tbuckley/cabot-search huggingface dataset:
Vitamin B12 (Vit B12) biochemical (BCH) deficiency (DEF) in non-diabetic breast cancer (BC) patients on NCIC CTG MA.32: A phase III randomized adjuvant BC trial comparing metformin (Met) to placebo (Pl).
Authors: Mira F. Liebman, William Brien, Wendy R. Parulekar, Karen A. Gelmon, Lois E. Shepherd, Jennifer A. Ligibel, Dawn L. Hershman, Priya Rastogi, Ingrid A. Mayer, Timothy J. Hobday, Julie Lemieux, Alastair Mark Thompson, Kathleen I. Pritchard, Timothy Joseph Whelan, Som Mukherjee, Haji I. Chalchal, Vanessa Bernstein, Vuk Stambolic, Bingshu E. Chen, Pamela Jean Goodwin
Journal: Journal of Clinical Oncology (2014)

542 Background: Met, a drug used to treat type 2 diabetes, is being evaluated as an anti-cancer agent. Long-term use is associated with BCH Vit B12 DEF in up to 30%; a subset may develop symptomatic DEF. It is unknown if Vit B12 DEF is due to diabetes or Met use. We examined Vit B12 DEF in NCIC CTG MA.32, an RCT of adjuvant Met vs Pl in non-diabetic BC patients (pts). Methods: This was a DSMC approved central lab analysis in the first 492 (of 3649) high risk N0/N1-3 BC pts receiving standard therapy randomized onto MA.32 (Met 850 mg bid vs Pl bid for 5 years). VitB12 was analysed in baseline and 6 month (mo) fasting plasma; levels <181 pmol/L were DEF, 181 to 221 pmol/L borderline. Methylmalonic acid (MMA) and homocysteine (HC) (elevated in clinical Vit B12 DEF) were assayed in those with Vit B12 levels <222 pmol/L at either time. Hgb was measured locally. Analysis used Spearman’s rank correlation coefficients and Wilcoxon signed rank test for continuous variables and Chi-square test for 2 by 2 tables. Results: Mean age was 52.4±9.7 yrs. 237 received Met and 255 Pl; arms were balanced for hormone receptors (73% +ve), BMI (mean 28.3 kg/m2), adjuvant chemo (88%), stage, type of surgery/radiation. Median (Inter Quartile Range) baseline Vit B12 was 390 (281 to 556) and 370 (290 to 552) pmol/L in the Met and Pl arms respectively (p=0.97). 6 mo median levels were MET 320 (244 to 419) and Pl 380 (286 to 546) pmol/L (p=0.0001). 15 pts (11 Met and 4 Pl) had BCH Vit B12 DEF (<181 pmol/L) at diagnosis; 15 Met and 3 Pl at 6 mo (p=0.004). Mean Hgb was similar at baseline 130.1±9.1 (MET) and 131.0±9.9 g/L (Pl), p=0.38 and 6 mo 131.3±9.5 (MET) and 132.7±9.6 g/L (Pl), p=0.11); and in those +/- BCH Vit B12 DEF. Of the 74 with Vit B12 <222 pmol/L (45 Met, 29 Pl), MMA was normal in all pts at baseline; 2 had elevated HC (>15 umol/L). At 6 mo 1 Met pt had MMA >0.4 umol/L and 3 (2 Met, 1 Pl) had HC >15 umol/L. Conclusions: There was an increased rate of BCH, but not clinical, Vit B12 DEF after 6 mo of Met. This suggests that Met (not diabetes) lowers VitB12 and supports recommendations to monitor Vit B12 with Met use. Longer follow-up will evaluate clinical VitB12 DEF. Clinical trial information: NCT01101438.
Is there any correlation between molecular subtypes and blood groups in breast cancer?
Authors: Nadire Kucukoztas, Arzu Oguz, Taner Babacan, Omer Dizdar, Samed Rahatli, Saim Furkan Sarici, Gul Sema Yildiran Keskin, Omer Diker, Serkan Akin, Ozden Altundag, Kadri Altundag
Journal: Journal of Clinical Oncology (2014)

e11554 Background: The correlation of ABO blood groups with some solid malignancies have been studied, including gastric, lung, breast and pancreatic cancer. The aim of this study was to analyse the relation between blood groups of the patients and molecular subtypes in a large cohort of breast cancer patients. Methods: The files of patients diagnosed with primary breast cancer were reviewed retrospectively. Molecular subtypes according to receptor status and serologically determined blood group and Rh factor were recorded. Qualitative variables were given as percent and the correlation between categorical variables was investigated using chi-square test. Results: A 3,191 breast cancer patients were reviewed retrospectively. 21 (0.7%) were male and 3,170 (99.3%) were female. Median age was 48 (19-92) years. Of 3,170 female patients, 207 (6.5%) were peri, 1,419 (44.5%) were post and 1,544 (48.4%) were premenapousal at the time of diagnosis. Two hundred sixty eight cases were found to have metastatic disease at first admission. According to molecular subtypes; 1,525 (47.8%) were Luminal A, 372 (11.7%) were Luminal B/Her2 negative, 368 (11.5%) were Luminal B/HER2 positive, 272 were (8.5%) HER2 positive and 375 (11.8%) were triple negative. In 279 patients (8.7%) molecular subtype determination was not possible. Of 2,530 patients the blood groups were O in 839 (33.2%), A in 1105 (43.7%), B in 390 (15.4%) and AB in 196 (7.7%) cases. Rh status was negative in 300 (11.8%) and positive in 2230 (88.2%) cases. There were no significant correlation found between blood groups or Rh status and molecular subtypes (p levels were 0.624 and 0.525, respectively). Conclusions: Despite recent studies showing blood group O had lower rate of Luminal types and higher rate of triple negative subtype, there was no significant correlation detected between blood groups or Rh status and molecular subtypes in this large scaled study.
Maximum severity score (MSS) of baseline patient-reported Lung Cancer Symptom Scale (LCSS) as a prognostic and predictive factor for overall survival (OS) in the Phase III SQUIRE study.
Authors: Martin Reck, Richard J. Gralla, Philip Bonomi, Mark A. Socinski, Victoria Soldatenkova, Javad Shahidi, Patrick Peterson, Jacqueline Brown, Coleman K. Obasaju, Nick Thatcher
Journal: Journal of Clinical Oncology (2015)

8099 Background: SQUIRE, a randomized, phase III study (N = 1093) demonstrated that the addition of necitumumab (N) to gemcitabine-cisplatin (GC) improved OS in patients with stage IV squamous NSCLC. We further analyzed the results by baseline MSS and other cofactors that preliminary models suggested were prognostic for OS in this study. Methods: This post-hoc analysis defined the MSS for each patient as the worst (highest) score of any individual LCSS item at baseline. MSS was evaluated as a prognostic and predictive factor for OS and progression-free survival (PFS) using Cox and Kaplan-Meier methods. Cox models included baseline ECOG performance status, sum of target lesions, number of metastatic sites, body mass index, platelets, hemoglobin, and leukocytes. Results: As a continuous variable, MSS was prognostic for OS (p < 0.001) with a statistically significant interaction (p = 0.006) with treatment effect. These results manifested as subgroup differences shown in the table below. Results for PFS and OS were consistent. Conclusions: Prognosis for survival worsened with increasing LCSS severity, as shown with the MSS. The addition of N to GC was increasingly effective as severity increased, providing the greatest survival benefit in patients with more severe symptoms or more severely reduced functional ability or quality of life. This observation suggests baseline LCSS can provide information supporting treatment choice. Clinical trial information: NCT00981058. Subgroup N+GC N = 545 N+GC N = 545 GC N = 548 GC N = 548 OS treatment effect hazard ratio, p-value (Low hazard ratio favors N+GC) PFS treatment effect hazard ratio, p-value (Low hazard ratio favors N+GC) MSS Cutoff value N Median OS, mo N Median OS, mo ≥ 15 490 11.6 489 9.5 0.82, 0.005 0.82, 0.006 ≥ 30 446 11.4 441 9.1 0.79, 0.002 0.79, 0.002 ≥ 45 370 11.1 377 8.3 0.76, 0.001 0.76, 0.001 ≥ 60 263 10.7 266 7.3 0.67, < 0.001 0.69, < 0.001 ≥ 75 172 10.1 160 6.9 0.70, 0.004 0.71, 0.006 < 15 33 9.3 35 16.4 1.76, 0.045 1.77, 0.037 < 30 77 12.9 83 15.7 1.22, 0.282 1.38, 0.066 < 45 153 13.3 147 15.2 1.14, 0.346 1.17, 0.228 < 60 260 12.6 258 13.0 1.06, 0.547 1.07, 0.493 < 75 351 12.4 364 11.7 0.92, 0.329 0.94, 0.468
Predictor: Randomized phase II study of preoperative afatinib in untreated nonmetastatic head and neck squamous cell carcinoma patients (HNSCC) aiming at identifying predictive and pharmacodynamic biomarkers of efficacy.
Authors: Christophe Le Tourneau, Jean-Pierre Delord, Gilles Dolivet, Olivier Capitain, Laurent Laccourreye, Jerome Fayette, Dominique De Raucourt, Frederic Peyrade, Olivier Malard, Frederic Rolland, Christine Orsini, Odette Mariani, Jerzy Klijanienko, Leanne de Koning, Ivan Bieche, Xavier Sastre, Nicolas Aide, Xavier Paoletti, Stéphane Temam
Journal: Journal of Clinical Oncology (2014)

TPS6105 Background: Identification of efficacy predictive biological biomarkers in HNSCC patients treated with anti-EGFR targeted therapy is still a challenge. In the recurrent/metastatic setting, sequential biopsies allowed correlating potential predictive and pharmacodynamic biomarkers with the outcome of patients treated with erlotinib (Agulnik M et al. J Clin Oncol. 2007;25:2184). Afatinib is an Erb-B family blocker that irreversibly blocks signaling from all relevant Erb-B family dimers and may overcome limitations of current EGFR-targeted treatment in HNSCC. We conduct a randomized phase II study with afatinib Methods: PREDICTOR is a UNICANCER sponsored multi-centre randomized phase II study of pre-operative afatinib aiming at identifying predictive and pharmacodynamic biomarkers of biological activity and efficacy in untreated non-metastatic HNSCC patients. Key eligibility criteria: confirmed non-metastatic HNSCC; T2-4N0-2 tumors (except T2N0 endolaryngeal tumors); planned date of surgery allowing the patient to receive 14 to 28 days of afatinib treatment; ECOG status 0-2. Target enrolment is 60 pts. Randomization is stratified on the site of primary tumor (oropharynx versus non-oropharynx). Pts are randomized 2:1 to receive afatinib (40mg/qd) OR no treatment (control arm). Dose adjustments are permitted according to the ocurrence of drug-related AEs (reduction to 30mg/qd). The primary endpoint is to identify predictive and pharmacodynamics biomarkers.Tumor samples are collected before treatment (biopsy) and after surgery (surgical specimen). Several molecules involved in the resistance to EGFR will be analyzed through different technics (Immunohistochemistry, High throughput protein analysis, FISH, PCR sequencing and qRT-PCR). Secondary endpoints include efficacy (tumor shrinkage), pathological response, metabolic response (FDG PET/CT scan assessment) and safety. Completion of pt recruitment and data analyses are awaited. Clinical trial information: NCT01415674.
Perceptions and consequences of cancer-related weight loss among patients with cancer and caregivers.
Authors: Joanne S Buzaglo, Alexandra K Zaleta, Kayla M Miller, Victoria Kennedy, Ellyn Specker Charap
Journal: Journal of Clinical Oncology (2017)

224 Background: Cancer-related weight loss affects up to 50% of individuals with cancer, yet our understanding of psychosocial consequences of this weight loss is limited. This study examined patient and caregiver perceptions of symptoms and consequences of cancer-related weight loss. Methods: Patients with self-reported weight loss (n = 15; 26% non-mBC, 13% colorectal, 13% MM, 13% ovarian, 35% other; mean BMI = 22.9) and caregivers of people experiencing weight loss (n = 15) were recruited through the online Cancer Experience Registry. Participants completed a one-hour phone interview about views about weight loss; transcribed responses underwent content and thematic analysis by three coders (agreement = 89%). Results: Across participants, the most commonly reported weight loss-related symptoms included appetite changes (80% of participants), nausea (73%), and taste changes (60%). Most bothersome consequences of weight loss for patients included fear of disease progression (53%), loss of identity (47%), caregiver burden worries (40%), anxiety (27%), and body image concerns/embarrassment about physical appearance (27%). Most bothersome consequences for caregivers were burden of providing care (80%), distress about physical appearance of the patient (80%), changed sense of patient identity (60%), fear of illness progression (53%), and family impact (40%). Weight loss acceptance varied by BMI; obese/overweight patients reported greater acceptance, citing improvements in body image and better physical fitness as reasons for acceptance. Only 33% of patients and 22% of caregivers reported that their healthcare team addressed cancer-related weight loss during medical visits. Conclusions: With respect to cancer-related weight loss, patients and caregivers most often identified psychosocial concerns as bothersome; concerns about weight loss causing changes in physical appearance were more prevalent among caregivers. These results support development of a psychometric measure to evaluate cancer-related weight loss and suggest the need for better integration of cancer-related weight loss concerns into survivorship care plans.
Real-world response monitoring and tolerability of imatinib-treated chronic myeloid leukemia patients captured in a retrospective research registry.
Authors: David D. Stenehjem, Frederick S. Albright, Min Amy Guo, Lei Chen, Karina Raimundo, Hillevi Bauer, Diana I. Brixner
Journal: Journal of Clinical Oncology (2012)

6583 Background: Monitoring tolerability and response to imatinib (IM) is an important aspect of chronic myeloid leukemia (CML) management. The objective of this study is to assess real-world tolerability and response monitoring in IM treated CML patients (pts). Methods: A comprehensive retrospective outcomes research registry of CML pts was created from the University of Utah electronic health record system. Study inclusion was limited to pts diagnosed with CML in chronic phase in 2001 to 2010 and treated with IM as a first-line therapy. Utilization and outcome of cytogenetic and molecular testing within 18 months of IM initiation, rates of adverse drug events (ADEs), and therapy modifications were evaluated by chart review. Results: A total of 92 pts were treated with IM as first-line therapy. Within the first 18 months of treatment, cytogenetic testing was recorded in 45 pts (49%) and of these 33 pts (73%) achieved a complete cytogenetic response (CCyR) in a median of 241 days (range: 110-542); molecular testing was completed in 48 pts (52%) and of these 24 pts (50%) achieved at least a major molecular response (MMR) in a median of 254 days (range: 99-546). Imatinib associated ADEs of any grade (n = 60) occurred in 42 (46%) pts resulting in dose reductions in 15 pts (36%) in a median of 77 days and discontinuation of IM occurred in 9 (21%) pts in a median of 130 days. The IM dose was increased to &gt;400 mg in 21 (23%) pts in a median of 457 days (range: 21-2112). Of pts diagnosed between 2006 to 2010 (n = 34; 37%), 8 (25%) pts transitioned to dasatinib or nilotinib in a median of 397 days (range: 147 to 1057). Reasons for therapy change included physician documented suboptimal response or treatment failure (n = 5) and ADEs to IM (n = 3). Conclusions: Utilization of cytogenetic and molecular testing within 18 months of IM initiation was lower than the National Comprehensive Cancer Network or European LeukemiaNet CML guidelines would suggest. Further research is warranted to understand limited response monitoring and outcomes in non-monitored pts. The ADE rate was similar to clinical trial data. The impact of ADEs on subsequent treatment and outcomes in CML pts deserves further study.
Squamous cell carcinoma of the posterior urethra: Outcomes following radical surgery and adjuvant chemo-radiotherapy.
Authors: Fabio Castiglione, Michelle Christodoulidou, Raj Nigam, Peter Malone, Anita Mitra, Asif Muneer
Journal: Journal of Clinical Oncology (2017)

425 Background: Squamous cell carcinoma (SCC) of the posterior urethra is rare and is associated with sexually transmitted infections, urethritis, chronic strictures or urethral surgery. Unlike anterior urethral SCC, the presentation of posterior urethral SCC is often late and there are currently no standardised treatment protocols. We present our series of posterior urethral SCC treated by radical surgery and bladder preservation by performing a pan-urethrectomy, radical prostatectomy with a bladder neck closure and chemoradiotherapy. Methods: We retrospectively collected data from patients diagnosed with posterior urethral SCC from a penile cancer database. Data including patient age, histological subtypes, surgical management, post-operative complications, chemo-radiotherapy and survival rates were recorded. Results: A total of 10 cases with histologically proven posterior urethral SCC were treated in a single centre. Median follow-up was 19 months (SD±10 months). Mean age at presentation was 49 years (SD±6.44) and usual type SCC (80%) was the most prevalent histological subtype followed by NOS and condylomatous SCC. The majority of cases were poorly differentiated SCC (70%), stage ≥ T3 and required radical surgery with total urethrectomy and radical prostatectomy. Complications included post-operative ileus (30%), wound infection (20%), sepsis (10%), perioperative transfusion was required in one patient. Lymphovascular invasion was present in 90% of cases and local recurrence occurred in 60% of patients. Only one patient was suitable for neo-adjuvant chemo-radiotherapy (cisplatin/5-FU) and a further 5 required adjuvant chemoradiotherapy following surgery. 60% of patients developed metastatic disease and 60% died with a median survival of 9.6 months (SD±5.3) from diagnosis to death. Conclusions: Posterior urethral SCC is rare and the late presentation means that neoadjuvant chemoradiotherapy is often not possible. Radical surgery requires a pan-urethrectomy and urinary diversion. Despite adjuvant chemoradiotherapy, posterior urethral SCC is associated with significant mortality with a median survivial of less than one year.
Impact of income and distress on patients' requests for social and emotional support: Findings from a community-based distress screening program.
Authors: Joanne S. Buzaglo, Melissa F Miller, Christopher Gayer, Victoria Kennedy, Mitch Golant
Journal: Journal of Clinical Oncology (2014)

e17679 Background: Given current standards for distress screening, it is essential to identify patients seeking psychosocial support. CancerSupportSource (CSS) is a validated, distress screening tool with a 2-pronged approach to successfully link high risk cancer patients to tailored resources. Specifically, CSS asks patients to: (1) Rate their level of concern about 25 biopsychosocial screening items; and (2) Select the type of help they want for each concern (e.g., talk with a staff person, connect with online resources, or provide written information). The study objective was to identify factors associated with requesting to “have a staff person talk with you”, holding distress level constant. Methods: A convenience sample of 251 English-speaking cancer survivors was recruited across 10 affiliates of a cancer support organization. Participants (90% female, median age 57 y) completed a web-based survey including CSS. Using multiple logistic regression analysis to model as a binary outcome we were able to delineate those individuals who did not select “have a staff person talk with you” for any of the 25 concerns on CSS (n=141) versus those who asked to “have a staff person talk with you” on one or more items (n=110). Level of distress was calculated as the sum of the problem ratings (0 to 4) for each of the 25 CSS items. Independent variables considered were age, gender, race, income, education, cancer site and stage, time since diagnosis, and time since completion of primary treatment. Results: Greater distress was significantly associated with an increased likelihood to ask to talk with a staff member (OR=1.06; 95%CI=1.03,1.08; p<0.001). Participants with lower income were more likely to ask to talk with a staff member (OR=1.24; 95%CI=1.02,1.52; p=0.035) adjusting for level of distress. Time since completion of primary treatment less than 6 months was also associated with greater likelihood to request help, but the association was confounded by participant distress level. Conclusions: Future research should evaluate efforts to provide tailored resources for low income survivors, particularly within the first six months post-treatment when distress levels are highest.
A Phase II Study of Pegylated Liposomal Doxorubicin (PLD), Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients with Relapsed/Refractory (R/R) Multiple Myeloma (MM)
Authors: James R. Berenson, Ori Yellin, Alan D. Cartmell, Thomas B. S. Woliver, Marshall S. Flam, Youram Nassir, Robert Vescio, Regina A. Swift
Journal: Blood (2010)
Treatment patterns, mortality, and costs of care in unfit patients (pts) with relapsed chronic lymphocytic leukemia (CLL).
Authors: Helen Varker, Xue Song, Nicole Meyer, Stephanie A. Gregory, Javier Pinilla-Ibarz, Scott David Ramsey
Journal: Journal of Clinical Oncology (2014)

7105 Background: CLL pts who are ineligible for treatment due to age or with major comorbidities and pts who relapse after initial therapy represent significant unmet needs for this disease. To better understand these populations, we examined the prevalence, treatments, outcomes, and costs for pts who might be considered unfit for chemotherapy and, among unfit treated pts, those who showed evidence of relapse after initial therapy. Methods: The Truven Health MarketScan Database was used to identify pts with newly diagnosed CLL in 2004-2013 using ICD-9-CM diagnosis codes. Pts were defined as unfit for chemotherapy if their age was ≥ 80 or had evidence of major comorbidity. Unfit and relapsed (U/R) pts were defined as having ≥ 2 lines of antineoplastic therapy where the 2ndline represented a change in therapy. Pts were followed from the index date until end of enrollment or death. Reimbursements were adjusted to 2013 dollars. Results: Of a total of 80,096 pts with CLL, 18,776 met the unfit criteria; and 1,109 pts met the U/R criteria. Unfit pts were 57% male, mean age of 69 (SD 18), and had a Charlson comorbidity score (CCI) of 2.4 (SD 2.0). Comorbidities at diagnosis: lipometabolic disorders (37%), hypertension (37%), diabetes mellitus (20%), chronic pulmonary disease (17%), congestive heart failure (7%), renal disease (7%). U/R pts were 63% male, mean age of 63 (SD 20), and had a CCI score of 3.4 (SD 2.2). Mean survival times for unfit and U/R pts were 26.7 (SD 23.8) months and 21.8 (SD 20.2) months, respectively. Among U/R pts, the most common 1st-line regimens were rituximab (R) ± prednisone(P)/ dexamethasone (D) (24.0%), R + bendamustine ± P/D (9.6%), and R + cyclophosphamide + fludarabine ± P/D (7.2%). Among U/R pts, per patient per month total costs by 1st and 2nd lines of therapies were $15,907 (SD $19,893) and $18,506 (SD $36,977) respectively. Conclusions: The most commonly used regimens for U/R CLL pts included rituximab. Survival for U/R after therapy is modestly lower than for those who might be considered unfit at diagnosis, suggesting that some who might otherwise be considered unfit can benefit from therapy. Medical costs were substantial for this cohort of pts.