Kooperativer Bibliotheksverbund

In: BJS Open, Oxford University Press (OUP), Vol. 6, No. 1 ( 2022-01-06)

Abstract: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Methods The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study (‘IMAGINE’) of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study (‘Tayside’) in major abdominal surgery (2011–2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Results In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655–0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323–0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881–0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity. Presented to Association of Surgeons in Training (ASiT) International Conference 2018 (Edinburgh, UK), European Society of Coloproctology (ESCP) International Conference 2018 (Nice, France), SARS (Society of Academic and Research Surgery) 2020 (Virtual, UK).

Type of Medium: Online Resource

ISSN: 2474-9842

URL: Article

DOI: 10.1093/bjsopen/zrab150

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2902033-5

In: Addiction Science & Clinical Practice, Springer Science and Business Media LLC, Vol. 12, No. S1 ( 2017-9)

Type of Medium: Online Resource

ISSN: 1940-0640

URL: Article

DOI: 10.1186/s13722-017-0087-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2492632-2

SSG: 15,3

In: British Journal of Surgery, Oxford University Press (OUP), Vol. 107, No. 2 ( 2020-01-05), p. e161-e169

Abstract: Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P & lt; 0·001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.

Type of Medium: Online Resource

ISSN: 0007-1323 , 1365-2168

URL: Article

DOI: 10.1002/bjs.11326

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2020

detail.hit.zdb_id: 2006309-X

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2635-2635

Abstract: Introduction: Randomized studies have demonstrated that compared to chemotherapy alone (ChemoTx), combined modality therapy (CMT) improves early event-free survival in HL patients with early stage disease. However, long-term follow up from randomized trials suggests that overall survival (OS) when receiving ChemoTx alone is equivalent or superior to OS compared with CMT. In addition, many studies have described late effects in HL survivors. While the negative impact of late-effects on LE have been estimated for pediatric HL patients (Yeh, Blood, 2012), these estimates have limited generalizability to adult HL patients due to differences in treatment regimens and exposure-related late-effects risks. To address this gap, we sought to develop an adjustable Markov model to predict LE for adult HL patients treated with contemporary therapy. Methods: We created a Markov "state transition model" in which a cohort of patients moves through different health states. The patient cohort (base case, 18 years old) starts with initial diagnosis, and upfront treatment with 12-year OS modeled from the CCG 5942 (Wolden, JCO, 2012; COG, updated data, 2015). Following the first 12 years, the probabilities of dying were modeled by summing background mortality rates and the mortality rate associated with late effects. Background mortality rate estimates came from the 2010 CDC gender-specific LE data. Late effects mortality rates were estimated from excess absolute risk (EAR) estimates due to late effects from the Childhood Cancer Study (CCSS) Cohort 1 subjects across all disease stages who were treated with extended field RT (EFRT), higher alkylating agent therapy, and less anthracycline compared to contemporary cohorts. (Castellino, Blood, 2011) Recognizing that recent comparisons of RT doses and fields from CCSS survivors to those treated with involved field radiotherapy (IFRT) have demonstrated a reduction in RT to healthy tissues of approximately 50% (Koh, Radiation Oncology, 2007), we assumed that this RT reduction would reduce incremental mortality risk attributable to therapy by 50%. Thus, for patients treated with CMT containing IFRT, we reduced the reported EAR estimate for the CCSS-1 HL patients by 50%. Furthermore, for HL patients treated with ChemoTx alone, we assumed incremental mortality risk would be reduced by 75% (i.e., EAR reduced by 75% for this group). Because late effects mortality rates were based on pediatric data, we conducted extensive sensitivity analyses on EAR estimates to portray the scope of uncertainty surrounding LE estimates. Results: We built on previous work on this topic by utilizing 12-year OS from CCG 5942 and by adapting data from the CCSS-1 cohort to reflect the impact of late effects on LE with more modern therapy (e.g. IFRT). 12-year OS for early stage, favorable risk HL patients treated on CCG 5942 was 98.9% and 100% for patients treated with ChemoTx and CMT, respectively. LE for an 18 year old without HL was 60.9 years. Without consideration of the burden of late effects (i.e., EAR=0), a patient with early stage, favorable risk HL had a LE similar to a healthy 18 year old without HL. For HL patients, LE with ChemoTx alone (base case, COPP/ABV) was 58.0 years and the LE for treatment with CMT (i.e., COPP/ABV + IFRT) was 55.7 years. Additionally, reduced LE was also apparent for HL patients who received ChemoTx alone (see Figure). Finally, in order to apply these data to individual HL patients, we created an adjustable model with variables including age, gender, risk group (favorable/unfavorable), and gender- and treatment-specific EAR that may potentially be applied to an individual HL patient. Conclusion: We created an adjustable Markov model that predicts LE for adult HL patients treated with contemporary therapy. This model, including longer term OS data, demonstrated that contemporary therapy reduces the late effects burden. However, for survivors of early stage HL, we found that LE loss due to late effects substantially exceeds LE loss due to HL. To further enhance this model for the potential application in adults with HL, further synthesis of available pediatric and adult data (accounting for contemporary therapy) is needed to account for differences in EAR by age and gender over a life span. Altogether, models that synthesize clinical trial data provide valuable information to providers and may help guide them and HL patients towards individualized therapeutic decisions. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2635.2635

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 23-24

Abstract: Although most patients (pts) with newly diagnosed stage III or IV Hodgkin lymphoma (HL) will be cured with initial therapy (tx), about 20-25% of pts will have relapsed or refractory (R/R) HL. The standard initial tx for adults with advanced stage HL, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), is associated with pulmonary toxicity due to bleomycin. Recent studies have demonstrated that in pts with a negative interim PET scan, the omission of bleomycin after 2 cycles is non-inferior with regards to survival. However, a significant proportion of pts have a positive interim PET scan and require escalation to BEACOPP - an effective but toxic regimen associated with secondary malignancies and infertility. Recently, the addition of brentuximab vedotin (BV) to AVD chemotherapy (BV-AVD) demonstrated improved modified and traditionally-defined progression-free survival (PFS) compared to ABVD. However, the BV-AVD regimen was associated with higher rates of neutropenia, sepsis, and peripheral neuropathy compared to ABVD, and there still was a ~20% failure rate. In adolescent and young adult pts with advanced stage HL, there is a similar ~20% failure rate using ABVE-PC (AB, vincristine, etoposide, prednisone, cyclophosphamide) and response-adapted radiation therapy (RT) - with RT use in a majority of pts. There remains room to improve outcomes in pediatric and adult pts with newly diagnosed advanced stage HL. The PD-1 pathway plays a critical role in the pathogenesis of HL and the disease is exquisitely sensitive to PD-1 blockade, as demonstrated in clinical trials of nivolumab and pembrolizumab in pts with heavily treated R/R HL. A phase II trial evaluating nivolumab combined with AVD (N-AVD) demonstrated promising safety and efficacy in pts with newly diagnosed HL. The incorporation of PD-1 blockade into front-line tx represents a clear opportunity to potentially improve the outcomes and tolerability of initial tx for pts with newly diagnosed advanced stage HL. A meeting was convened between the North American cooperative group Lymphoma Committee chairs, expert HL researchers and physicians, representatives from the Cancer Therapy Evaluation Program (CTEP), and patient advocates with the goals of harmonizing treatment approaches in advanced stage HL across pediatric and adult pts and reaching consensus regarding the optimal study design for a randomized trial incorporating PD-1 blockade into frontline tx for pts with advanced stage HL. Study champions were identified from each of the North American cooperative groups (SWOG, ECOG-ACRIN, Alliance, Canadian Cancer Trials Group, and Children's Oncology Group) and experts in imaging, radiation oncology, lymphoma biology and patient-reported outcomes were included in the study team. The resulting clinical trial - S1826, led by SWOG Cancer Research Network - represents the largest advanced stage HL study in the history of the North American cooperative groups and the first prospective collaboration between COG and the adult cooperative groups in HL. S1826 (NCT03907488) is a randomized, phase III study of N-AVD versus BV-AVD in pts with newly diagnosed advanced stage HL. Eligible pts must be 12 years or older and have stage III or IV HL. Pts are randomized 1:1 to receive 6 cycles of treatment with either N-AVD or BV-AVD. Pts randomized to BV-AVD are required to receive G-CSF prophylaxis for neutropenia. Pts are eligible to receive RT to residually metabolically active areas on the end of treatment (EOT) PET scan at the discretion of the treating investigator. Pts are stratified during randomization based on age, international prognostic score, and intention to use EOT RT. The primary endpoint is to compare the PFS in pts randomized to N-AVD versus BV-AVD. Secondary endpoints include overall survival, event-free survival, the EOT complete metabolic response rate, and the safety and tolerability of N-AVD compared to BV-AVD. Another key secondary endpoint will be a comparison of patient-reported symptoms and health-related quality of life (overall, fatigue, neuropathy) between the study arms. 940 eligible pts are expected to be accrued over 4 years with a total of 987 pts assuming an expected ineligible rate of 5%. The S1826 study represents an unprecedented effort across the North American clinical trial cooperative groups to improve the cure rate in advanced stage HL and harmonize treatment approaches across pediatric and adult pts. Figure Disclosures Herrera: Merck: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; AstraZeneca: Research Funding; Karyopharm: Consultancy; Immune Design: Research Funding; Pharmacyclics: Research Funding. Rutherford:Heron: Consultancy; Regeneron: Research Funding; Juno: Consultancy; Dova: Consultancy; Genentech/Roche: Research Funding; AstraZeneca: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy, Research Funding; Kite: Consultancy; LAM Therapeutics: Research Funding; Seattle Genetics: Consultancy. Parsons:Seattle Genetics: Consultancy. Prica:astra zeneca: Honoraria; seattle genetics: Honoraria; Gilead: Honoraria. Shipp:Ono Pharmaceutical: Honoraria; Celgene: Honoraria; Merck: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Bayer: Honoraria. Crump:Kite/Gilead: Consultancy; Roche: Consultancy; Servier: Consultancy. Kahl:BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy, Research Funding. Leonard:Miltenyi: Consultancy; Roche/Genentech: Consultancy; BMS/Celgene: Consultancy; MEI Pharma: Consultancy; Gilead/Kite: Consultancy; Bayer: Consultancy; ADC Therapeutics: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; GenMab: Consultancy; Sutro: Consultancy; Karyopharm: Consultancy. Smith:Karyopharm: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Astellas: Consultancy; Portola Pharmaceuticals: Consultancy; Kite Pharmaceuticals: Research Funding; Bayer: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136422

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: British Journal of Haematology, Wiley, Vol. 182, No. 2 ( 2018-07), p. 212-221

Abstract: We developed a novel simulation model integrating multiple data sets to project long‐term outcomes with contemporary therapy for early‐stage Hodgkin lymphoma ( ESHL ), namely combined modality therapy ( CMT ) versus chemotherapy alone ( CA ) via 18 F‐fluorodeoxyglucose positron emission tomography response‐adaption. The model incorporated 3‐year progression‐free survival ( PFS ), probability of cure with/without relapse, frequency of severe late effects (LEs), and 35‐year probability of LE s. Furthermore, we generated estimates for quality‐adjusted life years ( QALY s) and unadjusted survival (life years, LY ) and used model projections to compare outcomes for CMT versus CA for two index patients. Patient 1: a 25‐year‐old male with favourable ESHL (stage IA ); Patient 2: a 25‐year‐old female with unfavourable ESHL (stage IIB ). Sensitivity analyses assessed the impact of alternative assumptions for LE probabilities. For Patient 1, CMT was superior to CA ( CMT incremental gain = 0·11 QALY s, 0·21 LY s). For Patient 2, CA was superior to CMT ( CA incremental gain = 0·37 QALY s, 0·92 LY s). For Patient 1, the advantage of CMT changed minimally when the proportion of severe LE s was reduced from 20% to 5% (0·15 QALY s, 0·43 LY s), whereas increasing the severity proportion for Patient 2's LE s from 20% to 80% enhanced the advantage of CA (1·1 QALY s, 6·5 LY s). Collectively, this detailed simulation model quantified the long‐term impact that varied host factors and alternative contemporary treatments have in ESHL.

Type of Medium: Online Resource

ISSN: 0007-1048 , 1365-2141

URL: Issue

URL: Article

DOI: 10.1111/bjh.2018.182.issue-2

DOI: 10.1111/bjh.15255

Language: English

Publisher: Wiley

Publication Date: 2018

detail.hit.zdb_id: 1475751-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 17_suppl ( 2023-06-10), p. LBA4-LBA4

Abstract: LBA4 Background: The addition of BV to initial chemotherapy improves overall survival (OS) in adults and PFS in pediatric patients (pts) with AS HL. However, frontline BV adds toxicity, most pediatric pts receive radiation therapy (RT), and 7-20% of pts still develop relapsed/refractory (RR) HL. The PD-1 pathway is central to the pathogenesis of HL and PD-1 blockade is effective in RR HL. The adult and pediatric cooperative groups of the National Clinical Trials Network (NCTN) conducted the randomized, phase 3 S1826 trial to evaluate N-AVD vs BV-AVD in pts with newly diagnosed AS HL. Methods: Eligible pts were ≥12 years (y) with stage 3-4 HL. Pts were randomized 1:1 to either 6 cycles of N-AVD or BV-AVD. Recipients of BV-AVD were required to receive G-CSF neutropenia prophylaxis vs optional with N-AVD. Pre-specified pts could receive RT to residually metabolically active lesions on end of treatment PET. Pts were stratified by age, international prognostic score (IPS), and intent to use RT. Response and disease progression were assessed by investigators using 2014 Lugano Classification. The primary endpoint was PFS; secondary endpoints included OS, event-free survival, patient-reported outcomes (PROs), and safety. Results: 994 pts were enrolled from 7/9/19 to 10/5/22; 976 were eligible and randomized to N-AVD (n=489) or BV-AVD (n=487). Median age was 27y (range, 12-83y), 56% of pts were male, 76% were white, 12% were black, and 13% were Hispanic. 24% of pts were 〈 18y, 10% were 〉 60y, and 32% had IPS 4-7. So far, 〈 1% of pts received RT. At the planned 2nd interim analysis (50% of total PFS events) the SWOG Data and Safety Monitoring Committee recommended to report the primary results because the primary PFS endpoint crossed the protocol-specified conservative statistical boundary. 30 PFS events occurred after N-AVD vs 58 events after BV-AVD. With a median follow-up of 12.1 months, PFS was superior in the N-AVD arm [HR 0.48, 99% CI 0.27-0.87, one-sided p=0.0005); 1y PFS: N-AVD, 94%, BV-AVD, 86%. 11 deaths (7 due to adverse events, AE) were observed after BV-AVD compared to 4 after N-AVD (3 due to AE). The rate of grade (gr) ≥ 3 hematologic AE was 48.4% (45.1% gr ≥ 3 neutropenia) after N-AVD compared to 30.5% (23.9% gr ≥ 3 neutropenia) after BV-AVD. Rates (any gr) of febrile neutropenia (5.6% N vs 6.4% BV), pneumonitis (2.0% N vs 3.2% BV), ALT elevation (30.7% N vs 39.8% BV), and colitis (1% N vs 1.3% BV) were similar. Hypo/hyperthyroidism was more frequent after N-AVD (7%/3% N vs 〈 1% BV) while peripheral neuropathy (any gr) was more common after BV-AVD (sensory: 28.1% N vs 54.2% BV; motor: 4% N vs 6.8% BV). Conclusions: N-AVD improved PFS vs BV-AVD in pts with AS HL. Few immune AEs were observed and 〈 1% of pts received RT. Longer follow-up is needed to assess OS and PROs. S1826, the largest HL study in NCTN history, is a key step towards harmonizing the pediatric and adult treatment of AS HL. Funding provided by: National Cancer Institute of the National Institutes of Health U10CA180888 and U10CA180819 and Bristol-Myers Squibb. Clinical trial information: NCT03907488 .

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2023.41.17_suppl.LBA4

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2023

detail.hit.zdb_id: 2005181-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS8067-TPS8067

Abstract: TPS8067 Background: Treatment for pediatric cHL varies considerably from that in adult cHL. Hence there are gaps in risk prediction and optimal therapy for de-novo advanced stage disease across the adolescent and young adult (AYA) age spectrum. Early access to novel agents for AYA could be facilitated via collaboration with adult research groups through the U.S. National Cancer Institute’s National Clinical Trials Network (NCTN). The PD-1 inhibitor Nivolumab (Nivo) has safety and efficacy in relapsed and refractory disease in children and adults, but has not been evaluated in de-novo disease to date. Methods: North American cooperative group lymphoma chairs, Cancer Therapy Evaluation Program (CTEP) representatives and patient advocates met to establish consensus on the comparison arms and study design, based on recent historical approaches across adult and pediatric groups. Study champions were identified across North American cooperative groups and include expertise in imaging, radiation oncology, biology and patient-reported outcomes. A therapeutic study was designed with the primary aim being to compare progression-free survival with novel targeted agents in advanced stage cHL. S1826 (NCT03907488), led by SWOG Cancer Research Network, opened to accrual in July 2019. Eligibility criteria include age 〉 12 years, and Stage III or IV cHL. Patients are randomized (1:1) to 6 cycles of either Nivo-Adriamycin, Vinblastine, Dacarbazine (AVD) or Brentuximab vedotin (Bv)-AVD. Enrollment is stratified by age, baseline International Prognostic Score, and provider intent to use involved site radiation therapy (ISRT). Protocol-prescribed ISRT is response-adapted, based on end of therapy imaging. The primary endpoint is a comparison of progression-free survival between arms. Secondary clinical endpoints include comparison of: overall survival, metabolic response at the end of therapy, physician-reported adverse events, patient-reported adverse events, and health-related quality of life (overall, and specific to fatigue and neuropathy). This unique intergroup collaboration demonstrates the process and the feasibility of consensus study designs toward early adoption of targeted therapies and harmonization of treatment approaches for AYA populations. Clinical trial information: NCT03907488 .

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2020.38.15_suppl.TPS8067

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2020

detail.hit.zdb_id: 2005181-5

In: Annals of the Rheumatic Diseases, BMJ, Vol. 75, No. 1 ( 2016-01), p. 242-252

Type of Medium: Online Resource

ISSN: 0003-4967 , 1468-2060

URL: Article

DOI: 10.1136/annrheumdis-2014-205584

Language: English

Publisher: BMJ

Publication Date: 2016

detail.hit.zdb_id: 1481557-6

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2636-2636

Abstract: Introduction: There is no clear consensus regarding the optimal therapeutic approach for AYAs with HL. Prior registry data showed that HL AYA patients treated with ABVD had similar outcomes to their older counterparts (Foltz JCO 2006). However, SEER data have suggested that advances in HL survival among AYAs may be less robust compared with older populations (Bleyer NCI 2006). We sought to examine AYA patients treated on two recent, randomized pediatric and adult North American HL clinical trials (i.e., 17-21 years; the age group of those typically eligible for both pediatric- and adult-based HL clinical trials) by comparing outcomes of different age cohorts within E2496 as well as across the two different studies. Methods: We examined characteristics and outcomes of 114 newly diagnosed AYA HL patients aged 17-21 years treated on E2496 (ABVD vs. Stanford V [SV] chemotherapy, Gordon JCO 2013) trial and compared the failure free survival (FFS) and overall survival (OS) with patients ages 〉 21 years. In addition, we compared presenting features, planned treatment, FFS, and OS of these ECOG AYA patients with 391 newly diagnosed AYA HL patients between ages 17-21 years treated on the COG AHOD0031 (ABVE-PC backbone, Friedman JCO 2014). Unstratified and stratified log-rank tests as well as propensity score analysis were utilized to compare differences in patient outcomes. Results: In E2496, the 5-year FFS and OS rates for AYAs were 68% and 89%, respectively, with significant variations identified by patient age (see Table). There was no FFS difference between ECOG AYAs treated with ABVD vs. SV (P =0.66). However, FFS in AYAs were inferior to those ages 21 to 44 years in E2496 (P =0.005; see Figure, sections A and B). Interestingly, AYA outcomes on E2496 appeared more similar to patients aged 45-59 years. In examining COG and E2496 AYA patient characteristics, there was no significant difference in sex, race, or histology. Due in part to trial design differences, a larger proportion of E2496 AYAs were stage III or IV vs. COG AYAs (63% vs. 29%, P 〈 0.001) and had B symptoms (63% vs. 27%, P 〈 0.001); fewer E2496 patients had bulk disease (33% vs. 77%, P 〈 0.001). There was no significant difference in presentation with extralymphatic disease, anemia, or hypoalbuminemia. In terms of therapy, more COG AYAs received radiotherapy (76% vs. 66%, P =0.03), though in smaller doses (21 Gy vs. 36 Gy). In each group, 3 AYAs developed a second cancer. The 5-year FFS and OS for AYAs on the COG study were 80% and 97%, respectively (see Figure, sections C and D). For survival comparison across studies, COG AYAs appeared to have superior FFS compared with E2496AYAs (P =0.001). In stratified multivariable analyses (controlled for stage, anemia, and bulk), E2496 AYAs appeared to have worse FFS compared with COG AYAs in all strata except among the subgroup of patients with stage I/II without anemia. Furthermore, propensity score analysis with patients exactly matched on stage, anemia, and bulk disease confirmed the inferior FFS for E2496 AYAs compared with COG AYAs (P =0.004). Moreover, the AYA survival disparity across studies persisted after additional covariates were incorporated into the propensity score (i.e., age, gender, B symptoms, and hypoalbuminemia; P =0.026). Conclusions: AYA HL patients treated on E2496 had inferior outcomes compared with older patients (i.e., ages 22 to 44 years) treated within the same study, for unclear reasons, as well as to similarly matched AYA patients treated on COG AHOD0031. These outcomes may result from treatment regimen differences or dose-intensity, differing patient populations or risk profiles, biology, and/or other factors. Prospective examination of these issues in AYA HL patients is warranted. Table 1. Survival Outcomes Within E2496 by Age. PFS 3-yr 5-yr P 17-21 70% 68% 0.005 21-44 79% 76% 45-59 68% 68% 〉 =60 56% 48% OS P 17-21 93% 89% 〈 .0001 21-44 96% 93% 45-59 79% 76% 〉 =60 70% 58% Figure 1. Figure 1. Disclosures Smith: Pharmacyclics: Consultancy; Celgene: Consultancy. Advani:Seattle Genetics, Inc.: Research Funding; Genetech: Consultancy. Horning:Genentech: Employment. Shah:Seattle Genetics: Research Funding; Rosetta Genomics: Other: Grant support; Acetylon: Other: Advisory board; Plexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Spectrum: Other: Advisory board, Speakers Bureau; Bayer: Honoraria; Celgene: Other: Advisory board, Speakers Bureau; DeBartolo Institute for personalized medicine: Other: Grant support. Connors:Roche: Research Funding; Seattle Genetics: Research Funding. Leonard:Weill Cornell Medical College: Employment; Genentech: Consultancy; Medimmune: Consultancy; AstraZeneca: Consultancy; Spectrum: Consultancy; Boehringer Ingelheim: Consultancy; Vertex: Consultancy; ProNAI: Consultancy; Biotest: Consultancy; Seattle Genetics: Consultancy; Pfizer: Consultancy; Mirati Therapeutics: Consultancy; Gilead: Consultancy; Novartis: Consultancy. Gordon:Northwestern University: Employment; Dr Leo I. Gordon: Patents & Royalties: Patent for gold nanoparticles pending.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2636.2636

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7