bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and outcomes of persons with advanced cancer associated with having a family caregiver: A classification tree analysis.
Authors: Dionne-Odom J Nicholas , Raju Dheeraj , Hull Jay , Akyar Imatullah , Lyons Kathleen , Azuero Andres , Frost Jennifer , Bakitas Marie
Published: February 2017

29

Background: Little is known about the impact that having a family caregiver (FCG) has on individuals with advanced cancer. We examined patient characteristics and outcomes most associated with having versus not having a primary FCG. Methods: Secondary data analysis of a randomized controlled trial of an early palliative care intervention (Project ENABLE [Educate, Nuture, Advise, Before Life Ends]) for patients with advanced cancer and their primary FCGs (10/2010-9/2013). Sociodemographic and patient reported outcomes data were abstracted from the baseline questionnaires of 122 patients who enrolled with FCG and 85 patients who enrolled without a FCG. Sociodemographic variables included age, gender, education, race, social support (MSPSS: Multidimensional Scale of Perceived Social Support, score range: 12-84), and Karnofsky Functional status. Patient reported outcomes included symptom impact (QUAL-E Symptom Impact, score range: 4-20), quality of life (QOL) (Functional Assessment of Chronic Illness Therapy-Palliative Care, score range: 0-184), depression (Center for Epidemiological Studies-Depression Scale, score range: 0-60), perceived quality of care (Patient Assessment of Chronic Illness Care, score range: 20-100), and hospital days and emergency department visits in the past 3 months. Structured tree analysis was used to identify a set of variables strongly associated with the presence or lack of a FCG. Results: In the final model, for patients with MSPSS scores <52.5 (N=12), none had a FCG. For male patients with MSPSS scores >52.5 (N=105), 73% (N=77) had a FCG. For female patients with MSPSS scores >77.5 (N=29), 69% (N=20) had a FCG. For female patients with MSPSS scores <77.5 and QOL scores >126.1 (N=25), 20% (N=5) had a FCG. For female patients with MSPSS scores <77.5, QOL scores <126, and depression scores >26 (N=10), 20% (N=2) had a FCG. For female patients with MSPSS scores <77.5, QOL scores <126, and depression scores <26 (N=26), 77% (N=20) had a FCG. Conclusions: The final model suggests that having a FCG is highly associated with having high levels of perceived social support, being male, and lower levels of depression despite having lower QOL.
Likelihood of subsequent chemotherapy after acute rehabilitation in patients with advanced cancer.
Authors: Bromberg Isaac Martin , Knight Louise , Dy Sydney Morss
Published: February 2017

32

Background: Patients with advanced cancer suffer acute declines in their functional status for a variety of reasons, including progression of disease, adverse effects of medical or surgical treatment, and exacerbation of a chronic non-cancer condition. The use of rehabilitation services to improve functional status for patients with advanced cancer has been increasing, but the likelihood that a patient will achieve the goals of continued cancer treatment or extended survival has not yet been demonstrated. Times of transition in a patient’s course of illness present opportunities for discussion of goals of care. Methods: The objective of this study was to determine how often patients who were referred to acute rehabilitation (AR) returned to the cancer center for further chemotherapy. A secondary end-point was length of survival after referral. Records of patients admitted to the medical oncology service of an academic cancer center who were referred to AR between January 1, and December 31, 2012, were retrospectively reviewed for the following information: age, gender, race, primary malignancy type, subsequent chemotherapy, and date of death. Results: A total of 43 individual patients were referred for AR. Of these, 22 (51.2%) were 65 years of age or older, 30 (69.8%) were male, 32 (74.4%) were of white race. Primary hematologic malignancies accounted for 26 (60.5%) of the patients, 12 (27.9%) had non-brain solid primary tumors, and 5 (11.6%) had a primary brain tumor. For the 43 patients who qualified for AR, 33 (76.7%) were transferred to an AR facility, 9 (20.9%) were discharged to home, and 1 (2.3%) died in the hospital prior to discharge. Of those 33 patients who went to AR, 17 (51.5%) received further chemotherapy. Of note, 18 (54.5%) of the patients referred to AR died within 6 months (range 17-158 days), and 22 (66.6%) died within one year. Conclusions: Furthercancer treatment after an acute rehabilitation admission is a reasonable goal for patients with advanced cancer; however, these patients frequently have a limited life expectancy and should be considered for palliative care consultation prior to discharge to ensure a discussion about goals of care, in light of their overall prognosis.
Results from year 1 of an embedded supportive oncology practice.
Authors: Scarborough Bethann , Chai Emily , Holcombe Randall F. , Lee Eric , Goldstein Nathan
Published: February 2017

40

Background: We present the findings from our first year of a Supportive Oncology practice embedded in a quaternary care center’s outpatient cancer practice. Methods: One palliative medicine physician saw patients 4 days per week. Oncologists made referrals for symptom management, psychosocial support, advance care planning, or by predetermined triggers for palliative care. Results: 239 patients were referred for a total of 821 visits. Palliative care referrals increased over time; 0.6% of the cancer center’s patients were referred in the first quarter and 1.5% were referred in the third quarter. Referral reasons included symptom management/support (90%), goals of care (5%), or triggers (6%). Six to 9 symptoms were addressed at 41% of visits. Sixteen percent of patients initially referred for symptoms were later seen for conversations regarding goals of care. Of these patients, 76% discussed goals of care with their oncologist, 61% were referred to hospice and 47% enrolled in hospice. Supportive oncology visits were associated with decreased health care utilization, with a downward trend in Emergency Department visits (0.82 vs. 0.72 per patient) and inpatient admissions (0.91 vs. 0.84 per patient) after the initial palliative care visit compared to use before the visit. Approximately 17% of all Supportive Oncology patients enrolled in hospice. Conclusions: Our first year of an embedded palliative care practice focused on building collaborative relationships. The steady referral growth over time indicates that oncologists increasingly accepted the program. While only a small proportion of patients were referred, the high visit complexity reflects this population’s acuity. Decreased health care utilization may be due to better symptom control or care aligned with patients’ values. Early referrals for symptom management facilitate goals of care discussions later on, and the importance of delivering a unified message on treatment options is seen in the hospice referral rate of 61% for the subset of patients who discussed goals of care with palliative care and oncology. Embedding palliative care in oncology fosters expert symptom management, seamless communication, and trusting relationships between oncologists, palliative care, and patients.
A preliminary study of attitudes toward the assessment and management of cancer cachexia among medical oncologists and nurses.
Authors: Del Fabbro Egidio , Vigano Antonio A.L.
Published: February 2017

44

Background: A recent international consensus on the definition and classification of the cancer anorexia / cachexia syndrome (CACS) will facilitate clinical trial design, development of practice guidelines, and routine clinical management. Non-pharmacological interventions such as dietary counseling and promising new drugs have demonstrated improved outcomes in preliminary trials. Management of nutritional impact symptoms such as severe pain, depression, early satiety and chronic nausea also produce weight gain. These important advances contrast with the apparent low priority given to this condition by oncological societies worldwide. Our objective was to evaluate the attitudes of medical oncologists and nurses in the assessment and management of CACS in non-small cell lung cancer. Methods: Surveys were administered electronically to US-based, community medical oncologists (n=76 respondents) and oncology nurses (n=25), members of the Sermo research database which includes over 275,000 active healthcare providers, pre-qualified through telephone or online screening. A proprietary MedPulse tool achieved random geographic distribution of respondents through a staged query–response process. Results: 67% of medical oncologists selected weight loss as the most important criterion for diagnosing CACS in their daily practice, consistent with the consensus definition. However, only 4% of respondents described CACS as inevitable or very likely to develop in patients maintaining good performance status through first-line therapy. Community providers identified the management of symptoms that affect appetite as very important (58.8%), important (31.4%) or somewhat important (7.8%), but only 9.8% indicated they currently use a formal tool to evaluate these symptoms. 72% would consider using a brief assessment tool in clinical practice. Conclusions: Our surveys suggest community oncologists recognize the core criteria for the diagnosis of CACS, although there may be under-recognition of the condition’s prevalence. There is considerable interest in adopting a brief symptom assessment tool for screening, management and referral of affected or at-risk patients.
Managing symptoms when “the first step or two isn’t working”: Provider and patient perceptions of the role of specialty palliative care in symptom management in gynecologic oncology.
Authors: Lefkowits Carolyn , Kavalieratos Dio , Arida Janet , Teuteberg Winifred , Donovan Heidi , Courtney-Brooks Madeleine , Arnold Robert , Kelley Joseph L.
Published: February 2017

47

Background: Our objective was to describe gynecologic oncology (GO) providers’ and patients’ knowledge, attitudes and preferences related to utilization of specialist palliative care (SPC) for symptom management. Methods: Semi-structured qualitative interviews with 19 GO providers (7 physicians, 7 advanced practice providers, 5 nurses) and 30 patients with advanced or recurrent gynecologic cancer from an academic medical center. Key interview domains include: patient symptoms, perceived role of oncology team regarding symptom management, familiarity with SPC, and barriers and facilitators to utilization of SPC for symptom management. Qualitative analysis is underway. Results: 19 provider interviews and 29 patient interviews were completed. Preliminary findings indicate shared beliefs between providers and patients, including an overall willingness to involve SPC in symptom management. Although providers felt comfortable initially managing common symptoms, they expressed interest in involving SPC for complex or multiple symptoms. Patients do not expect their GO providers to manage severe symptoms, noting concerns of complex symptom management as burdensome to the GO team. Barriers to involving SPC in symptom management included: patients’ perceptions of SPC as synonymous with end-of-life care, and logistical issues (e.g., scheduling and transportation). When a distinction was drawn between SPC for symptom management and end-of-life care, patients were uniformly open to seeing SPC for symptom management. Conclusions: GO patients’ and providers’ perception of the role of oncology providers in symptom management is consistent with the concept of a primary palliative care provider, delivering initial management of common symptoms. Specialty palliative care services are seen as complementary to the GO providers’ skillset and particularly useful for severe or multiple symptoms. Implications include the importance of ensuring that oncology provider training includes dedicated attention to symptom management to enable them to fulfill the role of primary palliative care provider.
Integrating palliative care into care of patients with kidney cancer and melanoma.
Authors: Buss Mary K. , DeSanto-Madeya Susan , Lynch Jessica , Zerillo Jessica A. , McDermott David F.
Published: February 2017

56

Background: Early palliative care (PC) has been shown to improve quality of life (QOL), enhance quality end-of-life (EOL) care, and reduce costs, yet many cancer centers lack resources to provide outpatient palliative care services. Data is needed to identify the optimal timing and most effective and efficient model for integrating PC into the care of cancer patients. In order to understand what components of PC have the greatest impact on patients, we examined the acceptability of early PC among patients with kidney cancer (RCC) and melanoma (M) and describe the content of PC visits. Methods: In July 2013, the outpatient PC team at Beth Israel Deaconess Medical Center, including physician (MD), social worker (SW) and chaplain (chap) were invited to see patients within a clinic that specializes in seeing patients with advanced RCC and M. All patients completed data on symptom burden using the Edmonton Symptom Assessment Scale, measures of QOL and degree of psycho-social and spiritual support. Referral to PC was based on these metrics and physician discretion. Results: Of the 21 patients seen by PC, 57% had RCC; 76% male; 86% White; 57% married. Mean age was 62 (range: 36-87). At the 1st PC visit: All had locally adv/metastatic disease; 48% were being treated with curative intent; 29% had not yet started treatment; 57% rated pain 0 on 0-10 scale (range: 0-9). First PC visit content: 76% psychosocial support (including building rapport); 67% symptom management; 33% included advance care planning (ACP) and decision-making support. Ninety-one percent were seen >1 by PC; 19% seen by SW or chap; median PC visits: 3. Eighty-one percent completed health care proxy. Additional data on patient outcomes will be presented. Conclusions: Nearly half of patients seen by PC were being treated with curative intent, suggesting acceptability of early PC integration in patients with RCC and M. Symptom management and psychosocial support dominated the early PC visits.
Impact of a cancer of unknown primary (CUP) service on end-of-life planning for patients with metastatic cancer.
Authors: Weatherstone Katie , Stewart James , Marshall Jackie , Gillmore Roopinder
Published: February 2017

66

Background: Cancer of Unknown Primary (CUP) is the 4th most common cause of cancer death in England and Wales. [(Office for National Statistics, Mortality Statistics: Deaths registered in England and Wales. http://www.ons.gov.uk/ons/search/index.html?newquery=series+dr (accessed 1/7/14).] Patients with CUP have poor outcomes secondary to delayed, inappropriate investigations and poor treatment response. In line with NICE guidance [(NICE guidelines: CG 104 (July 2010).]. Metastatic malignant disease of unknown primary: diagnosis and management of metastatic malignant disease of unknown primary.) a CUP service was set-up at the Royal Free in June 2012. This analysis assessed its impact on patients diagnosed with metastatic cancer who were not fit for active treatment. Methods: Clinical notes were reviewed for all admissions with an imaging-based diagnosis of metastatic cancer. A retrospective analysis (January-April 2009) was compared to prospective data following the launch of the CUP service (June-December 2012). Results: The notes of 9 patients (2009) and 15 patients (2012) were compared (see table). Age and length of stay (LOS) were analysed using t-test, other data were compared using chi-squared test. All patients were reviewed by Oncology and Palliative Care teams. There was a significant reduction in mean LOS (6.7 days, 18.6 days p<0.004) and the number who died in hospital (7%, 67% p<0.002) with only one patient not dying in his preferred place. Conclusions: Prompt assessment by the CUP service facilitates early input from Oncology and Palliative Care teams resulting in reduced LOS and fewer deaths in hospital in keeping with the agenda of the End of Life Care Strategy [(End of Life Care Strategy: Promoting high quality care for all adults at the end of life (July 2008). DOH (England).]. [Table: see text]
Palliative treatment the malignant trachea-bronchial stenosis.
Authors: Yang Renjie
Published: February 2017

70

Background: To evaluate the safety and usefulness of interventional procedure and stent placement in palliative care the patients with malignant trachea-bronchial stricture. Methods: All 52 lung cancer patient, male 38, female 14, age from 27~82 years old. On pathological type: squamous cell carcinoma 31, small cell carcinoma 11, adenocarcinoma 8 and cystadenocarcinoma 2 cases respectively. Clinical symptoms consist of severe dyspnea, choke and fever. For the interventional materials are guide wire, single curved catheter, coaxial delivery set and expandable metallic stent (Gianturco Z stent, wallstent and home-made NiTi alloy stent). Results: Totally 62 stents were planted in 52 cases, successful rate was 100%. The symptoms of dyspnea immediately relieved after stent placement. The slight stimulate cough usually recovered within 1 week. Following the stenting 17 patients accepted radiation, 21 patients got systematic chemotherapy; and 3 cases done pulmonary lesions cryoablation. Stent inside stent was done in 7 cases because tumor ingrowth. The immediate imaging showed the stricture segment of trachea lumen was dilated in varied degree. The implanted stents were dilated perfectly within one week and there was no stent migration on follow up. Conclusions: The trachea-bronchial stenosis caused by lung cancer can be palliative managed by stent implantation. It’s a good method to improve patient’s quality of life and benefit for the patient continue therapeutics.
Stereotactic radiation therapy in painful bone metastases.
Authors: Katsochi Despina , Paraskevopoulou Chryssa , Kosmidis Sophia , Fotopoulou Ekaterini , Kollias George
Published: February 2017

74

Background: Disease local control and therefore pain relief is the main objective in patients with painful bone metastases. The introduction of Stereotactic Body Radiation Therapy in combination with image guided radiotherapy offers the opportunity to safely apply hypofractionated schemes. Methods: From May 2009 to May 2014, 104 patients with total 158 single or multiple bone metastases from several primary tumors were treated with Stereotactic Body Radiation Therapy with palliative intent. Concrete osteolytic or painful osteoblastic lesions of maximum length 3cm where treated with two hypofractionated schemes: 24Gy in 6 fractions or 21Gy in 3 fractions depending on lesion size and location. All patients were provided with MDStation software installed on a tablet that analyzes their behavioral change based on evaluation questionnaires on their clinical status and pain intensity. Results: All patients completed the treatment plan with no major toxicity. Follow up was scheduled at the end of the treatment, three and six months after. Total pain relief was achieved in 130 lesions (82%), while in the rest 28 sites (18%) pain was significantly less and patients decreased medication. Conclusions: Stereotactic Body Radiation Therapy for bone metastases is a very effective technique for pain management. Palliation is achieved quite promptly with minimal toxicity.
Dying for advice: Code-status discussions between resident physicians and patients with advanced cancer—A national survey.
Authors: Einstein David Johnson , Einstein Katherine Levine , Mathew Paul
Published: February 2017

83

Background: Patients with treatment-resistant advanced cancer rarely benefit from cardiopulmonary resuscitation (CPR) but infrequently discuss end-of-life care with a physician until hospitalized for deterioration. Admitting resident physicians may therefore conduct initial code-status discussions, but may elicit patients’ preferences without providing necessary guidance. Methods: We distributed a case-based survey to all United States internal medicine residency program directors, of whom 19 enrolled and forwarded the survey to their residents. 358 residents (response rate 22.0%) completed the survey. Results: Faced with a hypothetical case of an inpatient with treatment-refractory advanced cancer, nearly all residents felt CPR would not be helpful. Yet, fewer than half (46.7%) of residents were likely to discuss an estimate of prognosis and the value of CPR with the patient. Only 30% were likely to offer a specific recommendation on CPR. A majority (69%) of residents who were unwilling to make a recommendation stated that patients should make their decisions independently. Most residents report that a sense of responsibility is the primary reason to discuss code status independent of attending physicians, and that deference to patient autonomy prevented them from sharing knowledge of outcomes or offering guidance. Ultimately, a minority stated they were satisfied with end-of-life discussions. Conclusions: Internal medicine resident physicians in the United States are unlikely to share the poor prognosis or offer specific recommendations on CPR in treatment-refractory cancer principally because of a conflict with their concept of patient autonomy. Given the futility associated with CPR in this setting, these data define a major unmet need in training and practice.
Estimation of risk in cancer patients undergoing palliative procedures by the American College of Surgeons risk calculator.
Authors: Rodriguez Rodrigo Andres , McClain Molly , Fahy Bridget N. , Morris Katherine Teresa
Published: February 2017

93

Background: Surgical palliation is defined as the use of a procedure in patients with incurable disease to relieve symptoms. The American College of Surgeons Risk Calculator (ACSRC) was created based on data from the National Surgical Quality Improvement Program to predict the risk of surgical complications on a patient specific level. Whether the ACSRC can accurately predict the risk of postoperative complications following palliative procedures in cancer patients is unknown. The purpose of this study was to determine if the ACSRC accurately predicted postoperative complication rates in this setting. Methods: Our surgical oncology database of patients treated from 2011 to 2013 was queried. Thirty-two patients who underwent palliative procedures were identified. Data extracted included: demographics, comorbidities, site and stage of cancer, type of procedure and post-operative complication rate and type. Risk assessment was performed for each patient using the ACSRC. Actual frequency of complications and length of stay (LOS) were compared to ACSRC predicted rate of complications and LOS. Results: See Table. Conclusions: The ACSRC is a powerful tool for aid in surgical decision-making; however, in the case of palliative procedures, it overestimated the risk of postoperative complications and underestimated the LOS. Overestimation of postoperative complications could result in fewer patients being offered potentially beneficial palliative procedures. [Table: see text]
Does performing en bloc versus piecemeal mucosal resections affect outcomes in patients with intramucosal adenocarcinoma?
Authors: Chu Chuanlian , Leggett Cadman , Uno Kname , Lutzke Lori , WANG Kenneth
Published: February 2017

1

Background: Endoscopic resection (ER) is used to treat early esophageal cancers (EAC). With the advent of techniques such as ESD that can remove large lesions en bloc, it is important to determine if performing piecemeal resections of intramucosal cancers is detrimental. Aim: To evaluate the response rates in patients with esophageal intramucosal adenocarcinoma (IMC) who had a single ER (SR) compared to those treated with piecemeal resection (PR). Methods: This is a cohort study of patients being followed in our BE unit. Patients in a prospectively maintained database with EAC from Jan 1998 to Apr 2012 were assessed. IMC was defined as lesions that were intramucosal without extension into the submucosa. All T1a cancers were verified by two expert gastrointestinal pathologists. We compared the tumor characteristics and recurrence rate between the two groups of SR and PR of IMC. Results: A total of 197 IMC (T1a) lesions in 138 patients were identified. 88(44.7%) lesions were performed SR and 109(55.3%) were PR. Mean follow up time were 45 months (IQR 24-70.5) in SR and 39 months (IQR 26-52, P=0.067) in PR. Complete remission were found of 92.1% (81) in SR and of 93.6% (102) in PR (P=0.788) patients. The recurrence rate was 7.9% in the SR patients, and 6.4% in the PR patients (P=0.699). Median time to progression was 12 months in the SR group (IQR 8-23.5) and 11 months in the PR (IQR 8-22) (P=0.765) group. The mean survival duration was 116.3 months in the SR and 89 months in the PR (P=0.079). No statistical difference in 5-year survival rates was found between SR (83.2%) and PR (80.9%) (P=0.082). Cox proportional hazard model analysis showed local recurrence after EMR was not related to number of specimen resected or technique. Conclusions: PR appears to be as effective a therapy as en bloc for esophageal IMC. Using PR does not appear to affect clinical outcomes.
A multicenter, phase II study of trastuzumab plus capecitabine and oxaliplatin (XELOX) as first-line chemotherapy for HER2-positive advanced gastric cancer: Update results of efficacy and toxicity.
Authors: Gong Jifang , Liu Tianshu , Fan Qingxia , Bai Li , Bi Feng , Qin Shukui , Wang Jinwan , Xu Nong , Cheng Ying , Bai Yuxian , Liu Wei , Wang Liwei , Shen Lin
Published: February 2017

102

Background: The ToGA study showed trastuzumab plus chemotherapy prolonged OS in patients with HER2-positive AGC. Result of REAL2 study suggested that oxaliplatin may be as effective as cisplatin but more tolerable. To further improve treatment options, we initiated a study to evaluate the efficacy and safety of trastuzumab plus XELOX in Chinese patients with HER2-positive AGC. Methods: Simon two-stage design with primary endpoint of best confirmed response rate by RECIST 1.0 was applied. The sample size is calculated to be 46, assuming H0=40%, H1=60%, a=0.05, b =0.2. Considering 10% drop-out rate, the total number of subjects was planned to be 51. Patients with previously untreated, HER2-positive (IHC2+/Dual SISH positive, or IHC 3+), histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction were eligible. Trastuzumab was administered at a loading dose of 8 mg/kg followed by 6 mg/kg infusion every 3 weeks (q3w). Oxaliplatin was administrated as a 130mg/m2 infusion, q3w, up to 6 cycles. Capecitabine was given orally with 2000mg/m2d, d1-14, q3w. Trastuzumab and capecitabine were continued until disease progression or intolerable toxicity. The NCI-CTCAE version 4.0 is used to evaluate safety profiles. Results: 72 patients (362 patients at 13 centers were screened) were HER2 positive, of which 51 patients were enrolled. The majority of patients were HER2 IHC 3+ (38/51). Response was evaluated in 46 patients, one patient achieved CR and thirty-three patients achieved PR. Till June 2013, 29 patients progressed, 14 cases died, showing PFS of 312 days (95%CI:211-360). The most common AEs that are higher than grade 3 were thrombocytopenia (21.6%), neutropenia (13.7%), anemia (7.84%), leucopenia (3.92%), nausea/vomiting (3.92%), hand-foot syndrome (3.92%). 6 patients possess LVEF decrease by ≥10% and one patient discontinued trastuzumab infusion. Conclusions: The addition of trastuzumab to XELOX was well tolerated and the results demonstrated encouraging efficacy. Survival benefit of this regimen needs further follow-up of patients to be concluded. Clinical trial information: NCT01364493.
A comparison of carboplatin with paclitaxel and cisplatinum with 5-fluorouracil in definitive chemoradiotherapy in esophageal cancer patients.
Authors: Honing Judith , Smit Justin , Muijs Christina , Burgerhof Johannes , Beukema Jannet , Plukker John Theodorus , Hospers Geke
Published: February 2017

104

Background: In esophageal cancer (EC) patients not eligible for surgery definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard regime. Nowadays carboplatin and paclitaxel are also often used. In this study we compared survival and toxicity rates between both regimens. Methods: This multicentre study included 102 patients treated in five centres in the North Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU and 55 patients carboplatin/paclitaxel. Results: Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group (P=0.879, Hazard Ratio [HR] 0.97 confidence interval [CI] 0.62-1.51), with a median survival of respectively 16.1 (CI 11.8-20.5) and 13.8 (CI 10.8-16.9) months. Median disease free survival (DFS) was comparable (P=0.760, HR 0.93 CI 0.60-1.45) between the cisplatinum / 5-FU group (11.1 months, CI 6.9-15.3) and the carboplatin/paclitaxel group (9.7 months, CI 5.1-14.4). Groups were comparable except clinical T-stage was higher in the carboplatin/paclitaxel group (P=0.008), but a high clinical T-stage (cT4) was not related to OS and DFS in a univariate analysis (P=0.250 and P=0.201). A higher percentage of patients completed the carboplatin / paclitaxel regimen (82% compared to 57%, P=0.01). Hematological and non-hematological toxicity (≥ grade 3) was significantly lower in the carboplatin / paclitaxel group (4% and 18%) than in the cisplatinum/5-FU (19% and 38%, P=0.001). Conclusions: In this study we show comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared to cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with a higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment for cisplatinum/5-FU is a good candidate regimen for further evaluation.
A province-wide retrospective comparison of pathologic response and progression-free survival in locally advanced esophagus cancer patients treated with either cisplatin-5FU (CF) or carboplatin-paclitaxel (CP) concurrent with radiation (XRT) with or without surgery.
Authors: Schellenberg Devin , Peixoto Renata , Lee Andrea , Lim Howard John
Published: February 2017

107

Background: The 2012 CROSS trial demonstrated an overall survival (OS) benefit for neoadjuvant, concurrent Carboplatin-Paclitaxel (CP) and radiation versus surgery alone. Based on this trial, the standard chemotherapy treatment for locally advanced esophageal (LAE) cancer in British Columbia (BC) became CP instead of Cisplatin-5FU (CF). This study evaluates the pCR rates and progression free survival (PFS) of those patients treated immediately prior and immediately after the change in provincial standard. Methods: All BC patients with LAE cancer diagnosed between February 2010 and February 2013 who completed at least 40 Gy of neoadjuvant radiation were analyzed. Standard demographics, chemotherapy delivered, radiation dose, surgical pathology and follow-up data were collected. Pathologic response was compared by chi-squared analysis. Patients were followed until death or last follow-up. Survival was compared by log-rank test. Results: Seventy-three patients received CF and 39 received CP. The tumor characteristics of the subgroups were similar: squamous histology was 57% (CF) vs. 49% (CP), node positivity rate on pre-treatment PET scan was 66 vs. 67%, and median tumor length was 5.7 vs. 5.8 cm. Median radiation dose was 50 Gy in both arms. The CP arm was slightly older (Median 66 vs. 61 yo) and had a greater percentage of males (80% vs. 57%). Forty eight and 49% percent of patients were able to undergo resection. The pCR rates were 49% (CF) vs. 16% (CP) (p<0.01) in the surgical subgroups. Median FU was 14.5 (CF) vs. 9.3 (CP) months. Median PFS for all patients was 16.5 (CF) and 14.6 (CP) (p=0.44). Median PFS in surgical patients was 23.4 months (CF) and 14.6 months (CP) (p=0.16. Conclusions: In patients with similar tumor characteristics, XRT with CF resulted in greater pCR rates than with CP. The pCR rate in the CP subgroup is lower than the 29% seen in the trial. With relatively short follow-up, no difference in PFS has yet been identified. [Table: see text]
Updated results of a randomized phase II trial for neoadjuvant versus adjuvant docetaxel/cisplatin chemotherapy in patients with locally advanced gastric cancer.
Authors: Kim Young Woo , Ryu Keun Won , Choi Il Ju , Kook Myeong-Cherl , Park Young Iee , Kim Hark K.
Published: February 2017

111

Background: Recent phase III trials proved the role of adjuvant chemotherapy in patients with gastric cancer after D2 resection, but the optimal treatment sequence remains to be determined. Here we report long-term follow up results for the randomized phase II trial comparing between neoadjuvant and adjuvant docetaxel/cisplatin (DC) chemotherapy in patients with locally advanced gastric cancer (LAGC). Methods: Patients with LAGC (stage IIIA-IV) were stratified by Japanese staging system and randomized to either neoadjuvant or adjuvant weekly DC chemotherapy in the National Cancer Center of Korea from 2003 to 2005. FDG-PET/CT screening was employed to exclude patients with metastasis. Patients randomized to neoadjuvant arm received 3 cycles of DC regimen (docetaxel 36 mg/m2 and cisplatin 40 mg/m2 on days 1 and 8 every 3 weeks), followed by surgery (D2 dissection). In adjuvant arm, patients underwent surgery, followed by 3 cycles of the same DC chemotherapy regimen. Results: Neoadjuvant arm (n=43) demonstrated higher R0 resection rate than adjuvant arm (n=44) [81% v 73%], but the difference was not statistically significant. At a median follow-up for suriving patients of 7.2 years, there were no significant differences in OS and PFS between the two arms [Log rank P=0.93 and P=0.89, respectively]. Conclusions: The timing of perioperative DC chemotherapy does not affect the overall survival of patients with LAGC.
Phase I and pharmacokinetics/pharmacodynamics (PK/PD) study of MEK inhibitor, RO4987655, in Japanese patients with advanced solid tumors.
Authors: Yamada Yasuhide , Nokihara Hiroshi , Yamamoto Noboru , Fujiwara Yutaka , Tamura Yosuke , Wakui Hiroshi , Honda Kazunori , Nakamichi Shinji , Asahina Hajime , Tanabe Yuko , Kitazono Satoru , Mizugaki Hidenori , Yamazaki Naoya , Suzuki Shigenobu , Sasaki Junichi , Matsuoka Mieko , Tamura Tomohide
Published: February 2017

116

Background: RO4987655 is an oral and selective inhibitor of MEK, a key enzyme of the MAPK signaling pathway. This was a phase I, non-randomized, open-label, dose-escalation study in Japanese patients (pts) with advanced solid tumors. Primary objectives were determination of maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs), safety evaluation and PK analysis. Secondary objectives were PD analysis and exploratory analysis of RO4987655’s anti-tumor activity according to the RECIST 1.0 criteria. Methods: Patients received an oral single dose of RO4987655 (1, 2, 4, 5, and 6.5 mg) (Cycle 0) followed by continuous once daily dosing (QD, 1, 2, and 4 mg/day) then twice daily dosing (4, 5, and 6.5 mg BID, total daily dose: 8, 10 and 13 mg/day) in 28-day cycles. A 3 + 3 dose-escalation design was used. Blood samples for PK analysis were collected in Cycle 0 (Day 1, 2 and 3) and in Cycle 1 (Day 1, 8, 15 and 22). PD was evaluated by pERK inhibition in peripheral blood mononuclear cells (PBMCs) using FACS analysis. Results: In dose-escalation, 25 pts were enrolled. After the MTD was defined, 6 pts were added to the MTD dose for further confirmation of safety profile. Tumor types included esophageal (n=8), colorectal (n=8) and non-small cell lung cancer (NSCLC) (n=4). MTD was defined as 8 mg/day due to 4 DLTs of Grade 3 creatine phosphokinase (CPK) elevation. Most commonly related adverse events included dermatitis acneiform, CPK elevation, and eye disorders, particularly macular edema and visual impairment. Plasma concentration of RO4987655 appeared to increase in a dose-proportional manner with a plasma half-life of 4.32 to 21.1 hours. After multiple dose administration, steady-state conditions were reached by Cycle 1 Day 8. The inhibitory effects of RO4987655 on pERK in PBMCs increased in a dose-dependent manner. An esophageal cancer pt confirmed partial response with over 50% shrinkage and 6 pts including NSCLC noted as stable disease ≥16 weeks by independent assessment. Conclusions: RO4987655 is tolerable with a favorable PK/PD correlation in Japanese pts with advanced solid tumors. Exploratory analysis of biomarker is ongoing. Clinical trial information: JapicCTI-111490.
Adjuvant chemotherapy for elderly patients (age 70 or older) with gastric cancer after gastrectomy with D2 dissection: A single-center experience.
Authors: Jo Jae-Cheol , Baek Jin Ho , Koh Su-Jin , Kim Gyu Yeol , Cho Hong Rae , Kim Hawk , Park Jae Hoo , Min Young Joo
Published: February 2017

117

Background: Adjuvant chemotherapy for gastric cancer after gastrectomy with D2 dissection can be recommended. However, there are limited data of survival benefit in the elderly. We sought to investigate the use of adjuvant chemotherapy for patient ≥70 years old with stage II or III gastric cancer and identify its impact on survival. Methods: Patient ≥70 diagnosed with stage II or III gastric cancer at the Ulsan University Hospital from 2008-2012 were identified. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, chemotherapy used, toxicity, and survival. Results: A total of 277 patients ≥70 years old underwent gastrectomy with D2 dissection from 2008-2012. Of these, 94 patients were pathologically diagnosed as stage II or III gastric cancer. Among the 94 patients, 58.5% of patients (n=55) received adjuvant chemotherapy and 39 patients received regular check-up without chemotherapy. Fluoropyrimidine alone regimens including TS-1 (n=26) and Didox (n=22) were more commonly used compared with fluroropyrimidine-platinum combination regimens (n=7). With median follow-up of 30.9 (range, 0.8-65.5 months), the median relapse-free survival (RFS) of patients with adjuvant chemotherapy or regular follow-up only was 39.1 and 26.1 months (P = 0.027). Multivariate analysis revealed that the adjuvant chemotherapy was associated with longer RFS (hazard ratio 0.51; 95% confidence interval 0.27 – 0.98). There was a trend toward improved overall survival (OS) in the adjuvant chemotherapy group, with a median OS of 51.2 months compared with that of 44.5 months in the regular follow-up only group (P= 0.242). Toxicities in adjuvant chemotherapy were generally tolerated. Conclusions: In elderly patients (aged 70 or older) with stage II or III gastric cancer after gastrectomy with D2 dissection, adjuvant chemotherapy may carry a potential survival benefit for those who receive it. Further well-designed prospective studies are needed to confirm these finding.
Impact of sarcopenia on long-term prognosis of patients with esophageal cancer after surgery.
Authors: Hayashi Tsutomu , Ozawa Soji , Kamachi Kenichi , Kazuno Akihito , Ito Eisuke , Chino Osamu , Shimada Hideo , Makuuchi Hiroyasu
Published: February 2017

118

Background: Emerging evidence suggests that sarcopenia might have an adverse impact on the survival of patients with cancer. We herein investigated the impact of sarcopenia on the long-term outcome of patients with esophageal cancer after curative surgery by analyzing the muscle cross-sectional area using computed tomography (CT). Methods: Sarcopenia was assessed in 204 patients undergoing a macroscopic curative esophagectomy for the resection of esophageal cancer between January 2005, and December 2008 at Tokai University Hospital by measuring the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on CT images obtained before surgery. The measured total psoas area (TPA) was normalized according to the patient’s height. Sarcopenia was defined as a TPA of ≤525 mm/m2 for men, and ≤375 mm/m2 for women. The impact of sarcopenia was assessed after controlling for clinical factors using multivariate modeling. Results: The median follow-up period was 60 months. The median patient age was 64 years; 184 (90%) patients were male and 20 (10%) were female. The median TPA was 580 mm/m2 for the men and 386 mm/m2 for the women. Sixty-nine (34%) patients had sarcopenia (TPA ≤525 mm/m2 for men, 375 mm/m2 for women ). The overall five-year survival rates were 33% for the patients with sarcopenia, and 66% for those without sarcopenia. In a multivariate analysis, a low body mass index (BMI ≤ 18.5 kg/m2; hazard ratio [HR], 1.87 [P = 0.028]), pathological stage of disease (HR for stage I, 1.587 in stage II [P = 0.219], 4.146 in stage III [P < 0.001], and 6.712 in stage IV [P < 0.001]), tumor location (HR of upper thoracic for middle and lower thoracic, 2.350 [P = 0.002]), and sarcopenia (HR, 1.858 [P= 0.006]) were independently associated with the overall mortality. Conclusions: Sarcopenia is associated with an increased risk of overall mortality in esophageal cancer after curative surgery independent of tumor-specific factors and the BMI. The development of effective interventions for sarcopenia warrants further study to improve the prognosis of patients with esophageal cancer.
Gastric cancer new nomograms based on preoperative clinical prognostic factors.
Authors: Bando Etsuro , Kattan Michael W. , Ohori Makoto , Tokunaga Masanori , Tanizawa Yutaka , Kawamura Taiichi , Terashima Masanori
Published: February 2017

12

Background: Nomogram has been developed and shown to be more accurate than the conventional staging systems for predicting prognosis in gastric cancer patients. Preoperative clinical staging is a primary measure with which therapeutic strategies for gastric cancer is determined. While many reports have been published on the relationship between nomogram based on pathologic factors and survival outcomes, there were no reports of developing nomogram based on preoperative clinical factors. The purpose of this study was to firstly build a specific nomograms based on preoperative clinical prognosticators for predicting overall survival (OS) and disease-specific survival (DSS) in patients with primary gastric cancer for choosing accurate therapy preoperatively. Methods: We included patients with primary 2,807 gastric cancer patients, who had not been undergone prior chemotherapy, between 2002 and 2010. The priori chosen pre-operative prognostic covariates were sex, age, tumor site, tumor size, histologic subtype obtained by endoscopy, endoscopic macroscopic appearance, tumor depth, numbers of positive nodes and distant metastases on CT scan, and serum concentration of CEA/CA19-9. Internal validation was performed by applying the nomograms to the patients of an internal cohort calculated by bootstrap re-sampling method. The model's discriminative ability was estimated by means of Harrell’s C statistics. Results: At a median follow-up of 57 months, 612 deaths and 523 cancer-related deaths were recorded. Five-year OS and DSS rates were 64.3% and 72.4%. In Cox regression, depth and nodal involvement is the most powerful independent prognostic factors. And type4 is identified negative prognosticators. Sex and serum tumor markers have little effectiveness for survival outcome. The bootstrap-corrected Harrell’s C statistics for OS and DSS of our nomograms were 0.852 and 0.880, which was higher than that of TNM seventh edition (C=0.826, 0.822) or that of sixth edition (C=0.822, 0.801). Conclusions: These nomograms accurately predict OS and DSS of Japanese gastric cancer patients pre-operatively. Worldwide external validation should be necessary for practical use of our nomograms instead of TNM classification.
Safety, tolerability, and pharmacokinetics (PK) of rilotumumab in Japanese patients (pts) with advanced solid tumors.
Authors: Doi Toshihiko , Tang Rui , Zhang Yilong , Loh Elwyn , Lizambri Richard , Yasui Hirofumi
Published: February 2017

130

Background: Rilotumumab (R) is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor, the only known MET receptor ligand. The MET pathway has been identified as a potentially useful target for therapeutic blockade in oncology. R has been studied in multiple phase 2 trials either as monotherapy or combination therapy, including a phase 2 trial in gastric cancer combining R with epirubicin, cisplatin, and capecitabine. A phase 1 study was done to evaluate the safety, tolerability, and PK of R in Japanese pts. Methods: An open-label, dose-escalation study was performed with R at 10 mg/kg (Cohort 1A), escalating to 20 mg/kg (Cohort 1B) if no dose-limiting toxicities (DLTs) were observed. Key eligibility criteria were Japanese pts with unresectable locally advanced or metastatic carcinoma, age ≥ 20 yr, ECOG ≤ 1, and refractory to standard treatment (tx). Pts received R as an intravenous infusion on days 1 and 15 of each 28-day cycle, except for cycle 1 in which the day 15 dose was skipped to facilitate PK analysis. DLTs were evaluated in cycle 1. Results: A total of 9 pts were enrolled (1A, n = 3; 1B, n = 6). No DLTs were noted. As of 17 April 13, tx-emergent AEs were reported in 89% of pts. Tx-emergent AEs occurring in > 1 pt overall were vomiting (33%), diarrhea (22%), decreased hemoglobin (22%), hypoalbuminemia (22%), and nausea (22%). One grade 3 tx-emergent AE was observed (decreased hemoglobin; 10 mg/kg). Tx-related AEs were reported in 56% of pts. One grade ≥ 2 tx-related AE was observed (hypoalbuminemia; 20 mg/kg). 8 pts discontinued R due to disease progression; 1 pt remained on the investigational product. Mean exposure of R (Cmax and AUC) appeared to be doubled as dose increased from 10 to 20 mg/kg. The estimated mean CL was approximately 0.2 mL/hr/kg in both cohorts, suggesting a linear PK from 10 to 20 mg/kg. The terminal half-life of R was about 15 days. Conclusions: R monotherapy had an acceptable safety profile in Japanese pts with advanced solid tumors. These phase 1 safety and PK data support the further evaluation of R combined with chemotherapy in Japanese pts with MET-positive metastatic gastric cancer. Clinical trial information: NCT01791374.