tbuckley/cabot-search huggingface dataset:
A comparison of toxicity and outcome following BEACOPP therapy in adolescents and young adults with Hodgkin’s disease (HD) by pediatric and adult oncology cooperative groups
Authors: R. Sposto, K. M. Kelly, D. Villaluna, E. Gilman, B. Pfistner, V. Diehl
Journal: Journal of Clinical Oncology (2005)

6599 Background: As the peak incidence of HD occurs in adolescence, patients (pts) are treated on pediatric and adult cooperative protocols. Observed differences in outcomes have been attributed to the use of different treatments. Older pts are thought to develop more treatment related toxicity than children but this has not been investigated in HD. Escalated dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) was incorporated in trials by the COG (CCG-59704) and GHSG (HD9/HD12), allowing comparison of toxicity and outcome across different age groups. Methods: 4 groups were compared: COG age<16 yrs (n=68), COG age 16–21 yrs (n=31), GHSG age 16–21 yrs (n=310), GHSG age 21–30 yrs (n=610). Cumulative grade 3/4 toxicity rates for cycles 1–4 were compared when COG and GHSG criteria were equivalent. Second cancers, failure free survival (FFS) and overall survival (OS) were assessed. Results: COG pts were more likely to have stage IV, B symptoms, and bulky disease (due to differences in entry criteria), and nodular sclerosis histology. Pts <16 yrs were more likely to be female. Hematologic toxicities, infections and mucositis were greatest in pts <16 yrs, and lowest in pts 21–30 yrs (anemia 52.9% vs 12.7%, thrombocytopenia 51.5% vs 26.6%, mucositis 11.8% vs 3.7%, infection 30.9% vs 5.9%, respectively). Rates were equivalent in pts 16–21 yrs, irrespective of protocol. Outcome was excellent at 3 yrs for all groups (FFS/OS): COG age<16 yrs 95±3%/97±3%; COG age 16–21 yrs 93±8%/100±0%; GHSG age 16–21 yrs 88±2%/97±1%; GHSG age 21–30 yrs 90±1%/95±1%. The percentage pts developing a second cancer is low: COG <16yrs: 1.5%, 16–21 yrs: 0; GHSG 16–21 yrs 1.3%, 21–30 yrs 1.6%. Conclusions: Toxicity rates with BEACOPP are generally comparable in the 16–21 year age group in both the COG and GHSG trials. Hematologic toxicity, infections and mucositis are more frequent in pts <16 yrs. FFS and OS rates are high across ages. Second cancers are infrequent across each of these age groups and protocols. No significant financial relationships to disclose.
Oncologically endoscopic nasopharyngectomy for T1/T2a and selected T2b/T3 nasopharyngeal malignancies with nasopharynx resurfaced with posterior pedicle nasal mucoperiosteum flap.
Authors: M. Chen
Journal: Journal of Clinical Oncology (2010)

5574 Background: Endonasal endoscopic surgery is a minimal invasive approach but through which it is difficult to achieve oncologocal resections of nasopharyngeal malignancies due to the small operating space. The wound is difficult to recover and causes a persistent headache after operation for recurrent nasopharyngeal carcinoma (rNPC) patients due to the prior radiation. We have developed new techniques of oncologically endoscopic nasopharyngectomy (OEN) with nasopharynx resurfaced by a pedicle nasal mucoperiosteum flap (PNMF). Methods: From September 2004 to December 2009, 73 patients with nasopharyngeal malignancies received OEN with en bloc resection of tumor and 0.5-1.0cm margins through bilateral nostrils, including 59 locally rNPC, 6 newly untreated NPC with small nasopharyngeal nodus, and 8 other pathological types malignancies such as sarcoma, adenocarcinomas, and etc. According to the clinical staging system of NPC (UICC 2002), 32, 7, 26, and 8 cases were classified as T1N0M0, T2aN0M0, T2bN0M0, and T3N0M0, respectively. The nasopharyngeal defect was reconstructed with posterior pedicle middle turbinate or nasal septum mucoperiosteum flap based on the middle turbinate or nasal septum artery, branches of the sphenopalatine artery. Results: Among the 73 OEPs, 70 cases achieved en bloc resections of the tumors with negative surgical margins and no post-operation radiotherapy followed. The wounds healed in 8∼f16 weeks (median: 10w) in 23 rNPC patients with PNMF resurfaced, but 14∼f36 weeks (median: 18w) in rest rNPC cases without repair. No severe complication was observed except that 1 cases suffered internal carotid rupture and cured by interventional therapy. With median 26 months follow-up (range: 1 to 64m), the 2-year overall survival rate, local relapse-free survival rate, and progression-free survival rate were 87.5%, 83.3%, and 80.9%, respectively. Conclusions: Appropriate OEN is a minimally invasive, safe, and effective surgical modality for nasopharyngeal malignancies, even some high-selected newly untreated NPC. The PNMF is helpful to recover the nasopharyngeal wound for rNPC patients. No significant financial relationships to disclose.
Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.
Authors: David S. Alberts, Richard L. Rauck, Neha Parikh, Nicole Forman
Journal: Journal of Clinical Oncology (2014)

175 Background: Sublingual fentanyl spray is indicated for the treatment of breakthrough cancer pain (BTCP) in opioid-tolerant patients receiving around-the-clock (ATC) opioids. This post hoc analysis characterized patients receiving ATC transdermal fentanyl patch (TFP) who also received fentanyl sublingual spray for BTCP during a phase 3, randomized, placebo-controlled trial. Methods: Opioid-tolerant adults (n=130) receiving ATC opioids for baseline pain, with 1 to 4 episodes/day of BTCP, were enrolled in a 26-day open-label titration period and received fentanyl sublingual spray. Patients who successfully titrated to a stable, effective dose (100-1,600 mcg) of fentanyl sublingual spray entered a 26-day double-blind period. Patient satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM). Adverse events (AEs) were monitored throughout the study. Results: Of the 50 patients (mean age, 50 years) who were on ATC TFP at baseline, most were male (58%) and white (90%) with a mean of 2.4 BTCP episodes/day. The most common types of cancer were reproductive (22%), head and neck (14%), and lung (8%). The percentage of patients in each cancer stage was 0/I (14%), II (10%), III/IV (48%), or unknown/not applicable (28%). Thirty-two of 50 patients (64%) achieved an effective dose of sublingual fentanyl spray and entered the double-blind period. In the 32 patients, the mean baseline TFP dose at the beginning of double-blind period was 81.4 mcg. The mean daily number of BTCP episodes during the 26-day double-blind period was 2.3 (range, 1-5). Mean TSQM scores at baseline and end of the titration period, respectively, were as follows: effectiveness, 49.0 vs 78.3; side effects, 65.0 vs 94.4; convenience, 61.6 vs 73.8; and global satisfaction, 49.3 vs 72.8. The effective dose of fentanyl sublingual spray only moderately correlated with the mean TFP dose (r=0.4; P=0.03). During the double-blind period, 19 of 32 patients (59%) reported AEs; the most common AEs were nausea (9%) and peripheral edema (9%). No opioid overdoses were reported. Conclusions: The findings support that fentanyl sublingual spray relieves BTCP and is well tolerated in most patients receiving ATC transdermal fentanyl. Clinical trial information: NCT00538850.
Dose-volume analysis of radiation dermatitis among nasopharyngeal carcinoma patients treated with comcurrent cetuximab-cisplatin and intensity-modulated radiotherapy
Authors: M. K. Kam, B. B. Ma, S. F. Leung, E. P. Hui, S. L. Chan, B. K. Yu, S. K. Chiu, R. M. Chau, W. H. Kwan, A. T. Chan
Journal: Journal of Clinical Oncology (2008)

17015 Background: To investigate the impact of dose-volume parameters of skin on the severity of radiation dermatitis in a cohort of nasopharyngeal carcinoma (NPC) patients treated with concurrent cetuximab (C225), cisplatin, and intensity-modulated radiotherapy (IMRT). Method: 20 stage III-IVb NPC patients were treated with a loading dose of C225 (400 mg/m2), followed by IMRT (74 Gy to primary, 70 Gy to involved nodes, 62 Gy to subclinical region, 35 fractions) plus weekly cisplatin (30 mg/m2) and C225 (250 mg/m2) for 6–7 cycles during radiotherapy. The different level of worst skin toxicity (Grade 0–2 vs. 3–4) within 90 days from start of RT (NCI CTCAE v 3.0), and hyperpigmentation (mild or moderate) were compared with respect to various dose-volume parameters: total skin volume within radiation portal (Vt), volume of skin irradiated to different dose levels (Vdose), maximum (Dmax) and mean (Dmean) skin dose using Mann-Whitney test. Result: The incidence of grades 1, 2, 3 and 4 radiation dermatitis were 30%, 45%, 20% and 5%, respectively. Duration of ≥grade 3 toxicity was less than 2 weeks in all patients. 5 patients (25%) developed moderate hyperpigmentation at irradiated skin, which improved gradually over time. The range of Dmax, Dmean, and Vt are 70–80 Gy, 21–28 Gy, and 758–1415 c.c., respectively. There was no significant difference in Dmax, Dmean, Vt, V70 Gy, V60 Gy, V50 Gy, V40 Gy, V30 Gy, V20Gy or V10Gy between patients with <grade 3 or ≥grade 3 skin toxicity. Likewise, there was no significant difference in these dose-volume parameters between patients with or without moderate skin hyperpigmentation. Conclusion: The current study suggests that triple therapy (IMRT, cisplatin, C225) does not significantly increase the severity of radiation dermatitis as compared to bimodality treatment (either radiotherapy plus C225 or chemoradiation). Within the range of irradiated skin dose and volume in this study, there is no association between dosimetry factors and skin toxicity implying that radiation dermatitis may be dominated by other physical or genetic risk factors that influence individual’s normal tissue sensitivity. No significant financial relationships to disclose.
Clinical factors that affect breast cancer risk reduction decisions in high risk women tested for the BRCA1/2 genetic mutation
Authors: A. R. Uyei, K. R. Broglio, T. L. Solomon, K. J. Vogel, C. I. Amos, K. Lu, F. Meric-Bernstam, L. Strong, B. Arun
Journal: Journal of Clinical Oncology (2006)

1013 Background: Women with an increased risk for breast cancer have many risk reduction options including: prophylactic mastectomy, prophylactic oophorectomy, chemoprevention, and screening. Women without breast cancer make such decisions in a purely preventive setting and factors that affect their decisions are unclear. Method: We performed an IRB approved retrospective review of the medical records on women who underwent BRCA testing. We evaluated the women without a history of breast cancer to assess clinical characteristics and their relation to decision making. The risk reduction categories analyzed were: prophylactic mastectomy, prophylactic oophorectomy, tamoxifen, increased surveillance with MRI, and standard screening (clinical breast exam and mammography). Patient characteristics were tabulated by clinical decision group and the chi-square test or Fisher’s exact test was used. Results: From 2001, 627 patients have undergone genetic testing. 202 of these women did not have a history of breast cancer among whom 58 were mutation carriers. Most patients chose standard screening (47%) or increased surveillance (38%). 4% chose tamoxifen, 7% chose prophylactic mastectomy, 3% chose both prophylactic mastectomy and oophorectomy, and 5% chose oophorectomy. The tamoxifen group was too small to do further analysis. Increased surveillance did not show any significant association with any of the clinical factors that we evaluated. The majority of women who chose standard screening had a personal history of ovarian cancer (p&lt;0.0001) and had no family history of ovarian cancer (p=0.02). Prophylactic surgeries were significantly associated with positive BRCA status (p=0.01). Women with a family history of ovarian cancer tended to have prophylactic surgery (p=0.02). Women who had DCIS or a breast biopsy tended to have prophylactic mastectomies (p=0.0001 and p&lt;0.001 respectively). Conclusion: In breast cancer free women, BRCA status, family history of ovarian cancer, DCIS, and breast biopsy were associated with prophylactic surgeries. Having ovarian cancer or no family history of ovarian cancer were associated with standard screening. We are performing a questionnaire study to determine the reasons behind these women’s choices. No significant financial relationships to disclose.
Conversion chemotherapy combined with surgical treatment of unresectable advanced gastric cancer.
Authors: Yian Du, Pengfei Yu
Journal: Journal of Clinical Oncology (2015)

189 Background: Local advanced gastric cancer which could not receive R0 resection, or gastric cancer with single distant metastasis usually received palliative chemotherapy or entered into various clinical trials, and surgery usually roled as a symptomatic treatment. This study is to investigate the efficacy and safety of PCF chemotherapy combined with surgery in the treatment of these patients. Methods: From 2007.8 to 2012.8, 78 cases of local advanced gastric cancer which can not be treated with R0 resection(T4N2~3M0) or gastric cancer with single distant metastases(M1) were prospectively analysed. Patients were treated with 2~4 cycles of combined chemotherapy with paclitaxel (150mg/m 2 ,d1), cisplatin(25mg/m 2 , d1~3) and 5-fluorouracil (750 mg/m 2 , d1~3) ( repeated every 3 weeks), and were then treated with cytoreductive surgery: mainly treated with radical resection of gastric tumor, combined with extended lymph node dissection, pancreaticoduodenal resection, colon resection, ovariectomy, liver resection and tumor radio frequency, followed by another 2~4 cycles of postoperative PCF chemotherapy.The treatment completion rate, patients’ tolerance and overall survival time were analyzed. Results: 56 patients (71.8%) accomplished chemotherapy and surgical resection as planned. 47 cases had R0 resection(60.3%). Grade 3/4 toxic effects included bone marrow suppression(24.4%) and gastrointestinal reaction(37.2%), the overall response rate (CR+PR) was 73.1%(CR 2 cases, PR 55 cases). Survival analysis: the median survival time was 23.4 months. 1-year and 3-year survival rate was 68.1% and 33.5%. The OS of patients with surgical resection was much longer than that of the non-surgery group.(36.1 VS 10.0 months, P&lt;0.01). The OS of local advanced group was 38.6 months, and was significantly longer than 20.7 months of the distant metastasis group (P&lt;0.01), however, it had no significant difference compared to 31.3 months of the distant metastasis group with R0 resection. Conclusions: PCF chemotherapy combined with surgical resection were safe and effective, and can make survival benefits for patients with local advanced gastric cancer or gastric cancer with single distant metastasis.
A new instrumental platform for Trans-Anal Submucosal Endoscopic Resection (TASER)
Authors: Zacharias P Tsiamoulos, Janindra Warusavitarne, Omar Faiz, Andrew Castello-Cortes, Timothy Elliott, Simon T Peake, Paul Bassett, Brian P Saunders
Journal: Gut (2015)

### Message

Existing trans-anal approaches for complete excision of large and complex rectal polyps (CRPs) remain suboptimal due to technical complexity and inflexibility leading to the risk of inadequate excision and need for proctectomy, especially when using a single-channel flexible endoscope. Trans-Anal Submucosal Endoscopic Resection (TASER) provides a flexible endo-surgical platform with enhanced visualisation and therapeutic options delivered via an endoscope assisted by simultaneous, dynamic trans-anal retraction devices (Figure 1). Preliminary results in 17 patients with complex and very large (>5 cm) as well as recurrent polyps with severe submucosal fibrosis showed that the application of different endoscopic resection techniques was facilitated (Figure 2).



Figure 1 
Instrumental triangulation created with one endoscope and two laparoscopic retractors using the GelPoint path device; real time, ‘dynamic’ retraction (lift) of the polyp with the aid of retracting laparoscopic forceps.





Figure 2 
Complex rectal polyps (CRPs) (lower and mid rectal lesions) excised with Trans-Anal Submucosal Endoscopic Resection-endoscopic submucosal dissection (TASER-ESD) and TASER-ESD/EMR sessions (prior to the excision, post-polypectomy defect and follow-up scar free of recurrence).



### In more detail

The new platform was employed in 17 consecutive patients (mean age 63 years, 10 men/7 women) between January 2013 and June 2014, referred with CRPs, in a single-centre, observational cohort study. Prior to referral, all patients had had previous failed attempts with conventional endoscopic techniques. TASER involved placing the GelPoint path (Applied Medical, …
Prevalence of familial malignancy in a prospectively screened cohort of patients with leukemia.
Authors: A. Prasad, D. Liu, M. Rasul, N. Ahmed, K. Seiter
Journal: Journal of Clinical Oncology (2010)

6590 Background: Newer studies are giving increased understanding of the genetic origins of cancer. We conducted a pilot study to determine the prevalence of familial malignancy among adult leukemia patients admitted to a leukemia service from April 2009 to Dec 2009. Methods: An IRB approved screening questionnaire was used to ascertain information from 104 leukemia patients. Pts who were adopted or uncertain of their family history were excluded. Fisher's exact test for analyzing categorical variables and a two-sample t-test for continuous variables were used. Results: Of the 92 pts analyzed, 41 (44.6%) reported a first degree relative and 61 (66.3%) reported a first or second degree relative with cancer. At least one first degree relative with cancer was reported from 66.7% of CLL pts, 54.9% of AML pts, 37.5% of ALL pts, and 27.3% of CML pts. The median age was 55 yrs for those pts with either a first or second degree relative with cancer and 62 for those without a family history (p = ns). The most common cancers reported were breast (20% of pts reported an effected relative), colon (13%), lung (12%), leukemia (9%), unknown cancer (8%), prostate (6%) and stomach (5%). In many cases, the percentage of family members with a specific cancer type was similar to that reported for the general US population (Jemal et al, Cancer J Clin 2009; 59:225- 249). However, significant differences were noted when comparing our pts' family history with that of the US population for the following cancer subtypes: leukemia (9% our pts vs. 3% US), stomach (5% vs. 1%), colon (13% vs. 7%) and NHL (0% vs. 4%). Numerical differences that were not significant were noted for breast (20% vs. 13%), prostate (6% vs. 3%), bladder (1% vs. 5%) and esophagus (3% vs. 1%). Nine pts had 12 family members with leukemia. The median and mean age of these pts was 50 and 47 resp compared with the remaining pts who had a median age of 59 and mean of 57 (p = 0.04). Of these pts, 5 had AML, 3 had CML and 1 had ALL. Eight pts had a Li-Fraumeni pattern of familial clustering of cancer. Conclusions: The pattern of familial cancers may be different for pts with leukemia compared to the general population. We continue to accrue pts to determine if these differences effect treatment outcome. No significant financial relationships to disclose.
Abstract 12974: Long Sleep Duration and B-Type Natriuretic Peptide: Determinants of Left Ventricular Mass Index in the Japanese at High-Risk of Cardiovascular Disease
Authors: Michiaki Nagai, Satoshi Niijima, Satoshi Hoshide, Mami Takahashi, Masahisa Shimpo, Kazuomi Kario
Journal: Circulation (2014)

Introduction:  Recently, several studies have reported that long sleep duration was independently associated with left ventricular mass (LVM). On the other hand, B-type natriuretic peptide (BNP) was shown to be a useful indicator for the severity of essential hypertension, detecting cardiac hypertrophy. In this study, the relationships among self-reported sleep duration, BNP and LVM index (LVMI) were investigated in the Japanese at high-risk of cardiovascular disease. In addition, we investigated whether antihypertensive treatment moderated these relationships or not.   Hypothesis:  Sleep duration would be associated with LVMI interacted by antihypertensive treatment.   Methods:  Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, transthoracic echocardiography and BNP measurement were performed in the 1534 patients (65.7 years old, male 48.4%). A self-administered questionnaire included items on daily sleep duration was used.   Results:  According to the sleep duration (6h or less, >6 to 8h    Conclusions:  Long sleep duration and BNP were significant indicators of increased LVMI in the high-risk Japanese population. In those without CCBs, ARBs or diuretics, long sleep duration, interacted by BNP served as a strong marker for LVMI. CCBs, ARBs or diuretics might be important not to aggravate the hypertensive target organ damage caused by long sleep duration.
Prognostic significance of GP88 for breast cancer recurrence
Authors: G. Serrero, W. Kim, B. Yue, O. Ioffe, R. Barton
Journal: Journal of Clinical Oncology (2008)

22064 Background: Our laboratory focuses on the development of novel breast cancer biomarker with diagnostic or prognostic significance. We have identified a growth factor GP88 that plays a critical role in breast tumorigenesis. Pathological study have indicated that GP88 was highly expressed in invasive ductal carcinoma (IDC), in correlation with poor prognosis parameters whereas it was negative in normal mammary tissues and benign lesions. Here we present the results of a retrospective study to investigate whether high GP88 expression in IDC is associated with increased recurrence and decreased overall survival. Methods: This IRB approved study used 389 archival formalin-fixed, paraffin-embedded IDC cases with a minimum of 4 years follow-up, obtained from three tumor banks The clinical data included patients demographics such as age and race, tumor characteristics including tumor size, tumor grade, nodal status, disease stage and receptor status, time and type of first recurrence, time and status of last follow-up. GP88 expression was determined by immunohistochistry on five- micrometer sections. Cytoplasmic GP88 expression was scored as: <10% of cells staining - negative, >10% of cells staining - positive with positive staining graded from weak/focal (1+) to moderate/focal or diffuse (2+) to strong/diffuse (3+). The statistical analysis was based on evaluating the test performance for its ability to predict disease-free (DFS) and/or overall survivals (OS) using Kaplan Meier curves and the Cox proportional hazards models for quantification of risk. Results: The data show that ER+ cases with GP88 3+ had a HR of 2.29 (95% CI, 1.38–3.78; p<0.0013 for OS and a HR of 2.88 (95% CI 1.59–5.24; p<0.0005) for DFS. GP88 3+ remains highly significant for OS and DFS even when the data are adjusted for each of the covariates such as nodal status, disease stage, tumor grade, tumor size, supporting the findings that GP88 brings independent information on the recurrence risk and overall survival. Conclusion: This study demonstrates that high GP88 expression (3+) is associated with a higher risk of recurrence and increased mortality in ER+ IDC and provides a novel biomarker with prognostic significance in breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration A&G Pharmaceutical A&G Pharmaceutical