bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusually high rates of hypersensitivity to cetuximab in the middle-southern United States: Association with atopic phenotype
Authors: Allen R. M. , Goldberg R. M. , Berlin J. , Spigel D. , Stinchcombe T. E. , Sanoff H. K. , Hayes D. N. , Lin L. , O'Neil B. H.
Published: March 2020

9051

Purpose: To confirm the anecdotal observation that pts in North Carolina (NC) and Tennessee (TN) treated with cetuximab (C-mab) experience hypersensitivity reactions (HSR) at a much higher rate than that reported nationally and internationally (= 3%). Methods: Data from pts treated with C-mab on clinical trials (CTs, n = 88) at 3 research sites in TN and NC were analyzed for grade 3 or 4 HSR. Additional information was obtained from medical records under IRB approval at the University of North Carolina (UNC) for 90 pts (including 35 pts on CTs) to determine whether history of other significant allergy was a risk factor for HSR. Prior allergy was defined as history of H1 antagonist use, or notation in the medical record of significant drug allergy (excluding narcotic allergies), bee sting allergy, eczema, allergic reactive airways disease, or food allergy. Pearson's or Fisher's exact tests were used for comparison of proportions. Results: Data for 88 pts on CTs and an additional 55 pts treated outside of CTs was included in this analysis. Pts had a variety of tumor types, the most frequent being colorectal and lung For the CT group (n = 88), the overall rate of grade 3 to 4 HSR was 21.6%, significantly higher than the rate noted in any large published trial (p < 0.0001 for comparison to data from Cunningham et al). All HSRs occurred during the first dose. There was no apparent protection from HSR afforded by premedication with dexamethasone in either the CT cohort or the overall UNC cohort. Upon examination of medical records of 90 pts treated at UNC (14.4% gr 3/4 HSR overall), there was a strong relationship between prior allergy history and chance of HSR; 10/28 pts with any HSR vs. 7/62 without allergy history (p = 0.006), and grade 3/4 HSR occurred in 8/28 versus 5/62, respectively (p = 0.01). Conclusions: At the sites in neighboring Southern US states studied, HSR was far more common than reported in national studies. History of prior allergy is a strong predictor of HSR, although is not specific enough to be used as the sole means of excluding pts from therapy. Further investigation of more specific predictors of HSR in the US Middle South is warranted, and pts being treated with C-mab in the region should be observed particularly closely during their first infusion.

No significant financial relationships to disclose.
Bisphosphonate-induced osteonecrosis of the jaw: Risk factors and diagnostic utility of bone scans
Authors: O'Connor T. L. , Padmanabhan A. , Wilding G. , Sullivan M. , Solomon L. , Lamonica D.
Published: March 2020

9052

Background: Osteonecrosis of the jaw (ONJ) is a serious long-term effect of intravenous bisphosphonates. We report characteristics of patients with ONJ at Roswell Park Cancer Institute (RPCI) and utility of bone scans in its diagnosis. Methods: Patients were identified using RPCI database. ONJ diagnosed was staged using the system used for jaw osteoradionecrosis (Schwartz et al, Am J Clin Oncol, 2002). Controls included patients receiving bisphosphonates between July 2002 and 2006. Routine whole body bone scans were reviewed for jaw uptake. Statistical analysis was done using SAS 9.1. Results: Three hundred and fifty-four patients received intravenous bisphosphonates between July 2002 and 2006. Twenty-four (7%) were diagnosed with ONJ. Among patients with ONJ, fifteen (63%) had breast cancer, eight (33%) had multiple myeloma and one (4%) had lung cancer. Mean age was 56.8 years. (SD= 9.1) Thirteen patients (54%) had tobacco use, five (21%) had diabetes, nine (37.5%) had hypertension and twenty-three patients (96%) received chemotherapy. Five patients (21%) had caries, three (12.5%) had dental surgery, nine (37.5%) had periodontal disease, thirteen (54%) had extractions and one (4%) had prior dental trauma. Twenty-two patients (92%) presented with pain. Twelve patients (50%) had ONJ Stage 1, eight (33%) Stage 2 and four (17%) Stage 3. Median duration of exposure to bisphosphonates was 39 months. The difference between the average number of infusions in the ONJ group (11.2, CI: 11.3, 20.3) and control group (7.2, CI: 6.2, 8.2) was found to be significant (p<0.0009). Three patients (12.5%) had progressive ONJ. Thirteen patients with ONJ had bone scans and twelve (92%) showed jaw uptake. Among controls, one hundred and eighty-three had bone scans and one hundred and twenty-eight (70%) showed jaw uptake. This difference was not significant. (p=0.114, two-tailed Fisher's exact test). Conclusions: In our study, chemotherapy, smoking, prior dental extractions and the number of bisphosphonate infusions appear to be risk factors for ONJ. It has been recently reported (Chiandussi et al., Dentomaxillofacial Radiol. 2006) that bone scans can be used as a screening tool for ONJ, however, in our series jaw uptake on bone scan was not a reliable predictor for the development of ONJ.

No significant financial relationships to disclose.
A meta-analysis of anticoagulants as cancer treatment: Impact on survival and bleeding complications
Authors: Kuderer N. M. , Khorana A. A. , Lyman G. H. , Francis C. W.
Published: March 2020

9071

Background: There is substantial laboratory evidence that anticoagulants, in particular the low-molecular-weight heparins (LMWH), exert an antitumor effect, while clinical trials have reported conflicting results. This study represents the first comprehensive systematic review and meta-analysis of the evidence from randomized controlled trials (RCTs) evaluating specifically the impact of anticoagulants on survival and safety in cancer patients without venous thromboembolism (VTE). Methods: An exhaustive systematic literature review of RCTs was performed without language restrictions, including a comprehensive search of electronic databases through May 2006 with subsequent weekly updates to the end of 2006 (Medline, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, DARE, and major conference proceedings) and relevant article references. Two reviewers extracted the data independently. Primary study outcomes were 1-year overall mortality and all bleeding complications. Major and fatal bleeding complications were secondary outcomes. The meta- analysis was performed utilizing the Mantel-Haenszel method. Results: All identified 11 RCTs were performed in solid tumor patients. Anticoagulation significantly decreased overall mortality across all studies with a relative risk (RR) of 0.905 (95%CI: 0.847–0.967; p=0.003). The survival improvement appears not to be due to the prevention of fatal VTE. All bleeding complications (RR=2.309; 95%CI: 1.928–2.764; p<0.0001) and major bleeding events (RR=2.598; 95%CI; 1.936–3.488; p<0.0001) occurred more frequently with anticoagulation. The relative risk for mortality was 0.877 (95%CI: 0.789–0.975; p=0.015) with LMWH, compared to warfarin (RR=0.942; 95%CI: 0.854–1.040; p=0.239). Warfarin resulted in higher rates for all and major bleeding complications compared to LMWH (p<0.0001, respectively). Conclusions: Anticoagulants significantly improved overall survival in cancer patients while increasing the risk of bleeding complications. Despite these encouraging findings, given limitations of available data and the potential for life-threatening complications, the use of anticoagulants as antineoplastic therapy cannot be recommended until additional RCTs confirm these results.

No significant financial relationships to disclose.
Ten-year reproduction rates (10-RR) after cancer treatment: Comparison between patients (cases) and the normal population (controls)
Authors: Cvancarova M. S. , Magelssen H. , Fossa S.
Published: March 2020

9075

Background: Reproduction rates in cancer survivors are sparse, and the impact of the number of pre-diagnosis children and age at diagnosis on post-diagnosis parenthood is unknown. We assessed 10-RRs in cases and age- and gender- matched controls. Methods: After merging the Hospital Registry and the Medical Birth Registry of Norway, we analyzed 6,071 cases treated from 1971 to 1997 and aged 15–45 at diagnosis, and 30,355 controls, all born after 1950. All were followed from the recorded or simulated date of diagnosis. The primary outcome was the first post-diagnosis pregnancy (median observation time: 10 years, range: 0–35 years). 10-RRs and hazard rates (HRs, controls as reference) were computed by Cox proportional hazard multivariate regression models adjusted for age at diagnosis, stratified by gender and number of pre-diagnosis children. Results: 45% of cases and 56% of controls were childless at diagnosis. The table below displays 10- RRs and HRs for all cases and controls and the most frequent cancer types (cases given first). When 10-RR of cases is higher or not significantly different from the rates for controls, the cell is highlighted. In general, 10-RRs are the highest for those with one-time pre-diagnosis paternity. Conclusion: Contrary to observations in females, 10-RRs of the first post-cancer paternity in males are significantly increased for cases compared to controls. In addition, the 10-RR for male cases with one pre-diagnosis child exceeded the rates for males who were childless at diagnosis. Overall, 10-RRs are associated with gender, cancer type and pre-diagnosis parenthood.

[Table: see text]

No significant financial relationships to disclose.
Beliefs and concerns African American (AA) and white (W) patients (pts) with breast, lung, and colon cancer bring to bear on the decision to undergo chemotherapy
Authors: Smith D. , Polite B. N. , Hlubocky F. , Gehlert S. , Daugherty C. K.
Published: March 2020

9076

Background: AA have poorer stage-specific survival for breast, colon and lung cancer than whites and are also less likely to receive therapy for these cancers. This study seeks to explore the set of beliefs and concerns patients with primarily resected breast, lung, and colon cancer bring to bear on the decision to receive chemotherapy. Methods: Semi-structured interviews were conducted and recorded by a non-physician, African-American interviewer on patients with colon, breast, and lung cancer referred to medical oncology for chemotherapy. Grounded theory methods were used to analyze and code the interview transcripts. Results: A total of 27 interviews were conducted (17AA, 10W) including pts with breast (5), colon (6) and lung cancer (16). All but 7 of the pts were referred for adjuvant therapy. Three major themes emerged: (1) Patient versus physician control in decision making; (2) Absolute trust in one's physician versus qualified trust; (3) Major role of God in the decision making process versus a partnership or minimal role of God. In terms of decision-making, roughly equal portions of AA and W (53% vs 54%) expressed a patient centered locus of control. In the area of trust, AA were less likely to express an absolute trust in their physicians (59% vs. 80%). Finally, with respect to the role of God, AA were more likely to express a major role of God for their cancer and treatment (41% vs. 7%). Very few pts viewed the opinion or advice of family or friends as important and while many expressed concerns about the side-effects of therapy, very few identified that as being an important factor in their decision to undergo therapy. Conclusions: Issues of locus of control, physician trust and the role of God were areas identified as important in the chemotherapy decision-making process and for which variability existed among the pts interviewed. Analysis of these interviews informed the incorporation of validated measures of decision-making, physician trust, and the role of God as a locus of control in an ongoing close-coded survey of a similar cancer population.

No significant financial relationships to disclose.
Does quality of life improvement precede anemia correction in patients with chemotherapy-induced anemia treated with intravenous iron?
Authors: Henry D. H. , Dahl N. V. ,   G. The Ferrlecit Cancer Study Group
Published: March 2020

9082

Background: Combining intravenous (IV) iron with erythropoiesis-stimulating (ESA) therapy has been shown to increase Hgb response in treating anemia of cancer and chemotherapy. As part of a trial in anemic cancer patients on chemotherapy being treated with an ESA, we compared the effects of IV iron, oral iron, and no iron, on changes in patient-reported HRQOL. Methods: Prospective, randomized, controlled, multicenter trial. Major inclusions: pt starting chemotherapy cycle, Hb <11g/dL, ferritin >100 ng/mL or transferrin saturation >15%. Major exclusions: recent transfusion, ESA, or IV iron use, infection. All pts received epoetin alfa (40,000 U SQ/Wk for first 4 wks, then dose- adjusted per protocol). Pts were randomized to: No iron, PO FeSO4 325 mg tid, or IV ferric gluconate 125 mg IV weekly, for 8 weeks. Change in HRQOL was measured 4 weeks after start and at end of study (week 10, or last observation carried forward) using Functional Assessment of Cancer Therapy (FACT)-Anemia. Results: There were no significant between-group differences at baseline in mean Hb (10.2g/dL), TSAT (31.3%), or serum ferritin (421ng/mL) for the 129 evaluable patients, (mean age 65.3, 69% female). See Table . Hgb responses were significantly greater by end of study in evaluable pts receiving IV FG than oral iron or no iron. Only pts receiving FG reported a significant improvement in FACT-Fatigue subscale (FACT-F). This difference began at 4 weeks, while Hgb response was still similar between groups. No significant improvement in fatigue was reported by either the no iron (ESA alone) nor oral iron group. Conclusions: Combining IV iron with ESA therapy lead to an early and sustained clinically significant (=3) improvement in fatigue score, which preceded the improvement in Hgb response.

[Table: see text]

[Table: see text]
Racial/ethnic differences in adequacy of information and peer support for women with breast cancer
Authors: Janz N. K. , Mujahid M. , Hawley S. , Hamilton A. , Katz S.
Published: March 2020

9085

Background: Existing disparities in quality of care for women with breast cancer suggest the need to explore the adequacy of information and care support provided to patients. This study investigated whether racial/ethnic variation existed in receipt and usefulness of cancer-related information and availability of peer support. Methods: 2,030 women diagnosed with non-metastatic breast cancer and reported to the Los Angeles County, Surveillance Epidemiologic and End Results registry between 8/05–5/06, were identified and mailed a survey shortly after initial treatment. Latina and African American (AA) women were oversampled. Outcomes included self-reported receipt and perceived usefulness of treatment-related (recovery from surgery, radiation, chemotherapy) and survivorship-related (sexual functioning, relationships, nutrition, anxiety) information and experiences with other women with breast cancer. We report results on a 50% respondent sample (N=742) that will be updated based on a final sample of 1,400 women (projected response rate, 72%). Results: More women received information and found it useful regarding treatment than survivorship issues. After adjusting for age and education, a higher percentage of Latina women, compared to white and AA women, desired more information on treatment-related issues and survivorship-related issues (p<.01). A higher percentage of Latina women also reported having no contact with other women with breast cancer, either through the health care system or a family/friend (p<.001), and reported a desire for more contact as compared to white or AA women (42%, vs. 15% and 29%, respectively). Overall, women rated the benefit of talking to other women high, particularly in helping with emotional issues and few endorsed potentially negative consequences. Conclusions: Women with breast cancer expressed the need for more useful information and care support, especially about managing survivorship concerns. Particular focus is warranted with Latina women to provide desired information and greater opportunities for peer contact.

No significant financial relationships to disclose.
Results of a randomized double-blind clinical trial of Shugan-liangxue prescription for relieving hot flashes in breast cancer patients
Authors: Li P. , Sun H.
Published: March 2020

9086

Background: Hot flashes are a common side effect for BC pts during endocrine treatment. An oral solution of TCM is prescribed for the purpose of clearing heat and cooling blood. There is no phytoestrogen in TCM compound and each herbal with luciferase activity detection. 66 patients involved in the study from October 2004 to November 2006. Methods: A placebo controlled randomized double blind clinical trial was designed. The endpoint is hot flashes relieving. The second point is improving the sleeping disturbance. Sample numbers designed by statistician. Daily average of hot flashes was recorded by pts for a week as a baseline. The age, ER and PR status, hot flashes scores were distributed approximately equal between the two groups. Hot flashes scores were evaluated according to Kupperman menopausal index (KI). TCM or placebo liquid (100ml) was administrated orally three times a day for 3 weeks by a randomized envelope method. Results: Total 66 patients were evaluated. For hot flashes in placebo group 69.7%(23/33) no change, 30.3%(10/33) relieved, no pts report symptom disappear. There are 42.4%(14/33) hot flashes no change, 42.4 % (14/33) relieved, 15.2 %(5/33) hot flashes disappearance in TCM group (P=0.006). For sleeping disturbance in placebo group is 60.6%(20/33) no change, 39.4%(13/33) sleep improvement. In TCM group is 36.4%(12/33) no change, 63.6%(21/33) sleep improvement (P=0.049). Conclusions: According to the principle of TCM treatment hot flashes and ER and/or PR positive BC endocrine treatment characteristic, the TCM prescription is effective in alleviating tamoxifen-induced hot flashes and sleep disturbance while there is no phytoestrogen.

No significant financial relationships to disclose.
Understanding the choice of participating in clinical trials
Authors: Catania C. , De Pas T. M. , Goldhirsch A. , Radice D. , Adamoli L. , Medici M. , Verri E. , Marenghi C. , de Braud F. , Nolè F.
Published: March 2020

9091

Background: The choice of whether to participate in a clinical trial by patients (pts) with cancer can be influenced, beyond trial information, by patient's own emotional and cultural properties, including past history as well as prejudices. Our hypothesis was that a better knowledge of these cultural and emotional features might be useful to improve patients-doctor dialogue, leading patients to a more conscious motivation to make the choice. Methods: We developed a 17-items, multiple-choice and open-answer questionnaire, to capture motivations for participating, or declining to take part, in clinical trials. Further information included family relationships, schooling and clinical symptoms. Patients were required to have advanced lung or breast cancer and to have never discussed participation in a clinical trial. Results: The questionnaire was answered by all the 42 pts who received it. Eighty-three percent of pts were positive about their participation. Trust in the investigator (43%) or in the Institute (21%) and hope to receive a new chance for cure (71%), both for themselves and for others, were a major motivation for a positive answer. Forty-eight percent thought participation in a clinical trial as a sign that no other “standard” treatments are available; 19% were worried of unknown side effects and 76% considered detailed information on expected toxicity to be helpful in making the decision. Sixty percent of patients were afraid of losing “precious time” by participating in a trial; 9% felt exploited as “guinea pigs” and 31% had a some degree of fear that a clinical trial is primarily motivated by economical interests. The most important reasons for accepting an oral experimental drug were its easy use (46%) and having more freedom (36%) Conclusions: Italian patients with advanced breast or lung cancer positively viewed participation in a clinical trial. Several hopes, prejudices and fears have been captured by the questionnaire, which might lead to improve the informed consent documentation and the consciousness of patients in taking their choice. Validation of the findings in a larger cohort of patients will lead to a study on the effect of a specific intervention on informing patients about clinical research.

No significant financial relationships to disclose.
Quality of life and LhRH agonist therapy among prostate cancer patients who experience PSA failure
Authors: Kline K. F. , Sartor O. , Dandade N. A. , Nonzee N. J. , Vicuna B. D. , Bennett C. L.
Published: March 2020

9093

Background: Growing numbers of prostate cancer patients survive for extended periods of time after initial diagnosis and treatment. Many experience a biochemical relapse (“PSA failure”) some time after prostatectomy or pelvic radiation. LhRH agonist therapy can reduce PSA levels, but its impact on survival time and quality of life (QOL) is unclear. We evaluated these concerns among Veterans who experienced PSA Failure. Methods: Eligibility criteria included: receipt of primary therapy for prostate cancer followed by a PSA nadir and subsequent PSA rise to at least 0.2 ng/ml. Data sources include patients (interviewer administered survey instruments on health-related QOL at baseline, 3 and 12 months) and medical records (clinical and laboratory findings). Results: 69 patients from the Jesse Brown VA Medical Center in Chicago have enrolled in the study to date. At their baseline interviews, 30 patients (43.5%) were receiving LhRH agonists (46.1% of 39 African-American patients and 48.0% of 25 White patients). LhRH agonist patients reported worse health-related QOL in domains relevant to prostate cancer than watchful waiting (WW) patients ( Table ), including increased frequency of urination, difficulty controlling urination, greater erectile dysfunction, and more limits on sexual activity. LhRH agonist and WW patients reported similar levels of sexual satisfaction. Conclusion: Of the PSA failure patients studied in this sample, those receiving LhRH agonist therapy experience more problems with urinary and sexual function than those who opted for WW. Longitudinal study will provide information about whether the LhRH therapy causes these side effects, or whether symptomatic patients are more likely to choose LhRH therapy than those with few prostate cancer symptoms.

[Table: see text]

No significant financial relationships to disclose.
The effect of corticorelin acetate on peritumoral brain edema: An interim report of an open-label study as part of a phase III program
Authors: Carr L. , Mechtler L. , Recht L. , Hormigo A. , Paleologos N. , Alksne J. F. , Arenson E. , Raizer J. , Shulman M. G. ,   CAPBrainEdema [Corticorelin Acetate Peritumoral Brain Edema] Study Group
Published: March 2020

9095

Background: Steroid treatment of peritumoral brain edema (PBE) in patients with malignant brain tumors (BTs) is frequently associated with debilitating steroid side effects. The investigational agent corticorelin acetate injection, a synthetic peptide identical to h-corticotropin-releasing factor (hCRF), compared favorably to dexamethasone in reducing PBE in animal models of primary or metastatic BT. Toxicology and clinical studies including a pilot study in patients with malignant BTs published in ASCO's Annual Meeting Proceedings, showed hCRF to be safe and virtually devoid of steroid side effects. Methods: Following completion of follow-up periods for one of 2 randomized, double-blind phase III trials comparing corticorelin acetate to placebo or dexamethasone, patients with primary or metastatic BTs, PBE on pre-randomized study MRIs, and Karnofsky Performance Scores =50 were enrolled in an open-label extension study in which they took 1.0 mg corticorelin acetate by subcutaneous injection bid. We tapered dexamethasone maximally as tolerated. Patients were assessed every 4 weeks. Results: Of 47 patients who received open-label corticorelin acetate for up to one year, 28 patients continue to take it. Corticorelin acetate was safe and well tolerated, with no related deaths or SAEs. Patients typically refractory to reducing steroids - including at least 5 patients >55 years of age, 7 patients with recurrent brain tumor, and 11 patients in whom prior attempt(s) to reduce dexamethasone had been unsuccessful – reduced dexamethasone with improvement or resolution of steroid side effects. We will present data in the first 30 patients to take corticorelin acetate for at least 12 weeks [the largest and longest-treated group reported to date] including changes in steroid side effects correlated with net cumulative changes in dexamethasone, and treatment-emergent AEs. Conclusions: This interim analysis supports corticorelin acetate's long-term safety, tolerability, and steroid-sparing potential. The outcome of the ongoing randomized trials may determine whether this innovative agent leads to fundamental changes in the management of PBE in patients with primary or metastatic BTs.

[Table: see text]
Skin events (SE) among 1,126 patients (Pts) treated with lapatinib (L), an oral dual ErbB1/2 tyrosine kinase inhibitor (TKI)
Authors: Sweetman R. , Lacouture M. E. , Koehler M. , Laabs S. , Preston A. , Blackwell K. L.
Published: March 2020

9102

Background: Lapatinib (L) is active as a single agent and in combination with capecitabine in pts with ErbB2+ve breast cancer. Safety profile from > 5,000 pts demonstrates infrequent Grade (G)3/4 (10%) adverse events, with drug discontinuation (disc) required in (<2%) events. SEs were commonly reported and were likely due to ErbB1 inhibition in the epidermis, as hypothesized with the other ErbB1 TKIs. However, the SE with L appear to differ clinically from other TKIs. Methods: SE in 1,126 pts reported in 8 L trials ( EGF20001 , EGF20002 , EGF20003 , EGF20004 , EGF20008 , EGF20009 , EGF20014 , + EGF100151) were pre-defined as dermatitis, drug eruption, dry skin, pruritus/urticaria, skin disorder, skin infection, nail, and hair disorder. SE were characterized based on CTC grading, and examined as to their relationship to L dose, length of L exposure, tumor type, concurrent treatment, time to onset from L initiation, and time to resolution with L dose- reduction or disc. Furthermore clinical management, skin biopsies, photos, and outcome were examined. Results: Pts were treated with L monotherapy 1,000–1,500mg daily (N=928), or in combination with capecitabine (C) (N=198). Non-L containing arms of studies EGF100151 (N=191; C alone) and EGF20001 (N=197; tamoxifen alone) served as controls. Among all L treated pts, 54% experienced SE mostly as G1/2, and 69% L+C pts experienced G1–3 SE with 50% G2. Majority of SE were deemed not specific to L and were rarely severe (no G4). Only 1% required drug disc. Most frequently reported SEs were dermatitis/drug eruption (38% all grade; 3% G3) (8% all grade, 1% G3). The frequency of SE with L at 1,500 mg QD was 57%, 1250 mg QD was 41%, and 500 BID was 63%. Most SE developed early (45% day 1–14) and persisted a median of 29 days. The majority of L pts (82%) did not require intervention (ie, dose reduction, hold, or withdraw). Conclusions: This large collection of L treated pts demonstrates that SE related to L therapy are low grade, infrequently require intervention or dose reduction, and rarely cause drug disc. Further attempts to identify pts at high risk for skin toxicity, its management, and the pathophysiology of L related SE are ongoing.

No significant financial relationships to disclose.
Do most newly diagnosed advanced NSCLC patients need nutritional intervention?
Authors: Swinton N. , Kasymjanova G. , Steinberg T. , Lajeunesse L. , Dajczman E. , Kreisman H. , Small D. , Agulnik J. S. , Kawadoi J. , MacDonald N.
Published: March 2020

9108

Background: Depletion of nutritional reserves and significant weight loss are commonly noted in patients (pts) with non-small cell lung cancer (NSCLC). The Patient Generated Subjective Global Assessment (PG-SGA) is a nutritional screening tool for cancer pts, recommended by the Oncology Network of Dietitians of Canada and the American Dietetic Association. The PG-SGA categorizes total scores into 4 ranges for nutritional triage: 0–1 requires no intervention, 2–3 requires education, 4 - 8 requires intervention by a dietitian, and =9 requires urgent symptom control and nutrition intervention. (Ottery, 2000). Methods: We determined the prevalence of malnutrition in 92 newly diagnosed advanced NSCLC pts (stages 3 / 4) in an outpatient clinic who had completed a baseline PG-SGA. We also investigated the association between CRP (an inflammatory marker which correlates with poor prognosis) and the PG-SGA. PG-SGA score was based on the sum of 4 subscales: symptoms, weight history, food intake and functional status. Results: 92 pts (M 48, F 44) aged 65 ±11 years were studied. 21 (23%) pts had a PG-SGA score of 0–3, 23 (25%) 4–8, and 48 (52%) of 9 or greater. The most common symptoms accounting for a high PG-SGA score were: no appetite 37 (40%), pain 27 (29%), constipation 26 (28%), feeling full 24 (26%), dry mouth 22 (24%) and taste changes 19 (21%). 51 (55%) pts lost 0–4.9% of their body weight in the past month, 17 (19%) had a weight loss of 5–9.9% and 24 (26%) had a weight loss =10 %. In pts with a PG-SGA score of 0–3 the median CRP was 7.0 mg/L (range: 0.7–66.0), in those with a score of 4–8 the median CRP was 41.8 mg/L (0.8–266.1) and in those with a score of =9 the median CRP was 18.5 mg/L (0.3–219.0) (p=0.02). Conclusion: At time of diagnosis, 77% of advanced NSCLC pts were in need of nutritional intervention; 52% required urgent intervention. The PG-SGA is a simple screening tool which should be incorporated into patient care in outpatient oncology clinics.

No significant financial relationships to disclose.
Steroids and immunosuppressive agents potentiate the cytotoxicity of the EGFR inhibitor erlotinib (E) in human skin keratinocytes whereas Vit K3 exerts a protective effect: Implications for the management of the skin rash
Authors: Perez-Soler R. , Zou Y. , Li T. , Ling Y.
Published: March 2020

9124

Background: Skin toxicity secondary to EGFR inhibitors is treated symptomatically with topical and systemic combinations of steroids, antibiotics, antihistamines, and immunosuppressive agents with variable and often unsatisfactory results. Vit K3 prevents EGFR inhibition induced by E and cetuximab in human A431 tumor cells, probably through an effect on the phosphatase (Perez-Soler, ASCO 2006). We studied the cytotoxic effects of different agents used to treat the EGFR inhibitor-mediated skin rash on human immortalized skin keratinocytes exposed to the EGFR inhibitor E as well as the potential protective effect of Vit K3. Methods: The cytotoxicity of E in the presence of non cytotoxic concentrations of hydrocortisone, minocycline, cyclosporine-A, diphenhydramine, and Vit K3 was assessed by MTT assay in human HaCat cells, a cell line derived from human basal epidermal cells. Results: E cytotoxicity was enhanced by 2–5 fold by cyclosporine A and hydrocortisone, not affected by minocycline and diphenhydramine, and reduced by 5-fold by Vit K3. Vit K3 25–50 μM induced EGFR activation and prevented E's inhibitory effect on EGFR. Conclusions: Steroids and immunosuppressive agents may potentiate the cytotoxic effect of anti-EGFR agents in the skin, thus providing a possible explanation for the erratic and mixed therapeutic results often observed with the use of these agents. Vit K3 was the only agent capable of abrogating the cytotoxic effect of E in this clinically relevant model of normal human skin. A topical formulation of Vit K3 is undergoing preclinical evaluation. Supported by NCI CA 91784 and 113630 and a grant from Hana Biosciences.

No significant financial relationships to disclose.
Feasibility of tailored exercise for improving sleep disruption in women with metastatic breast cancer
Authors: Mustian K. M. , Griggs J. , Palesh O. , Morrow G.
Published: March 2020

9129

Background: Women diagnosed with metastatic breast cancer (MBC) live for months and years. Long-term effects of cancer and its treatment result in chronic symptoms, such as sleep disruption (SDN) that diminish quality of life (QOL). Exercise reduces SDN and minimizes QOL deficits in women with early stage breast cancer during adjuvant treatment, but the feasibility and efficacy of exercise for women with advanced disease is not well established. This phase I pilot study assessed the feasibility and efficacy of a tailored exercise intervention for reducing SDN in women with MBC. Methods: Women with MBC (N=12; mean age=50; disease-free interval 0–10yrs) participated in an 8-week, low to moderately intense, exercise intervention (3x's/wk). The program included flexibility, core stability, aerobic, and resistance training. Results: The intervention was safe, well-tolerated with no adverse events, and well-liked by patients and oncologists. The participants exercised an average of 3.5 days (SD=1.5) a week for 58 minutes (SD=12.9) per exercise session at a moderate intensity (RPE of 3.6; SD=1.2) during the 8-week intervention. Patients spent an average of 25 minutes (SD=7.8) in cardiovascular exercise, 21 minutes (SD=5.5) in resistance exercise, and 10 minutes (SD = 2.2) in flexibility and core stability exercise per exercise session. Paired t-tests showed statistically significant improvements in SDN (Pittsburgh Sleep Quality Index) from baseline to week 4 (mean change=2.56; SE=.96; t1,8 = 2.70, p ≤.05). SDN Also improved from baseline to week 8 (mean change=2.13; SE=1.22). Conclusion: Phase II and III randomized, controlled trials are warranted to substantiate the efficacy of this tailored exercise intervention for improving SDN and, ultimately, QOL and survival among women with MBC. Supported by Roche Biomedical and NCI grant 1R25CA102618

No significant financial relationships to disclose.
Antioxidants and toxicity of cancer chemotherapy: A systematic review of the evidence from randomized controlled trials
Authors: Block K. I. , Koch A. C. , Mead M. N. , Tothy P. , Newman R. A. , Gyllenhaal C.
Published: March 2020

9130

Background: Much debate has focused on whether or not antioxidants interfere with the efficacy of cancer chemotherapy. The objective of this study is to systematically review the medical literature to compile results from randomized, controlled clinical trials evaluating the effects of concurrent use of antioxidants with chemotherapy on toxic side effects. Methods: We performed a search of literature from 1966-December 2006 using MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch and EMBASE databases. Randomized, controlled clinical trials reporting mitigation of chemotherapy toxicity were included in the final tally. The searches were performed in duplicate following a standardized protocol. No meta-analysis was performed due to heterogeneity of cancers and chemotherapy regimens. Results: Of 848 articles considered, 32 trials met the inclusion criteria. Antioxidants evaluated were: glutathione (9), melatonin (6), vitamin A (1), an antioxidant mixture (3), N-acetylcysteine (3), vitamin E (5), selenium (1), L-carnitine (1), Co-Q10 (2) and ellagic acid (1). Subjects of most studies had advanced or relapsed disease. Conclusions: One of the 32 studies included reported evidence of significant increase in toxicity from the concurrent use of antioxidants with chemotherapy. In 18 studies, antioxidant groups experienced significantly lower toxicity than control groups. Statistical power and poor study quality were concerns with some of the studies. We have reported elsewhere that randomized trials of various antioxidants given with chemotherapy did not demonstrate an adverse effect on treatment response or survival. Well-designed studies evaluating larger populations of patients given antioxidants concurrently with chemotherapy are thus warranted.

No significant financial relationships to disclose.
Identification of genomic DNA signatures predicting relapse in low- and intermediate-risk neuroblastoma using a case control design and high-density SNP genotyping: A Children's Oncology Group (COG) study
Authors: Attiyeh E. F. , Mosse Y. P. , Diskin S. , Hou C. , Attiyeh M. A. , Baker D. , Strother D. , Schmidt M. , London W. B. , Maris J. M.
Published: March 2020

9500

Background: Neuroblastoma (NB) is a childhood malignancy with a heterogeneous clinical course. Clinical and genomic markers are powerful predictors of outcome and are used to stratify cases for treatment intensity, but imprecision remains. Methods: We identified all disease recurrences from the recently closed COG low- (P9641: 903 eligible, 63 events) and intermediate-risk (A3961: 467 eligible, 40 events) NB phase III trials. To date, tumor DNA from 35 cases and 90 controls (P9641/A3961 patients without event) was used for whole genome copy number and genotype evaluation on the Illumina HumanHap550 (550K SNPs) array. An in-house algorithm was developed to assign genomic copy number and loss of heterozygosity based on probe intensity (log R ratio) and degree of allelic imbalance (B allele frequency). Results: A total of 988 chromosomal aberrations were identified; 231 (23.4%) were whole chromosome (WC) copy number aberrations (CNA). Unsupervised hierarchical clustering identified 10 tumor subsets, with 2 highly enriched with cases showing progression events (13/21; 61%), and 2 dominated by WC gains (chromosomes 2, 6, 7 and 18) with only 2/20 events. Regional aberrations most highly associated with EFS included loss of 11q14-qter (p=0.036), and gain of 11p (p=0.003), 11q13 (p=0.020), and 17q23-qter (p=0.005). Other regional CNAs at borderline univariate significance for EFS included partial gain at 2p, 2q, 6q, 7q, 12q and 13q. The pattern 11p and proximal 11q gain associated with loss of distal 11q was associated with relapse and death (p=0.006 and p=0.023). Conclusion: Whole genome SNP genotyping detects patterns of chromosomal CNAs predictive of EFS, even in situations where events are rare such as low- and intermediate- risk NB. These data support chromosomal 11 and 17 structural CNAs as being most highly predictive of relapse in otherwise favorable NBs, but also suggest that other CNAs likely cooperate and may improve precisions for risk prediction. These data can be used to identify patients eligible for chemotherapy reduction/elimination, and perhaps others for intensification. Ongoing analyses of the remaining samples will extend these conclusions.

No significant financial relationships to disclose.
Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols: Final report
Authors: Dhall G. , Grodman H. , Ji L. , Sands S. , Gardner S. , Allen J. , Sposto R. , Finlay J.
Published: March 2020

9507

Background: The use of dose-intensive chemotherapy with autologous hematopoietic cell rescue (AuHCR) is a potentially curative approach to the management of infants and young children with non-metastatic (M-0) medulloblastoma, with the additional benefit of avoiding the late effects of irradiation. We report the results of the “Head Start” I (1991 to 1997) and “Head Start” II (1997 to 2002) clinical trials, using this approach, to treat children with M-0 medulloblastoma, who were less than three years of age at diagnosis. Methods: Twenty one children were enrolled on these two serial studies. After surgery, patients received a uniform induction chemotherapy regimen consisting of five cycles of vincristine, cisplatin, cyclophosphamide and etoposide. Following completion of induction, all patients underwent myeloablative consolidation chemotherapy using carboplatin, thiotepa and etoposide followed by AuHCR, and did not receive irradiation. Irradiation was used only at relapse. Quality of life (QoL) and social and emotional behavior were evaluated on “Head Start” I, and cognitive functioning was evaluated on “Head Start” II survivors. Results: The five-year event-free (EFS) and overall survival (OS) rates (±SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 ± 11% and 70 ± 10%, 64 ± 13% and 79 ± 17%, and 29 ± 17% and 57 ± 19%, respectively. The five-year EFS and OS (±SE) for patients with desmoplastic and classical medulloblastoma were 67 ± 16% and 78 ± 14%, and 42 ± 14 and 67 ± 14%, respectively. Young age (<2 years versus 2 to 3 years) at diagnosis did not appear to impact adversely upon outcome. There were four treatment related deaths. A majority of survivors (71%) avoided irradiation altogether. Neuropsychological functioning in children surviving without irradiation was well within the normal range for most patients. Conclusions: The strategy of brief intensive chemotherapy without irradiation for young children with M-0 medulloblastoma has eliminated the need for craniospinal irradiation in over half (52%) of the patients, with preservation of QoL and cognitive functioning in the majority.

No significant financial relationships to disclose.
Randomized phase III trial comparing vincristine, actinomycin, cyclophosphamide (VAC) with VAC/V topotecan/cyclophosphamide (TC) for intermediate risk rhabdomyosarcoma (IRRMS). D9803, COG study
Authors: Arndt C. A. , Hawkins D. S. , Stoner J. A. , Wharam M. D. , Rodeberg D. A. , Parham D. M. , Meyer W. H. ,   Children's Oncology Group
Published: March 2020

9509

Background: IRRMS was defined as nonmetastatic alveolar (A) RMS or undifferentiated sarcoma (UDS); stage (stg) 2 and 3, group (gr) III embryonal (E) RMS; stg 4 ERMS <10y. IRRMS had a 5 yr failure free survival (FFS) of 64% on IRS IV. Since T alone and with C has significant activity in RMS, we tested whether alternating VAC/VTC improved FFS for IRRMS compared with VAC alone. Methods: Patients (pts) < 50 y with IRRMS with adequate organ function were randomized to 39 wks of VAC (V=1.5 mg/m2, A=0.045 mg/kg, C=2.2 g/m2 q 3 wk) vs VAC alternating with VTC (T=0.75 mg/m2/d ×5, C=250 mg/m2/d ×5 q 3 wk), with additional wkly V; doses adjusted for age <3y; local therapy was after wk 12. Pts with parameningeal RMS/meningeal extension (PME) were nonrandomly treated with VAC and immediate XRT. Primary study endpoint was FFS. The study was designed with 80% power (5% 2-sided alpha level) to detect an increase in 5 yr FFS from 64% to 75%, a relative risk (RR) of 0.64, with VAC/VTC, requiring 518 randomized pts. Results reflect the 3rd of 4 planned analyses (75% information); O'Brien Fleming adjusted alpha level is 0.0166; and Cox PH model was used. Results: 620 eligible pts were entered from 9/99 to 8/05: 266 randomized to VAC, 253 to VAC/VTC, 101 PME patients were nonrandomly treated with VAC. Treatment strata were ERMS stg 2/3, gr III 37%; ERMS grp IV <10 y 6%; ARMS/UDS stg 1 or gr I 16%; ARMS/UDS other 25%; PME 16%. 3% of pts were <1 y, 69% 1–9 y, 28% ≥10 y; 13% of pts were stg 1; 26% stg 2; 54% stg 3; 7% stg 4. 77% pts had gr III tumors. Primary tumor sites were PM in 35% pts, extremity 15%, bladder/prostate 16%, retroperitoneal/perineal 15%, other 19%. Median follow up is 2.4 yrs. FFS at 2 yrs is 77% with VAC and 72% with VAC/VTC. Observed data are inconsistent with hypothesized improvement under VAC/VTC (RR=1.20, 98.34% CI: 0.78–1.85, p=0.3). Similar patients on IRS IV had 2 yr FFS of 77%. 2 yr survival (OS) with VAC: 91%; VAC/VTC: 87% (RR=0.94, CI: 0.55–1.59, p=0.8). There were 12 2nd malignancies and 10 deaths as first events. 4 of 10 deaths were from hepatopathy, which decreased in incidence following dose changes for A and C. Conclusions: In IRRMS, VAC/VTC does not significantly improve FFS nor OS versus VAC, and outcome is similar to IRS IV.

No significant financial relationships to disclose.
Activation of the PI3K/Akt pathway in neuroblastoma
Authors: Sartelet H. , Castain M. , Fabre M. , Bosq J. , Rougemont A. , Michiels S. , Vassal G.
Published: March 2020

9523

Background: Neuroblastoma is a pediatric malignant neurorectodermal tumor with still a poor survival in children over 1 year of age. In cancer, the PI3K/Akt pathway contributes to tumor aggressiveness (proliferation, metastasis). It is a major target for novel anti- cancer therapies. The objective was to study the activation of the PI3K/Akt pathway in NB. Methods: 101 patients (median age 2.5 years, range: 0–13) with a resected neuroblastoma (16 stage I; 7, II; 22, III; 48, IV and 8, IVS) were included. Tissue microarrays were constructed containing 101 primary tumors, 39 paired metastases and 56 paired normal tissues. Immunohistochemical staining was performed on sections using antibodies against PI3K, Akt and phosphoAkt (S-473). The expression of membrane receptors (EGFR, HER-2, VEGFR1, VEGFR2, PDGFRa, PDGFRβ, IGF1Rβ, TrkB), proteins directly interfering with AKT (PTEN, mTOR) and downstream proteins (phospho-p70S6 kinase, 4eBP1) was studied. The intensity was evaluated by a semi-quantitative score based on the percentage of positive cells. The Wilcoxon signed rank test was applied for the comparison of paired data and adjusted for multiple testing using the False Discovery Rate criterion. Spearman correlation values (rho) were used to compare the expression between genes in the primary tumors. Results: 60% of the tumors expressed PI3K, 80% AKT and 73% pAKT. In addition, phospho-p70S6 kinase and 4eBP1p were expressed in 95% and 85%. All these proteins had a higher expression in tumors as compared with paired normal tissues (fdr-adjusted p<0.001). Akt and pAkt showed a tendency for higher expression in metastases as compared to paired primary tumors (raw p<0.05 for both, but fdr-p=0.11 and fdr-p=0.17 respectively). While EGFR, IGF1Rβ, TrkB, PDGFRa and PDGFRβ were significantly more expressed in primary tumors as compared to normal tissues (fdr-p<0.05), only IGF1Rβ seemed more expressed in metastases (fdr-p=0.09). A significant positive correlation was found between pAkt and the following: VEGFR1, VEGFR2 and IGF1Rβ (rho>0.34, p<0.001), phospho-p70S6 kinase and mTOR(rho>0.26, p<0.01). Conclusions: The PI3K/Akt pathway is activated in neuroblastoma and could be an attractive target for novel therapies. In addition, the data suggested that VEGFR and IGF1R are preferentially committed to this pathway activation.

No significant financial relationships to disclose.