tbuckley/cabot-search huggingface dataset:
FDG-PET for staging of rhabdomyosarcoma
Authors: M. L. Klem, R. Grewal, L. H. Wexler, H. Schöder, P. A. Meyers, S. L. Wolden
Journal: Journal of Clinical Oncology (2005)

8545 Background: Complete staging of rhabdomyosarcoma is critical for delivery of appropriate therapy. Current diagnostic tools have known limitations. We have evaluated the role of 18F fluorodeoxyglucose positron emission tomography (PET) in the staging of patients with rhabdomyosarcoma. Methods: Since 1997, 60 patients with rhabdomyosarcoma underwent 159 PET scans. Of these, 21 patients with a median age of 11 years had a PET scan as part of their initial staging evaluation, before or within 13 days of initiation of therapy. Twelve patients had alveolar and 9 had embryonal histology. Primary sites included parameningeal (11), extremity (4), trunk (3), bladder/prostate (2), and head and neck (1). Results from CT, MRI, bone scan, and pathology within 1 month of the PET were compared. Results: A total of 83 sites were evaluated. All 21 patients had positive PET scans at the primary site. Twenty six PET positive sites at primary or nodal regions were biopsied and in all sites disease was confirmed. Standardized uptake value (SUV) for the primary site at the time of diagnosis ranged from 2.4 to 12.7 (mean 5.7). All SUVs prior to therapy were ≥4. There was no significant difference in SUV when evaluated by primary site or histology. PET showed involvement of regional lymph nodes in 12 patients. Five of the 12 patients underwent lymph node biopsy, all confirming involvement. In 3 of these cases, CT or MRI failed to detect the regional involvement identified on PET. At 11 sites, CT or MRI was equivocal for detection of regional or distant spread. In these cases, PET confirmed disease in one case and excluded disease in 10 cases. PET failed to capture sites of disease visualized by CT, MRI, or bone scan at 10 sites, including pelvic, paraaortic, mediastinal, cervical and retropharyngeal lymph nodes as well as vertebral bodies. When comparing PET to the final clinical determination of disease extent, PET was 83% sensitive and 97% specific. Conclusion: These preliminary data indicate that PET is a useful adjunct in the initial staging of rhabdomyosarcoma. In 3 of 21 cases (14%), therapy was altered because of nodal disease detected only on PET. A prospective study of PET for staging of rhabdomyosarcoma is warranted. No significant financial relationships to disclose.
Intermittent erlotinib in combination with docetaxel (DOC): Phase I schedules designed to achieve pharmacodynamic separation
Authors: A. M. Davies, P. N. Lara, D. H. Lau, P. C. Mack, P. H. Gumerlock, D. R. Gandara
Journal: Journal of Clinical Oncology (2005)

7038 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) given concurrently with chemotherapy do not improve patient (pt) outcomes compared with chemotherapy alone in advanced non-small cell lung cancer (NSCLC). One explanation is antagonism due to TKI-induced G1 arrest, reducing cell cycle phase-dependent activity of chemotherapy (Gumerlock: ASCO, 2003). We hypothesized that pharmacodynamic separation by intermittent delivery of EGFR-TKI with chemotherapy would increase efficacy. Based on our pre-clinical studies and pharmacologic considerations, we proposed two schedules for testing intermittent erlotinib in combination with DOC. Methods: Two dose escalating phase I trials (Arm A and Arm B) were conducted simultaneously. DOC every 21 days in both arms (70–75 mg/m2 IV). Arm A: erlotinib given weekly days 2, 9, 16 (600–800 mg). Arm B: erlotinib given days 2–16 (150–300 mg). Dose limiting toxicity (DLT) was defined as: grade 4 platelets, grade 3 platelets with bleeding, febrile neutropenia, grade 4 ANC ≥ 7 days, or any ≥ grade 3 non-heme toxicity. Results: 42 pts with advanced solid tumors were treated, including 22 NSCLC. Characteristics: Age range 34–83; Sex: 22 M; KPS ≥90/<90 = 19/23; Median cycles: 4. Treatment was generally well tolerated. DLTs included febrile neutropenia, mucositis, and diarrhea. Grade 1/2 acneform rash: 88%. Febrile neutropenia: 19%. Arm A MTD: DOC 70 mg/m2 and weekly erlotinib 600 mg. Arm B MTD: DOC 70 mg/m2 and erlotinib 200 mg day 2–16. Of 22 NSCLC patients there were 4 partial responses, 4 minor responses, and 5 stable disease. 4 NSCLC patients remain on therapy at 23, 22, 15 and 10 months. Correlative science studies are ongoing. Conclusions: 1. We report the first clinical trial testing intermittent EGFR inhibition plus chemotherapy to overcome hypothesized antagonism of concurrent administration. 2. Intermittent dosing of erlotinib plus DOC is feasible and an active combination. 3. Efficacy of the Arm B regimen is being examined in a phase II trial for second-line NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Genentech
Evaluation of the state of health of patients with localized prostate cancer (cT1-cT2) compared to the normal population.
Authors: M. J. Mathers, S. Roth, M. Gerken, M. Klinkhammer-Schalke, F. Hofstädter, A. Heidenreich, T. Klotz
Journal: Journal of Clinical Oncology (2010)

6115 Background: PSA testing and early disease detection have improved survival rates of men with prostate cancer, but insufficient data exist on the long-term survival of patients with localised prostate cancer. We examined relative survival of patients with localised prostate carcinoma cT1-cT2 (stage I and II) compared to the standardised age-adjusted rates of the normal population. Methods: Epidemiologic and clinical data from patients with cancer diagnosed from 1998 to 2007 were extracted from the cancer registry of the tumor centre in Regensburg, Germany. All patients had histologically-confirmed cancer in one of the following locations: C61 (prostate, n = 2,087), C18- 20 (colorectum, n = 1,560), C50 (breast, n = 2,958) and C67 (bladder, n = 1,941 for stage 0a and n = for 698 for stage I). Kaplan-meier analysis was used to estimate the overall survival rates in the patient cohorts. These rates were compared to the expected survival rates in a comparable set of individuals from the general population, using official life-tables for Germany stratified by age and sex. Results: 8 years after diagnosis, patients with stage I and II localised prostate cancer had an approx. 10% increase in survival compared with the normal male population (relative survival [RS] = 1.09.3). Patients with stage I colorectal cancer, stage I breast cancer, and stage 0a bladder cancer did not have different survival rates than the normal population (RS = .97.6, RS = .99.1, RS = 1.03.1, respectively). Patients with stage I bladder cancer had an approximately 14% decrease in survival compared to the normal population (RS = .86.9%). Conclusions: Men with stage I-II localised prostate carcinoma have improved survival compared with the normal male population. This finding cannot be explained solely by the administration of prostate cancer treatments, which historically do not affect survival until several years after treatment, suggesting that men who participate in PSA screening may have better overall health behaviors and care than men who do not participate in screening. Future research should examine how treatment choice, especially an “active surveillance” approach to care, affects survival in these patients more than 8 years after diagnosis. No significant financial relationships to disclose.
Pre-treatment nomogram to predict potency after treatment for localized prostate cancer.
Authors: Joseph Zabell, Martin G. Sanda, Mark S. Litwin, Jose Francisco Suarez, Meredith M. Regan, Christopher Saigal, Lorna Kwan, Tianming Gao, Danny Rabah, Eric A. Klein, Michael W. Kattan, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2016)

32 Background: Radical prostatectomy (RP), external beam radiotherapy (EBRT), and brachytherapy are commonly utilized treatments for localized prostate cancer and may negatively impact sexual function to varying degrees. Patient-, disease-, and treatment-specific factors may all impact post-treatment sexual function. We aimed to evaluate predictors of post-treatment impotency, and develop a prognostic nomogram using prospective, patient-reported data from multiple validated health-related quality-of-life (HRQOL) instruments. Methods: Between 1999 and 2011, patient-reported data regarding treatment-related effects on erectile function were obtained from 2668 patients enrolled in one of four prospective longitudinal HRQOL protocols from the United States and Spain. Patients were treated with RP (n=1,294), EBRT (n=630), or brachytherapy (n=744). Although different HRQOL instruments were used in each protocol, questions pertaining to quality and frequency of erections were identical across the different instruments. Patient responses were obtained at baseline and 2 years after treatment. The endpoint of the model was impotency at 2 years post-treatment. Logistic regression analysis was used to model clinical information and outcome data. Internal validation was performed using bootstrapping. Results: 1,306 patients were potent at baseline and had 24-month follow-up. Differences in baseline patient characteristics such as patient age, ethnicity, and disease severity existed between the treatment groups. The impotency rate at 2 years was 62%, 53%, and 41% for patients treated by RP, EBRT, and brachytherapy, respectively. In multivariable analysis, age, PSA, modality of treatment, frequency of preoperative erections, diabetes, and hypertension were associated with post-treatment impotency (all p&lt;0.05). A nomogram based on the predictive parameters had a concordance index of 0.726 and predictions were well-calibrated with observed outcome. Conclusions: A validated nomogram that predicts 2-year risk of impotency after treatment of localized prostate cancer has been developed and is anticipated to be useful for patient counseling regarding treatment options.
Association of partial nephrectomy with a long-term survival advantage in patients between age 20 and 44 with renal cell carcinomas ≤ 4 cm: An analysis of the SEER database.
Authors: Michael R. Daugherty, Gennady Bratslavsky
Journal: Journal of Clinical Oncology (2013)

408 Background: PN decreases the risk of developing chronic kidney disease as opposed to RN. While prior studies have demonstrated the survival advantage of PN in older patients, they have been criticized by selection bias in procedure selection due to comorbidities. We hypothesized that the long-standing effects of renal preservation would manifest in a survival advantage of a younger patient population, where this selection bias is minimized. Methods: The SEER 18-registries database was queried for patients between the ages of 20 to 44 that were surgically treated with either PN or RN for RCC between 1993 and 2003. We have excluded patients with metastatic or locally advanced disease and included patients with localized tumors ≤4 cm with known grade. The histologies selected were clear cell, papillary, chromophobe, sarcomatoid, collecting duct, and renal cell. The final cohort consisted of 222 and 494 subjects treated with PN and RN respectively. Chi-square analysis compared tumor variables and patient characteristics. Cancer-specific and overall survival rates were compared at 5 and 10 years using Kaplan-Meier analyses. Results: There were no differences between patients treated by PN or RN in demographics or tumor characteristics. Additionally, there was no difference in cancer-specific survival between the two groups at 5 or 10 years (p= 0.34 and p = 0.1 respectively). While there was no difference in 5-year overall survival (98.2% vs. 95.5%, p = 0.07), the patients treated with PN had an advantage in 10-year overall survival compared to patients treated with RN (94% vs. 89.7%, p = 0.025). Conclusions: Present SEER analyses demonstrate that when compared to RN, PN results in improved overall survival in patients treated for small, localized RCC. As expected, the survival advantage is observed late and supports the importance of long-term renal functional preservation. The present study of a younger patient population allows for minimizing selection bias in choosing surgical procedure due to comorbidities and provides further support for maximal renal preservation in patients with a life expectancy of 10 years or more.
A Comparative Analysis of Chromosome 13 Gene Expression and Copy Number Changes in Multiple Myeloma Using Array-Based Methods.
Authors: Angela S. Baker, Tae-Hoon Chung, Tyler S. Pidgeon, Catherine Mancini, Tammy Price-Troska, Scott Van Wier, Gregory J. Ahmann, Rachel Rempel, Philip R. Greipp, Robert A. Kyle, S. Vincent Rajkumar, Angela Dispenzieri, Morie A. Gertz, Laurakay Bruhn, Paige Anderson, Michael Barrett, Michael Bittner, Seungchan Kim, P. Leif Bergsagel, Rafael Fonseca, John Carpten
Journal: Blood (2005)
Immunophenotypic analysis of clinical scale tumor infiltrating lymphocytes generated from a patient with ipilimumab-treated melanoma.
Authors: M. Donia, N. Junker, E. Ellebaek, M. H. Andersen, P. thor Straten, I. M. Svane
Journal: Journal of Clinical Oncology (2011)

e13012 Background: Adoptive cell transfer (ACT) with tumor infiltrating lymphocytes (TIL) is an effective treatment for advanced melanoma, but to our knowledge generation of clinical scale TILs has not been applied so far to ipilimumab-experienced patients Methods: We have generated clinical scale “young TILs” from an ipilimumab-treated melanoma patient using a classical two step method. TIL microcultures were initiated and minimally expanded from tumor fragments, and subsequently underwent a 14-day rapid expansion protocol (REP) for generation of large cell numbers, as required by current ACT protocols. Results: “Young TIL” minimally expanded bulk culture contained a large quantity of CD3-CD56brightCD16- cells alongside an atypical CD4CD8 double negative (DN) T cell subset. Clinical scale TIL generation was feasible, but only the CD3+ TILs present in the bulk culture could be efficiently expanded by the classical REP currently used in clinical practice. Further analyses showed that CD4CD8 DN T cells were expressing a gamma/delta T cell receptor. In addition, cells in the clinical grade cell product were able to recognize autologous tumor in vitro. Conclusions: Although our study demonstrates that TIL generation to quantities required for current ACT protocols was feasible in an ipilimumab-treated melanoma patient, these data warrant further investigations on the clinical application of ACT in patients treated with this new immune modulating agent.
Phase II multicenter study of second-line FOLFIRI plus cetuximab (FLIER) in patients with KRAS wild-type metastatic colorectal cancer: Final analysis of survival and additional analysis of BRAF, PI3CA mutations.
Authors: Yasuhiro Miyake, Shigeyoshi Iwamoto, Shoichi Hazama, Fuminori Goda, Chu Matsuda, Kenji Amagai, HIroyuki Bandou, Mutsumi Fukunaga, Naoki Nagata, Junichi Sakamoto, Hideyuki Mishima
Journal: Journal of Clinical Oncology (2012)

481 Background: Survival advantage of second line FOLFIRI plus cetuximab in patients with KRAS wild-type metastatic colorectal cancer has not been well reported. Since mutations in codons 12 and 13 of the KRAS gene predict lack of response to Cetuximab, mutations of V600E BRAF and PI3CA have been controversial. Methods: The aim of this study was to assess the efficacy of second-line FOLFIRI plus cetuximab in KRAS wt mCRC. Primary endpoint was response rate, other secondary endpoints were PFS, OS and safety. KRAS, BRAF, PI3CA tests by direct sequence were performed in Yamaguchi University. The starting dose of irinotecan was 150mg/ m 2 (approved dose in Japan), but decreased to 100mg/m 2 with UGT1A1 *28,*6 homozygous or both heterozygous. Results: From December 2008 to November 2009, 112 pts were preregistered. 67 (59.8%) pts were KRAS codon 12, 13 wt, and 60 pts were enrolled: 39 males (65%), 21 females (35%); median age was 62 years (range 37-82). The incidence of UGT1A1*28, *6 homozygous was 2.8%, 4.7% respectively. Grade 3/4 adverse events were leucopenia 26.7%, neutropenia 43.3%, paronychia 10.0%, skin toxity (fissure) 10.0% and acne 5.0%. The confirmed response rate (RECIST) was 31.7% (19/60). The median progression free survival and overall survival were 7.5 (C.I. 5.2-10.1) and 19.5 (C.I. 11.7-22.2) months respectively. Three pts had BRAF mutations and tumor shirinkage were +50.9%, +12%, +85.6% respectively. Two pts had PI3CA mutations and tumor shirinkage were +4%, +44%, respectively. Conclusions: FLIER was the first multicenter phase II trial with prospective analysis of KRAS as a predictive biomarker for cetuximab in second-line mCRC in Japan. Second-line FOLFIRI+cetuximab is well-tolerated and active. Mutations in BRAF and PI3CA gene seemed to be lack of response to cetuximab.
Prospective quality review of breast care navigation and treatment: Fox Chase Cancer Center Partners’ (FCCCP) initiative.
Authors: Lori J. Goldstein, Richard J. Bleicher, Steven J. Cohen, Elaine Sein, Margaret Anne O’Grady, Patricia A. Keeley, Bonnie J. Miller, Elyse Slater, Tianyu Li
Journal: Journal of Clinical Oncology (2012)

85 Background: There is increasing emphasis on quality metrics and process improvement for breast cancer treatment. FCCC designed a study to measure compliance with NCCN breast cancer guidelines at 11 FCCCP institutions. Methods: A relational data base was created to track indicators for operational timing, access, treatment modalities, and variance data in a population of breast cancer patients diagnosed and receiving first course of treatment at participating FCCCP institutions for 2009 calendar year. Pilot was conducted to ensure integrity of data collection tool in the previous year. Activation workshop, quarterly on site quality monitoring plan, real time quarterly reports to cancer committee, and benchmarking data were embedded in study. The primary objective was to benchmark participating institutions against each other and national benchmarks. Secondary objectives were to assess causes for variance and explore the role nurse navigation plays in real time quality metrics. Results: See Table. Conclusions: This novel prospective quality study demonstrated significant compliance with established breast cancer metrics across a large community hospital affiliate program. The impact of navigation appears greatest in reducing time between screening and diagnostic testing, demonstrating that navigation’s benefits extend beyond patient satisfaction to improvement of quality metrics. [Table: see text]
Health-related quality of life among women with a history of breast cancer in Europe.
Authors: P. Anhoury, M. DiBonaventura, R. Wagner
Journal: Journal of Clinical Oncology (2011)

e19615 Background: Due to the improvement in breast cancer (BC) detection and treatment, the prevalence of women with a history of BC is increasing. Yet, few international community-based studies have been conducted to examine the health-related quality of life (HRQoL) of women following diagnosis and treatment. Methods: Using data from the 2010 EU (UK, Germany, France, Italy, and Spain) National Health and Wellness Survey (NHWS), women with a history of breast cancer (BC+ group) were compared with women without a history of breast cancer (BC- group) on HRQoL (using the physical (PCS) and mental component summary (MCS) scores and health state utilities (SF6D) from the SF-12v2) controlling for demographics (age, education, etc), comorbidity burden (Charlson comorbidity index), and health characteristics (smoking, etc). Further, among just the BC+ group, predictors of HRQoL were examined. Results: A total of 579 women (2.0%) reported a history of BC in the EU. The mean age for BC+ women was 60.6 (standard deviation (SD)=10.1) and women had been diagnosed a mean of 9.6 years (SD=7.2). Most BC+ women were currently cancer free (76.9%) though 33.7% were still receiving drugs (hormonal therapies or others). Despite being mostly cancer free, BC+ women reported significantly lower levels of PCS (Adjusted means = 45.8 vs. 48.3, p<.05) and health state utilities (Adjusted means = 0.69 vs. 0.71, p<.05) relative to BC- women, even after adjusting for demographics, comorbidity burden, and health characteristics. No significant differences were observed on MCS scores. Subsequent analyses of just the BC+ group revealed that the primary predictors of health state utilities included age (b=0.002), employment (b=0.43), exercise behavior (b=0.04), alcohol use (b=0.04), comorbidity burden (b=-0.01), years diagnosed (b=0.002), and current cancer stage (b’s=-0.01 to -0.08) (all p’s<.05). Conclusions: The diminished HRQoL in BC+ women in the EU may be related to long-term persistent complications from BC treatments. From a public health perspective, prevention initiatives, special support and further attention on improving HRQoL among these women should be given, particularly as the prevalence rates of those with a history of cancer continue to rise.
Does incidence of rash predict treatment response to lapatanib in breast cancer?
Authors: J. M. Parma, A. C. Pavlick, J. C. N. Chang, M. F. Rimawi, M. Trivedi
Journal: Journal of Clinical Oncology (2011)

e11127 Background: Inflammatory papulopustular rash with acneiform distribution is a common dermatologic toxicity, which occurs in more than 30% of patients receiving lapatinib, a dual inhibitor of EGFR and HER2, for the treatment of HER2 over-expressing breast cancer. This adverse effect is a class effect of drugs that target EGFR, including erlotinib, cetuximab, and gefitinib and has been associated with superior treatment response. Although plausible, there is no evidence to date that the development of rash correlates with treatment response to lapatinib in breast cancer. We hypothesized that breast cancer patients who develop rash on lapatinib treatment will have a better treatment response. Methods: We prospectively enrolled 49 patients with locally advanced HER2-positive breast cancer (>/= 3 cm) on a clinical trial of neoadjuvant monotherapy with lapatinib (1500 mg per day for 6 weeks). Patients were followed for rash, which was graded using NCI CTCAE criteria, during the course of lapatinib treatment. Any rash that was considered lapatinib-related was counted as an event regardless of the severity. Primary endpoint of the trial was overall response rate, assessed by objective bidimensional tumor measurements and defined by at least 50% reduction in the product of the largest perpendicular diameters of the breast lesion according to standard WHO criteria. Results: Forty-seven patients were evaluated and were divided into two groups: with and without rash. We found that among 32 (68%) patients who experienced rash, 22 (69%) responded to treatment; whereas, 10 (31%) did not. Out of 15 (32%) patients who did not have rash, 11 (73%) responded to treatment; whereas, 4 (27%) did not. The difference was not statistically significant (p= 1.0, Fisher’s exact two-sided test). Two patients, who did not have post-treatment measurements, were excluded from analysis. Conclusions: In the neoadjuvant setting, incidence of rash did not predict clinical efficacy with lapatinib monotherapy in treatment-naïve locally advanced HER2-positive breast cancer patients.