Publications by authors named "Adrienne Groman"

54 Publications

Correlation between perioperative outcomes and long-term survival for non-small lung cancer treated at major centers.

J Thorac Cardiovasc Surg 2020 Dec 3. Epub 2020 Dec 3.

Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY; Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY. Electronic address:

Background: The public is placing increased emphasis on specialty specific rankings, thereby affecting patients' choices of clinical care programs. In the spirit of transparency, public reporting initiatives are underway or being considered by various surgical specialties whose databases rank programs based on short-term outcomes. Of concern, short-term risk avoidance excludes important comparative cases from surgical database participation and may adversely affect overall long-term oncologic treatment team results. To assess the validity of comparing short-term perioperative and long-term survival outcomes of all patients treated at major centers, we studied the correlations between these variables.

Methods: The National Cancer Database was queried for patients diagnosed with non-small cell lung carcinoma (NSCLC) between 2008 and 2012, yielding 5-year follow-up data for all patients at centers treating at least 100 patients annually. Mortality (30- and 90-day), unplanned 30-day readmissions, and hospital length of stay were modeled using logistic regression with sex, race, age, Charlson-Deyo combined comorbidity, extent of surgery, income, insurance status, histology, grade, and analytic stage as predictors, all with 2-way interaction terms. The differences between the predicted rates and observed rates were calculated for each short-term outcome, and the average of these was used to create a short-term metric (STM). A similar approach was used to create a long-term metric (LTM) that used overall survival as a single dependent variable. Centers were ranked into deciles based on these metrics. Visual plotting as well as correlation coefficients were used to judge correlation between STM and LTM.

Results: A total of 298,175 patients from 541 centers were included in this analysis, of whom 102,860 underwent surgical resection for NSCLC. The correlation between STM and LTM was negative using parametric estimates (Pearson correlation coefficient = -0.09 [P = .03] and -0.22 [P < .01]) and nonparametric estimates (Spearman rank correlation coefficient = -0.09 [P = .02] and -0.22 [P < .01]) for squamous cell carcinoma and adenocarcinoma, respectively.

Conclusions: Short-term perioperative outcome rankings correlate poorly with long-term survival outcome rankings when cancer treatment centers are compared. Factors explaining this discrepancy merit further study. Rankings based on short-term outcomes alone may be incomplete for public reporting.
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http://dx.doi.org/10.1016/j.jtcvs.2020.11.108DOI Listing
December 2020

Approach to Resectable N1 Non-Small Cell Lung Cancer: An Analysis of the National Cancer Database.

J Surg Res 2021 Mar 3;259:145-153. Epub 2020 Dec 3.

Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York; Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York.

Background: In patients with clinical N1 disease, minimally invasive surgery (MIS) has potentially better perioperative outcome compared to open thoracotomy. Additionally, whether adjuvant or neoadjuvant chemotherapy produces the best long-term survival is still debatable.

Methods: We queried The National Cancer Database for patients with clinical N1 NSCLC who underwent surgical resection between 2010 and 2014. Comparison between patients receiving MIS and patients who underwent open thoracotomy was done using an intention-to-treat analysis. Comparison was also done among neoadjuvant, adjuvant chemotherapy, and only surgery. Proportional hazard models were used to evaluate the effects of surgical approach and timing of chemotherapy on overall survival.

Results: A total of 1440 and 3942 patients underwent MIS and open thoracotomy respectively. MIS achieved better surgical margins (90.0% versus 88.6%) and shorter length of stay (6.5 ± 6.5 versus 7.3 ± 6.4 d, P ≤ 0.01) compared to open thoracotomy. There were no differences in 30-day and 90-day mortality, nor readmission rates. Neoadjuvant and adjuvant chemotherapy were administered to 13.5% and 57.2% of patients respectively. There was no significant difference in the 5-year overall survival between MIS and open thoracotomy (46% versus 46% P = 0.08). There was significantly better 5-year overall survival in neoadjuvant and adjuvant chemotherapy versus only surgery, but no difference between neoadjuvant and adjuvant chemotherapy (48% versus 47% versus 44%, P < 0.01).

Conclusions: In clinical N1 NSCLC, MIS does not compromise oncological quality or overall survival when compared to open thoracotomy. Overall survival improved in patients treated with chemotherapy but there is no difference when given as neoadjuvant versus adjuvant chemotherapy.
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http://dx.doi.org/10.1016/j.jss.2020.11.024DOI Listing
March 2021

Risk-stratified analysis of pasireotide for patients undergoing pancreatectomy.

J Surg Oncol 2020 Aug 30;122(2):195-203. Epub 2020 May 30.

Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Background And Objectives: Pasireotide was shown in a randomized trial to decrease the rate of postoperative pancreatic fistula (POPF). However, retrospective series from other centers have failed to confirm these results.

Methods: Patients who underwent pancreatoduodenectomy or distal pancreatectomy between January 2014 and February 2019 were included. Patients treated after November 2016 routinely received pasireotide and were compared to a retrospective cohort. Multivariate analysis was performed for the outcome of clinically relevant POPF (CR-POPF), with stratification by fistula risk score (FRS).

Results: Ninety-nine of 300 patients received pasireotide. The distribution of high, intermediate, low, and negligible risk patients by FRS was comparable (P = .487). There were similar rates of CR-POPF (19.2% pasireotide vs 14.9% control, P = .347) and percutaneous drainage (12.1% vs 10.0%, P = .567), with greater median number of drain days in the pasireotide group (6 vs 4 days, P < .001). Multivariate modeling for CR-POPF showed no correlation with operation or pasireotide use. Adjustment with propensity weighted models for high (OR, 1.02, 95% CI, 0.45-2.29) and intermediate (OR, 1.02, CI, 0.57-1.81) risk groups showed no correlation of pasireotide with reduction in CR-POPF.

Conclusions: Pasireotide administration after pancreatectomy was not associated with a decrease in CR-POPF, even when patients were stratified by FRS.
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http://dx.doi.org/10.1002/jso.25949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369221PMC
August 2020

Two- Versus Four-Times Weekly Acupuncture-Like Transcutaneous Electrical Nerve Stimulation for Treatment of Radiation-Induced Xerostomia: A Pilot Study.

J Altern Complement Med 2020 Apr 27;26(4):323-328. Epub 2020 Jan 27.

Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Xerostomia occurs in the majority of patients undergoing chemoradiation therapy for head and neck cancer (HNC). Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) treatment has been studied as an encouraging modality to improve salivary function and related symptoms. The purpose of this study was to compare ALTENS treatment by using a four-times weekly schedule for 6 weeks versus a twice-weekly schedule for 12 weeks with a validated xerostomia scale at 15 months from the start of ALTENS treatment. This single-center randomized study was conducted in 30 patients treated with radiotherapy with or without chemotherapy for HNC between 2014 and 2017, who had at least grade 1 or 2 symptomatic dry mouth (xerostomia) according to CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0). These patients were randomly assigned to receive ALTENS four-times weekly for 6 weeks or two-times weekly for 12 weeks. The University of Michigan 15-item Xerostomia-related Quality of Life Scale (XeQoLS) was administered at 6, 9, 15, and 21 months from the start of ALTENS treatment. A random-effects generalized linear model was used to model the overall XeQoLS score at the 15-month endpoint; adjusted for a random time effect, a fixed treatment arm, and interaction of time and treatment. Comparison between arms was based on a 0.05 nominal significance level. XeQoLS decreased for all patients (although not statistically for each arm) from a mean of 22 and 21 at baseline (in the four times per week and twice weekly arms) to 12 in both arms at 15 months, with no difference between arms ( = 0.68). There were no attributable grade 1-3 adverse events. Arms were balanced for age, gender, race, and baseline xerostomia. This study demonstrates that both ALTENS regimens are safe, well tolerated, and appear to be equally effective. We now routinely make ALTENS units available for home use.
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http://dx.doi.org/10.1089/acm.2019.0131DOI Listing
April 2020

Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics.

Blood Adv 2020 01;4(2):253-262

Roswell Park Comprehensive Cancer Center, Buffalo, NY.

There is a paucity of data regarding outcomes and response to standard therapy in patients with limited-stage (LS) agressive B-cell lymphoma (LS-ABCL) who harbor MYC rearrangement (MYC-R) with or without BCL2 and/or BCL6 rearrangements. We conducted a multicenter retrospective study of MYC-R LS-ABCL patients who received either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or more intensive immunochemotherapy (IIC) plus or minus consolidative involved-field radiation therapy (IFRT). One hundred four patients from 15 academic centers were included. Forty four patients (42%) received R-CHOP, of whom 52% had IFRT. Sixty patients (58%) received IIC, of whom 40% had IFRT. Overall response rate was 91% (84% complete response [CR]; 7% partial response). Patients with double-hit lymphoma (DHL; n = 40) had a lower CR rate compared with patients with MYC-R only (75% vs 98%; P = .003). CR rate was higher in the IFRT vs no-IFRT group (98% vs 72%; P < .001). Median follow-up was 3.2 years; 2-year progression-free survival (PFS) and overal survival (OS) were 78% and 86% for the entire cohort, and 74% and 81% for the DHL patients, respectively. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort and in DHL patients. Our data provide a historical benchmark for MYC-R LS-ABCL and LS-DHL patients and show that outcomes for this population may be better than previously recognized. There was no benefit of using IIC over R-CHOP in patients with MYC-R LS-ABCL and LS-DHL.
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http://dx.doi.org/10.1182/bloodadvances.2019000875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988401PMC
January 2020

Role of Adjuvant Chemotherapy in Pulmonary Carcinoids: An NCDB Analysis.

Anticancer Res 2019 Dec;39(12):6835-6842

Division of Hematology & Oncology, Roswell Park Comprehensive Cancer Center, University at Buffalo School of Medicine, Buffalo, NY, U.S.A.

Background/aim: Typical carcinoids (TC) and atypical carcinoids (AC) are rare diseases. A paucity of randomized studies and disagreements among various guidelines makes the management challenging.

Patients And Methods: Using codes for TC (8240) and AC (8249) in the National Cancer Database (NCDB), all surgically resected cases from 2004-2014 were included to evaluate the need for adjuvant chemotherapy.

Results: A total of 6,673 cases were included, 88% were TCs and 12% were ACs. From 2004 to 2014, the proportion of TCs went up from 1.3% to 1.8% and ACs from 0.1% to 0.3% of all lung malignancies. TC patients did well with surgery alone in all stages. AC patients with stage I [5-year overall survival (OS) - 84% vs. 52%; S vs. S+CT] and stage II disease (5-year OS - 81% vs. 55%; S vs. S+CT) showed better OS trend with surgery alone, while stage III patients showed some benefit with the use of adjuvant chemotherapy (5-year OS - 46% vs. 54%; S vs. S+CT). These results supported the National Comprehensive Cancer Network (NCCN) guidelines.

Conclusion: No benefit was seen from adjuvant chemotherapy in TCs. While the adjuvant therapy may add benefit in stage III AC, the numbers are small and did not reach statistical significance.
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http://dx.doi.org/10.21873/anticanres.13900DOI Listing
December 2019

The association of nodal upstaging with surgical approach and its impact on long-term survival after resection of non-small-cell lung cancer.

Eur J Cardiothorac Surg 2020 05;57(5):888-895

Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA.

Objectives: Proponents of open thoracotomy (OPEN) and robot-assisted thoracic surgery (RATS) claim its oncological superiority over video-assisted thoracic surgery (VATS) in terms of the accuracy of lymph node staging.

Methods: The National Cancer Database was queried for patients with non-small-cell lung cancer (NSCLC) undergoing lobectomy without neoadjuvant therapy from 2010 to 2014. Nodal upstaging rates were compared using a surgical approach. Overall survival adjusted for confounding variables was examined using the Cox proportional hazards model.

Results: A total of 64 676 patients fulfilled the selection criteria. The number of patients who underwent lobectomy by RATS, VATS and OPEN approaches was 5470 (8.5%), 17 545 (27.1%) and 41 661 (64.4%), respectively. The mean number of lymph nodes examined for each of these approaches was 10.9, 11.3 and 10 (P < 0.01) and upstaging rates were 11.2%, 11.7% and 12.6% (P < 0.01), respectively. For patients with clinical stage I disease (N = 46 826; RATS = 4338, VATS = 13 416 and OPEN = 29 072), the mean lymph nodes examined were 10.6, 10.8 and 9.4 (P < 0.01), and upstaging rates were 10.8%, 11.1% and 12.1% (P < 0.01), respectively. A multivariable analysis suggested an association with improved survival with RATS and VATS compared with OPEN surgery [hazard ratio (HR) = 0.89 and 0.89, respectively; P < 0.01] for patients with all stages. In stage I disease, VATS but not RATS was associated with increased overall survival compared with the OPEN approach (HR = 0.81; P < 0.01).

Conclusions: RATS lobectomy is not superior to VATS lobectomy with respect to lymph node yield or upstaging of NSCLC. Increased nodal upstaging by the OPEN approach does not confer a survival advantage in any stage of NSCLC and may be associated with decreased overall survival.
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http://dx.doi.org/10.1093/ejcts/ezz320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179045PMC
May 2020

Geographic and demographic features of neuroendocrine tumors in the United States of America: A population-based study.

Cancer 2020 02 12;126(4):792-799. Epub 2019 Nov 12.

Division of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, University at Buffalo School of Medicine, Buffalo, New York.

Background: The incidence of neuroendocrine tumors (NETs) is rapidly rising. There are very few studies investigating the role of sociodemographic factors in NETs. This study was aimed at examining how geographic and sociodemographic characteristics shape outcomes in the NET population.

Methods: A retrospective analysis using the Surveillance, Epidemiology, and End Results database was performed, and the NET patient population from 1973 to 2015 was studied. Univariate and multivariable analyses were performed to evaluate patients' disease-specific survival (DSS) and overall survival (OS). Geographic and sociodemographic factors, including the location of residence (urban area [UA] vs rural area [RA]), sex, race, insurance status, and marital status, were included in the analysis.

Results: A total of 53,034 patients (5517 in RAs and 47,517 in UAs) were included in the analysis. The incidence of NETs was found to be rising in both RAs and UAs but more rapidly in RAs (with the highest incidence in 2006-2015: 5.93 per 100,000 in RAs vs 4.10 per 100,000 in UAs). Patients from RAs presented at advanced stages in comparison with patients from UAs (regional, 18% vs 16%; distant, 15% vs 13%; P < .01). In the multivariable model, RA patients had a trend toward poorer OS (hazard ratio, 1.05; P = .053) in comparison with UA patients. The multivariable analysis showed significantly worse DSS and OS for uninsured, single, and male patients in comparison with insured, married, and female patients, respectively.

Conclusions: This study has identified sociodemographic disparities in NET outcomes. Access to health care could be a potential contributing factor, although differences in environmental exposure, health behavior, and tumor biology could also be responsible.
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http://dx.doi.org/10.1002/cncr.32607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870292PMC
February 2020

One Versus Three Fractions of Stereotactic Body Radiation Therapy for Peripheral Stage I to II Non-Small Cell Lung Cancer: A Randomized, Multi-Institution, Phase 2 Trial.

Int J Radiat Oncol Biol Phys 2019 11 22;105(4):752-759. Epub 2019 Aug 22.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Purpose: Stereotactic body radiation therapy for early stage non-small cell lung cancer is a standard of care for medically inoperable patients. Our aim was to compare Common Terminology Criteria for Adverse Events thoracic grade 3 or higher adverse events (AEs) of 30 Gy in 1 fraction (arm 1) versus 60 Gy in 3 fractions (arm 2).

Methods And Materials: This was a randomized multi-institutional, phase 2, 2-arm clinical trial. Medically inoperable patients with biopsy-proven peripheral T1/T2N0M0 non-small cell lung cancer were enrolled. Patients were randomized to arm 1 or arm 2 and stratified by performance status. The primary endpoint was Common Terminology Criteria for Adverse Events thoracic grade 3 or higher AEs. Secondary endpoints were local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life.

Results: Between September 2008 and April 2015, 98 patients were randomized. Median follow-up was 53.8 months. Ten patients were lost to follow-up, 1 in arm 1 and 9 in arm 2. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no grade 4 or 5 AEs. There were no differences in LC, PFS, or OS (P = .68, .86, and .94, respectively). Arm 1 reported better social functioning (P = .006) with less dyspnea (P = .016) in follow-up at 6 months.

Conclusions: This randomized phase 2 study demonstrated that 30 Gy in 1 fraction was equivalent to 60 Gy in 3 fractions in terms of toxicity, LC, PFS, and OS. Quality of life measures of social functioning and dyspnea favored single-fraction SBRT.
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http://dx.doi.org/10.1016/j.ijrobp.2019.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043929PMC
November 2019

Cutaneous Leiomyosarcoma: A SEER Database Analysis.

Dermatol Surg 2020 02;46(2):159-164

Pathology and Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Background: Cutaneous leiomyosarcoma is a rare dermal neoplasm usually arising from the pilar smooth muscle. It is considered a relatively indolent neoplasm, and there is debate whether designation as sarcoma is appropriate. Owing to some conflicting data in the literature, however, its behavior warrants further clarification.

Objective: To determine the clinical behavior and demographic and pathologic characteristics of cutaneous leiomyosarcoma.

Materials And Methods: The Surveillance, Epidemiology and End Results database was used to collect data on cutaneous leiomyosarcoma and 2 reference populations: cutaneous angiosarcoma (aggressive) and atypical fibroxanthoma (indolent). Demographic and oncologic characteristics were examined, and overall survivals (OS) and disease-specific survivals were compared.

Results: Leiomyosarcoma and atypical fibroxanthoma displayed lower stage (localized: 69.7% and 66.8% respectively), smaller size (<3 cm: 90.5% and 72%), and lower rates of disease-specific mortality (2.9% and 7.8%) compared with angiosarcoma. Patients with leiomyosarcoma had a 5-year disease-specific survival rate of 98% and OS rate of 85%.

Conclusion: Cutaneous leiomyosarcoma shows outcomes similar to atypical fibroxanthoma. It is nearly always indolent and should be distinguished from more aggressive cutaneous and subcutaneous sarcomas. Clear communication of the biologic potential may be best achieved using alternate diagnostic terminology such as "atypical intradermal smooth-muscle neoplasm."
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http://dx.doi.org/10.1097/DSS.0000000000002029DOI Listing
February 2020

Radiation With Neoadjuvant Chemotherapy Does Not Improve Outcomes in Esophageal Squamous Cell Cancer.

J Surg Res 2019 04 24;236:259-265. Epub 2018 Dec 24.

Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York. Electronic address:

Background: Neoadjuvant treatment improves survival for patients undergoing esophagectomy for esophageal cancer. Recent evidence suggests that neoadjuvant chemoradiation offers no advantage over chemotherapy alone before surgical resection for adenocarcinoma histology. We sought to examine if this applies to patients with squamous cell histology.

Materials And Methods: The National Cancer Database was queried for patients who underwent treatment for squamous cell carcinoma of the esophagus from 2004 to 2012. Patients who underwent neoadjuvant chemotherapy before esophagectomy were compared with those undergoing chemotherapy and radiation before surgical resection. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariate and multivariate proportional hazards modeling results were used to assess the effect of treatment on overall survival. Relative prognosis was summarized using estimates and 95% confidence limits for the hazard ratio. Unadjusted differences in overall survival and disease-specific survival between the treatment are shown using Kaplan-Meier methods.

Results: A total of 902 patients underwent neoadjuvant therapy before surgical resection during the study period, with 827 receiving chemotherapy and radiation, and 75 receiving chemotherapy alone preoperatively. The 30- and 90-d mortality for patients undergoing neoadjuvant chemotherapy and radiation followed by surgery were 5.4% and 10.4% compared to 5.5% and 11.1% for patients who received chemotherapy alone preoperatively (P = 0.963 and P = 0.856), respectively. Median overall survival for patients receiving chemotherapy and radiation was 36.0 mo versus 40.8 mo for chemotherapy alone. The 5-y survival was 39% for the chemotherapy and radiation group and 43% for the chemotherapy group (logrank P = 0.7212).

Conclusions: For patients undergoing neoadjuvant treatment before planned surgical resection of squamous cell carcinoma of the esophagus, the addition of radiation to neoadjuvant chemotherapy did not improve long-term survival and did not appear to impact short-term outcomes postoperatively. Further study with a randomized phase III trial is needed.
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http://dx.doi.org/10.1016/j.jss.2018.11.052DOI Listing
April 2019

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity.

Biol Blood Marrow Transplant 2019 04 6;25(4):689-698. Epub 2018 Oct 6.

BMT Program, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m, Mel 50 mg/m, and TBI 400 cGy (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m, Mel 75 mg/m, and TBI 400cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m and Mel 140 mg/m. Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis wasdecreased for FluMelTBI versus FluMel (P < .01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (P = .03). On multivariate analysis, OS (P = .05) and PFS (P = .05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.
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http://dx.doi.org/10.1016/j.bbmt.2018.09.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451676PMC
April 2019

Minimally Invasive Approaches Do Not Compromise Outcomes for Pneumonectomy: A Comparison Using the National Cancer Database.

J Thorac Oncol 2019 01 5;14(1):107-114. Epub 2018 Oct 5.

Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York; Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York. Electronic address:

Introduction: Minimally invasive approaches are increasingly being used for the conduct of complex surgical procedures. Whether the benefits of minimally invasive approaches compared to thoracotomy for sublobar and lobar lung resection for NSCLC are realized for patients undergoing pneumonectomy is not clear.

Methods: The National Cancer Database was queried for patients who underwent pneumonectomy for NSCLC from 2010 to 2014. Case data from patients who underwent resection by minimally invasive surgery (MIS) were compared with those from patients who received thoracotomy (open) in an intention-to-treat analysis. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariable and multivariable logistic models and proportional hazards model were used to assess the effect of surgical approach on 30-day and 90-day mortality and overall survival. Relative prognosis was summarized using odds ratios and hazards ratios estimates and 95% confidence limits.

Results: A total of 4,938 patients underwent pneumonectomy during the study period, of which 755 (15.3%) were completed by MIS. No difference was noted in 30- and 90-day mortality rates for MIS compared to open approaches (6.8% and 12.3% versus 6.7% and 11.9%, respectively; p = 0.9 and 0.86, respectively). Tumor histology and stage characteristics were similar between the two groups. The mean number of lymph nodes examined was higher in the MIS group compared to the open thoracotomy group (17.1 ± 0.4 versus 16.1 ± 0.2, p = 0.034). The conversion rate for the MIS cohort was 36.7%. Surgical approach was not associated with any difference in perioperative mortality with univariable or multivariable analysis. MIS was associated with improved overall survival on univariable analysis, but this was not evident with multivariable analysis.

Conclusions: Pneumonectomy performed by minimally invasive approaches does not compromise perioperative mortality or long-term outcomes. Further investigation into the impact of minimally invasive approaches on perioperative outcomes for whole-lung resection is warranted.
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http://dx.doi.org/10.1016/j.jtho.2018.09.024DOI Listing
January 2019

Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

Am J Clin Pathol 2018 Oct;150(5):393-405

Pathology and Anatomical Sciences, University at Buffalo-The State University of New York.

Objectives: To assess bone marrow (BM) sampling in academic medical centers.

Methods: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed.

Results: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent.

Conclusions: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.
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http://dx.doi.org/10.1093/ajcp/aqy066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166687PMC
October 2018

Clinicopathological characteristics and outcomes of rare histologic subtypes of gallbladder cancer over two decades: A population-based study.

PLoS One 2018 11;13(6):e0198809. Epub 2018 Jun 11.

Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.

Background: There is limited literature about the clinicopathological characteristics and outcomes of rare histologic variants of gallbladder cancer (GBC).

Methods: Using SEER database, surgically managed GBC patients with microscopically confirmed adenocarcinoma, adenosquamous/squamous cell carcinoma and papillary carcinoma were identified from 1988 to 2009. Patients with second primary cancer and distant metastasis at presentation were excluded. The effect of clinicopathological variables on overall survival (OS) and disease specific survival (DSS) were analyzed using univariate and multivariate proportional hazards modeling. All associations were considered statistically significant at an alpha error of 0.01.

Results: Out of 4738 cases, 217 adenosquamous/squamous (4.6%), 367 papillary (7.7%), and 4154 adenocarcinomas (87.7%) were identified. Median age was 72 years. Higher tumor grade (grade 2, 3, 4 versus grade 1), higher T stage (T2, T3, T4 versus T1), lymph node positivity (N1 versus N0) and adenosquamous/squamous histology (versus adenocarcinoma) had worse OS and DSS (p < .001). Papillary GBC had better OS and DSS than adenocarcinoma (HR = 0.7; p < .001). Radical surgery (versus simple cholecystectomy) had better OS (HR = 0.83, p = 0.002) in multivariate analysis. OS rates at 3 and 5 years were 0.56 and 0.44 for papillary, 0.3 and 0.22 for adenocarcinoma, and 0.14 and 0.12 for adenosquamous/squamous histology, while DSS rates at 3 and 5 years were 0.67 and 0.61 for papillary, 0.38 and 0.31 for adenocarcinoma, and 0.17 and 0.16 for adenosquamous/squamous subtypes respectively.

Conclusion: Papillary GBC had better survival outcomes while adenosquamous/squamous GBC had worse survival outcomes compared to gallbladder adenocarcinoma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198809PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995371PMC
January 2019

Effect of the number of lymph nodes examined on the survival of patients with stage I non-small cell lung cancer who undergo sublobar resection.

J Thorac Cardiovasc Surg 2018 07 4;156(1):394-402. Epub 2018 Apr 4.

Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, NY; Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY.

Objectives: Early stage lung cancer is being detected at a higher frequency with the implementation of screening programs. At the same time, medically complex patients with multiple comorbidities are presenting for surgery, with a concomitant rise in rates of sublobar resection. We sought to examine the effect of sampling lymph nodes on the outcomes of patients who undergo sublobar resection for small (<2 cm) stage I non-small cell lung cancer (NSCLC).

Methods: All patients in the Surveillance, Epidemiology, and End Results database from 2004 to 2013 with small (<2 cm) stage I NSCLC who underwent sublobar resection (wedge/segmentectomy) and no other cancer history were included. The association of the number of lymph nodes examined (LNE; categories none, 1-3, 4-6, 7-9, >9) with the overall survival as well as disease-specific survival were examined using univariate as well as multivariate analyses while controlling for covariates such as age, size (<1 cm, >1 cm), grade, histology (adenocarcinoma vs others), and extent of resection (wedge/segmentectomy).

Results: Data from 3916 eligible patients were analyzed. Seven hundred fifteen patients (18.3%) had segmentectomy. No lymph nodes were examined in 49% and 23% of wedge resection and segmentectomy patients, respectively. Among all eligible patients, 1132 (29%), 474 (12%), 228 (6%), and 328 (8%) patients had 1 to 3, 4 to 6, 7 to 9 and >9 LNE, respectively. Univariate analyses showed significant associations between overall and disease-specific survivals with age, grade, histology, sex, extent of surgery, and LNE. The association between the number of LNE and survival remained significant even after adjusting for significant covariates including extent of sublobar resection (hazard ratio for groups with LNE 1-3, 4-6, 7-9, and >9 compared with 0 LNE were 0.79, 0.77, 0.68, and 0.45 for overall survival; P < .001) and 0.85, 0.77, 0.71, and 0.44 for disease-specific survival (P < .05), respectively. In multivariate modeling, LNE was retained as a significant variable and extent of resection was not. In patients in whom at least 1 lymph node was examined, extent of resection was not predictive of outcome.

Conclusions: Many patients having sublobar resection for early stage NSCLC in the United States do not have a single lymph node removed for pathologic examination. The number of LNE is associated with improved survival, presumably due to avoidance of mis-staging. This association seems greater than the association with extent of resection (segmentectomy vs wedge resection). Appropriate lymph node examination remains an important part of resection for lung cancer even if the resection is sublobar.
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http://dx.doi.org/10.1016/j.jtcvs.2018.03.113DOI Listing
July 2018

Combined surgery and radiation improves survival of tonsil squamous cell cancers.

Oncotarget 2017 Dec 10;8(68):112442-112450. Epub 2017 Aug 10.

Department of Head and Neck/Plastic and Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA.

Objective: The study evaluated the addition of surgery (S) to radiation (RT) on survival of squamous cell carcinomas (SCC) of tonsillar-fossa (TF) in a modern cohort with similar epidemiology and treatment as current patients.

Study Design: Retrospective analysis utilizing Surveillance, Epidemiology, and End Results (SEER) Program data.

Results: For all stages combined TF patients who received S+RT had superior OS ( < 0.01) and DSS ( < 0.01). For each stage OS and DSS was superior for S+RT ( < 0.05). In multivariate analysis, HRs for OS were statistically significantly higher for TF patients (stage 2, 3, and 4) receiving RT alone ( < 0.001).

Materials And Methods: TF SCC patients treated with either S+RT or RT alone between 2004 and 2011 were examined ( = 6,476). Primary outcome measures included overall survival (OS) and disease specific survival (DSS). Cox proportional hazard ratios (HR) were estimated for patients treated with S+RT compared to RT alone.

Conclusions: OS and DSS were superior for all stages combined and for stages 2, 3, and 4 in TF patients who received S+RT compared to RT alone.
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http://dx.doi.org/10.18632/oncotarget.20122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762522PMC
December 2017

Effects of a novel peptide Ac-SDKP in radiation-induced coronary endothelial damage and resting myocardial blood flow.

Cardiooncology 2018 18;4. Epub 2018 Dec 18.

Department of Pathology, Division of Thoracic Pathology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA.

Background: Cancer survivors treated with thoracic ionizing radiation are at higher risk of premature death due to myocardial ischemia. No therapy is currently available to prevent or mitigate these effects. We tested the hypothesis that an endogenous tetrapeptide N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) counteracts radiation-induced coronary vascular fibrosis and endothelial cell loss and preserves myocardial blood flow.

Methods: We examined a rat model with external-beam-radiation exposure to the cardiac silhouette. We treated a subgroup of irradiated rats with subcutaneous Ac-SDKP for 18-weeks. We performed cardiac MRI with Gadolinium contrast to examine resting myocardial blood flow content. Upon sacrifice, we examined coronary endothelial-cell-density, fibrosis, apoptosis and endothelial tight-junction proteins (TJP). In vitro, we examined Ac-SDKP uptake by the endothelial cells and tested its effects on radiation-induced reactive oxygen species (ROS) generation. In vivo, we injected labeled Ac-SDKP intravenously and examined its endothelial localization after 4-h.

Results: We found that radiation exposure led to reduced resting myocardial blood flow content. There was concomitant endothelial cell loss and coronary fibrosis. Smaller vessels and capillaries showed more severe changes than larger vessels. Real-time PCR and confocal microscopy showed radiation-induced loss of TJ proteins including-claudin-1 and junctional adhesion molecule-2 (JAM-2). Ac-SDKP normalized myocardial blood flow content, inhibited endothelial cell loss, reduced coronary fibrosis and restored TJ-assembly. In vitro, Ac-SDKP localized to endothelial cells and inhibited radiation-induced endothelial ROS generation. In vivo, labeled Ac-SDKP was visualized into the endothelium 4-h after the intravenous injection.

Conclusions: We concluded that Ac-SDKP has protective effects against radiation-induced reduction of myocardial blood flow. Such protective effects are likely mediated by neutralization of ROS-mediated injury, preservation of endothelial integrity and inhibition of fibrosis. This demonstrates a strong therapeutic potential of Ac-SDKP to counteract radiotherapy-induced coronary disease.
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http://dx.doi.org/10.1186/s40959-018-0034-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497419PMC
December 2018

Risk and benefit of neoadjuvant therapy among patients undergoing resection for non-small-cell lung cancer.

Eur J Cardiothorac Surg 2018 03;53(3):656-663

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.

Objectives: Neoadjuvant therapy has emerged as a favoured treatment paradigm for patients with clinical N2 disease undergoing surgical resection for non-small-cell lung cancer. It is unclear whether such a treatment paradigm affects perioperative outcomes. We sought to examine the National Cancer Database (NCDB) to assess the impact of neoadjuvant therapy on perioperative outcomes and long-term survival in these patients.

Methods: All patients with a history of non-small-cell lung cancer undergoing anatomical resection between 2004 and 2014 were included. Thirty-day and 90-day mortality of all patients having neoadjuvant therapy versus those who did not were compared. In addition, the impact of neoadjuvant therapy on the overall survival of patients with clinical N2 disease was examined.

Results: Of the 134 428 selected patients, 9896 (7.4%) patients had neoadjuvant chemotherapy. Patients undergoing neoadjuvant therapy had a higher 30-day (3% vs 2.6%; P < 0.01) and 90-day mortality (6.5% vs 4.9%; P < 0.01). This association remained after adjusting for covariates. Among patients with clinical N2 disease (n = 10 139), 42.3%, 35.3% and 22.4% of patients had neoadjuvant, adjuvant and no chemotherapy, respectively. Univariable, multivariable and propensity score-weighted analyses indicated no difference in survival between patients receiving neoadjuvant and adjuvant chemotherapy.

Conclusions: Neoadjuvant therapy may adversely affect perioperative outcomes without providing a survival advantage compared with adjuvant therapy in clinical N2 stage patients. Randomized controlled trials need to be conducted to examine this issue further.
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http://dx.doi.org/10.1093/ejcts/ezx406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018932PMC
March 2018

Conditional Survival-Based "Abbreviated" Routine Cancer Surveillance for Pathologic Stage IB Melanoma.

Am Surg 2017 Nov;83(11):1256-1262

A negative sentinel lymph node biopsy (SLNB) for stage IB (T1b/T2a N0) melanoma would predict an excellent long-term prognosis. Combined with the concept of conditional survival, an "abbreviated" cancer surveillance strategy was implemented to reduce the number of visits and total length of follow-up. Retrospective review of all pathologic stage IB melanoma patients (negative SLNB) at a single institution between 2006 and 2008 after implementation of an "abbreviated" cancer surveillance; clinic visits every six months for five years followed by one annual visit (total follow-up six years). Patient demographics, tumor characteristics, and information regarding recurrences were obtained. Recurrence-free, disease-specific, and overall survival were calculated. Eighty-seven patients underwent the "abbreviated" cancer surveillance. Median age was 55.4 years and 50.6 per cent were male. Median Breslow thickness was 1.1 mm (range 0.5-2.0 mm) and 1.1 per cent were ulcerated. Primary tumor site was 49 per cent extremities, 39 per cent trunk, and 12 per cent head/neck. Median follow-up was 68.6 months. Five-year recurrence-free, disease-specific, and overall survivals were 89, 95, and 88 per cent, respectively. During surveillance, 10 patients had concerning symptoms or physical findings prompting subsequent workup, all of which were negative for recurrence/metastases. There were only three true melanoma recurrences; all were distant metastases and presented symptomatically between scheduled follow-up visits. In light of the excellent prognosis for pathologic (SLNB negative) stage IB melanoma, an "abbreviated" cancer surveillance schedule based on conditional survival would reduce both direct and indirect costs in this cohort. The few recurrences were symptomatic and unlikely to have changed with more intensive surveillance.
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November 2017

Immunomodulation by Entinostat in Renal Cell Carcinoma Patients Receiving High-Dose Interleukin 2: A Multicenter, Single-Arm, Phase I/II Trial (NCI-CTEP#7870).

Clin Cancer Res 2017 Dec 22;23(23):7199-7208. Epub 2017 Sep 22.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.

On the basis of preclinical data suggesting that the class I selective HDAC inhibitor entinostat exerts a synergistic antitumor effect in combination with high-dose IL2 in a renal cell carcinoma model by downregulating Foxp3 expression and function of regulatory T cells (Treg), we conducted a phase I/II clinical study with entinostat and high-dose IL2 in patients with metastatic clear cell renal cell carcinoma (ccRCC). Clear cell histology, no prior treatments, and being sufficiently fit to receive high-dose IL2 were the main eligibility criteria. The phase I portion consisted of two dose levels of entinostat (3 and 5 mg, orally every 14 days) and a fixed standard dose of IL2 (600,000 U/kg i.v.). Each cycle was 85 days. The primary endpoint was objective response rate and toxicity. Secondary endpoints included progression-free survival and overall survival. Forty-seven patients were enrolled. At a median follow-up of 21.9 months, the objective response rate was 37% [95% confidence interval (CI), 22%-53%], the median progression-free survival was 13.8 months (95% CI, 6.0-18.8), and the median overall survival was 65.3 months (95% CI, 52.6.-65.3). The most common grade 3/4 toxicities were hypophosphatemia (16%), lymphopenia (15%), and hypocalcemia (7%), and all were transient. Decreased Tregs were observed following treatment with entinostat, and lower numbers were associated with response ( = 0.03). This trial suggests a promising clinical activity for entinostat in combination with high-dose IL2 in ccRCC patients and provides the first example of an epigenetic agent being rationally combined with immunotherapy. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712266PMC
December 2017

Phase I Study of Dalteparin in Combination With Sunitinib in Patients With Metastatic Clear Cell Renal Carcinoma.

Clin Genitourin Cancer 2017 Jul 14. Epub 2017 Jul 14.

Genitourinary Program, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN. Electronic address:

Background: Based on the tumor-driven concomitant activation of angiogenesis and coagulation we conducted a phase I combination study of sunitinib with the low molecular weight heparin dalteparin in patients with metastatic clear cell renal cell carcinoma (ccRCC).

Materials And Methods: Patients received standard treatment with sunitinib (50 mg daily, 4 weeks on, 2 weeks off). During the second week of no sunitinib in the first cycle (week 6) patients received dalteparin monotherapy (in escalating doses). Combination therapy of the 2 agents was administered from the second cycle onward. Seventeen patients were enrolled at 3 dose levels of dalteparin.

Results: Diarrhea and fatigue were the most frequent reported drug-related toxicities (41%). One dose-limiting toxicity (grade 3 anemia) was observed at the highest dose level of dalteparin. There were 4 partial responses (24%) and the median progression-free survival in this study was 14 months (95% confidence interval, 8.0-23.4). Anti-factor Xa levels were increased during combination therapy compared with dalteparin monotherapy.

Conclusions: Combination therapy of sunitinib with therapeutic doses of dalteparin is safe and well tolerated. The increased anti-factor Xa levels during combination treatment suggest that sunitinib might increase the anticoagulation activity of dalteparin. The positive safety profile warrants prospective evaluation of the clinical benefit of this combination strategy in patients with ccRCC.
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http://dx.doi.org/10.1016/j.clgc.2017.07.004DOI Listing
July 2017

Chemotherapy Extravasation: Establishing a National Benchmark for Incidence Among Cancer Centers.

Clin J Oncol Nurs 2017 Aug;21(4):438-445

City of Hope.

Background: Given the high-risk nature and nurse sensitivity of chemotherapy infusion and extravasation prevention, as well as the absence of an industry benchmark, a group of nurses studied oncology-specific nursing-sensitive indicators. 
.

Objectives: The purpose was to establish a benchmark for the incidence of chemotherapy extravasation with vesicants, irritants, and irritants with vesicant potential.
.

Methods: Infusions with actual or suspected extravasations of vesicant and irritant chemotherapies were evaluated. Extravasation events were reviewed by type of agent, occurrence by drug category, route of administration, level of harm, follow-up, and patient referrals to surgical consultation.
.

Findings: A total of 739,812 infusions were evaluated, with 673 extravasation events identified. Incidence for all extravasation events was 0.09%.
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http://dx.doi.org/10.1188/17.CJON.438-445DOI Listing
August 2017

Clinical characteristics of adenosquamous esophageal carcinoma.

J Gastrointest Oncol 2017 Feb;8(1):89-95

Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.

Background: Current published information of adenosquamous carcinoma (ASC) of the esophagus in the United States is limited to isolated case reports. We sought to study the clinical characteristics of this tumor using the Surveillance, Epidemiology and End Results (SEER) database.

Methods: Relevant data of all patients with esophageal cancer in the SEER database diagnosed from 1998-2010 was obtained. Demographic, grade, stage, treatment and survival characteristics of patients with ASC were summarized and compared to those patients with adenocarcinoma (ACA) and squamous cell carcinoma (SqCC). Univariate analyses across comparison groups were performed using Wilcoxon rank sum test for continuous covariates and the Pearson Chi-square test for categorical covariates. To evaluate the association of selected covariates to survival by histology, unadjusted and adjusted proportional hazards models were generated for the entire study population. To further control for the difference in covariates among the histology groups, propensity weighted Cox regression modeling was performed using the inverse propensity to treat weighting (IPTW) approach.

Results: Of 29,890 patients with the histological subgroups, only 284 patients had ASC (1%). Patients with ACA had a higher grade (72.9% with grade III/IV) and presented with advanced stage (48.2% distant disease) than their comparison group. Patients with ASC had worse overall survival compared to ACA but not SqCC in both univariate and multivariate analyses (OR =0.76; P<0.05 and OR =0.86; P<0.05 respectively). These results were further confirmed by the propensity weighted Cox regression analysis. Analysis of the ASC population alone demonstrated that decreasing stage, radiation therapy (OR =0.59; P<0.001) and surgery (OR =0.86; P<0.001) were associated with better overall survival, but grade was not.

Conclusions: ASC of the esophagus is a rare histological variant comprising 1% of esophageal ACA in the Unites States. This histological subtype presents in later stages, at a higher grade and portends a poorer survival than the more common ACA. Radiation therapy and surgical resection of appropriate stage patients provide the best chance of survival.
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http://dx.doi.org/10.21037/jgo.2016.12.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334041PMC
February 2017

A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer.

Am J Clin Oncol 2018 07;41(7):649-655

Mayo Clinic, Phoenix, AZ.

Objectives: Vascular endothelial growth factor overexpression, seen in 42% to 76% of biliary tract cancers (BTCs), correlates with poor survival. We explored the safety/efficacy and potential biomarkers for bevacizumab in combination with gemcitabine-capecitabine in advanced BTCs.

Patients And Methods: Inoperable stage III/IV BTC patients in our prospective study were given 1000 mg/m of gemcitabine (on days 1, 8), 650 mg/m of capecitabine (on days 1 to 14), and 15 mg/kg of bevacizumab (on day 1) in 21-day cycles. Circulating tumor cells and quality of life were assessed at baseline and before cycle 2 and 3.

Results: In total, 50 patients with gallbladder cancer (22%), intrahepatic (58%), and extrahepatic (20%) cholangiocarcinoma, received a median of 8 treatment cycles for median treatment duration of 5.8 months. Common grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (16%), fatigue (20%), infections (14%), and hand-foot syndrome (10%). There were 12 partial response (24%), 24 stable disease (48%) with clinical benefit rate of 72%. Median progression-free survival was 8.1 months (95% confidence interval, 5.3-9.9). Median overall survival was 10.2 months (95% confidence interval, 7.5-13.7). Circulating tumor cells were identified at baseline in 21/46 patients (46%), who had lower median overall survival compared with those without (9.4 vs. 13.7 mo; P=0.29). Patients with quality of life scores greater than the group median by the end of first cycle of treatment had improved survival compared with those who did not (13.3 vs. 9.4 mo; P=0.39).

Conclusions: Addition of bevacizumab to gemcitabine/capecitabine did not improve outcome in an unselected group of patients with advanced BTC compared with historical controls. The selective benefit of vascular endothelial growth factor inhibition in BTC remains to be explored.
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http://dx.doi.org/10.1097/COC.0000000000000347DOI Listing
July 2018

Subsite variation in survival of oropharyngeal squamous cell carcinomas 2004 to 2011.

Laryngoscope 2017 05 3;127(5):1087-1092. Epub 2016 Nov 3.

Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York, U.S.A.

Objectives/hypothesis: To evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors.

Study Design: Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011.

Methods: The cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival.

Results: The cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa.

Conclusions: In this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy.

Level Of Evidence: 4 Laryngoscope, 127:1087-1092, 2017.
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http://dx.doi.org/10.1002/lary.26369DOI Listing
May 2017

Efficacy, Safety, and Potential Biomarkers of Sunitinib and Transarterial Chemoembolization (TACE) Combination in Advanced Hepatocellular Carcinoma (HCC): Phase II Trial.

Am J Clin Oncol 2018 04;41(4):332-338

Departments of Medical Oncology.

Objectives: To evaluate the safety/efficacy and explore biomarkers for a rationally designed combination of sunitinib and transarterial chemoembolization (TACE) in a prospective phase 2 study of advanced hepatocellular carcinoma (HCC).

Methods: Inoperable HCC patients with Child-Pugh A disease received 37.5 mg sunitinib from days 1 to 7 followed by TACE on day 8. Sunitinib was resumed from days 15 to 36 followed by 2 weeks off. Patients received subsequent sunitinib cycles of 4 weeks on and 2 weeks off. Dynamic contrast-enhanced magnetic resonance imaging and circulating soluble biomarkers were assessed at baseline, day 8, day 10, and day 36.

Results: Sixteen patients with liver only (n=10) and extrahepatic disease (n=6) were enrolled. After a median follow-up of 12.8 months, 2 partial responses, 11 stable disease, and 3 clinical deteriorations were seen for a clinical benefit rate of 81%. Median progression-free survival (PFS) was 8 months (95% CI, 4.3-9.3) and overall survival was 14.9 months (95% CI, 6.3-27.1). Eleven of 16 patients (69%) had grade 3/4 toxicities attributable to sunitinib, the most frequent being thrombocytopenia, amylase/lipase elevations, lymphopenia, and fatigue. Mean K (volume transfer constant) and viable tumor percent in consented patients decreased by 27% and 14.8%, respectively, with combination therapy. Soluble vascular endothelial growth factor receptor-2 (sVEGFR2) levels, cytokines (interleukin-8, interleukin-21), and monocytes decreased with combination therapy. Estimated sunitinib IC50 values of 15 and 10 ng/mL modulated K and AUC90. sVEGFR2 levels decreased with K and AUC90.

Conclusions: Encouraging progression-free survival and overall survival were seen with acceptable toxicity in our study of sunitinib and TACE combination in advanced HCC. Potential imaging and serum biomarkers showed increased benefit with combination therapy.
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http://dx.doi.org/10.1097/COC.0000000000000286DOI Listing
April 2018

Progression of gingival squamous cell carcinoma from early to late stage after invasive dental procedure.

Gen Dent 2016 Mar-Apr;64(2):38-43

Early presentation of gingival squamous cell carcinoma (GSCC) is at times misdiagnosed as a benign inflammatory or reactive oral condition. Some misdiagnosed patients undergo unnecessary, invasive dental procedures, resulting in delayed cancer diagnosis and an increased risk of accelerated disease progression due to disruption of the periosteum and cortical bone. The records of 58 patients with biopsy-proven GSCC were retrospectively reviewed. The sample included 32 patients who underwent an invasive dental procedure (IDP) prior to cancer diagnosis and 26 patients who did not undergo an IDP (non-case group). Patients from both groups initially presented with similar symptoms. The median duration of symptoms at initial clinical presentation was 6 months for the IDP group and 2 months for the non-case group. In IDP patients, symptoms worsened after the IDP was rendered, with 37.5% presenting with a severe-grade symptom. In both groups, the majority of lesions were found on the posterior mandible and had a histologic grading of moderately differentiated GSCC. The odds of the IDP group having late-stage disease were 2.94 times greater than the odds for the control group. Stage T3/T4 malignancy was diagnosed in 77.4% of the IDP patients versus 53.8% of non-case patients. Disease-specific mortality was comparable; however, surgical treatment was significantly more extensive in the IDP group than in the non-case group. The disruption of alveolar periosteum in undiagnosed oral cancer patients results in significant delay in diagnosis, necessitating more complicated treatment regimens because of local tumor progression.
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March 2017

Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck.

World J Clin Oncol 2015 Oct;6(5):166-73

Michael Mix, Anurag K Singh, Shiva Dibaj, Adrienne Groman, Wainwright Jaggernauth, Youcef Rustum, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.

Aim: To investigate whether selenomethionine (SLM) reduces mucositis incidence in patients with head and neck squamous cell cancer (HNSCC) undergoing concurrent chemoradiation (CRT).

Methods: In this multi-institutional, randomized, double-blind phase II trial, patients with Stage III or IV HNSCC received SLM 3600 μg/m(2) or placebo twice daily for 7 d prior to CRT, once daily during CRT, and daily for 3 wk following CRT. CRT consisted of 70 Gy at 2 Gy per fraction with cisplatin 100 mg/m(2) IV on days 1, 22, and 43.

Results: Eighteen patients were randomized, 10 received SLM, and there were no differences in baseline factors. There was no difference in mucositis or patient-reported side effects between groups. There was no difference in overall or relapse-free survival at 12 mo.

Conclusion: Addition of SLM to CRT for HNSCC was well-tolerated but did not lower the incidence of severe mucositis or improve quality of life or survival outcomes.
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http://dx.doi.org/10.5306/wjco.v6.i5.166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600191PMC
October 2015

A Formal Palliative Care Service Improves the Quality of Care in Patients with Stage IV Cancer and Bowel Obstruction.

Am J Hosp Palliat Care 2017 Feb 10;34(1):20-25. Epub 2016 Jul 10.

1 Department of surgical oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.

Background: Patients with stage IV cancer and bowel obstruction present a complicated management problem. The aim of this study was to evaluate the role of the palliative care service (PC) in the management of this complex disease process.

Methods: A retrospective analysis was conducted of all patients admitted to Roswell Park Cancer Institute with stage IV cancer and bowel obstruction from 2009 to 2012 after the institution of a formal PC. This cohort was matched to similar patients from 2005 to 2008 (no palliative care service or NPC). Patient characteristics and outcomes included baseline demographics, comorbid conditions, do-not-resuscitate (DNR) status, laboratory parameters, medical and surgical management, length of stay, symptom relief, and disposition status.

Results: A total of 19 patients were identified in the PC group. Based on the PC group baseline characteristics, 19 patients were identified for the NPC group using matched values. Regarding outcomes, there were significant differences in the medication regimens (narcotics, octreotide, and Decadron) between the 2 groups. In the PC group, 14 of 19 patients showed improvement compared to 9 of 19 in the NPC group. Nearly 60% of patients in the PC group had a formal DNR order versus 10.5% in NPC ( P = .002). A significantly higher percentage of patients were discharged to hospice in the PC group (47.4% vs 0.0%, P = .006).

Conclusion: Palliative care consultation improves the quality of care for patients with stage IV cancer and bowel obstruction, with particular benefits in symptom management, end-of-life discussion, and disposition to hospice.
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http://dx.doi.org/10.1177/1049909115603960DOI Listing
February 2017