bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of gamma-H2AX in circulating tumor cells (CTC) from patients receiving ABT-888 (veliparib) in combination with carboplatin on a phase I dose-escalation study (OSU-10080/NCI8609).
Authors: Garcia-Villa A.
Published: February 2017

58

Background: Non-invasive methods to accurately measure DNA damage induced by PARP inhibitors in the tumors are crucial in identifying the optimal biological dose and schedule of these novel agents. With the use of an antibody that targets the histone H2AX, which becomes phosphorylated on serine residue 139 (γ-H2AX), it is possible to measure DNA DSB in the cell. But repeated biopsy in patients with metastatic breast cancer is not feasible. We propose here to quantify γ-H2AX in CTCs as a measurement of DNA damage in the tumor in patients receiving veliparib (ABT-888), an oral PARP inhibitor and carboplatin on a phase I study.

Methods: CTCs were isolated in 10 mL of peripheral blood using negative selection with immunomagnetic tagging and removal of CD45 positive cells at 3 time points. Immunocytochemical staining for nucleus (DAPI), pan-cytokeratin CD45, and γ-H2AX was completed on available samples. Double staining for nucleus and cytokeratin with high nucleus to cytoplasm ratio defined a CTC. The γ-H2AX foci present in the nucleus of the CTCs will be counted by immunocytochemistry (ICC) analysis.

Results: We negatively enriched blood sample from enrolled patients with metastatic breast cancer (n=6). CTCs were observed in all samples (55CTCs/mL of blood - 2000CTCs/mL of blood). Thus far 3 out of 6 patient samples have been analyzed. The number of CTCs per mL of blood after enrichment at baseline has a mean of 293, a median of 140 and a range of (684-140) At time point 1 the mean is 1071.33, the median is 1151 and the range is (1151-63). ICC analysis on the CTCs demonstrated the presence of γ-H2AX positive cells.

Conclusions: Our novel negative depletion method for isolating CTCs allows for separation of a wider range of CTCs, since it does not assume presence of epithelial markers before separation. This leads to improved yield and purity allowing better ICC detection of various markers directly on CTCs. Development and validation of the above methodology to determine γ-H2AX foci in CTCs will help in identifying a novel, non-invasive biomarker that can be used to assess the effect of DNA damaging agents during therapy.
Incidental breast lesions detected on diagnostic CT scans: A 3-year prospective study.
Authors: Ismail A. R.
Published: February 2017

69

Background: With increasing usage of diagnostic cross sectional radiology tests, patients are presenting to rapid access one-stop breast clinic with incidental breast lesions.

Methods: A prospective study over a 3-year period, collecting details of all patients shown to have breast abnormalities detected by computed tomography (CT) scans done for various reasons. These patients were assessed by clinical breast examination coupled with mammography, ultrasonography and tissue biopsy if indicated.

Results: An increasing trend has been seen in the total number of thoracic CT scans with 1,939 scans in 2005 and 5,215 scans in 2010 (169% increase). 26 patients were included in this study with CT scans showing incidental breast lesions in the last three years. They were all women with age range of 50-92 (median 82.5) years. The clinical indications of CT scans included evaluation of the abnormal chest radiograph (8, 31%), preoperative evaluation of non-breast malignancy (3, 11%), infectious diseases (3, 11%), weight loss (7, 27%) and miscellaneous (5, 20%). These 13 breast cancer patients constitute 1.36% of 956 breast cancers diagnosed over this three-year period. 8 out of 13 breast cancer patients in this group (62%) had metastases at the time of diagnosis.

Conclusions: A significant number of breast lesions incidentally found on CT scans are shown to be breast cancers (50%). These patients need rapid access to one-stop breast clinic for full evaluation.

[Table: see text]
Axillary node staging for microinvasive breast cancer: Is it justified?
Authors: Lyons J. M. , Stempel M. , Van Zee K. J. , Cody H. S.
Published: February 2017

7

Background: DCIS with microinvasion (DCISM) is a lesion for which prognosis may be intermediate between that of DCIS and invasive breast cancer, but for which the role of axillary lymph node staging remains controversial. Here we report clinical characteristics and outcome in 112 patients with DCISM, with a particular focus on the role of sentinel lymph node (SLN) biopsy.

Methods: From our prospective database we retrospectively identified 112 patients with a diagnosis of DCISM who had undergone SLN biopsy between 1996 and 2004 at Memorial Sloan-Kettering Cancer Center. Median follow up was 6 years.

Results: We found positive SLN in 12% (14/112) of all patients, macrometastases in 2.7% (3/112) and micrometastases in 10% (11/112). We performed axillary dissection (ALND) in all patients with macrometastases (3/3), finding additional positive nodes in 66% (2/3), and in 27% of those with micrometastases (3/11), finding no additional positive nodes. Among patients with negative SLN (38% of whom received systemic therapy), there were 5 loco-regional recurrences (1 in the ipsilateral axilla, and 4 in the ipsilateral breast, all DCIS) and 4 contralateral second primary breast cancers. Among patients with positive SLN (86% of whom received systemic adjuvant therapy), there were no loco-regional or distant recurrences.

Conclusions: Positive SLN were present in 12% of our patients with DCISM, none of whom experienced recurrence at 6 years’ follow up. SLN biopsy may be justified for DCISM, but is clearly most beneficial to identify a very small subset of DCISM patients (2.7%, with SLN macrometastases) who could benefit from systemic adjuvant therapy. Our data imply that between 125 and 250 SLN biopsy procedures would be required to avoid breast cancer mortality in 1 patient, and do not support the routine use of ALND for SLN-positive patients. We recommend a critical reappraisal of routine SLN biopsy for DCISM.
Recurrence rates and long-term survival in women diagnosed with breast cancer at age 40 and younger.
Authors: Buckley J. M. , Coopey S. , Samphao S. , Specht M. C. , Hughes K. S. , Gadd M. , Taghian A. G. , Smith B. L.
Published: February 2017

70

Background: Young age at diagnosis of breast cancer has been reported to be an independent risk factor for disease recurrence. However, there is little data on long term survival of young patients. We present long term follow up of a large cohort of women diagnosed with breast cancer at age 40 and younger. We determined rates of loco-regional recurrence (LRR), distant recurrence, and overall survival and adjusted for the patient and tumor characteristics which potentially predict outcomes.

Methods: Following Institutional Review Board approval, data from the medical records of 628 women diagnosed with breast cancer at age 40 or younger between 1996 and 2008 were collected. Survival curves were estimated using the Kaplan Meier method.

Results: Median age was 37 years (range: 21-40) and median follow-up was 72 months (range: 5-177). The rates of LRR as a first site of recurrence were 5.56% at 5 years and 12.11% at 10 years. In the entire population, with median follow-up of 72 months, there was no difference in the rates of loco-regional failure between patients who underwent breast conserving therapy (7.34%) compared to mastectomy (7.40%) (p=0.980). The rates of distant recurrence as a first event were 10.65% at 5 years and 14.58% at 10 years. Overall survival was 93.1% at 5 years and 87.26% at 10 years. 79.1% of patients received systemic therapy. For patients who developed disease recurrence, either LRR or distant, median time to first recurrence was 35 months (range: 3-167).

Conclusions: Women aged 40 and younger at diagnosis of breast cancer have a good prognosis, with low overall recurrence rates at 5 and 10 years. Local recurrence in our cohort is lower than in prior studies, suggesting advances in therapy have made breast conservation a safe option in young breast cancer patients.
Breast cancer characteristics in yielders and nonyielders of nipple aspiration fluid.
Authors: Brutus V. , McGathey C. , Kmiecik T. , Bethke K. P. , Jeruss J. S. , Hansen N. M. , Khan S. A.
Published: February 2017

71

Background: Nipple aspirate fluid (NAF) is an attractive biosample for the investigation of breast cancer risk factors. The reported NAF yield rate varies from 30% to 90% in various studies, raising questions about its value as a risk assessment and about the generalizability of data generated in NAF-yielders to non-yielders. To date, there is no data regarding the characteristics of breast cancers that arise in NAF-yielders and non-yielders.

Methods: We examined breast cancer characteristics in NAF yielders and the non NAF yielders in an on-going case control study assessing the hormone concentrations of NAF in breast cancer cases and healthy screening controls. 299 women with recently diagnosed breast cancer were recruited from the Lynn Sage Breast Center. NAF collection was performed from the non cancer breast in the clinic, either before surgery or more than one week post-operatively. NAF yielders produced at least 2 ul of NAF. Each patient completed a detailed study questionnaire. Breast cancer characteristics were recorded on each participant.

Results: Among 299 recruited patients 130 (40%) were non NAF yielders (group A) and 169 (60%) were NAF yielders (group B). The association of breast cancer risk factors was compared between them. There were no significant differences in the tumor characteristics. The tumor size, grade, number of positive lymph nodes, and fraction of hormone receptor positive, HER2 positive, and triple negative tumors was similar in NAF-yielders and non-yielders (smallest p value 0.295, for histology, ductal versus lobular). Among the major breast cancer risk factors, the only significant differences were that NAF yielders were younger than non-yielders (50.8 vs. 53.6 years, p < 0.0001) and were more likely to have a history of post-menopausal hormone use (27% among NAF yielders and 7% among non-yielders, p < 0.0001).

Conclusions: Tumor characteristics of NAF-yielders and non-yielders are similar, suggesting that there is no qualitative difference between these two groups. The risk predictors developed in yielders can apply to non-yielders.
Nomograms for predicting the risk of arm lymphedema after axillary dissection in breast cancer.
Authors: Bevilacqua J. L. B. , Kattan M. W. , Yu C. , Koifman S. , Mattos I. E. , Koifman R. J. , Bergmann A.
Published: February 2017

8

Background: Lymphedema (LE) after axillary dissection (AD) is a multifactorial, chronic, and disabling condition that currently affects an estimated 4 million people worldwide. Although several risk factors have been described, it is difficult to estimate the risk in individual patients. We therefore developed nomograms based on a large data set.

Methods: Clinicopathological features were collected from a prospective cohort study of 1,054 women with unilateral breast cancer undergoing AD as part of their surgical treatment from 8/2001 to 11/2002. LE was defined as a volume difference of at least 200 mL between arms at 6 months or more after surgery. The cumulative incidence of LE was ascertained by the Kaplan-Meier method, and Cox proportional hazards models were used to predict the risk of developing LE based on the available data at each timepoint: (I) preoperatively; (II) within 6 months from surgery; and (III) 6 months or later after surgery.

Results: The 5-year cumulative incidence of LE was 30.3%. Independent risk factors for LE were age, body mass index, ipsilateral arm chemotherapy infusions, level of AD, location of radiotherapy field, development of postoperative seroma, infection, and early edema. When applied to the validation set, the concordance indexes were 0.706, 0.729, and 0.736 for models I, II, and III, respectively.

Conclusions: The proposed nomograms can help physicians and patients to predict the 5-year probability of LE after AD for breast cancer. Free online versions of the nomograms will be available.
Effect of axillary dissection for occult detected sentinel nodes metastases on survival: NSABP B-32.
Authors: Julian T. B. , Anderson S. J. , Mamounas E. P. , Krag D. N. , Weaver D. , Ashikaga T. , Harlow S. P. , Wolmark N.
Published: February 2017

80

Background: In NSABP B-32 trial 5,611 women with invasive breast cancer were randomly assigned to sentinel lymph node biopsy (SLNB) plus axillary dissection (Group [Grp] 1) or SLNB alone (Grp 2). There was no significant difference in OS or DFS reported between the two groups. Initial permanent pathologic assessment of the SLNs at participating sites was designed to identify all macrometastases >2 mm and consisted of slicing the SLNs at approximately 2.0 mm intervals, embedding all slices in paraffin tissue blocks, and examining one hematoxylin and eosin stained slide from each block. Routine use of IHC or sectioning of deeper levels was prohibited. SLN paraffin tissue blocks from cases with pathologically negative SLNs were later evaluated centrally for occult metastases deeper in the blocks. This study evaluates group outcomes related to occult metastases.

Methods: Routine and cytokeratin IHC stains were used at two widely spaced additional levels. Using this technique, occult metastases were detected in 15.9% of the patients (pts) with initially negative SLNs (616 / 3884 cases). Of the 616 cases, 431 (69.8%) had isolated tumor-cell clusters, 171 (27.9%) had micrometastases, and 14 (2.3%) had macrometastases (Weaver D, et al: N Engl J Med, 2011).

Results: 316 (16.4%) of 1924 pts had occult metastases in Grp 1 and 300 (15.3%) of 1960 in Grp 2. Non-sentinel node status was available in 312/316 pts in Grp 1; 23 (7.4%) had positive non-sentinel nodes. In pts with occult metastases, there were no significant differences in OS or DFS between groups (Grp 2 vs. Grp 1 OS HR: 0.89, p=0.62; DFS HR: 0.79, p=0.16). There were no significant differences in OS or DFS between the groups in pts who were negative for occult metastases (Grp 2 vs. 1 OS HR:1.25, p=0.07; DFS HR: 1.11, p=0.22).

Conclusions: A more detailed assessment of the SLNs with deeper sectioning and IHC staining detected a significant level of occult metastases in clinically node negative pts. However, no benefit was seen by the addition of axillary dissection in pts with occult SLN metastases. Supported by NCI: U10-CA-12027, U10-CA-37377, U10-CA-69974, U10-CA-69651, and ARRA ROI CA 74137
Outcomes by breast cancer subtype in patients treated with accelerated partial breast irradiation.
Authors: Wilkinson J. B. , Shah C. , Amin M. , Shaitelman S. F. , Nadeau L. , Chen P. , Wallace M. , Mitchell C. , Grills I. S. , Martinez A. A. , Vicini F. A.
Published: February 2017

83

Background: To determine clinical outcomes for patients treated with accelerated partial breast irradiation (APBI) based on breast cancer subtype.

Methods: We evaluated 516 consecutive patients who received APBI with a minimum follow-up of 6 months. Methods of APBI delivery included interstitial brachytherapy (n=221), balloon-based brachytherapy (n=201), and 3D-CRT (n=106). Women were assigned a breast cancer subtype (BCST) based on results of testing for estrogen (ER), progesterone (PR), and human epidermal growth factor (HER2/neu) receptors. Those without test results for all three receptors were excluded. 278 patients were eligible and submitted for analysis. Receptor subtypes were approximated as follows: ER+, PR+/–, and HER-2 negative [luminal A (LA), 164 pts.]; ER+, PR+/–, and HER-2 positive [luminal B (LB), 81 pts.]; ER/PR–, HER-2+ [HER-2 (H2), 5 pts.], and ER/PR/HER-2 negative [basal (B), 28 pts.]. An analysis was then performed to estimate IBTR, RNF, DM, DFS, CSS, and OS.

Results: Mean age was 66 years, median follow-up was 4.9 yrs. Basal and H2 subtype patients had higher histologic grades (Gr. 3 = 75% vs. 10% LA/LB, p<0.001), larger tumors (13.0mm vs. 10.7mm LA/LB, p=0.05), and were more likely to receive chemotherapy (68% vs. 15% LA/LB, p<0.001). Basal subtype patients were also more likely to be African American (18% vs. 4% LA/LB, p=0.002). Margin and nodal status were similar between all BCSTs. At five years, IBTR rates were 2.9%, 3.2%, 0%, and 4.8% for LA, LB, H2, and B subtypes, respectively (p=0.75). The IBTR within the B subtype group was due to a single elsewhere failure, the rate of which was not statistically different than that for the LA subtype (2.9%, p=0.30). DM was only seen in LA (2.5%) and LB (1.4%) (p=0.87). Disease-free survival (95-100%), CSS (97%-100%), and OS (80-100%) (Table) were also not statistically different (p=0.98, 0.85, 0.24, respectively) between BCST categories.

Conclusions: Five-year local control rates after treatment with APBI are excellent for luminal, HER2, and triple-negative phenotypes of early-stage breast cancer. Further study of BCST is important and may be useful when counseling patients on adjuvant treatment options following breast-conserving surgery.
The DOC combination in advanced gastric cancer: Preliminary data of a phase II study.
Authors: Pancotti A. , Santomaggio A. , Cianci G. , Scipioni T. , Martella F. , Foglia R. , Marchetti P.
Published: February 2017

104

Background: We describe activity of first line chemotherapy in advanced gastric carcinoma with docetaxel (DTX), oxaliplatin (OHP) and capecitabine (CAP).

Methods: Patients (pts) were enrolled in the phase II study, if they had the main subsequent criteria: histologically confirmed diagnosis of advanced gastric cancer (AGC) (local advanced or metastatic disease); normal renal and hepatic function; no myocardial infarction or angina pectoris; no uncontrolled severe diseases or active infections. Treatment schedule: DTX at fixed dose of 65 mg/m2 on day 1, OHP at fixed dose of 110 mg/m2 on day 1, CAP at fixed dose of 1,600 mg/ m2 with crhonomodulation in trhee daily administration from day 1 to day 14, every 3 weeks. Dose-limiting toxicity (DLT): G3 non-haematological or G4 haematological. Study design: Simon two-stage phase II optimal design with power (1- b) 80%, error a 5%, error b 20%, P0 40%, P1 60%. Planned sample size: I stage 7/16, II stage 23/46. Primary endpoint was response rate (RR). Secondary endpoints were time to progression (TTP), overall survival (OS), toxicity and quality of life.

Results: 38 pts were enrolled: 24 men and 14 women, median age of 58 years (range 50-67). Median number of cycles per pts was 4,5 (range 3-6). Total cycles administered: 41. Cumulative G3-4 toxicities were: neutropenia 21%, anemia 14%, asthenia 9%. G1-2 toxicities were: diarrhea 22%, neurotoxicity 18%. Median received-DI of DTX: 20 mg/mq/week (93% of recommended-DI), OHP 35 mg/mq/week (95%), CAP 7,000 mg/mq/week (94%) per patient, respectively. Overall pts were assessable (according to intent-to-treat analysis) with 58% (a0.05, CI + 29) of objective responses (OR): 7 partial responses, 4 stable disease and 1 progression. The disease control rate (DCR) was 91%. TTP and OS not done because median follow-up was of 8 months (2-15) only.

Conclusions: The combination DOC is tolerable without G3-4 toxicity and preliminary data show very high activity.

No significant financial relationships to disclose.
Radiation oncologist density and esophageal cancer mortality.
Authors: Aneja S. , Yu J. B.
Published: February 2017

116

Background: Although the use of radiation therapy to treat esophageal cancer is increasing, there exists a geographic variation among the distribution of radiation oncologists. The impact of this variation on esophageal cancer (EC) outcomes remains unexplored. The goal of this study was to determine the effect of radiation oncologist density on EC mortality.

Methods: Using county- level data from the 2008 Area Resource File, National Program for Cancer Registries, and U.S. Centers for Disease Control, a multivariate regression model was constructed for EC mortality, controlling for county-level categorized radiation oncologists density, demographics, socioeconomic status, and existing hospital facilities.

Results: There was a statistically significant reduction in esophageal cancer mortality (reduction ranging from 22% to 79% p < 0.001) associated with counties that possessed at least one radiation oncologist. However, increasing the county density to greater than two radiation oncologists per 100,000 people had no statistically significant reduction in EC mortality.

Conclusions: The presence of a radiation oncologist is associated with lowered mortality for EC within that county, but increasing radiation oncologist density does not yield further improvements. Therefore, as the use of radiation therapy to treat EC increases, a detailed understanding of distribution of the radiation oncologists is essential for providing the greatest improvement in EC mortality outcomes.

[Table: see text]

No significant financial relationships to disclose.
Phase II trial of S-1 combined with oxaliplatin (SOX) as neoadjuvant chemotherapy for locally advanced gastric cancer.
Authors: Chen L.
Published: February 2017

122

Background: Previous phase II trial with combination therapy of S-1 plus oxaliplatin (SOX) demonstrated high response rate and well tolerability in patients with untreated advanced gastric cancer. The aim of this phase II trial was to evaluate the efficacy and safety of SOX as neoadjuvant chemotherapy for locally advanced gastric cancer (AGC).

Methods: Eligibility criteria included a histologically proven AGC with stage IIIb, IIIc (AJCC 7th edition), at least 1 measurable lesion, no prior chemotherapy, ECOG 0∼2, adequate hepatic, renal, and bone marrow function. Enrolled patients were staged by EUS and CT. The neoadjuvant chemotherapy consisted of 3-4 cycles of oxaliplatin (130 mg/m2) on day 1 and S-1 (80 mg/m2/day) for 14 days with 7 days rest. After chemotherapy, the patients underwent surgery.

Results: From Dec 2009 to Sep 2010, 35 patients (IIIb; 19pts, IIIc; 16pts) were enrolled. The median age of the patients was 54.6 years (range; 20-72 y). All patients were available for evaluating the clinical responese and adverse events. The overall response rate was 68.5% (1CR, 23 PR, 9 SD, 2 PD). 32 patients underwent surgical resection. Of them, 27 patients underwent standard D2 surgery and 5 patients had palliative surgery. 25 patients had R0 resection. Postoperative pathological examination showed that most of the surgical patients were in T4a stage. According to Lauren classification, 71.9% patiens (23/32pts) were diffuse type, SOX showed higher respons rate (1CR, 20 PR, 2 SD, RR: 91.3%) among these patients. Major grade 3/4 hematological toxicities were anemia (5.7%), neutropenia (5.7%) and liver dysfunction (8.6%) and non-hematological toxicities were anorexia (5.7%) and vomiting (11.4%). But most of the adverse events were managable.

Conclusions: Neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX) showed high response rate and and R0 resection rate for locally advanced GC, especially for diffuse type patients. All the patients did not have severe toxicity during the process of chemotherapy. This is the preliminary results, and the survival benefit in locally advanced GC patients that respond to SOX neoadjuvant chemotherapy needs to be addressed by a randomized-controlled trial.

No significant financial relationships to disclose.
Phase I dose-finding study of epirubicin, oxaliplatin, and S-1 (EOS) in patients with previously untreated advanced gastric cancer (AGC).
Authors: Sym S. , Hong J. , Park J. , Cho E. , Lee W. , Chung M. , Park Y. , Lee J. , Shin D.
Published: February 2017

123

Background: To determine the recommended dose (RD) and dose-limiting toxicity (DLT) of EOS combination in patients with previously untreated AGC.

Methods: Previously untreated patients with histologically proven metastatic or recurrent AGC and ECOG performance status 0-2 were enrolled. Fixed dose of epirubicin (50 mg/m2) and oxaliplatin (130 mg/m2) was administered i.v. on day 1. The dose of S-1 was escalated as following schedule: Level I: 30 mg/m2, Level II: 40 mg/m2, Level III: 45 mg/m2, Level IV: 50 mg/m2. S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 21 days. DLTs were evaluated during the first two cycles of treatment.

Results: Nineteen patients were enrolled: 13 patients in dose-escalation phase and 6 patients in the extension at the RD. Median age was 53 years (range, 40-71 years). At dose level II, 1 DLT (grade 4 neutropenia lasting more than 5 days) was found among 6 patients while at dose level III, 2 DLTs (grade 3 diarrhea and nausea) were observed among 4 patients. Therefore, the dose level II was determined as RD. Cumulative (all cycles) grade 3/4 toxicity included neuropenia (58%), leucopenia (32%), thrombocytopenia (11%), diarrhea (11%), and nausea (5%). Of 13 patients with measurable lesions, 8 achieved partial response and 3 showed stable diseases, and the objective response rate was 62% (95% CI, 36-88%). The median progression-free survival was 6.5 months (95% CI, 4.7-8.2 months).

Conclusions: The RD of the EOS regimen in patients with previously untreated AGC was epirubicin 50 mg/m2 and oxaliplatin 130 mg/m2 on day 1 and S-1 40 mg/m2 twice a day on days 1-14 of every 21-day cycle. This regimen seems to have promising preliminary activity.

No significant financial relationships to disclose.
Population-based analysis of multimodality treatment of gastric cancer.
Authors: Cen P. , Xing Y. , Wray C. J. , Fallon M. B. , Machicao V. I. , Dougherty D. , Amato R. J.
Published: February 2017

124

Background: Limited data is available for the role of multimodality management for gastric adenocarcinoma and its outcome in the community.

Methods: We retrospectively reviewed the outcomes for 341 patients (pts) who were diagnosed with gastric cancer in a community-based health-care system, including 9 hospitals, from 2000 to 2009.

Results: 148/341 pts had undergone surgery and were included in the analysis. Median age at diagnosis was 68 year (range: 32-96), 56% were male, 55% were Caucasian and 25% were black. The stage distribution was as follows: 27% (40 pts) localized, 61% (90 pts) locally advanced and 12% (18 pts) with distant metastasis. 98 pts (66%) received surgery alone, 22 pts (15%) received perioperative chemotherapy, and 28 pts (19%) received perioperative chemo-radiation. After a median follow-up time of 5.2 yrs, the median OS for the entire group was 1.9 years, and 88 deaths had occurred at the last follow up. By stage, the median OS was 7 yrs, 2.3 yrs, and 0.3 yrs for localized stage, regional stage, and metastatic disease, respectively. The 5-yr survival was significantly better in pts who received perioperative chemo-radiation (68%), compared to those who received with surgery alone (33%) or perioperative chemotherapy (0%) (p=0.002). The 5-yr survivals by stage and treatment are shown in the table.

Conclusions: Perioperative chemo-radiation was associated with a significantly better OS compared to surgery alone. Trimodality therapy for gastric cancer appears to be underutilized in the community setting described here. The survival advantage of surgery plus chemoradiation compared to surgery plus chemotherapy remains controversial and should be investigated in clinical trials.

[Table: see text]

No significant financial relationships to disclose.
Palonosetron versus other 5-HT3–receptor antagonists for chemotherapy-induced nausea and vomiting prevention in patients with noncolon gastrointestinal cancers.
Authors: Balu S. , Craver C. , Gayle J. , Buchner D.
Published: February 2017

129

Background: This study analyzed the risk of chemotherapy induced nausea and vomiting (N&V) [CINV] associated with palonosetron versus other 5-HT3 receptor antagonists (5-HT3-RAs) initiation among patients with non-colon gastrointestinal cancers receiving chemotherapy (CT) in a hospital outpatient setting.

Methods: Patients diagnosed with any non-colon gastrointestinal cancer initiating any CT and antiemetic prophylaxis with palonosetron (Group 1) or other 5-HT3-RAs (Group 2) for the first time (index date) between 4/1/2007-3/31/2009 were identified from the Premier Perspective database. Patients included were aged ≥ 18 years, with no evidence of N&V, CT, and antiemetic medication in the 6 month pre-index date period, and with at least 36 consecutive months of data. A negative binomial GLM regression analysis was done estimating the number of CINV events (identified through either ICD-9-CM codes for N&V and/or volume depletion or CINV-related rescue medications 1 day after CT administration) in the follow-up period (first of 8 CT cycles or 6 months post index date) between the 2 groups (after matching on CT and specific CT cycle).

Results: Of 658 identified patients, 215 initiated on palonosetron (Group 1; 32.7%). Group 1 patients were significantly younger [61.7 (SD: 11.3) vs. 62.2 (12.1) years; p = 0.0073], a higher percent received highly emetogenic chemotherapy (27.4% vs. 19.4%; p < 0.0001), and comprised of less African Americans (7.0% vs. 13.3%). In the follow-up period, the unadjusted number of CINV events per patient per CT cycle for Group 1 patients was lower versus Group 2 patients, though statistically non-significant (4.7 vs. 5.2; p = 0.1714). However, after controlling for differences in demographic and clinical variables, the regression model predicted a statistically significant reduction (30.9%) in the total CINV events per patient per CT cycle in favor of Group 1 patients; p = 0.0086.

Conclusions: In this analysis, patients with non-colon gastrointestinal cancers initiated on palonosetron were more likely to experience a significantly lower rate of CINV events per patient per CT cycle versus those initiated on other 5-HT3-RAs.

[Table: see text]
The use of small-caliber, covered, self-expandable metal stents for palliation of severe malignant dysphagia.
Authors: Kucera S. , Harris C. L. , Vignesh S. , Klapman J. , Barthel J. S.
Published: February 2017

134

Background: Self-expandable covered metal stents are an important component of palliative care for malignant dysphagia; however significant complication rates have been associated with large diameter stents. We hypothesized that small-caliber, fully covered, self-expandable metal stents (sccSEMS) would prove adequate palliation of dysphagia in the absence of major complications.

Methods: Prospective observational study of 17 patients presenting with severe malignant dysphagia between 12/1/08 and 7/30/10. 31 sccSEMS with internal diameters ranging from 8 mm to 16 mm were placed in 17 patients with pre-stent luminal diameters of < 8 mm (n = 13) or 8-10 mm (n = 4). 7 tracheobronchial stents (internal diameter 14–16 mm), 2 biliary stents (internal diameter 8–10 mm), and 22 specially constructed esophageal stents (internal diameter 12–16 mm) were placed. All stents were placed under direct endoscopic vision without fluoroscopic support. Dysphagia scores, migration rates, and complications were identified through review of endoscopy reports, outpatient clinical encounters, and 24-hour post-procedure phone surveys. Anticipated stent migration was defined as events which occurred during chemoradiation. Unanticipated stent migration was defined as events which occurred in the absence of treatment.

Results: The post-stent median dysphagia score improved (decreased) from 3 to 2 (p = 0.0003). The overall median duration of first stent placement was 64 days, IQR 32 – 110 days. The overall migration rate was 35.5% (11/31). The anticipated migration rate was 60% (9/15); the unanticipated migration rate was 18.2% (2/11) (p = 0.051). All 11 of the migrated stents were retrieved endoscopically without complication. 9.7% (3/31) of patients reported self-limited sore throat or chest pain within 24-hours of stent placement. All 3 patients were managed conservatively without need for narcotic analgesics, hospitalization, or repeat endoscopy. No other complications occurred.

Conclusions: The direct endoscopic placement of sccSEMS in patients presenting with severe malignant dysphagia significantly improved dysphagia scores, provided excellent durability, and resulted in no major complications.

No significant financial relationships to disclose.
Endoscopic and endosonographic staging in the management of cancer of the stomach and the esophagogastric junction.
Authors: Töppler G. , Röper H. , Cameron S. , Füzesi L. , Beham A. , Ramadori G.
Published: February 2017

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Background: Staging of the primary tumor in patients with advanced adenocarcinoma of the stomach or the esophagogastric junction under chemotherapy is not generally recommended [ESMO clinical recommendations; Ann Oncol 2009]. RECIST criteria do not detect local tumor regression adequately. Standards for endoscopic staging throughout therapy have not yet been established.

Methods: Here we report on20 consecutive patients with locally advanced esophago or gastric adenocarcinoma which were treated with EOX or EOF (epirubicin, oxaliplatin, capecitabine or 5-FU). After two cycles of chemotherapy, therapeutic efficacy was assessed by gastroscopy (EGD), endosonography (EUS), ultrasonography (US) and CT-scan. EGD staging criteria included luminal occlusion, the aboral length of tumor involvement, tumor exulceration, formation of polypoid tissue or superficial ulcers, and gut motility. EUS-staging criteria included uT-staging of the different layers of the esophagogastric wall as well as of the adjacent lymph-nodes. Surgery was then performed within 2 to 4 weeks after the end of the third chemotherapy cycle.

Results: In all patients, an early response to chemotherapy was observed by EGD and EUS, including regression of tumor size (length and depth), and appearance: former exulcerative tissue became rather polypoid and less vulnerable, and motility was regained in areas were tumor regression was observed. For the assessment of local tumor behaviour under chemotherapy, CT-scan was of limited help, as it was only able to monitor lymphadenopathy. Only in 3/20 cases there was a concordance between the EUS and CT-scan, as verified by histopathological review of the surgical specimen.

Conclusions: EGD and EUS monitor early tumor response of the primary to chemotherapy adequately in all our cases of locally advanced esophago or gastric adenocarcinoma. Endoscopic measures are helpful for the assessment of early treatment response, and might help to direct therapeutic strategies.

No significant financial relationships to disclose.
A comparison of surgical resection for distal esophageal, gastroesophageal junction, and proximal gastric cancers in the Memphis metropolitan area (MMA).
Authors: Evangelist M. C. , Orr W. S. , Ul-Haq M. , Farooq A. , Khattak A. , Denbo J. , Mahmoud A. , Dilawari R. A. , Sachdev J. C. , Osarogiagbon R. U.
Published: February 2017

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Background: The incidence of distal esophageal (DE) and gastroesophageal junction (GEJ) tumors has increased rapidly in recent decades. They are often included in gastric cancer trials. The 7th AJCC staging has reclassified tumors of the DE, GEJ, and proximal stomach (PS) as esophageal cancers. We compared the historical management of these tumors in our community.

Methods: Review of all curative-intent DE, GEJ, and PS cancer resections at two healthcare institutions in the MMA from 1999-2008.

Results: Seventy patients were identified (Table). Males predominated. The histology was adenocarcinoma in 48% of DE, 91% of GEJ, and 100% of PS cancers. Preoperative endoscopic ultrasound (EUS) was performed in 10% of DE, 6% of GEJ, and 7% of PS patients. Neoadjuvant therapy was given to 29% of DE, 35% of GEJ and 0% of PS patients. R0 resection rates were similiar. Fewer DE and GEJ patients had up to 15 lymph nodes removed, yet lymph node metastasis was identified in 52% and 35% respectively, compared to 20% of PS patients (Table). Five-year survival rates were numerically higher in the DE and GEJ patients.

Conclusions: We identified differences in DE, GEJ, and PS tumors in a community setting with respect to preoperative management and lymph node sampling. Reclassification of DE, GEJ, and PS tumors by the AJCC suggests these groups now be treated uniformly as esophageal cancers, a shift from previous management as gastric cancers. Further, prospective evaluation is needed to assess the patterns of management and outcomes in tumors of the DE, GEJ and PS.

[Table: see text]

No significant financial relationships to disclose.
Locally advanced esophageal cancer: Actual 5-year survival comparing neoadjuvant and adjuvant chemoradiation.
Authors: Davis C. S. , Johns J. R. , Abood G. J. , Baker T. A. , Zank D. , Nagda S. , Aranha G. V. , Godellas C. V. , Shoup M.
Published: February 2017

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Background: Patients undergoing esophagectomy for locally advanced esophageal cancer are often candidates for chemoradiotherapy (CRT). It is unclear if there is a survival advantage for CRT when administered in the neoadjuvant (NCRT) versus the adjuvant (ACRT) setting. We report a single institution experience with actual long-term follow-up of patients with resected esophageal cancer treated with NCRT or ACRT.

Methods: Following IRB approval, a retrospective review of 123 patients undergoing Ivor-Lewis esophagectomy between January 1, 1990 through December 31, 2001 was conducted. Clinicopathologic variables were analyzed, and survival was determined from hospital records, the Social Security Death Index, and direct patient follow-up. All patients were followed for at least five years, and survival was assessed by Kaplan-Meier analysis.

Results: Of the 123 patients, 65 had surgery alone for early esophageal cancer and were excluded from the analysis. Of the remaining 58, 31 received NCRT and 27 received ACRT. There was no difference between groups for length of operation, blood loss, or complication rate. With all patients having at least 5 years of follow-up, the overall 1-year survival was 65% and 67% (p=0.866), 3-year survival was 42% and 33% (p=0.508), and 5-year survival was 26% and 22% (p=0.755) for the NCRT and ACRT groups, respectively (Table 1). Among those in the NCRT group, patients with a complete or partial response (n=20) had an improved 1-year survival as compared to those with no response at all (n=11; p=0.025). However, this difference did not persist at 3 and 5-years (p=0.224 and p=0.896, respectively).

Conclusions: In this study, all patients with locally advanced esophageal carcinoma who underwent Ivor-Lewis esophagectomy with either NCRT or ACRT were followed for at least 5 years. Not only was there no difference in perioperative morbidity or mortality, but the overall 5-year survival was almost identical between groups. Therefore, as NCRT may be better tolerated and more easily administered, we advocate its use over ACRT in those with locally advanced esophageal cancer.

No significant financial relationships to disclose.
Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-3).
Authors: Shah M. H. , Ito T. , Lombard-Bohas C. , Wolin E. M. , Van Cutsem E. , Sachs C. , Winkler R. E. , Lincy J. , Hobday T. J. , Yao J. C.
Published: February 2017

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Background: There is an unmet medical need for effective treatments for patients with advanced pNET. Systemic therapies for advanced pNET are limited both by toxicity and efficacy. Everolimus, an oral mTOR inhibitor, has shown promising antitumor activity in 2 phase II studies, leading to further investigation in the largest phase III randomized controlled trial completed in pNET patients.

Methods: Patients with advanced low- or intermediate-grade pNET were randomly assigned to everolimus 10 mg/d orally + best supportive care (BSC; n = 207) or placebo + BSC (n = 203). Long-acting somatostatin analogs (SSAs) were permitted as BSC during the study. The primary endpoint was progression free survival (PFS). At progression (RECIST), patients could be unblinded and those randomly assigned to placebo were offered open-label everolimus.

Results: Compared with placebo, everolimus reduced the risk of progression by 65% and increased median PFS by more than 6 months, from 4.6 to 11.0 months (HR = 0.35; 95% CI: 0.27-0.45; p < 0.0001), by investigator review (primary endpoint). Median PFS by central review was consistent (HR = 0.34; 95% CI: 0.26 to 0.44; p < 0.001] in favor of everolimus. Eighteen-month PFS estimates were 34% for everolimus (95% CI: 26-43) vs 9% (95% CI: 4-16) for placebo. Everolimus demonstrated a significant PFS benefit across all patient subgroups according to baseline characteristics and prior SSA use. Prior SSA use was 49% in the everolimus arm and 50% in the placebo arm. Updated analyses of the impact of concomitant SSA will be reported. The most common drug-related adverse events were stomatitis, rash, diarrhea, fatigue, and infections (primarily upper respiratory); most were grade 1 or 2. Stomatitis (6.9% vs 0%), anemia (6% vs 0%), and hyperglycemia (5% vs 2%) were the most common grade 3-4 events.

Conclusions: Everolimus significantly prolonged PFS compared with placebo in patients with advanced pNET in this large phase III clinical trial. This benefit was seen across all patient subgroups. Treatment resulted in a significant 6.4-month prolongation in median PFS. Everolimus had an acceptable and predictable safety profile.

[Table: see text]
Influence of underlying liver disease on response to sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Bouattour M. , Faivre S. J. , Dreyer C. , Paradis V. , Raymond E.
Published: February 2017

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Background: Based on SHARP and Asia-Pacific trials, sorafenib is the first active therapy registered in advanced-stage HCC. The clinical benefit of sorafanib was not evaluated according to underlying liver disease. We aim to evalute results of sorafenib in specific subgroups of patients with various etiology of underlying liver disease.

Methods: Between Jan 2006 and Sep 2009, patients with advanced HCC treated with sorafenib in our institution were analyzed. Response evaluated by RECIST criteria, overall survival (OS) and time to progression (TTP) were assessed in each subgroup according to the etiology of liver disease.

Results: At the time of analysis, 134 patients were registered. Median age was 63.4 years (range 34–85) and a majority of patients were male (80%). Diagnosis of HCC was pathologically proven in 81% of cases. Patients were classified BCLC stage B and C in 25% and 75%, respectively. Etiology of underlying liver disease was hepatitis B, hepatitis C, alcohol consumption, and NASH in 17%, 25%, 32%, and 13%, respectively (others etiologies in 13% of cases). Demographic characteristics, Child-Pugh class and BCLC tumor stage, and prior therapy were similar for each subgroup. Overall duration of sorafenib treatment was comparable in all subgroups. Among 101 patients evaluable, only two had a partial response (2 %), and median OS was 9.5 months (95% CI: 7.35-11.67). Median TTP was significantly shorter in patient with hepatitis B compared with those with hepatitis C infection (4.4 and 7.3 months respectively; p: 0.036). This difference was not observed in patients with alcohol consumption compared to those with NASH (6.4 vs. 5.2 months; p=0.7). Median OS in patients with hepatitis C infection was 8.4 months and 6.1 months in those with hepatitis B infection (p value: 0.7). No significant difference was observed in patients with alcohol abuse compared with those with NASH (14.2 and 9.9 months respectively; p: 0.72).

Conclusions: Overall, clinical benefit of sorafenib does not appear to be influenced by liver disease etiology. However, in patients infected with hepatitis B, progression under sorafenib seems to occur earlier, suggesting a possible role of hepatitis B chronic disease on the outcome.

No significant financial relationships to disclose.
Use of endoscopic ultrasound scoring to estimate the malignant potential of branch duct type intraductal papillary-mucinous neoplasms of the pancreas.
Authors: Lee S. , Cho J. Y.
Published: February 2017

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Background: Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are characterized by intraductal papillary epithelial growth, mucin hypersecretion, and cystic dilation of main or branch pancreatic ducts. However, it is still difficult to differentiate between benign and malignant, when it only involves the branch duct. The purpose of this study was to evaluate the role of endoscopic ultrasound (EUS) scoring in predicting malignancy in branch-duct type IPMNs, thus providing a convenient guideline to a clinician before considering surgical resection.

Methods: We retrospectively reviewed all patients between Dec 1997 and April 2010 who underwent diagnostic and/or preoperative EUS for IPMNs. Borderline malignancy and invasive carcinoma were defined as a malignancy.

Results: Of the 32 patients (mean age, 62 years), 13 male and 19 female were identified. Twelve people underwent operation, and there were 23 benign cases, and 9 malignant cases (borderline, n=6; invasive carcinoma, n=3). Among the six parameters (age, cyst size, mural nodule, associated main pancreatic duct dilation, patulous opening, thick septum) that have been known as important parameters for predicting malignancy in main duct type IPMNs, four were significant by Fisher's exact tests—namely, cyst size (p=.002), mural nodule (p =.003), associated main pancreatic duct dilation (p =.001), patulous opening (p =.05). In sizing the cysts, we scored 0 (cyst size ≤10 mm), 1 (11-20 mm), 2 (21-30 mm), 3 (>30 mm). In sizing the mural nodules, we scored 0 (no mural nodule), 1 (<5 mm), 2 (5-<10 mm), 3 (≥10 mm). For main pancreatic duct dilation, we scored 2, if there presented any associated main pancreatic duct dilation, and 0 if not. For the patulous opening, we scored 1 for present, 0 for not. Patients were dispersed from the highest score nine, to the lowest score zero. Mean score for benign cases was 2.47 (±1.59 SD), and 6.33 (±1.87 SD) for malignant cases (p =.001).

Conclusions: We strongly recommend a radical surgery for patients scoring above 7(score 7, 8, 9), and a consideration of operation for scoring between 4 and 6, and careful follow up for scoring below 3.

No significant financial relationships to disclose.