bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the care of cancer patients with ureteral strictures managed with percutaneous nephrostomy tubes.
Authors: Sabir Sharjeel H , Patel Rakhi , Lin Brenda , Ahrar Judy , Tam Alda , Ahrar Kamran
Published: February 2017

e264

Background: Ureteral strictures resulting from either active disease or the sequelae of cancer therapy are often managed with percutaneous nephrostomy (PCN) tubes. PCN tubes divert urine from the kidney into drainage bags, which are cumbersome to care for and potential sources of infection. In contrast, percutaneous nephroureteral (PCNU) tubes by allowing internal drainage can preclude the need for a urine drainage bag. Our goal was to implement a coordinated care program in interventional radiology (IR) designed to increase the number of patients whose PCN tubes were converted to PCNU tubes, thus preventing the long-term problems associated with urine drainage bags. Methods: An IRB approved retrospective review of all PCN tubes placed in IR from 2011-2013 was undertaken to get baseline statistics. After review of this data, a prospective care coordination program was implemented in which patients without contraindications for conversion to PCNU tubes had an attempt at conversion during their planned 3 month PCN tube exchange. The baseline and 1 year follow up data were collected. A Fisher’s exact test was used to calculate the significance of the intervention. Results: Our baseline data demonstrated on average 9% of PCN placements per year were being converted to PCNU tubes. After implementation of the prospective care coordination program from 7/2014 to 7/2015, 257 patients had PCN tubes placed. 217 patients had completed 3 month follow up at time of analysis. Of these, 30 (14%) patients had an attempt at PCNU placement because of the prospective program. Among these patients 19/30 (63%) had a successful PCNU placement. 20 (9%) patients had PCNU placement at the request of referring physicians. Overall, 39 (18%) patients had a PCNU tube placed after implementation of the program. 2/39 patients had difficulties with their PCNU tubes requiring return to PCN tubes. Conclusions: An active coordinated care program in IR aimed at preventing the long-term problems associated with PCN tubes and urinary drainage bags can increase the percentage of patients who receive PCNU tubes from 9% to 18% (p = 0.002).
Changes in demographic characteristics and motives for becoming a hospice/palliative care volunteer: Results of single institution 9 years educational program.
Authors: Wojtacki Janusz , Paczkowska Agnieszka , Majkowicz Mikolaj , Cieśnik Anna , Gurgul Natalia , Slomska Ewelina , Szczeluszczenko Aneta
Published: February 2017

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Background: Voluntary activities are essential in many different aspects of hospice and palliative care. The interest in becoming a volunteer lowers in many communities. Better knowledge of volunteers’ characteristics and wider understanding of their motivations seem to be crucial for more sufficient volunteers’ recruitment and retain. Methods: Self-reported demographic details and data on motives for hospice / palliative care volunteering were collected from initial questionnaire forms fulfilled by all consecutive participants of the teaching course for medical voluntary cancer patients caregivers (16 editions; April-2006-November-2014; no data for 2009) at Rev. Eugeniusz Dutkiewicz Hospice SAC, Gdańsk, Poland. Results: all 562 records were analyzed: 1) mean volunteers age was 35,73+14,69 years and significant trend (p < 0.001) for increasing age was observed (e.g.: mean age values + SD were: 2007: 28.41+11.82; 2011: 37.19+14.93; 2014: 41.31+12.16); 2) the vast majority of volunteers were females (82.03%), who already completed education; 3) 67 of study participants declared professional connections with medicine (19.47%), 42 (12.21%) - pedagogy or 38 (11.05%) – psychology; 4) 241 (42.88%) volunteers declared full current professional activity, 174 (30.96%) were unemployed, 50 (8.89%) - retired; 5) participants mostly reported motives for volunteering which might be categorized as altruistic (67.08%: “I want to help others”) – the percentage increased significantly during the study period (p < 0.012); 6) the next two most frequently indicated motives represented category of personal gain (29.36%: “I want to improve my skills”; 26.87%: “volunteering is the way of my personal development” – not significant trend for time). Conclusions: 1) Results showed that some demographic features as well motives for hospice / palliative care volunteering changed over the time in our community - it warrants some individualization in recruitment process recognition for volunteers coordinators; 2) the study will continue to identify the volunteers’ subgroup with the greatest probability to retain at service for longer period of time.
Assessment of adequacy of pain management in advance cancer patients.
Authors: Singh Harminder , Banipal Raja
Published: February 2017

e283

Background: Cancer prevalence in India is estimated around 2.0-2.5 million, 0.7- 0.8 million new cases identified every year, and cancer deaths reported per year is 0.4-0.5 Million. The objective of this study was to estimation of the prevalence of inadequate cancer pain management in patients with advanced cancer. Methods: Adequacy of pain management, that is Pain Management Index calculated for each patient. It is simple indexes which usually indicate a connection of the reported level of pain to the potency of the analgesics prescribed Results: 211 patients were recruited with most prevalent cancer type was genitourinary, diagnosed in 28.7% patients, followed by breast cancer 23.1% and head & neck cancer 20.3%. Among 211 patients with cancer, 76.85% patients had inadequate pain management and 23.14% had better control of pain. Association of inadequacy of pain were done with age, gender, occupation, family history, duration and cancer types, signification relation was observed with age group and analgesic use. (See table.) Conclusions: Our inadequate pain management prevalence rate of about 78% was far too high so this study will highlight the importance of true status of cancer pain management. It also emphasized that systematic recording of pain intensity and follow up further enhance the entire pain management mechanism including dose titration to change of new formulation. [Table: see text]
Second-line chemotherapy with paclitaxel for elderly patients with advanced gastric cancer.
Authors: Ohba Akihiro , Takashima Atsuo , Nishiuchi Takamasa , Honma Yoshitaka , Iwasa Satoru , Okita Natsuko , Kato Ken , Hamaguchi Tetsuya , Nagashima Kengo , Boku Narikazu
Published: February 2017

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Background: Survival benefits of second-line chemotherapy such as weekly paclitaxel (wPTX) for patients with advanced gastric cancer (AGC) were shown in several phase 3 trials. However, these trials included a small proportion of elderly patients, and few elderly patients receive second-line therapy in clinical practice. The aim of this study was to compare the efficacy and safety of second-line chemotherapy with wPTX between elderly and non-elderly patients. Methods: The subjects of this retrospective study were AGC patients who received wPTX as second-line chemotherapy between January 2002 and August 2014, fulfilling the following selection criteria; 1) pathologically proven metastatic or recurrent gastric adenocarcinoma, 2) receipt of wPTX after platinum or fluoropyrimidine containing chemotherapy. Patients were divided into two groups by age: ≥ 75 years old (elderly group) and < 75 years old (non-elderly group). Response rate (RR) in patients with measurable lesions, overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) and adverse events were evaluated. Hazard ratios of survival were adjusted by prognostic factors using Cox proportional hazard model. Results: A total of 272 patients, 31 elderly and 241 non-elderly, were selected in this study. RRs were 6.2% (1/16) in the elderly group and 12.7% (15/118) in the non-elderly group (p = 0.69). While PFS was similar between two groups (median 2.4 vs. 3.6 months, adjusted hazard ratio [HR] 1.18, p = 0.46), the elderly group showed shorter OS than the non-elderly group (median 5.1 vs. 6.1 months, adjusted HR 1.49, p = 0.06), associated with relatively shorter PPS (median 2.2 vs. 2.6 months, adjusted HR 1.40, p = 0.11). There were no remarkable differences in the incidences of grade 3 or higher adverse events between the two groups (hematologic 38.7 vs. 41.1%; non-hematologic 25.8 vs. 23.7%). No treatment related deaths were observed in either group. Third-line chemotherapy was administered in 19.4% of elderly group and 35.3% of non-elderly group (p = 0.11). Conclusions: It is suggested that second-line chemotherapy with wPTX for AGC may be tolerable and have some clinical benefits for elderly patients as well as for non-elderly patients.
Efficacy and safety of irinotecan monotherapy as third line treatment for advanced gastric cancer.
Authors: Kawakami Takeshi , Machida Nozomu , Kawahira Masahiro , Kawai Sadayuki , Kito Yosuke , Yoshida Yukio , Hamauchi Satoshi , Tsushima Takahiro , Todaka Akiko , Yamazaki Kentaro , Yokota Tomoya , Fukutomi Akira , Onozawa Yusuke , Yasui Hirofumi ,   ASCO-GI Author's Group
Published: February 2017

113

Background: Several randomized trials demonstrated the survival benefit in advanced gastric cancer patients (AGC pts) receiving irinotecan or taxanes as second-line chemotherapy (SLC). Taxanes are used for SLC in daily clinical practice in Japan because of its less toxicity, especially in AGC pts with peritoneal dissemination, compared with irinotecan. Although irinotecan is often administered after refractory or intolerant to taxanes as SLC, the efficacy and safety of irinotecan as third-line chemotherapy (TLC) is still unclear. Methods: We retrospectively investigated the data of AGC pts administered irinotecan 150mg/m2 as TLC every two weeks until disease progression, unacceptable toxicity, or pts’ refusal between December 2002 and June 2015. Inclusion criteria were (1) age 75 years or less (2) refractory or intolerant to fluoropyrimidine with or without platinum as first-line chemotherapy (3) refractory or intolerant to taxanes as SLC. Results: A total of 52 pts were analyzed. Pts’ characteristics were as follows: median age, 66 (range, 33-75) years; male/female, 35/17 pts; ECOG PS 0-1/2, 42/10 pts; peritoneal dissemination +/-, 32/20 pts; ascites +/-, 22/30 pts, number of metastatic sites 1-2/3-4, 44/8 pts. Median follow-up period was 548 (141-1931) days. Median progression-free survival was 70 days (95%CI 49-137) and median overall survival was 144 days (95%CI 120-231) from the initiation of irinotecan administration. Response rate and disease control rate was 10.8% and 50.4%, respectively. Relative dose intensity was 74.7% (56 mg/m2/week); 14 pts needed dose reduction in the first course, and 22 pts after the second course. Grade 3 or 4 neutropenia, anemia, diarrhea, nausea, and febrile neutropenia were observed in 13 (25%), 21 (40.4%), 5 (9.6%), 3 (5.8%) and 3 (5.8%) pts, respectively. No treatment-related death was observed. Conclusions: This study suggests that irinotecan monotherapy as TLC has acceptable anti-tumor effect and has manageable toxicity in appropriately selected AGC pts.
Survival outcome of metastatic adenocarcinoma of esophagogastric junction in the trastuzumab era.
Authors: Narita Yukiya , Hasegawa Hiroko , Komori Azusa , Mitani Seiichiro , Masuishi Toshiki , Taniguchi Hiroya , Kadowaki Shigenori , Ura Takashi , Ando Masashi , Ito Seiji , Yatabe Yasushi , Tajika Masahiro , Muro Kei
Published: February 2017

117

Background: Previous studies have reported no differences in treatment outcomes between metastatic adenocarcinoma esophagogastric junction (AEGJ) and gastric adenocarcinoma (GAC). However, after the approval of trastuzumab (Tmab) for the treatment of metastatic AEGJ and GAC survival outcomes remain unclear. Methods: We retrospectively reviewed clinicopathological characteristics, treatment outcomes, and prognoses of 289 consecutive patients with AEGJ and GAC who received ﬁrst-line chemotherapy from March 2011, when Tmab was approved in Japan, to December 2013 at Aichi Cancer Center Hospital. Prognostic factors were identified using Cox multivariate regression analysis. IHC3+ or IHC2+/ISH+ tumors were defined as HER2 positive. Results: Of 289 patients, 45 (16%) had AEGJ. Patients with AEGJ were signiﬁcantly younger with lesser lung metastases than those with GAC. HER2-positive rates in AEGJ tended to be greater than those in GAC, but this difference was not statistically significant (22% vs. 16%; P = 0.35). The rates of platinum doublet therapies were not significantly different (72% vs. 78%; P = 0.47). The objective response rate (ORR) was 27% with AEGJ and 40% with GAC (P = 0.17). The median follow-up duration was 12.1 and 11.9 months, respectively. Progression-free survival was similar for both the groups [hazard ration (HR) = 0.97; P = 0.83), while the median overall survival (OS) period was numerically longer for AEGJ than that for GC (14.7 vs. 12.4 months; HR = 0.99; 95% confidence interval = 0.69–1.39; P = 0.92). In patients with AEGJ, an ECOG performance status of 2 and HER2 negativity were signiﬁcantly associated with poor prognosis, as estimated by the multivariate analyses of OS. The analyses that were limited to patients treated with Tmab as the first-line chemotherapy revealed no significant differences in ORR and median OS between AEGJ and GAC. Conclusions: Even in the Tmab era, there were no significant differences in survival outcomes between metastatic EGC and GAC.
The examination of appropriate surveillance after resection of GIST from 115 recurrent patients.
Authors: Wada Noriko , Takahashi Tsuyoshi , Masuzawa Toru , Kawata Junji , Nishida Toshirou , Kurokawa Yukinori , Nakajima Kiyokazu , Miyazaki Yasuhiro , Makino Tomoki , Yamasaki Makoto , Takiguchi Shuji , Mori Masaki , Doki Yuichiro
Published: February 2017

12

Background: Previous studies have proposed some risk classifications and contributed to the prediction of the prognosis in gastrointestinal stromal tumor (GIST) patients after resection. However, optimal postoperative surveillance has not been established yet. We investigated the characteristics of GIST patients who developed recurrence after resection to establish optimal postoperative surveillance for recurrence. Methods: Between July 1978 and November 2014, 115 patients developed recurrence after macroscopically complete resection for primary GIST. We investigated the clinicopathological factors, time to recurrence (TTR) and first recurrence sites to determine the optimal duration and methods of surveillance. We also compared the characteristics between the two subgroups with TTR ≤ 5 years or > 5 years. Results: The median age was 60 (15-84) years old and 62% of the patients were men. The most common primary tumor site was the stomach (39%), followed by the small intestine (37%), duodenum (11%), large intestine (10%) and esophagus (2%). The median tumor size was 8.5 (1.5-30.0) cm and the median mitotic count was 4 (0-165) /50 HPF. The site of recurrence was liver (57%), followed by peritoneum (48%), local (21%), bone (4%) and lymph node (2%). Almost all patients, except one lung recurrence by esophageal GIST, showed primarily recurrence in the abdominal site. The median period of recurrence after resection 21 (1-172) months and 12% of the recurrence occurred over 5 years. We divided the two groups by the period of recurrence, Early-group (E) ( ≤ 5 years), and Late-group (L) ( > 5 years). Comparing the two groups, E group showed a smaller size (median, 3.5 vs. 9.0 cm) (p < 0.001) and a lower risk classification (p < 0.001) than L group. Although liver recurrence was the most frequent in E group (60 %), local recurrence was the most frequent in L group (43 %). Conclusions: Twelve percent of the recurrence occurred over 5 years, and almost all patients showed primarily recurrence within the abdomen. This may indicate that postoperative surveillance after complete resection for primary GIST is recommended over 5 years by abdominal examination.
Neoadjuvant and adjuvant, floxuridine, leucovorin, oxaliplatin, and docetaxel (FLOD) in patients with locally advanced operable gastroesophageal adenocarcinoma: A phase II study with pathologic responses and long term follow-up.
Authors: Ardalan Bach , Gombosh Miriam , Franceschi Dido , Avisar Eli , Yakoub Danny , Ribeiro Afonso , Garrido Jose , Merchant Nipun , Livingstone Alan S
Published: February 2017

124

Background: A complete pathological response to neoadjuvant chemotherapy without the use of radiation has infrequently been reported in operable chemo-naïve stage III gastro esophageal adenocarcinoma patients. Methods: Twenty-nine patients were enrolled in this study. Neoadjuvant therapy consisted of Floxuridine, Leucovorin, Oxaliplatin, and Docetaxel and was administered in 2, four week cycles. Chemotherapy consisted on day one and day fifteen; Oxaliplatin, Docetaxel, FUDR, and Leucovorin. The latter two drugs were given concurrently over twenty four hours. On day eight, chemotherapy consisted of Docetaxel, FUDR, and Leucovorin. Following therapy, patients underwent surgical resection. Those patients having residual disease were offered adjuvant chemotherapy. Patients having a complete pathological response were not offered any further therapy. Results: Twenty-four out of twenty-nine patients completed neoadjuvant therapy and underwent esophagectomy. Two were declared inoperable after treatment. Three patients died prior to surgery. The median follow-up of all patients is now sixty months. The median overall survival has not been reached at sixty months. Five yr actual OS is 51%. Clinical response to neoadjuvant therapy was seen in (72.4%) patients. Complete pathological response to neoadjuvant therapy was seen in (16.7%) who are disease free at sixty month follow-ups. Seven out of twenty-four patients achieved partial pathological response (29.1%) and received adjuvant chemotherapy. They are all alive (100%). Eight patients achieved less than partial pathological response and received adjuvant chemotherapy, four out of eight are alive at sixty months (50%). Grade three and four toxicities were seen in sixteen out of twenty nine patients during neoadjuvant therapy. Grade three and four toxicities were seen in six out of fourteen patients during adjuvant therapy. Conclusions: Our chemotherapy regimen of Floxuridine, Leucovorin, Oxaliplatin and Docetaxel (FLOD) has resulted in long term survival in patients with adenocarcinoma of the esophagus. Clinical trial information: NCT00448760.
Patterns of radiotherapy and its impact on survival in patients with locally advanced gastric and gastroesophageal junction adenocarcinoma: Before and after the publication of the MAGIC trial.
Authors: Lin Chi , Bhirud Abhijeet , Bennion Nathan Ronald
Published: February 2017

125

Background: The intergroup 0116 trial for locally advanced gastric (GA) and gastroesophageal junction adenocarcinoma (GEJA) established postoperative chemoradiation therapy as the standard of care. However, since the publication of the MAGIC trial in 2006, some physicians prefer perioperative chemotherapy rather than postoperative chemoradiation. The goal of this study is to examine the use of radiotherapy (RT) and its impact on survival in patients diagnosed 3 years prior to and after the publication of the MAGIC trial. Methods: Patients with stage T2-4 or N+ and M0 GA (3339) or GEJA (1868) diagnosed between 2004 and 2009 who have had a primary tumor resection with at least 3 years of follow up were identified from the SEER database. Regression models were used to analyze factors influencing the use of RT and its effect on survival. Kaplan Meier plots and log-rank tests were used for survival comparisons. Results: From 2004 to 2009, there was no change in the ratio of RT/no RT. About 33% of patients with GA and 53% with GEJA received RT. Multivariate regression analysis showed that patients with T2-3 disease, N+ disease, and younger patients were more likely to receive RT in both GA and GEJA. The median follow-up for GA and GEJA, was 73 and 68 months and median survivals of 27 and 26 months respectively. RT improved median survivals from 20 to 46 months for GA and from 20 to 31 months for GEJA (p < 0.0001). After adjusting for stage and age, patients who received RT had higher odds of surviving 3 years or longer for both GA (OR 2.20, 95% CI 1.86-2.60) and GEJA (OR 1.46, 95% CI 1.19-1.80). Further analysis revealed that RT improved survivals in patients diagnosed either before or after 2006 for both GA and GEJA. Conclusions: The publication of MAGIC trial in 2006 has not affected the patterns of using RT on locally advanced GA or GEJA. Patients who did not receive RT after 2006 continue to have worse survival rates compared to those who have had RT. Further studies are warranted to evaluate the effect of combining the MAGIC chemotherapy regimen and RT on survival and quality of life of these patients.
A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: OGSG1203 (HERBIS-5).
Authors: Nishikawa Kazuhiro , Sakai Daisuke , Kawada Junji , Kawabata Ryohei , Kawase Tomono , Oka Yoshio , Sugimoto Naotoshi , Shimizu Takeshi , Nishijima Junichi , Hasegawa Hiroko , Endo Shunji , Isozaki Yutaka , Kimura Yutaka , Matsuyama Jin , Kurokawa Yukinori , Shimokawa Toshio , Fujitani Kazumasa , Satoh Taroh
Published: February 2017

128

Background: Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. Continuous administration of trastuzumab beyond first progression is expected to contribute to the benefit of chemotherapy for HER2-positive gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in Japanese patients with advanced HER2-positive chemo-refractory gastric cancer. Methods: Intravenous infusion of irinotecan every 2 weeks at a dose of 150 mg/m2; intravenous infusion of trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Administration of irinotecan and trastuzumab were repeated in independent schedules. The primary endpoint was disease control rate. The secondary endpoints were adverse events, response rate, time-to-treatment failure, progression-free survival, overall survival, and response rate stratified by prior trastuzumab use. This study was conducted by the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG). Results: From October 2012 to Augst 2014, 30 patients were enrolled and one patient withdrew before study treatment. Accordingly, 29 patients were assessable for efficacy and safety. The disease control rate was 65.5% [95% C.I. 45.7 - 82.1%], and the response rate was 20.7% [95% C.I. 8.0 - 39.7%]. The median progression free survival and the median overall survival were 3.7 and 7.5 months, respectively. The major grade 3/4 toxic effects were neutropenia (24%); anemia (24%); leucopenia (21%); anorexia (11%); fatigue (14%); hypoalbuminemia (24%); and hypokalemia (14%). One death (NOS) was considered to be related to the study. Conclusions: The results of combination Trastuzumab with irinotecan showed feasible and promising efficacy against advanced HER2-positive chemo-refractory gastric cancer. These findings indicated that trastuzumab continuation use might be beneficial. Clinical trial information: 000008626.
Clinical impact of preoperative albumin to globulin ratio in gastric cancer patients with curative intent.
Authors: Toiyama Yuji , Okigami Masato , Yasuda Hiromi , Ohi Masaki , Tanaka Koji , Inoue Yasuhiro , Mohri Yasuhiko , Kusunoki Masato
Published: February 2017

13

Background: Albumin to globulin ratio (AGR) has mainly been used as a clinical indicator for multiple myeloma or other immunoproliferative diseases. Recently, AGR has been reported to predict long term mortality in patients with nasopharyngeal carcinoma, colorectal cancer, lung cancer and breast cancer. However, clinical impact of preoperative AGR in gastric cancer (GC) has not yet been addressed. Therefore, we, for the first time, investigated the association between AGR and clinico-pathological findings including overall survival (OS) and disease free survival (DFS) in GC patients with curative intent. Methods: Clinicopathological findings including preoperative laboratory data (carcinoembryonic antigen [CEA], carbohydrate antigen [CA] 19-9 and AGR) from 384 curative GC patients were assessed as indicators of early recurrence and poor prognosis in this retrospective study. AGR was calculated as [AGR = albumin/ (total protein - albumin)]. The cut-off value of AGR was 1.4 in current study. Results: Several pathological categories related with tumor progression such as lymph node metastasis, tumor serosal invasion, large tumor size, venous invasion were significantly associated with lower AGR levels. In addition, significant negative correlation between AGR and age was found. Among preoperative serum markers, AGR was an independent predictor of early recurrence in curative GC patients after adjusted by age and sex. On the other hand, 2 pathological factors such as lymph node metastasis and serosal invasion were independent factors to identify early recurrence in curative GC patients among postoperative categories. Furthermore, sub analysis revealed that GC patients with AGR < 1.4 showed significant poorer DFS in both lymph node metastasis and serosal invasion group, respectively. Conclusions: Preoperative AGR may represent a simple, potentially useful predictive biomarker for selecting GC patients who might need neoadjuvant chemotherapy. Furthermore, AGR may select candidates who are better to introduce more intensive adjuvant chemotherapy after curative operation in stage II-III GC.
Preoperative prediction of peritoneal metastasis in gastric cancer as an indicator for neoadjuvant treatment.
Authors: Mori Koichiro , Toiyama Yuji , Ohi Masaki , Nagano Yuka , Uratani Ryo , Oki Satoshi , Okigami Masato , Yasuda Hiromi , Saigusa Susumu , Tanaka Koji , Inoue Yasuhiro , Mohri Yasuhiko , Kusunoki Masato
Published: February 2017

14

Background: Although Gastric cancer (GC) mortality has been reduced by advances in new treatments and in chemotherapy, it still has a poor prognosis and high mortality. One of the reasons for poor prognosis is that at the time of diagnosis advanced GC with metastatic disease is often detected and it is frequently accompanied by peritoneal metastasis. Imaging studies are frequently used to predict peritoneal metastasis, however, these modalities did not obtain consistently high sensitivity and specificity in assessing peritoneal metastasis. Therefore, we investigated whether the combination of several serum markers and clinical factors could be used for preoperative prediction of peritoneal metastasis in GC as an indicator for neoadjuvant treatment. Methods: A total of 493 patients with GC were enrolled in our Hospital. Preoperative serum tumor markers [carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9], systemic inflammatory marker C-reactive protein (CRP), host immune markers [neutrophil and lymphocyte counts and their ratio (NLR)], albumin as a nutritional marker, and objective preoperative clinical factors were available as indicators of postoperative peritoneal metastasis. Results: This study included a total of 344 men and 149 women who were classified according to UICC TNM Classification: 264 patients had stage I disease, 79 stage II, 78 stage III and 72 stage IV. Specific clinical factors, including tumor size, histopathology of biopsy sample, and tumor morphology, were significantly correlated with peritoneal metastasis. CA19-9, lymphocyte count and NLR were also predictive factors for peritoneal metastasis. Multivariate analysis identified the clinical factors tumor morphology and histopathology, and laboratory markers CA19-9 and lymphocyte count as independent factors predictive for peritoneal metastasis. Next, a combination of independent predictive factors achieved high predictive accuracy (0.882) for peritoneal metastasis preoperatively. Conclusions: A combination of preoperative tumor features and serum parameters is an alternative method to preoperatively discriminate patients with GC with peritoneal metastasis from those without.
Trastuzumab induced cardiotoxicity in HER2-positive metastatic esogastric cancers.
Authors: Martin-Babau Jerome , Eusen Yves , Verveur Cedric , Trouboul Fanny , Cheneau Caroline , Jestin Le Tallec Veronique , Simon Helene , Metges Jean-Philippe
Published: February 2017

152

Background: Trastuzumab is widely used in Her2 positive metastatic esophageal and gastric cancers along with chemotherapy. Cardiotoxicity of trastuzumab has been described precisely in Her2 positive breast cancers and occurs with asymptomatic lowering of LVEF (Left Ventricular Ejection Fraction) in up to 10% of cases. Esogastric cancer patients are usually older and have more comorbidities than patients followed for breast cancer. Methods: This monocentric retrospective study measured the incidence of symptomatic and asymptomatic cardiotoxicity in patients treated for metastatic esogastric cancers and its potential impact regarding overall survival from October 2009 to September 2015. Patients should receive trastuzumab with chemotherapy during the period of study for treatment of Her2 positive metastatic esogastric cancer as first-line chemotherapy. Results: 27 patients received trastuzumab along with chemotherapy during the period of study. Median age was 62.3 years, sex ratio 21 M/6 W. The median number of cycles of trastuzumab was 5 cycles. The asymptomatic cardiotoxicity rate, defined by a drop of more than 10% of LVEF between the enrollment echocardiogram and the third month treatment echocardiogram, was of 22%. Symptomatic cardiotoxicity was observed in two patients (7.4%), with one cardiac failure and one myocardial infarction, with no associated death. Cardiovascular comorbidities and cardiac irradiation which is recurrent in this indication did not appear as a predictive factor of cardiotoxicity (p = 1). Overall survival of patients was not statistically modified by the occurring of cardiotoxicity even if we noted a trend to better outcome of the patients presenting an asymptomatic LVEF lowering. Conclusions: This study is to our knowledge the first to focus specifically on the cardiotoxicity of trastuzumab in esogastric metastatic Her2 positive cancer in the real world. These patients seem to be at a higher asymptomatic cardiac risk than breast cancer patients. However cardiovascular comorbidities didn’t appear as predictive factors of trastuzumab induced cardiotoxicity and should not prevent patient from benefiting of this treatment.
Pathologic and clinical outcomes in cT2N0 esophageal cancer: A cohort study.
Authors: Bhuchar Gauri , Altujjar Mohammad , Raja Siva , Murthy Sudish C. , Raymond Daniel , Videtic Gregory M.M. , McNamara Michael J. , Khorana Alok A. , Adelstein David J. , Sohal Davendra
Published: February 2017

157

Background: The management of clinically staged T2N0 (cT2N0) esophageal cancer remains controversial and clinical staging can be inaccurate. We evaluated concordance between clinical and pathologic staging as well as outcomes in a cohort study of patients initially staged as cT2N0. Methods: We conducted a cohort study of consecutive patients with esophageal cancer staged as cT2N0 after imaging (CT, PET scans) and endoscopic ultrasound, who underwent surgical resection and were followed at the Cleveland Clinic from Jan 2000 to Jun 2014. Clinical, chemotherapy (CT), radiation (RT), pathologic, and survival details were evaluated. For statistically significant associations, adjusted hazard ratios (HR) with 95% confidence intervals (CI) and 2-sided p-values are presented. Results: The study population comprised 66 consecutive patients with cT2N0 esophageal cancer. Median age was 60 years; 76% were male; 97% were Caucasian. Gastroesophageal junction was the primary site in 56%; distal esophagus in 29%; middle esophagus in 14%; histology was adenocarcinoma in 62 (94%) cases. 20 patients received preop treatment (Rx): CT+RT (15), CT (5). In patients without preoperative Rx (n = 46, 70%), pathologic staging was > T2N0 in 54% (n = 25; T3 = 17, T4 = 1, N+ = 20), < T2N0 in 37% (n = 17), and T2N0 in 9% (n = 4). No < T2N0 or T2N0 patient received postop Rx. Of 25 > T2N0, 15 received postop Rx: CT+RT (14), CT (1). 5-fluourouracil-cisplatin was the most common CT regimen. Median overall survival (mOS) after 7 years of median follow-up was: overall, 48 mths (34 deaths, 52%); < T2N0/T2N0, 93 mths; > T2N0 with postop Rx, 69 mths; > T2N0 without postop Rx, 15 mths (p > 0.05 for comparison). Only node-positive disease on pathology was associated with mortality (mOS for N+ vs. N- was 28 vs. 118 mths, HR for mortality = 2.74, 95% CI = 1.30-5.76, p = 0.008); T-stage, surgical margins, timing or type of therapy were not. Conclusions: Clinical staging of cT2N0 esophageal cancer is concordant with pathologic staging in less than 10% of patients; a majority are under-staged. Strong consideration should be given to pre- or post-operative treatment in this population. Improvements in clinical staging approaches are urgently needed to avoid over- and under-treatment in this setting.
Correlation of locoregional treatment failures with radiotherapy target volumes after radiochemotherapy for esophageal cancer.
Authors: Gani Cihan , Fischer Stefan Georg , Zips Daniel
Published: February 2017

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Background: Radiotherapy is a mainstay in curative treatment concepts of esophageal cancer. Despite extensive treatment fields locoregional recurrences are frequent. We therefore aimed to evaluate the exact patterns of locoregional recurrence and correlate these recurrences with radiotherapy target volumes. Methods: Diagnostic PET-CT or CT imaging studies showing locoregional recurrences after preoperative or definitive radiochemotherapy for squamous or adenocarcinoma of the esophagus were matched with CT scans used for treatment planning. Distance of the recurrence from the Clinical Target Volume (CTV), Planning Target Volume (PTV) and the dose at the failure site were the determined. Target volume definition was in line with international standards. Results: We identified 104 patients treated with either definitive (n = 81) or preoperative radiochemotherapy (n = 23). After exclusion of patients with a history of second malignancies we found 25 locoregional recurrences in 20 patients. Median time to locoregional failure was 8 months (range 2-26 months). Six of 25 recurrences (24%) were located intraluminal in the initial Gross Tumor Volume (GTV), three of 25 (12%) were in-field nodal failures and five (20%) more than 1 cm distant from the PTV. Nine (36%) locoregional recurrences occurred within 1 cm of the cranial or distal end of the CTV, between the CTV and PTV or out-of-field adjacent to the PTV. Two patients developed anastomotic recurrence after surgery. Conclusions: Matching of diagnostic CTs showing local recurrences with radiotherapy planning CT data set allows the correlations of local recurrences with target volumes. Despite extensive safety margins, field margin recurrences remain a considerable problem in the treatment of esophageal cancer. The use of advanced radiotherapy techniques might facilitate larger treatment volumes without increasing toxicity.
Factors predictive of tumor recurrence and overall survival in patients with esophageal cancer who have pathologic complete response after neo-adjuvant therapy.
Authors: Gangi Alexandra , Hoffe Sarah E. , Frakes Jessica M. , Almhanna Khaldoun , Pena Luis , Fontaine Jacques , Blackham Aaron Udell , Pimiento Jose Mario
Published: February 2017

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Background: Pathologic complete response (pCR) to neoadjuvant therapy is presumably associated with favorable outcomes in patients (pts) with esophageal cancer, but reported survival rates vary. This study evaluates patterns of recurrence after curative esophagectomy and identifies factors predictive of recurrent disease and overall survival (OS) in patients with pCR. Methods: An IRB-approved, retrospective review of a prospective esophageal cancer database was conducted. Patient demographics, perioperative data, and outcomes were examined. Recurrences were classified as locoregional (LR) or systemic. Cox regression model and Kaplan–Meier (KM) plots were used for survival analysis. Results: 837 pts with invasive esophageal cancer treated at a single institution from 1994 to 2013 were identified. 176 pts underwent neoadjuvant therapy followed by surgery and had pCR. Of these, 93.7% had adenocarcinoma and 6.3% had squamous cell cancer. Mean age was 56.6 and most pts were white (96.6%) males (79.5%). Median follow up was 42.6 months. 95 pts were treated before 2007 and 81 after. Most pts (85%) underwent transthoracic esophagectomy. All 176 pts received chemotherapy and radiation; dose-specific information was available on 144 pts, of whom most received 50.4 Gy (45%). 170 pts had recurrence data available: 39 (22.9%) had recurrent disease at a mean of 18.3 months; 5 (2.9%) with LR and 34 (20%) with systemic disease. On multivariate analysis, when evaluating patient demographics, pretreatment stage, type of surgery, type of chemotherapy, and number of lymph nodes resected, only pretreatment stage was associated with recurrence (p = 0.04). Median time to recurrence was 26.3 months for LR disease and 10.9 months for systemic disease (p = 0.3). KM estimates determined that pre-treatment stage and time of treatment ( < 2007 or ≥ 2007) were predictive of improved OS (p < 0.01, = 0.03). Conclusions: The incidence of disease recurrence in pts who experience pCR is low. The pretreatment stage and time of treatment were independent predictors of improved OS. Enhancing treatment strategies to maximize pCR would improve outcomes in pts with esophageal cancer.
NETTER-1 phase III: Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate.
Authors: Strosberg Jonathan R. , Wolin Edward M. , Chasen Beth , Kulke Matthew H. , Bushnell David L , Caplin Martyn E. , Baum Richard P. , Kunz Pamela L. , Hobday Timothy J. , Hendifar Andrew Eugene , Oberg Kjell E. , Lopera Sierra Maribel , Kwekkeboom Dik J. , Ruszniewski Philippe B. , Krenning Eric
Published: February 2017

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Background: Currently, there are limited therapeutic options for patients with advanced midgut neuroendocrine tumors progressing on first-line somatostatin analog therapy. Methods: NETTER-1 is the first Phase III multicentric, randomized, controlled trial evaluating 177Lu-DOTA0-Tyr3-Octreotate (Lutathera) in patients with inoperable, progressive, somatostatin receptor positive midgut NETs. 230 patients with Grade 1-2 metastatic midgut NETs were randomized to receive Lutathera 7.4 GBq every 8 weeks (x4 administrations) versus Octreotide LAR 60 mg every 4-weeks. The primary endpoint was PFS per RECIST 1.1 criteria, with objective tumor assessment performed by an independent reading center every 12 weeks. Secondary objectives included objective response rate, overall survival, toxicity, and health-related quality of life. Results: Enrolment was completed in February 2015, with a target of 230 patients randomized (1:1) in 36 European and 15 sites in the United States. At the time of statistical analysis, the number of centrally confirmed disease progressions or deaths was 23 in the Lutathera group and 67 in the Octreotide LAR 60 mg group. The median PFS was not reached for Lutathera and was 8.4 months with 60 mg Octreotide LAR [95% CI: 5.8-11.0 months], p < 0.0001, with a hazard ratio of 0.21 [95% CI: 0.13-0.34]. Within the current evaluable patient dataset for tumor responses (n = 201), the number of CR+PR was 19 (18.8%) in the Lutathera group and 3 (3.0%) in the Octreotide LAR 60 mg group (p < 0.0004). Although the OS data were not mature enough for a definitive analysis, the number of deaths was 13 in the Lutathera group and 22 in the Octreotide LAR 60 mg group (p < 0.019 at interim analysis) which suggests an improvement in overall survival. Conclusions: The Phase III NETTER-1 trial provides evidence for a clinically meaningful and statistically significant increase in PFS and ORR, and also suggests a survival benefit in patients with advanced midgut NETs treated with Lutathera. Clinical trial information: NCT01578239.
Angiogenic gene expression in primary neuroendocrine tumors and their metastases.
Authors: Milosavljevic Tanja , Hall Michael Anthony , Del Valle Luis , Juge Elise , Zabaleta Jovanny , Boudreaux J Philip , Wang Yi-Zarn , Anthony Catherine T. , Woltering Eugene
Published: February 2017

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Background: Neuroendocrine tumors (NETs) are neoplasms arising from the cells of the nervous, endocrine and hormonal systems. They most commonly originate in the small bowel (SB) and frequently metastasize to the lymph nodes (LNs) and/or liver (LV). Current treatment of metastatic NETs involves a variety of approaches including antiangiogenic therapies. Our group demonstrated that there are significant histologic and functional differences between the primary NETs and their nodal or organ metastases. We hypothesized that sampling of multiple tumor sites within the same individual will reveal differential expression profiles of angiogenesis-related genes. Methods: Tissue-matched normal and tumor tissue samples were obtained from patients with well differentiated NETs who underwent simultaneous removal of their primary tumor, nodal, and organ metastasis. High quality RNA was extracted from each tumor site using TRIzol and RNeasy Mini kit. Gene expression of 28 well-documented angiogenesis-related genes was assessed using Custom Quantitative RT-PCR array. These gene expression trends were validated by Illumina microarray and TaqMan analysis. Immunohistochemistry (IHC) staining was performed using Avidin-Biotin-Peroxidase complex, with the markers: SSTR2 and FGFR3. Results: Normal SB, LN, and LV gene expression of 28 genes was compared to that of the tumor sample at each tumor site [4-fold change, p ≤ 0.01]. A consistent up-regulation of SSTR2 and SSTR1 was seen in 18/24 (75%) samples. Up-regulation of FGFR3 and SSTR5 was observed in 13/24 (50%) of tumors. TGFA and IGF were consistently down-regulated in 12/24 (50%) and 10/24 (42%) of tumor samples, respectively. Six genes expression trends were validated by TaqMan analysis and Illumina microarray analysis. IHC staining revealed higher SSTR2 and FGFR3 protein expression in all three tumor sites compared to the control. Conclusions: Expression of angiogenesis-related genes varies between the primary tumor (SB) and metastatic sites (LV, LN) within the same individual. We found a positive correlation between SSTR2 and FGFR3 gene and protein expression levels in all three tumor sites.
Pancreatic cancer: Survival in clinical trials versus the real world.
Authors: Sarkar Reith Roy , Matsuno Rayna , Murphy James Don
Published: February 2017

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Background: Physicians often use clinical trial data to estimate expected survival for their patients, however clinical trial results may not generalize to a broader population. Given the need for accurate prognostication, we examined whether the survival of clinical trial pancreatic adenocarcinoma patients was similar to “real world” patients. Methods: We conducted a literature search using Pubmed to identify pancreatic adenocarcinoma Phase III trials published between 2005 and 2012. We excluded secondary or pooled analyses, trials with second-line treatments, and non-randomized studies. We compared clinical trial patients to a cohort of patients from the Surveillance, Epidemiology, and End Results (SEER) program, matching for diagnosis year, age and stage of disease. We evaluated for differences in median survival, 1-year survival, and 2-year survival. Results: We identified 27 trials (3 metastatic, 16 mixed metastatic and locally advanced, 3 locally advanced, and 5 resectable) that fit our search criteria, consisting of 8,438 patients. Compared to SEER the median survival was higher in 98% of the individual clinical trial arms by an average of 3.7 months (p = 0.001). The 1-year overall survival rate was higher in 100% of the clinical trial arms by an average of 12.3% (p <.0001). The 2-year overall survival was higher in 76% of the clinical trial arms by an average of 5.1% (p <.0001). The survival differences between SEER and clinical trials were greatest for patients with metastatic pancreatic cancer. Conclusions: We found that clinical trial patients have profoundly improved survival compared to patients in the SEER database, suggesting that clinical trial survival estimates may not generalize to “real world” patients with pancreatic cancer. Patient performance status, underlying comorbidity, and differences in treatment could not be assessed in SEER, though these factors likely explain a portion of the survival differences. These findings suggest that physicians should use caution when extrapolating survival estimates from clinical trials to the real world.
Functional imaging tests and CT scan: Detection of new metastases and clinical usefulness in digestive neuroendocrine neoplasms follow-up.
Authors: Merola Elettra , Pavel Marianne E. , Panzuto Francesco , Capurso Gabriele , Cicchese Noemi , Rinke Anja , Gress Thomas Mathias , Iannicelli Elsa , Prosperi Daniela , Pizzichini Patrizia , Kump Patrizia , Lipp Rainer , Partelli Stefano , Falconi Massimo , Wiedenmann Bertram , Delle Fave Gianfranco
Published: February 2017

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Background: Digestive Neuroendocrine Neoplasms (DNENs) express in up to 80% of cases somatostatin receptors (SSTRs), which can be detected by Functional Imaging Tests (FITs). FITs are needed at DNENs first diagnosis to define therapy but their role in follow-up (FU) is unclear. Moreover, with the introduction of targeted therapies, RECIST criteria are showing difficulties to assess tumor response to these drugs. The aim of this study was to evaluate, in metastatic DNENs FU, the diagnostic yield of FITs associated to Computed Tomography scan (CT) in terms of detecting new distant metastases (primary outcome) and of clinical usefulness (secondary outcome). Methods: Retrospective analysis of stage IV DNENs expressing SSTRs and with at least 24 month-FU. From 1995 to 2008 FIT performed was Octreoscan (OCT), subsequently it was 68Ga-DOTA- PET/CT (GaPET). CT was repeated every 6-12 months, FIT yearly. FU time was divided into 12 month-“units”, in which each patient had faced at least 1 CT and 1 FIT. Units were analyzed separately and then compared to each other. The gold standard adopted was the result of the imaging tests, the surgical and pathological findings collected for each patient during FU. Clinical usefulness was defined as “appropriate changes” in management (indication to further imaging tests, surgery, biopsy, change in therapy) due to CT and/or FITs. Results: Interim analysis of 381 units (median 3 per patient, range 2-7) obtained from 121 patients included so far (67.8% metastatic since diagnosis). New lesions were detected by CT alone in 82.3% of cases; adding OCT, the diagnostic yield was 9.6%, while adding GaPET 21.7% (P<0.05). CT was responsible in 83.5% of cases of useful changes in patients management; adding OCT, the diagnostic yield was 9.7% (P<0.05), while with GaPET 27.9% (P<0.05). Conclusions: In metastatic DNENs FU, the addition of FITs to CT significantly improves the detection rate of new lesions; this advantage influences clinical practice increasing the clinical usefulness, especially when GaPET is adopted.