pinecone/core-2020-05-10-deduplication huggingface dataset:
Pilot study of duloxetine for treatment of aromatase inhibitor‐associated musculoskeletal symptoms

BACKGROUND:  Approximately 50% of postmenopausal women with hormone receptor‐positive early stage breast cancer treated with an aromatase inhibitor (AI) develop musculoskeletal symptoms. Standard analgesics are relatively ineffective. Duloxetine is a serotonin norepinephrine reuptake inhibitor with proven efficacy for treatment of multiple chronic pain states. The authors investigated the hypothesis that duloxetine is efficacious for treatment of AI‐associated musculoskeletal symptoms.    METHODS:  The authors performed a single‐arm, open‐label phase 2 study of duloxetine in postmenopausal women with breast cancer who developed new or worsening pain after treatment with an AI for at least 2 weeks. Patients were treated with duloxetine for 8 weeks (30 mg for 7 days, then 60 mg daily). The primary endpoint was a 30% decrease in average pain score over 8 weeks, and secondary outcomes included change in average and worst pain, pain interference, depression, sleep quality, and hot flashes. Statistical analysis was done with  t  tests for paired data.    RESULTS:  Twenty‐one of 29 evaluable patients (72.4%) achieved at least a 30% decrease in average pain, and 18 of 23 patients (78.3%) who completed protocol‐directed treatment continued duloxetine. The mean percentage reduction in average pain severity between baseline and 8 weeks was 60.9% (95% confidence interval [CI], 48.6%‐73.1%), and in maximum pain severity it was 59.9% (95% CI, 47.0‐72.7%). The most common adverse events were grade 1 or 2 fatigue, xerostomia, nausea, and headache.    CONCLUSIONS:  Duloxetine appears to be effective and well tolerated for treatment of AI‐associated musculoskeletal symptoms. Future randomized, placebo‐controlled studies are warranted. Cancer 2011;. © 2011 American Cancer Society.      Bothersome musculoskeletal symptoms affect about half of women with early stage breast cancer treated with aromatase inhibitors. In this pilot clinical trial, treatment with duloxetine appeared to significantly improve pain and functioning, and was relatively well tolerated
Efficient delivery of radical cystectomy after neoadjuvant chemotherapy for muscle‐invasive bladder cancer

BACKGROUND:  Cystectomy delay >90 days after a diagnosis of muscle‐invasive bladder cancer (MIBC) adversely affects pathologic stage and survival outcomes in patients who undergo primary surgery. After neoadjuvant chemotherapy (NAC), the impact of the timing of cystectomy delivery on these outcomes is uncertain. Poor communication between urologic and medical oncologists can result in cystectomy delay after systemic treatment. The authors of this report hypothesized that a delay in cystectomy delivery after NAC is associated with adverse survival outcomes.    METHODS:  An eligible cohort of 153 patients with MIBC received NAC and underwent radical cystectomy between 1990 and 2007. At the authors' institution, the genitourinary team strives to schedule patients for surgery at the time of initial evaluation or after their first chemotherapy cycle. Clinicopathologic characteristics, including timing of cystectomy, chemotherapy delivery, vital status, and reasons for excessive surgical delay, were analyzed retrospectively using an institutional database. A Cox proportional regression model was used to test the association between the timing of cystectomy delivery and survival.    RESULTS:  The median follow‐up for all patients was 3.6 years. The median time to cystectomy was 16.6 weeks and 6.9 weeks from the first and last day of NAC, respectively. In multivariate analyses, the timing of cystectomy delivery from the termination of NAC did not significantly alter the risk of survival. The most common reason for cystectomy delivery beyond 10 weeks (28 patients; 18%) was procedural scheduling.    CONCLUSIONS:  Cystectomy delivery within 10 weeks after NAC did not compromise patient survival and, thus, provided a reasonable window for patient recovery and surgical intervention. Cancer 2012;. © 2011 American Cancer Society.      The authors analyzed the timing between the termination of neoadjuvant chemotherapy and cystectomy and assessed its impact on the survival of patients with muscle‐invasive bladder cancer. By using a multidisciplinary approach, the authors determined that the median time to cystectomy was 6.9 weeks. The results indicated that undergoing cystectomy within 10 weeks after the completion of neoadjuvant chemotherapy did not compromise cancer‐specific or overall survival
Post-Therapy Pathologic Stage and Survival in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Chemoradiation

BACKGROUND: Neoadjuvant chemoradiation before surgery is an emerging treatment modality for pancreatic ductal
adenocarcinoma (PDAC). However, analysis of prognostic factors is limited for patients with PDAC treated with neoadjuvant
chemoradiation and pancreaticoduodenectomy (PD). METHODS: The study population was comprised of
240 consecutive patients with PDAC who received neoadjuvant chemoradiation and PD and was compared with 60
patients who had no neoadjuvant therapy between 1999 and 2007. Clinicopathologic features were correlated with
disease-free survival (DFS) and overall survival (OS). RESULTS: Among the 240 treated patients, the 1-year and 3-
year DFS rates were 52% and 32%, with a median DFS of 15.1 months. The 1-year and 3-year OS rates were 95% and
47%, with a median OS of 33.5 months. By univariate analysis, DFS was associated with age, post-therapy tumor
stage (ypT), lymph node status (ypN), number of positive lymph nodes, and American Joint Committee on Cancer
(AJCC) stage, whereas OS was associated with intraoperative blood loss, margin status, ypT, ypN, number of positive
lymph nodes, and AJCC stage. By multivariate analysis, DFS was independently associated with age, number of positive
lymph nodes, and AJCC stage, and OS was independently associated with differentiation, margin status, number
of positive lymph nodes, and AJCC stage. In addition, the treated patients had better OS and lower frequency of
lymph node metastasis than those who had no neoadjuvant therapy. CONCLUSIONS: In patients with PDAC who
received neoadjuvant chemoradiation and subsequent PD, post-therapy pathologic AJCC stage and number of positive
lymph nodes are independent prognostic factors. Cancer 2012;118:268-77. VC 2011 American Cancer Society.PublishedN/
Sentinel lymph node biopsy is accurate and prognostic in head and neck melanoma

BACKGROUND:  Sentinel lymph node biopsy (SLNB) has emerged as a widely used staging procedure for cutaneous melanoma. However, debate remains around the accuracy and prognostic implications of SLNB for cutaneous melanoma arising in the head and neck, as previous reports have demonstrated inferior results to those in nonhead and neck regions. Through the largest single‐institution series of head and neck melanoma patients, the authors set out to demonstrate that SLNB accuracy and prognostic value in the head and neck region are comparable to other sites.    METHODS:  A prospectively collected database was queried for cutaneous head and neck melanoma patients who underwent SLNB at the University of Michigan between 1997 and 2007. Primary endpoints included SLNB result, time to recurrence, site of recurrence, and date and cause of death. Multivariate models were constructed for analyses.    RESULTS:  Three hundred fifty‐three patients were identified. A sentinel lymph node was identified in 352 of 353 patients (99.7%). Sixty‐nine of the 353 (19.6%) patients had a positive SLNB. Seventeen of 68 patients (25%) undergoing completion lymphadenectomy after a positive SLNB result had at least 1 additional positive nonsentinel lymph node. Patients with local control and a negative SLNB failed regionally in 4.2% of cases. Multivariate analysis revealed positive SLNB status to be the most prognostic clinicopathologic predictor of poor outcome; hazard ratio was 4.23 for SLNB status and recurrence‐free survival ( P  < .0001) and 3.33 for overall survival ( P  < .0001).    CONCLUSIONS:  SLNB is accurate and its results are of prognostic importance for head and neck melanoma patients. Cancer 2012;. © 2011 American Cancer Society.      This is the largest single‐institution series of patients with head and neck melanoma (n = 353) to date. The authors demonstrate sentinel lymph node biopsy to be reliable (99.7% identification rate), accurate (19.7% positive sentinel lymph node biopsy rate and 4.2% false‐omission rate), and strongly prognostic of survival on multivariate analysis
Underascertainment of radiotherapy receipt in Surveillance, Epidemiology, and End Results registry data

BACKGROUND:  Surveillance, Epidemiology, and End Results (SEER) registry data have been used to suggest underuse and disparities in receipt of radiotherapy. Prior studies have cautioned that SEER may underascertain radiotherapy but lacked adequate representation to assess whether underascertainment varies by geography or patient sociodemographic characteristics. The authors sought to determine rates and correlates of underascertainment of radiotherapy in recent SEER data.    METHODS:  The authors evaluated data from 2290 survey respondents with nonmetastatic breast cancer, aged 20 to 79 years, diagnosed from June of 2005 to February 2007 in Detroit and Los Angeles and reported to SEER registries (73% response rate). Survey responses regarding treatment and sociodemographic factors were merged with SEER data. The authors compared radiotherapy receipt as reported by patients versus SEER records. The authors then assessed correlates of radiotherapy underascertainment in SEER.    RESULTS:  Of 1292 patients who reported receiving radiotherapy, 273 were coded as not receiving radiotherapy in SEER (underascertained). Underascertainment was more common in Los Angeles than in Detroit (32.0% vs 11.25%,  P  < .001). On multivariate analysis, radiotherapy underascertainment was significantly associated in each registry (Los Angeles, Detroit) with stage ( P  = .008,  P  = .026), income ( P  < .001,  P  = .050), mastectomy receipt ( P  < .001,  P  < .001), chemotherapy receipt ( P  < .001,  P  = .045), and diagnosis at a hospital that was not accredited by the American College of Surgeons ( P  < .001,  P  < .001). In Los Angeles, additional significant variables included younger age ( P  < .001), nonprivate insurance ( P  < .001), and delayed receipt of radiotherapy ( P  < .001).    CONCLUSIONS:  SEER registry data as currently collected may not be an appropriate source for documentation of rates of radiotherapy receipt or investigation of geographic variation in the radiation treatment of breast cancer. Cancer 2011;. © 2011 American Cancer Society.      This study found that the Los Angeles Cancer Surveillance Program, among the largest Surveillance, Epidemiology, and End Results (SEER) registries, coded that radiation was not received in nearly a third of cases in which breast cancer patients themselves reported radiation receipt, whereas ascertainment of radiation receipt was much more complete in another large SEER registry, that of the Metropolitan Detroit Cancer Surveillance System. SEER registry data as currently collected may not be an appropriate source for documentation of rates of radiotherapy receipt or geographic disparities
Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia: an effective but myelosuppressive regimen to be offered to patients with advanced disease.

BACKGROUND: The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced promising results in chronic lymphocytic leukemia and other lymphoproliferative disorders. The authors report the final results from a multicenter, prospective study examining FCR in Waldenstrom macroglobulinemia (WM).METHODS: Forty-three patients with symptomatic WM that was untreated or pretreated with 1 line of chemotherapy received rituximab 375 mg/m(2) intravenously on day 1 and fludarabine 25 mg/m(2) and cyclophosphamide 250 mg/m(2) intravenously on days 2 through 4. FCR was repeated every 28 days for up to 6 courses.RESULTS: The overall response rate was 79%, and the major response rate of 74.4%, including 11.6% complete remissions (CRs) and 20.9% very good partial remissions. An amelioration of the quality of responses was observed during follow-up, leading to 18.6% of CRs. No differences in terms of responses were observed among previously treated or untreated patients. Among the clinical and laboratory features that were considered, only the β2-microglobulin level had a significant impact in terms of achieving a major response. The major toxicity reported was grade 3/4 neutropenia, which occurred in 45% of courses and was the main reason for treatment discontinuation. After the end of treatment, 19 patients (44%) had long-lasting episodes of neutropenia. Three patients developed myelodysplastic syndrome during follow-up.CONCLUSIONS: The FCR regimen was capable of neutralizing adverse prognostic factors and proved to be active in patients with WM, leading to rapid disease control and good-quality responses. Because myelosuppression was the main concern, further studies are warranted to optimize dosages and treatment duration
Selective detection of histologically aggressive prostate cancer

BACKGROUND:  Limited survival benefit and excess treatment because of prostate‐specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy.    METHODS:  Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model.    RESULTS:  The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all  P  < .001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71,  P  < .01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (<10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75‐0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD >0.1 ng/mL/cc or abnormal DRE. When PSAD is <0.1 ng/mL/cc, family history or obesity can identify biopsy candidates.    CONCLUSIONS:  A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer. Cancer 2011. © 2011 American Cancer Society.      A predictive model incorporating age, family history, obesity, prostate‐specific antigen density, and digital rectal examination has been proposed in detecting aggressive prostate cancer. Using these criteria, ¼ of prostate biopsies can be avoided
Optical fiber‐based in vivo quantification of growth factor receptors

BACKGROUND:  Growth factor receptors such as epidermal growth factor receptor 1 and human epidermal growth receptor 2 (HER2) are overexpressed in certain cancer cells. Antibodies against these receptors (eg. cetuximab and transtuzumab [Herceptin]) have shown therapeutic value in cancer treatment. The existing methods for the quantification of these receptors in tumors involve immunohistochemistry or DNA quantification, both in extracted tissue samples. The goal of the study was to evaluate whether an optical fiber‐based technique can be used to quantify the expression of multiple growth factor receptors simultaneously.    METHODS:  The authors examined HER2 expression using the monoclonal antibody trastuzumab as a targeting ligand to test their system. They conjugated trastuzumab to 2 different Alexa Fluor dyes with different excitation and emission wavelengths. Two of the dye conjugates were subsequently injected intravenously into mice bearing HER2‐expressing subcutaneous tumors. An optical fiber was then inserted into the tumor through a 30‐gauge needle, and using a single laser beam as the excitation source, the fluorescence emitted by the 2 conjugates was identified and quantified by 2‐photon optical fiber fluorescence.    RESULTS:  The 2 conjugates bound to the HER2‐expressing tumor competitively in a receptor‐specific fashion, but they failed to bind to a similar cell tumor that did not express HER2. The concentration of the conjugate present in the tumor as determined by 2‐photon optical fiber fluorescence was shown to serve as an index of the HER2 expression levels.    CONCLUSIONS:  These studies offer a minimally invasive technique for the quantification of tumor receptors simultaneously. Cancer 2012;. © 2011 American Cancer Society.      The paper describes the in vivo quantification of human epidermal growth receptor 2 using a minimally invasive 2‐photon optical fiber fluorescence detection technique. The proof of concept for the simultaneous in vivo quantification of multiple receptors is provided
Interval to biochemical failure as a biomarker for cause‐specific and overall survival after dose‐escalated external beam radiation therapy for prostate cancer

BACKGROUND:  After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause‐specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose‐escalated EBRT.    METHODS:  From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause‐specific survival (CSS) and overall survival (OS) were evaluated.    RESULTS:  There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate‐risk or high‐risk disease, respectively. Biochemical failure impacted CSS ( P  < .0001) but not OS ( P  = .36). However, a short interval to biochemical failure predicted decreased CSS ( P  < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4‐13.0) and OS ( P  < .0001; HR, 4.8; 95% CI, 2.3‐10.3) when compared with a long interval to biochemical failure. The 8‐year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure ( P  = .1; HR, 0.7; 95% CI, 0.4‐1.1) and 38% with a short interval to biochemical failure ( P  < .0001; HR, 3.7; 95% CI, 2.3‐5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death ( P  < .0001; HR, 18.1; 95% CI, 8.4‐39) and all cause mortality ( P  = .0027; HR, 1.5; 95% CI, 1.2‐2.1), whereas a long interval to biochemical failure did not.    CONCLUSIONS:  The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose‐escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012. © 2011 American Cancer Society.      Because biochemical failure does not predict for overall survival after radiotherapy (RT) in prostate cancer, a short interval to biochemical failure (defined as <18 months after finishing therapy) is tested as a biomarker for both cause‐specific and overall survival. Among 710 patients treated with dose‐escalated RT at the University of Michigan, a short interval to biochemical failure is found to be prognostic of both cause‐specific and overall survival
Preferences for colorectal cancer screening tests and screening test use in a large multispecialty primary care practice

BACKGROUND:  The purpose of this study was to identify factors associated with colorectal cancer (CRC) screening test preference and examine the association between test preference and test completed.    METHODS:  Patients (n = 1224) were 50‐70 years, at average CRC risk, and overdue for screening. Outcome variables were preference for fecal occult blood test (FOBT), colonoscopy (COL), sigmoidoscopy (SIG), or barium enema (BE), measured by telephone survey, and concordance between test preference and test completed assessed using medical records.    RESULTS:  Thirty‐five percent preferred FOBT, 41.1% COL, 12.7% SIG, and 5.7% BE. Preference for SIG or COL was associated with having a physician recommendation, greater screening readiness, test‐specific self‐efficacy, greater CRC worry, and perceived pros of screening. Preference for FOBT was associated with self‐efficacy for doing FOBT. Participants who preferred COL were more likely to complete COL compared with those who preferred another test. Of those screened, only 50% received their preferred test. Those not receiving their preferred test most often received COL (52%).    CONCLUSIONS:  Lack of concordance between patient preference and test completed suggests that patients' preferences are not well incorporated into screening discussions and test decisions, which could contribute to low screening uptake. Physicians should acknowledge patients' preferences when discussing test options and making recommendations, which may increase patients' receptivity to screening. Cancer 2011. © 2011 American Cancer Society.      Lack of concordance between patient preference and test completed suggests that patients' preferences are not well incorporated into screening discussions and test decisions, which may hinder screening completion. Physicians should acknowledge patients' preferences when discussing test options and making recommendations, which may increase patients' receptivity to screening