tbuckley/cabot-search huggingface dataset:
Prospective assessment of symptoms and quality of life in localized rectal cancer patients receiving chemoradiotherapy.
Authors: J. M. Herman, K. A. Griffith, A. K. Narang, M. M. Zalupski, N. S. Azad, J. Chan, L. Olsen, J. Efron, T. S. Lawrence, E. Ben-Josef
Journal: Journal of Clinical Oncology (2011)

504 Background: Neoadjuvant conformal chemoradiotherapy (CRT) is an important component of treatment for locally advanced rectal cancer, yet its morbidity has not been well characterized using quality of life (QOL) instruments. The present study attempts to establish a baseline distribution of QOL scores before, during, and after CRT and to correlate these changes with symptoms. Methods: Patients undergoing 3-4 field neoadjuvant CRT for localized rectal cancer were prospectively enrolled at two institutions. Fifty patients completed the QOL instruments at three time points: pretreatment, week 4 of treatment, and 1 month post-treatment. QOL information was captured using three validated questionnaires, the EORTC QLQ-30, QLQ-38, and QLQ-29. Additionally, institutional symptom inventories and CTCAE toxicity data were collected. Results: Average age was 59.2 years and 72% were men. During CRT, patients had a statistically significant decline in global QOL (70 to 60, p = 0.0024), which normalized (71) following completion of treatment. During therapy, patients also experienced a significant increase in GI symptoms (21 to 27, p = 0.028), urinary symptoms (16 to 30, p &lt; 0.0001), male sexual dysfunction (23 to 34, p = 0.013), and chemotherapy related side effects (8 to 20, p = 0.0001). While these measures returned to baseline 1 month post-CRT, overall sexual function (25 vs. 37, p = 0.0062) and sexual enjoyment (53 vs. 67, p = 0.0070) remained persistently low compared to pretreatment levels. Diarrhea (27%) and proctitis (22%) were the most common grade 3 toxicities. Those patients who experienced grade 3 toxicity during treatment showed markedly decreased global QOL (mean difference = 34). Conclusions: While rectal cancer patients experienced impaired QOL during neoadjuvant CRT, the vast majority of measures normalized one month after treatment. In contrast, significantly decreased sexual function and enjoyment persisted. This data can be used as a baseline to compare future neoadjuvant conformal CRT regimens and/or assess the toxicity and QOL of new RT modalities such as intensity modulated radiation therapy. No significant financial relationships to disclose.
Detection of hereditary nonpolyposis colorectal cancer (HNPCC) in non-Caucasian patients.
Authors: Maria C. Russell, Miguel A. Rodriguez-Bigas, George J. Chang, John Michael Skibber, Barry W. Feig, Y. Nancy You
Journal: Journal of Clinical Oncology (2012)

417 Background: HNPCC is the most common hereditary colorectal cancer (CRC) syndrome. Its characterization has been limited to Caucasians in Europe or North America, and non-Caucasians in their countries of descent. Little is known about HNPCC in ethnically diverse patients in the U.S. Methods: Patients whose self-reported ethnicity was not Caucasian and who were the probands in their families to undergo germline testing (GT) for DNA mismatch repair (MMR) genes between 1998 and 2011 were identified. Tumor microsatellite (MSI) testing was informative if immunohistochemistry (IHC) showed MMR protein loss of expression, and/or if PCR-based MSI testing showed &gt;30% markers shifted. Tumor studies guided further GT. Results: Fifty-eight unrelated probands (female, 53.4%) included 19 (32.8%) who were Hispanic, 18 (31.0%) African-American, 18 (31.0%) Asian, and 3 (5.2%) Arabic/Other. Amsterdam I, II and revised Bethesda criteria were satisfied in 9 (15.5%), 14 (24.1%) and 43 (74.1%) respectively. They were affected by 106 malignancies, most commonly: CRC (73.9%), endometrial (10.9%), small bowel (5.4%) and skin (sebaceous neoplasm, 3.3%). The CRCs arose from proximal colon (51.5%), distal colon (25%), rectum (16.2%) or multifocal/other (7.4%), at a median age of 46 (IQR: 38-55). PCR-MSI results were concordant with abnormal IHC, although less for MSH6 and PMS2. In GT, pathogenic mutations were detected in only a minority of patients ( Table ). Conclusions: Ethnically diverse patients with informative tumor MSI results exhibited low rates of detectable pathogenic mutations. Caution should be exercised when GT is utilized to detect HNPCC in the absence of tumor studies as patients to be managed as HNPCC may be missed. [Table: see text]
Quality of life (QoL) and therapy management in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI and aflibercept in Germany, Switzerland, and Austria (GSA): Interim results of the noninterventional QoLiTrap-study.
Authors: Ralf Hofheinz, Josef Thaler, Roger Von Moos
Journal: Journal of Clinical Oncology (2016)

681 Background: QoLiTrap (AIO-LQ-0113) is a non-interventional study to assess the QoL and clinical outcomes of mCRC patients treated with Aflibercept and Folfiri in Germany, Austria and Switzerland. This interim analysis shows the first results of the study. Methods: QoL is assessed by EORTC-QLQ C30 questionnaires that are filled in by the patients at baseline and before every therapy cycle. Clinical data (overall survival, progression-free survival (PFS), response to treatment, therapeutic sequences) are reported by participating physicians. Results: The first 277 patients who completed at least baseline and 2 additional EORTC questionnaires were included in this analysis. Median cycle number at the time of analysis was 6 (including patients still on therapy). Therapeutic sequences comprised treatment with Bevacizumab (B) (48%), anti-EGFR (13%), both (13%) or no biological (14%) before Aflibercept (A) (n.d.: 12%). Median PFS was similar in B (PFS: 6.6 months, CI[5.4;8.9]) and anti-EGFR (PFS: 7 months, CI[4.7,12.1]) pre-treated patients. Complete or partial remission was observed in 22%, Stable Disease in 52% and Progressive Disease in 26% of all patients with evaluated response (n=144). Main grade 3-5 adverse events were hypertension (15.9%) and diarrhea (6%). Only minor changes in EORTC global health score were observed from baseline (57.50; sd: 20.39; n=277) to cycle 6 (52.27; sd: 20.6; n=114). Conclusions: In clinical practice A is used in various therapeutic sequences in GSA. This interim analysis provides encouraging results with a tumor control rate of 74% in patients with response documentation and similar median PFS values for B and anti-EGFR pretreated patients. The decline in global health status was moderate. No unexpected safety signals were observed. This study is supported by Sanofi. Clinical trial information: AIO-LQ-0113.
The American Board of Internal Medicine
Authors: Richard J. Baron, David Johnson
Journal: Annals of Internal Medicine (2015)

Letters6 January 2015The American Board of Internal MedicineRichard J. Baron, MD and David Johnson, MDRichard J. Baron, MDFrom American Board of Internal Medicine, Philadelphia, Pennsylvania, and University of Texas Southwestern Medical Center, Dallas, Texas.Search for more papers by this author and David Johnson, MDFrom American Board of Internal Medicine, Philadelphia, Pennsylvania, and University of Texas Southwestern Medical Center, Dallas, Texas.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5039-4 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Given the ongoing debate about the value of MOC, we are not surprised that our commentary generated many comments. We value these constructive remarks as we work to enhance the MOC program. Readers may not be aware that the ABIM recently announced plans to make changes to MOC on the basis of similar valuable feedback received from many specialty societies and diplomates over the past few months. The planned changes, as well as other potential modifications still under discussion, are outlined in a letter to the internal medicine community dated 10 July 2014 and posted on the ABIM ... Author, Article, and Disclosure InformationAuthors: Richard J. Baron, MD; David Johnson, MDAffiliations: From American Board of Internal Medicine, Philadelphia, Pennsylvania, and University of Texas Southwestern Medical Center, Dallas, Texas.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2478. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe American Board of Internal Medicine: Evolving Professional Self-regulation Richard J. Baron and David Johnson The American Board of Internal Medicine: Evolving Professional Self-regulation Richard J. Baron and David Johnson The American Board of Internal Medicine Edward Volpintesta The American Board of Internal Medicine Timothy Kleinschmidt The American Board of Internal Medicine Joseph J. Weiss The American Board of Internal Medicine Joseph J. Weiss The American Board of Internal Medicine Edward Volpintesta The American Board of Internal Medicine Timothy Kleinschmidt Metrics 6 January 2015Volume 162, Issue 1Page: 76-77KeywordsDecision makingDisclosureEmotionsForecastingMotivationSyphilis ePublished: 6 January 2015 Issue Published: 6 January 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
HAUSP gene acts as a tumor suppressor through p53 pathways in non-small cell lung cancers
Authors: D. Masuya, D. Liu, J. Nakano, T. Nakashima, S. Ishikawa, K. Kontani, H. Yokomise, C.-L. Huang
Journal: Journal of Clinical Oncology (2005)

7202 Background: Recent studies have reported that herpesvirus-associated ubiquitin-specific protease (HAUSP) is a novel p53-interacting protein, and directly stabilizes the tumor suppressor p53 by deubiquitination. Therefore, HAUSP gene might play an important role in carcinogenesis, as one of the tumor suppressor genes in human cancers. In order to clarify this possibility in non-small cell lung cancers (NSCLCs), we evaluated the HAUSP gene expression and p53 gene status in relation to target genes of p53, such as p21 and bax. Methods: Eighty-four NSCLC patients were investigated. p53 gene status was evaluated by PCR-SSCP following sequencing. RT-PCR was performed to evaluate gene expression of HAUSP, p21 and bax. In addition, p21 and bax protein expression were confirmed by immunohistochemistry. Results: Fouty-six carcinomas (54.8%) had reduced expression of HAUSP, and 30 carcinomas (35.7%) had mutations of p53. Concerning tumor histology, HAUSP gene expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (P=0.002), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (P=0.029). There was no significant correlation between HAUSP gene expression and p53 gene status. Concerning expression of target genes of p53, p21 gene expression was significantly lower in the HAUSP-reduced tumors than in HAUSP-positive tumors (P=0.015). In addition, p21 gene expression was significantly lower in tumors with either reduced HAUSP expression or mutant p53 than in tumors with both positive HAUSP expression and wild type p53 (P =0.037). Furthermore, bax gene expression was also significantly lower in HAUSP-reduced tumors than in HAUSP-positive tumors (P=0.002). The bax gene expression was significantly lower in tumors with either reduced HAUSP expression or mutant p53 than in tumors with both positive HAUSP expression and wild type p53 (P =0.002). Conclusion: These results have suggested that the reduction of HAUSP gene expression might play an important role in carcinogenesis of NSCLCs through p53 pathways, by regulating gene expression of p21 and bax. No significant financial relationships to disclose.
Long-term responses observed with lenalidomide therapy for patients with relapsed or refractory multiple myeloma
Authors: S. Jagannath, P. G. Richardson, S. Zeldenrust, M. Alsina, K. Wride, J. B. Zeldis, R. Knight, M. Olesnyckyj, K. C. Anderson
Journal: Journal of Clinical Oncology (2008)

8525 Background: Lenalidomide is a potent immunomodulatory drug and long-term administration in responding patients may have clinical benefit to patients. Early results from this phase II study previously determined that Len was active and well-tolerated in pts with relapsed/refractory MM (Richardson Blood 2006). Here, we present long-term follow-up results of pts that remained on therapy. Methods: Len (30 mg qd or 15 mg bid on days 1–21 every 28 days) was given to pts with relapsed/refractory MM in a multi-center, open-label, randomized phase II study. Concomitant Dex was permitted in pts with disease progression or stable disease. Treatment was continued as tolerated until disease progression. Response was assessed monthly using modified EBMT criteria and toxicity using NCI-CTCv2. No follow-up was done for pts who came off study drug. Overall survival was not included in follow-up. Results: From May 2002 to July 2003 102 were enrolled on the study, and 15 were still on therapy (11 on 30 mg qd and 4 on 15 mg bid) as of December 2006. 60% had received ≥3 prior anti-MM therapies, including radiation therapy (40%) and stem cell transplantation (27%). With a median follow-up of 4.1 yrs, pts receiving 30 mg qd spent 4.2 years on study drug; pts on 15 mg bid had 4.1 years. All pts had Len dose reductions or interruption, but all stayed on study drug. Average daily dose was 25 mg for pts on 30 mg qd and 12 mg for pts on 15 mg bid. Len monotherapy was given to 6 pts, while 9 received concomitant Dex. Median time to dose reduction was 19.6 months for pts on 30 mg qd and 2.5 months for pts on 15 mg bid. A partial or complete response was achieved in 11 pts. Of 6 pts on Len monotherapy, 4 responded (1 progressed after 3.7 yrs) and 2 had stable disease (SD). Of 9 pts who received concomitant Dex, 7 responded and 2 had SD. The most common grade 3/4 toxicity was neutropenia (67%). No grade 3/4 thrombocytopenia, anemia, peripheral neuropathy, or DVT was reported. Conclusions: A subset of pts responding to Len with or without dex, could remain on treatment for at least 4.1 years. Len can be considered as an effective, durable, and well tolerated therapy for heavily pretreated pts with relapsed/refractory MM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Corporation Celgene Corporation, Millennium Celgene Corporation Celgene Corporation, Millennium
Cancer spectrum among Irish DNA mismatch repair gene mutation carriers.
Authors: Michael P. Farrell, Tomas Lyons, Darragh S Gogarty, Naoise Maria Dorman, Loretto O' Brien, Padraic M. Mac Mathuna, David J. Gallagher
Journal: Journal of Clinical Oncology (2013)

424 Background: Pathogenic germline mismatch repair (MMR) mutations confer a high lifetime risk of colorectal cancer (CRC). Certain extra-colonic malignancies are also considered part of the Lynch syndrome (LS) spectrum including endometrial cancer, gastric, ovarian, small intestine, uroepithelial, pancreas, brain and skin cancer. A genotype-phenotype association has been reported. MSH2 mutation carriers appear to have a higher risk of developing extra-colonic cancer than individuals with a MLH1 mutation. We investigated the cancer spectrum in Irish LS kindreds and the likely association of these cancers with MMR deficiency. Methods: We identified 52 LS patients and family members with confirmed pathogenic DNA MMR mutations among 14 kindreds. Clinical data was extracted from the medical records and cancer diagnoses were confirmed from medical records and pathology reports. Tumour tissue was acquired. Immunohistochemistry (IHC) was completed for 4 MMR proteins and tumour lymphocyte infiltration is ongoing. Results: Spectrum of cancers identified include: CRC, endometrial , gastric, ovarian, renal, breast, prostate, urothelial, NHL, CML, lung, vocal cord, sebaceous carcinoma and cervix. Median age of diagnosis was 44. Thirteen individuals were diagnosed with two primary malignancies, 11 individuals were diagnosed with three primaries and one individual had four cancers. IHC analysis of three breast cancer cases demonstrated loss of MMR protein expression consistent with familial mutation. Conclusions: Early-onset cancers not traditionally considered manifestations of LS were identified in 14 LS kindreds. An additional 60 pedigrees are being worked up and further IHC and lymphocyte quantification will be reported at the meeting. An expanded LS-associated spectrum of malignancies may exist in certain families.
Improvement of time to develop treatment plan at a specialized sarcoma center.
Authors: Adriana Chavez, Prachee Singh, Jaime Anderson, Andrea Aleman, Colleen Jernigan, Vinod Ravi
Journal: Journal of Clinical Oncology (2012)

127 Background: Treatment of new patients at the MD Anderson Sarcoma Medical Oncology Clinic can take up to 1 to 2 weeks from their initial consultation depending on the information available for review. Treatment delays can result in poor patient outcomes, adversely affecting the quality of care provided. There are numerous processes involved in the development of a treatment plan that could be improved to reduce the time to finalization of treatment plan. Methods: We undertook a quality improvement project involving key clinic and administrative team members. We performed detailed process mapping and developed a cause and effect diagram to identify and prioritize opportunities for improvement. We measured the time in hours from the patient’s initial appointment to finalization of a treatment plan. Baseline data (before process improvement implementation) was collected retrospectively through chart review. Post-implementation data was collected prospectively. For process improvement, we focused on two deficiencies that were regarded as the key causes of delay to develop a finalized treatment plan (1) insufficient data for decision making at the time of new patient visit, and (2) delays in obtaining diagnostic imaging. Results: Due to insufficient data for decision-making available at the time of initial consultation, the median time to develop a treatment plan is 72 hours. After initiating process improvement, the median time to develop a treatment plan decreased to approximately 7 hours. Conclusions: Improving the quality of data available for the medical oncologist prior to initial consultation greatly enhances the rapid development of finalized treatment plan. Availability of an early treatment plan improves patient outcomes, diminishes patient anxiety, and decreases the costs incurred by the patient awaiting a treatment plan at a specialized oncology clinic.
Correlation between radiographic progression-free survival (rPFS) and overall survival (OS): Results from PREVAIL.
Authors: Michael J. Morris, Tomasz M. Beer, Yohann Loriot, Celestia S. Higano, Andrew J. Armstrong, Cora N. Sternberg, Johann S. De Bono, Bertrand F. Tombal, Teresa Parli, Suman Bhattacharya, Andrew P. Krivoshik, De Phung, Dana E. Rathkopf
Journal: Journal of Clinical Oncology (2016)

182 Background: In PREVAIL, enzalutamide (ENZA) significantly improved OS (hazard ratio [HR] 0.71; P &lt; 0.0001) and rPFS (HR 0.19; P &lt; 0.0001) compared with placebo in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Using data from the final analysis at 439 rPFS events we showed a strong correlation between investigator and central review. Here we report sensitivity analyses (SAs) from the final analysis of investigator-assessed rPFS and the association between investigator-assessed rPFS and OS. Methods: The coprimary endpoint of rPFS was defined as time from randomization to the earliest objective evidence of centrally assessed radiographic progression, defined by PCWG2 guidelines for bone disease and RECIST v1.1 for soft-tissue disease, or death within 168 days of treatment discontinuation. Bone progression was captured using a validated bone scan data capture assay. Four SAs were performed on investigator-assessed rPFS to evaluate the impact of: (1) progression in bone, (2) clinical progression, (3) a required confirmatory scan for soft-tissue disease progression, and (4) all deaths, regardless of length of time after study drug discontinuation. Associations of investigator-assessed rPFS and OS were calculated using Pearson’s correlation coefficient, Spearman’s rho, and Spearman’s rho estimated through the Clayton copula. Results: Treatment effects remained significant with each SA, with HRs of (1) 0.21 (95% confidence interval [CI] 0.18, 0.27), (2) 0.21 (95% CI 0.17, 0.26), (3) 0.23 (95% CI 0.19, 0.30), and (4) 0.23 (95% CI 0.19, 0.30) (P &lt; 0.0001 for each). Results of rPFS and OS associations are presented in the table below. Conclusions: SAs of rPFS in PREVAIL demonstrated a robust and consistent treatment benefit with ENZA. We observed a modest association between rPFS and OS. However, some unaccounted factors, such as post-protocol treatment, could have reduced the strength of the association of rPFS and OS in the placebo arm. Clinical trial information: NCT01212991. [Table: see text]
The potential role of somatostatin analogues in the treatment of gastrointestinal (GI) cancers.
Authors: J. Hasskarl, M. Kaufmann, H. Schmid, D. C. Metz
Journal: Journal of Clinical Oncology (2011)

150 Background: Somatostatin receptors (sstr) are expressed in various normal and malignant tissues, including non-neuroendocrine GI solid tumors. Gastric cancer (GC) cells mainly express sstr 2 and sstr 5 , colorectal cancer (CRC) cells predominantly express sstr 1 followed by sstr 5 and sstr 2 , and hepatocellular carcinoma (HCC) cells express mainly sstr 5 as well as sstr 1,2,3 . Somatostatin analogues (SAs) may have direct and indirect antitumor activity. Octreotide and lanreotide primarily target sstr 2 , whereas the new agent pasireotide has high affinity for sstr 1,2,3 and sstr 5 . Methods: Published data evaluating the antitumor properties of SAs in GI tumors were reviewed. Results: The table lists the results of clinical studies in which SAs were evaluated as antitumor therapies in GI cancers. Conclusions: Although octreotide and lanreotide are efficacious in the treatment of symptoms of neuroendocrine tumors, these agents have demonstrated mixed results in the antitumor treatment of non-neuroendocrine GI tumors. Data suggesting potential favorable outcomes with SAs alone or in combination with other agents have been seen in solid tumors with predominant sstr 2 expression such as GC. Novel SAs such as pasireotide may have improved antitumor effects in non-neuroendocrine solid tumors expressing multiple sstr compared with octreotide and lanreotide. [Table: see text] [Table: see text]