , Shah Prashant C. , Cohen Steven J. , Scott Walter J.
Published: February 2017

126

Background: The optimal neoadjuvant treatment regimen for esophageal cancer has yet to be defined. Methods: We analyzed a prospective database of esophageal cancer patients treated with cisplatin/5-FU/RT (A) or carboplatin/paclitaxel/RT (B) then esophagectomy. Endpoints were pathologic response (pCR), recurrence, and overall survival. Covariates (age, gender, clinical stage, Charlson comorbidity index (CCI), and ECOG PS) were adjusted via propensity score weighting from logistic regression. Differences in survival curves were compared using weighted Kaplan Meier methods and Wilcoxon tests. Landmark analysis compared differences in outcomes at least six months after surgery. Results: From January 2008 to June 2013, 71 patients received induction RT (50.4 Gy), with 38 and 33 patients in groups A and B, respectively. Patient demographics were similar (Table 1). Operative procedure, R0 resections, and operative complications did not differ (operative mortality 1/71, 1.4%; anastomotic leak rate 10% A vs. 9% B, p=1.0). Median follow-up was 18.2 and 9.1 months for groups A and B, respectively. There was no difference in overall survival (p=0.88) or total number of recurrences (11/38, 29% A vs. 10/33, 30% B). Landmark analysis revealed a difference in recurrence at least 6 months after surgery: time to recurrence was shorter in group B (median time to recurrence 31 mos A vs. 18 mos B, p=0.02). pCR was seen in 13/38 (34%) A and 9/33 (27%) B (p=0.53). In patients with pCR, there was a trend toward more recurrences in group B (2/13, 15% A v 4/9, 44% B, p=0.14). Conclusions: Six months after surgery patients receiving induction carboplatin/paclitaxel/RT had shorter time to recurrence compared to cisplatin/5-FU/RT. In those with pCR a trend towards increased distant recurrences was seen with carboplatin/paclitaxel/RT, which may have less systemic efficacy in esophageal cancer than cisplatin/5-FU/RT. This should be evaluated in larger series. [Table: see text]
Survival outcomes of schirrhus gastric cancer treated by multidisciplinary treatments: Putative impact on prognosis by DCS NAC.
Authors: Yamashita Keishi , Hosoda Kei , Katada Natsuya , Moriya Hiromitsu , Mieno Hiroaki , Kikuchi Shiro , Watanabe Masahiko
Published: February 2017

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Background: Among gastric cancer, schirrhus exhibited the poorest prognosis, and many patients die even after curative resection due to recurrence. Although progress of multidisciplinary treatments of advanced gastric cancer is outstanding, recent clinical outcome is obscure by such intensive treatments. Methods: Among the 5,664 gastric cancer patients who underwent gastrectomy between 1971 and 2013 in the Kitasato University Hospital, 287 of shirrhus gastric cancer were included (5%). We divided the total periods into early (1971-2004) and late period (2005-2013), and compared their prognosis. Multivariate proportional hazard model was applied to the significant univariate prognostic factors (p<0.05), and identified independent prognostic factors (IPFs). Finally we compared the IPFs in terms of periods, and discuss the most appropriate treatments. Results: (1) Five-year survival rate was 13% and 31% in the early and late periods, respectively (p=0.0010). Between the periods, there were significant differences of pT (p=0.013), CY (p<0.0001), and Margin status (p=0.041). (2) Univariate prognostic factors were age (p=0.032), pT (p=0.0009), pN (p<0.0001), P (p=0.0033), CY (p=0.0002), and Margin status (p<0.0001). Multivariate proportional hazard model elucidated IPFs of pN (pN0-2 vs pN3a-X, p<0.0001) and Margin status (positive vs negative, p=0.0003). If the 2 factors were combined, patients with pN0-2 plus margin negative showed much better survival (about 40% of 5-year OS) than otherwise cases (below 10%)(p<0.0001). (3) Comparison of the IPFs between early and late periods, margin positive cases were significantly less infrequent in the late period. This may be aggressive application of neoadjuvant chemotherapy of DCS (Docetaxel/CDDP/S1). Conclusions: Due to recent progress of multidisciplinary treatments of preoperative aggressive chemotherapy and surgery with curative intent for negative margin for schirrhus gastric cancer, its 5-year survival was dramatically improved. pN0-2 patients were promising for reasonable prognosis if negative margin is secured, so intraoperative diagnosis must be urgently developed.
Utility of the OSNA assay in sentinel node mapping for early gastric cancer.
Authors: Takeuchi Hiroya , Nishi Tomohiko , Nakamura Rieko , Takahashi Tsunehiro , Wada Norihito , Kawakubo Hirofumi , Saikawa Yoshiro , Omori Tai , Kitagawa Yuko
Published: February 2017

13

Background: Recent studies on sentinel node (SN) mapping for early gastric cancer have shown acceptable results in terms of detection rate and accuracy to determine lymph node (LN) status. Accurate detection of nodal metastasis including micrometastasis during surgery is indispensable for clinical application of minimized gastrectomy based on SN mapping and biopsy. However, histopathological diagnosis of micrometastasis using frozen sections has to be considered as limitations for intraoperative pathology. We hypothesized that one-step nucleic acid amplification (OSNA) assay may allow the PCR-based intraoperative diagnosis to be applicable to SN mapping for early gastric cancer. Methods: A prospective study of SN mapping using the OSNA (One-step nucleic acid amplification) assay has been conducted for patients with cT1N0M0 gastric cancer at our institution. All SNs and randomly selected non-SNs were examined by routine histopathological diagnosis and the OSNA assay. Results: Histological examination was performed in in 1,732 LNs (286 SNs and 1,446 non-SNs) from 43 patients with cT1N0M0 gastric cancer. We also evaluated 439 LNs (286 SNs and 153 non-SNs) with histological examination and the OSNA assay from the 43 patients. Histological LN metastasis was revealed in 6 (14.0%) of 43 patients. All (100%) of the 6 patients with LN metastasis showed positive SNs by histological examination. The diagnostic accuracy to predict the LN status based on SN concept by histological examination was 100%. The concordance rate between the OSNA assay and the histological examination of paraffin specimens was 0.970 (95 % CI, 0.950–0.984). Discordant results were observed in 13 LNs (3.0 %). Sensitivity and specificity of the OSNA assay compared to the histological examination were 0.636 (95 % CI, 0.407–0.828) and 0.988 (95 % CI, 0.972–0.996), respectively. The OSNA assay to evaluate the SNs status was comparable with intraoperative pathological diagnosis of frozen sections of SNs in terms of concordance rate (0.981), sensitivity (0.800) and specificity (0.995). Conclusions: Our results suggest that the OSNA assay may be a useful tool for the intraoperative detection of metastasis in SNs for patients with early gastric cancer.
Survival impact of esophagectomy after chemoradiation for adenocarcinoma of the esophagus.
Authors: Shridhar Ravi , Freilich Jessica , Hoffe Sarah E. , Almhanna Khaldoun , Fulp William J. , Yue Binglin , Meredith Kenneth L.
Published: February 2017

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Background: To determine the impact of esophagectomy on survival in patients with adenocarcinoma (AC) of the esophagus cancer after chemoradiation (CRT). Methods: A database of esophageal cancer was queried for nonmetastatic patients with AC treated between 2000 and 2011 with CRT. Overall survival (OS) and recurrence-free survival (RFS) curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. Results: We identified 154 patients (60 without surgery; 94 with surgery) who were included in the analysis. The only differences between the 2 groups were more advanced stage and younger age in the surgery group. Patients undergoing surgery had significantly higher survival. Median and 5 year OS for surgical patients was 4.1 years and 43.6% versus 1.9 years and 35.6% for non surgical patients (p=0.007). MVA for OS and DFS revealed that factors associated with increased survival were surgical resection, tumor length <5 cm, male gender, and lower stage. Age, tumor location, radiation dose/technique, and induction chemotherapy were not prognostic. There was a trend towards improved survival on univariate analysis (p=0.10) and MVA (p=0.063) for surgery patients compared to non-surgical patients who were healthy enough for surgery pre-CRT (n=38), and no difference in OS in nonsurgical patients healthy enough for surgery post-CRT (n=22). Conclusions: Esophagectomy after CRT dramatically improves survival in patients with AC after CRT. Trimodality therapy should continue to remain the standard of care for esophageal AC. However, surgery should be performed at high volume centers.
Clinical response to neoadjuvant therapy to predict success of adjuvant chemotherapy for esophageal adenocarcinoma.
Authors: Tam Vernissia , Hooker Craig M. , Molena Daniela , Hulbert Alicia , Lee Beverly , Kleinberg Lawrence , Yang Stephen C. , Forastiere Arlene A. , Brock Malcolm
Published: February 2017

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Background: Evidence informing current guidelines advising postoperative chemotherapy following trimodality therapy for esophageal cancer are limited. Our objective was to identify patients with locally advanced esophageal adenocarcinoma treated with trimodality therapy who may benefit from adjuvant chemotherapy. Methods: A single institution retrospective study was performed in 308 patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation followed by surgery between 1989-2012. Kaplan-Meier analysis compared postoperative survival by clinical response to trimodality therapy and the use of adjuvant chemotherapy. Cox proportional hazards regression models estimated the association of adjuvant chemotherapy with survival. Results: After trimodality treatment, 93 out of 308 patients(30%) received adjuvant chemotherapy. Partial response to trimodality treatment was observed in 150(48%) patients; 50 of whom received adjuvant therapy. The median survival for partial responders who received adjuvant therapy vs. those receiving trimodality therapy alone was 53.2 vs. 27.6 months, respectively (p=0.047). Patients with complete response or no response to trimodality therapy showed no difference in median survival with the addition of adjuvant chemotherapy. Univariate Cox regression revealed a 26% decrease in relative hazard for long-term survival amongst patients who received adjuvant chemotherapy compared to no adjuvant therapy (HR=0.74, 95% CI 0.55-0.98). This association remained stable after adjusting for clinical response to trimodality therapy, age, and ASA score (aHR=0.75, 95% CI 0.55-1.01). Conclusions: Adjuvant therapy for patients with locally advanced esophageal adenocarcinoma was associated with a 26% decrease in relative hazard for mortality compared to trimodality treatment alone. Long-term survival following adjuvant therapy was dependent on initial response to trimodality therapy. Partial responders may benefit most from adjuvant chemotherapy.
Risk factors that affect continuation of S-1 chemotherapy as an adjuvant setting after radical gastrectomy for gastric cancer.
Authors: Kobayashi Daisuke , Tanaka Chie , Iwata Naoki , Kanda Mitsuro , Yamada Suguru , Nakayama Goro , Fujii Tsutomu , Sugimoto Hiroyuki , Koike Masahiko , Nomoto Shuji , Fujiwara Michitaka , Kodera Yasuhiro
Published: February 2017

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Background: Based on the evidence from ACTS-GC trial, postoperative S-1 administration for 12 months is the current standard of care in Japan for patients with pathological Stage II/III gastric cancer treated with D2 gastrectomy. However, the proportion of patients who actually tolerated 12 months of treatment in the ACTS-GC trial was 65.8%. In the present study, we explored the risk factors that could affect the compliance of S-1 adjuvant therapy. Methods: This retrospective study selected 68 consecutive patients who underwent curative gastrectomy for gastric cancer and received S-1 chemotherapy at our institution between 2003 and 2012. Associations between S-1 compliance, adverse effects and clinical characteristics were analyzed. Results: 51 patients were male, and 17 were female. Patient age ranged between 20 and 80 years (median: 64.0). 47 patients (69%) completed the prescribed S-1 treatment for 1 year. In addition, 5 patients discontinued treatment due to recurrence within 1 year, and 3 patients due to reasons irrelevant to the S-1 toxicity. These 55 patients were designated as non-AE group. The remaining 13 patients (19%) were obliged to discontinue S-1 due to adverse effects within 1 year (AE group). The percentage of female was higher in the AE group (46% versus 20% in the non-AE group). The median age of patients was significantly higher in the AE group (72 versus 63 in the non-AE group, p=0.004). Although there was no difference in the serum creatinine level at the beginning of the treatment, creatinine clearance (CCr) of AE group was significantly lower at 65 mL/min (83 mL/min for the non-AE group, p=0.04). Median body weight loss during the first 3 postoperative months in the AE group (13% of the original weight) was significantly higher (10% in the non-AE group, p=0.04), although the median body weight before treatment didn’t differ between the two groups. Dose reduction was more diligently conducted among the population with CCr< 60 in the non-AE group (4/7) than in the AE group (1/5). Conclusions: Female, old age, low CCr and greater body weight loss affect compliance of the S-1 adjuvant chemotherapy. Meticulous dose modification is required for those with risk for discontinuation.
Phase I study of biweekly docetaxel, cisplatin, and S-1 combination neoadjuvant chemotherapy for stage III gastric cancer.
Authors: Kunisaki Chikara , Makino Hirochika , Kimura Jun , Oshima Takashi , Ota Mitsuyoshi , Takagawa Ryo , Kosaka Takashi , Akiyama Hirotoshi , Endo Itaru
Published: February 2017

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Background: It is unclear neoadjuvant chemotherapy for stage III gastric cancer can provide satisfactory outcomes. Therefore, we conducted a phase I study to clarify recommend dose (RD) of biweekly docetaxel, cisplatin, and S1 combination neoadjuvant chemotherapy for stage III gastric cancer. Methods: A dose escalation method was employed. S1 (80mg/m2/day; day1-7, 15-21) and docetaxel (20mg/m2/day; day1, 15) were fixed and cisplatin (day1, 15) was increased by 5mg/m2 from level I (20mg/m2/day). Each course was lasted for one month. Toxicity was examined by the CTCAE version 4.0 during two courses. Results: A total of 21 patients (male/female=14/7, mean age=63 years) was enrolled in this study. Of these, nine stage IIIA, nine stage IIIB, and three stage IIIC were included. In level I, There was no DLT case. In level II, we encountered perforation of gastric cancer in one case without any other DLT in the remaining five cases. In level III, IV, V, and VI, we did not encounter any cases with DLT. So, we decided that the RD of cisplatin was 50mg/m2/day (Level VI), which is regarded as maximum safety dose in the outpatient clinic. Response status was as follows: one PR case, 19 non CR/non-PD cases and one PD case. Total gastrectomy was performed in 14 cases, and distal gastrectomy in seven cases. Histologically, grade 1a was found in 13 cases, grade 1b in three cases, grade 2 in four cases, and grade 3 was one case. Five cases (23.8%) suffered from postoperative complications (two anastomotic leakage; one pneumonia; one pancreatic fistula; one chyloascites) although all cases recovered conservatively. Conclusions: RD of cisplatin was 50mg/m2/day in biweekly docetaxel, cisplatin, and S1 combination neoadjuvant chemotherapy for stage III gastric cancer. Phase II study is now going on to confirm the usefulness of this treatment.
Combining cetuximab with FOLFOX regimen as the first-line therapy of KRAS wild-type advanced gastric cancer.
Authors: Yeh Yung-Sung
Published: February 2017

157

Background: Gastric cancer is one of the most common cancers worldwide with a high incidence in Asian countries, including Taiwan. For patients with recurrent or non-resectable advanced gastric cancer (AGC), chemotherapy or the combination of target and chemotherapy was chosen for therapy in AGC patients. We prospectively analyzed the safety and efficacy of cetuximab combined with FOLFOX4 as the first-line setting in patients with AGC. Methods: From January 2010 to January 2013, a total of 20 patients with histologically confirmed unresectable advanced/recurrent gastric cancer were enrolled into this study. Direct sequencing of KRAS mutation status was performed before the treatment. All patients received cetuximab 500 mg/m2every 2 weeks, and chemotherapy was administered with FOLFOX regimen of oxaliplatin at 85 mg/m2 plus leucovorin 200 mg/m2 on the first day of treatment, followed by 5-fluorouracil (5-FU) via a 24-hour continuous infusion of 1000 mg/ m2 5-FU on days 1-2 biweekly. Therapy was continued until disease progression or intolerable adverse events or receiving surgical resection. Results: All tumor tissues of 20 AGC patients were KRAS wild-type. With the median therapy of 6 cycles (4-8 cycles), clinical efficacy, according to RECIST criteria, showed an overall response rate of 55% (11/20), and 20% (4/20) of patients exhibited stable disease as well as 25% (5/20) who had progressive disease. Radical resection could be obtained in 30% (3/10) of unresectable patients as the neoadjuvant therapy. The median time to progress (TTP) was 8.3 months and the median overall survival (OS) was 12.2 months. The grade III-IV adverse events was observed in 4 of 20 (20%) patients, including 15% of neutropenia (3/20), 5% of skin rash (1/20), 10% of nausea and vomiting (2/20) as well as 15% of asthenia (3/20). Conclusions: Cetuximab combined with FOLFOX as the first-line therapy for KRAS wild-type AGC patients appears to have favorable efficacy and safety, and the possibility of conversion to radical resection. Grade 3-4 adverse events were relatively uncommon. Despite this preliminary favorable outcome; however, a long-term result and large scale clinical trial is mandatory to verify it.
Prospective trial of proton reirradiation of locally recurrent esophageal cancer.
Authors: Berman Abigail T. , Fernandes Annemarie Therese , Both Stefan , Varillo Kristi , Ben-Josef Edgar , Metz James M. , Plastaras John Peter
Published: February 2017

159

Background: Local recurrences of esophageal cancer occur in approximately 25% of patients and cause significant morbidity. Their treatment after esophagectomy and chemoradiation is particularly challenging. A second course of radiotherapy in a previously radiated field carries the risk of radiation-induced tissue injury. Proton therapy (PRT) may offer an advantage in the re-irradiation setting due to the lack of exit dose and potential sparing of normal tissues. Methods: Between 6/2011 and 8/2013, 10 adult patients (pts) with locally recurrent esophageal cancer, initially cT1b-T4N0-1, in or near prior treatment fields began reirradiation. Toxicity was graded according to the Common Toxicity Criteria version 4.0. Acute toxicity was defined as occurring within 90 days from start of PRT. Results: The median follow-up was 7.9 months (1-23) from the start of retreatment, and 15 months (2.4-27.8) from the development of local recurrence. Mean age was 70 (53-91). ECOG PS was 0 (n=4), 1 (4), 2 (2). Eight pts had intraluminal and two had paratracheal nodal recurrences. Eight of the pts had adenocarcinoma and two squamous cell carcinoma. Median CTV size was 138 cc (32-390). Seven received concurrent chemotherapy. The median total dose was 54.0 Gy (50.4-61.2); all pts were treated with PRT exclusively (9 double scatter and 1 uniform scanning), except for two pts who were treated with 15-30% IMRT. The median prior dose was 55.8 Gy (45-70). The median interval between radiation courses was 31.4 mos (12-105). Maximum acute toxicity was grade 2 (30%), 3 (30%), and 4 (40%). Of the grade 4 toxicities, one was an esophagopleural fistula and respiratory failure unlikely related to RT, and 3 were neutropenic toxicities possibly related to RT. Three pts developed metastatic disease at a median of 28 mos after starting RT. Three pts developed in-field locoregional recurrence at a median of 13 mos. Five pts died after a median of 13 mos. Conclusions: Preliminary results using PRT for reirradiation of esophageal cancers shows that local control can be achieved in a large proportion of pts with moderate but acceptable acute toxicity. Further follow-up on these pts is needed to assess the long-term utility of PRT reirradiation. Clinical trial information: NCT01126476.
Correlation of pretreatment nuclear GLI-1 labeling indices (LIs) with initial SUV (iSUV) in esophageal cancer (EC) patients undergoing trimodality therapy (TMT): A potential pathway to esophageal preservation.
Authors: Wadhwa Roopma , Wang Xuemei , Izzo Julie , Skinner Heath D. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Ross William A. , Hofstetter Wayne Lewis , Maru Dipen M. , Rice David C. , Sudo Kazuki , Shiozaki Hironori , Blum Mariela A. , Chen Qiongrong , Jin Jiankang , Song Shumei , Baladandayuthapani Veera , Ajani Jaffer A.
Published: February 2017

18

Background: For the purpose of understanding clinical behavior of EC, imaging and biomarkers have not been correlated. We attempted to correlate iSUV with a variety of biomarkers (NF-kB, SHH, ALDH1, ABCB1, survivin, and BCRP) including pre-treatment nuclear Gli-1 LIs in patients with EC who had undergone TMT. Methods: 128 patients were analyzed. The iSUV and pre-treatment nuclear Gli-1 LIs were assessed among others. Post-treatment residual cancer status in the resected specimen was also correlated (P0=0% residual cells, P1=1-50% residual cells, and P2=>50% residual cells) with iSUV and nuclear Gli-1 LIs. The Kruskal-Wallis test was performed to find correlations between (1) iSUV and P status; and (2) between nuclear Gli-1 LIs and P status. Results: The Pearson’s correlation coefficient between iSUV and nuclear Gli-1 LIs was 0.21 (p = 0.02). Pre-treatment nuclear Gli-1 LIs were strongly associated with the P status (p<0.0001) but iSUV was not (as has been reported in the literature; PMID: 17532577, 23247658, and 23994746). iSUV, most likely, is not correlative with the P status because of its narrow range compared to that of nuclear Gli-1 LIs.Conclusions: Our data, for the first time, demonstrate that iSUV can be a surrogate for pre-treatment nuclear Gli-1 LIs in EC. This correlation can be exploited in the development of predictive strategies for esophageal preservation. Pre-treatment nuclear Gli-1 is a strong candidate for the biomarker-based predictive model(s). From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. Supported by UTMDACC Multidisciplinary Research Grants, CA138671, CA172741, and CA129926 From the NCI (JAA), and Generous Donors. [Table: see text]
Utility of PET/CT as initial staging work up for early pancreatic cancer.
Authors: Prithviraj Gopi Kesaria , Kothari Nishi , Yue Binglin , Kim Jongphil , Springett Gregory M. , Malafa Mokenge Peter , Hodul Pamela Joy , Kim Richard D.
Published: February 2017

183

Background: In pancreatic cancer, early detection and complete surgical resection with negative margins offers the only cure for the disease. Work up to evaluate resectability includes triple phase helical scan CT of the pancreas and endoscopic ultrasound (EUS). A paucity of data exists in using PET/CT scan as staging work up in early resectable pancreatic cancer. The objective of our study was to determine if PET/CT prevents futile laparotomy by detecting occult metastatic disease in patients with resectable/borderline pancreatic cancer. Methods: We looked at our institutional PET/CT data base incorporating National Oncologic PET Registry (NOPR) with diagnosis of resectable or borderline pancreatic cancer from 2005-2012. Clinical, radiographic, and pathologic follow-up was evaluated, including age, gender, evidence of metastatic disease, and initial CA 19–9 levels. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT. The confidence interval was computed using the exact binomial distribution. The effect on the change was evaluated by the multiple logistic regression model. The final model was selected using the backward elimination method. Results: 287 patients with early stage (resectable or borderline) pancreatic cancer who received PET/CT as part of initial staging workup were identified. Upon initial work up (CT + EUS), 62% of patients were considered resectable and 38% were borderline resectable. However, PET/CT findings changed the management in 11.9% (n=34) of patients (95% CI: 0.084 – 0.162). 33 patients were upstaged to stage IV and 1 patient was upstaged to stage III. Median time from CT to PET/CT was 5 days. Metastatic lesions were confirmed with biopsy in 21 patients. The proportion in the change in treatment plan is significantly higher in patients who were borderline resectable (p=0.005; OR=2.94; 95% CI: 1.38 – 6.26). In 204 patients who were taken to surgery, 17.7% (n=36) were found to have metastatic disease intraoperatively. Conclusions: PET/CT helped improve detection of occult metastases, ultimately sparing these patients a potentially unnecessary operation. The role of PET/CT scan should be validated in prospective study.
Association of adiponectin in patatin-like phospholipase domain-containing 3 (PNPLA3) associated hepatic steatosis.
Authors: Beg Muhammad Shaalan , Singal Amit G. , Ayers Colby , Saleem Sadia , Marrero Jorge A. , Yopp Adam C. , Scherer Philipp , Turer Aslan
Published: February 2017

184

Background: The I148M polymorphism (rs738409) of the patatin-like phospholipase domain-containing 3 (PNPLA3) gene is strongly associated with hepatic triglyceride content (HTGC) and the development of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), which are themselves risk factors for hepatocellular cancer (HCC). Serum adiponectin affects insulin resistance and carcinogenesis and has also been associated with HTGC. Whether these risk factors are additive in predisposing to HTGC is unknown. We evaluated the impact of adiponectin and PNPLA3 genotypes on HTGC in a large community cohort. Methods: The Dallas Heart Study (DHS) is a multi-ethnic population based study of Dallas County residents. HTGC was quantified using H-MR spectroscopy. Univariate and multivariable logistic and linear regression models were generated to test the association between HTGC and log adiponectin stratified by PNPLA3 genotype (CC, CG and GG). Models were adjusted for age, gender, race, hypertension, diabetes, HOMA-IR and BMI. Results: There were 2,259 patients who had complete clinical, biochemical, imaging, and genotyping data and were included in this analysis. Median age was 44 and 47% were male. Race distribution was 48% Black, 32% White, and 18% Hispanic. The prevalences of PNPLA3 genotypes were 61% CC (wild type), 32% GC and 7% GG. The median concentration of adiponectin was 6.6 ug/ml. Adiponectin was an independent predictor HTCG across all genotypes after adjusting for covariates (CC b=-0.34, GC b=-0.42, GG b=-0.38, p<0.005 for each). HTGC decreased across gender and race-stratified quartiles of adiponectin for each PNPLA3 genotype, and the qualitative effect was greatest in the I148M homozygotes (table). Conclusions: Adiponectin is independently associated with hepatic steatosis across all three PNPLA3 genotypes. The combination of at-risk PNPLA3 genotypes and hypoadiponectemia is associated with a high risk of hepatic steatosis. Future studies will need to address downstream HCC risk and whether manipulation of adiponectin level may be of clinical benefit. [Table: see text]