bluuebunny/crossref_metadata_2025 huggingface dataset:
Concomitant chemoradiotherapy using docetaxel, cisplatin, and 5-FU for the patients with advanced squamous cell carcinoma of the temporal bone.
Authors: Shiga Kiyoto , Katagiri Katsunori , Ogawa Takenori , Kato Kengo , Asada Yukinori , Kobayashi Toshimitsu
Published: March 2020

e16020

Background: Chemotherapy using TPF protocol has been showed efficacy in the neo-adjuvant setting for head and neck squamous cell carcinoma (SCC) so far. However, effectiveness of concomitant chemoradiotherapy (CCRT) using TPF protocol has not yet been clearly distinguished. On the other hand, prognoses of the patients with advanced stage SCC of the ear invading extra-temporal bone were very poor. The aim of this study was to determine the safety and efficacy of newly developed CCRT using TPF protocol in patients with SCC of the temporal bone. Methods: Patients with previously untreated T4 disease were eligible for the study. Eleven patients were enrolled between December 2001 and August 2010. Treatment consisted of radiotherapy administered once daily to a total dose of 70 Gy, concomitant with 120 hour infusions of 5-FU (600 mg/m2/day), docetaxel (50 mg/m2, day 2) and cisplatin (60 mg/m2, day 2) given during first and fifth weeks of radiotherapy. These drug doses were determined from the results of our former phase I study to assess the dose limiting toxicity of this protocol. Median follow-up period was 33 months. Results: Nine patients completed this protocol. Bone marrow suppression was the most common adverse event observed through this study. Grade 4 leukopenia and neutropenia were observed in 1 (9%) and 3 (27%) of the patients and also those grade 3 events were observed in 3 (27%) and 1 (9%) of the patients. Grade 3 lymphopenia and hemoglobin were observed in 7 (64%) and 1(9%) patients. Although all patients showed dermatitis and alopecia at any grade, other grade 3 or 4 adverse events were obviously less than in patients with oropharyngeal or hypopharyngeal cancer using the same treatment protocol during the same period. Complete remission of primary tumor was obtained in all patients but one who rejected second course of TPF. Local recurrences were observed in three patients and one of them underwent salvage surgery. The disease-specific and over-all survival rates at 60 months of the patients were 77.8% and 70.7%, respectively. Conclusions: Our data suggested that CCRT using TPF protocol was feasible and very effective in patients with advanced stage SCC of the ear and temporal bone.
Phase II study: Docetaxel-cisplatin and pro drug tegafur (TPF) as neoadjuvant treatment in advanced patients with head and neck cancer (HNC): Results and correlation between tandem magnesium/creatinine and toxicity.
Authors: Santos Ortega Manuel , Esquerdo Gaspar , Cervera Grau Jose Manuel , Barrajon Enrique , Rodriguez Villalva Silvia , De Piaggio Marina , Peiro Rafael , De Sanctis Rita , Espinoza Venegas Macarena Paz
Published: March 2020

e16025

Background: Due to hospital control difficulties of patients with HNC, a phase II with oral fluoropyrimidines was conducted. Oral administration of 5-FU itself is not feasible owing to the high activity of dihydropyridine dehydrogenase (DPD) in the gut wall. To bypass this problem, oral fluoropyrimidine derivatives were developed in the form of 5-FU prodrugs. This phase II Trial focuses on the oral 5-FU prodrug tegafur to allow similar responses and toxicities. On the other hand a secondary objective was to correlate the effect of CDDP that induces renal injury through multiple pathways. For that reason, the correlation between Mg/Cr and Toxicity was studied. Methods: From 2006 to 2011 seventeen patients with locally advanced head and neck carcinomas were treated in our institution. A phase II clinical trial was conducted as neoadjuvant treatment [docetaxel 75 m2 d-1, cisplatin 75 mgm2 d-1, and tegafur 800 mg twice daily for 14 days, administered every 21 days with GCSF support]. If tumor response, patients received radiotherapy (RT) 70 Gy concomitant with weekly cisplatin 25mg/m2. If no response, palliative surgery or RT or/second line of chemotherapy was administered.) Results: Sixteen were male, one female, three died (2 sepsis secondary to neutropenia grade IV/ 1 secondary to direct tumor complication after 1st course of chemotherapy). Only 14 patients were evaluable for response [mean age was 54,24]. Toxicity grade >2 was present in a range [13,33-21,43%]. Partial responses (PR) were present in 9 patients (52,94%), complete response or no evidence of disease in 3 (17,63%). After RT witth weekly cisplatin the diseas control was 70,57%. An association trend was detected between hypomagnesaemia and a greater toxicity. Conclusions: The implementation of an oral chemotherapy regimen has been feasible and effective with similar results to other studies. The idiosyncrasy of patients with HNC have kept their prized autonomy and independence. A new study is in progress to assess more accurately magnesium levels as predictors of severe toxicities when platinum is used.
Triweekly carboplatin alone in the treatment of oropharyngeal carcinoma with definitive concurrent chemoradiation: Outcomes of 120 unselected patients and a comparison to the RTOG 0129 regimen results.
Authors: Iganej Shawn , Buchschacher Gary L. , Abdalla Iman A.
Published: March 2020

e16031

Background: In 2002, due to the significant toxicities associated with triweekly high-dose cisplatin, we decided to routinely use triweekly carboplatin in the treatment of locally advanced head and neck cancer patients as our standard definitive concurrent chemoradiation drug, the outcomes of which are reported here. Methods: From August of 2002 through May of 2009, newly diagnosed patients with stage III (22%) or IVA/B (78%) oropharyngeal squamous carcinoma were treated with carboplatin (AUC=5) x 3 on days 1, 22 and 43 along with concurrent conventional RT (N=67) or IMRT (N=53) to 70 Gy. Individuals treated with induction chemotherapy or definitive surgery of any kind prior to concurrent chemoradiation, and surviving/recurrence-free patients with less than 24 months of follow-up were excluded, leaving 120 patients for this analysis. The median age was 58 (range 42-85). Feeding tubes were not placed prophylactically. Planned post chemoRT neck dissections were not performed. HPV/P16 status was not determined in any patients prior to treatment. Seventy-one patients (59%) had a significant history of tobacco use, 38 of whom were current smokers. Results: With a median follow-up of 64 months (range 32-108) for surviving patients, 15 (12.5%) had a loco-regional recurrence (LR), and a total of 9 patients (7.5%) failed distantly, including one with simultaneous LR. Only 26 (22%) patients required feeding tubes during or shortly after (< 90 days) chemoRT; 90% received 3 cycles of carboplatin and planned RT dose was delivered in 98%. The 3-year loco-regional control and overall survival rates for the entire group were 88% and 82%, respectively; these rates for 92 patients eligible for RTOG 0129 (T2N2-3, T3-4 any N) were 86% and 77%. At last follow-up, only 3% were feeding-tube dependent. Conclusions: This first ever report of concurrent triweekly carboplatin alone with radiotherapy at a large U.S. institution for locally advanced oropharyngeal carcinoma suggests that it is better tolerated and more feasible than concurrent triweekly high-dose cisplatin, with similar/favorable disease control and survival rates.
Rapidly alternating chemotherapy and radiotherapy in advanced laryngeal cancers.
Authors: Hasegawa Yasuhisa , Fujimoto Yasushi , Yoshino Kunitoshi , Hanai Nobuhiro , Ozawa Taijirou , Hirakawa Hitoshi , Suzuki Hidenori , Ijichi Kei
Published: March 2020

e16032

Background: Rapidly alternating chemotherapy and radiotherapy (ACR) is a minor variation of concurrent chemoradiation (CCR). This scheduling and 5-fluorouracil (5-FU) pretreatment followed by cisplatin (FP) treatment have been tested in advanced laryngeal cancers. ACR allows the simultaneous administration of both treatment modalities without increasing toxicity, while pretreatment with 5-FU induces long arrest in S-phase, and enhances cisplatin cytotoxicity (Cancer Chemother Pharmacol, 2008). We conducted a phase II clinical trial to evaluate these hypotheses. Methods: Eligibility: histologically proven squamous cell carcinoma of larynx with stage III or IV, PS 0-1, age <= 75, adequate organ functions, and no prior chemotherapy. Chemotherapy consisted of administration of continuous infusion of 5-FU at 700 mg/m2/day on days 1-5, and 2-hour infusions of cisplatin at 80 mg/m2/day on day 6 (1st week). Once-daily radiotherapy of 36 Gy in 18 fractions was given starting on day 8 (2nd -5th week). Sequentially, FP treatment was repeated twice (6th week) for responders, and radiotherapy of 30 Gy in 15 fractions was given (7-9th week) in total 66 Gy. Results: From 4/2007 to 11/2010, 27 patients (pts) were enrolled. Patient characteristics were median age of 67 (49-74) years; gender, 26 male and 1 female; subsite, glottis 16 pts (59%) and supraglottis 11 (41%); stage, III 15 pts (56%), IV 12 (44%). 23 responders (85%) completed radiotherapy, and of them 20 pts (87%) received two courses of chemotherapy. 20 primary sites (74%) achieved CR by ACR. 4 non-responders (15%) underwent early salvage surgery. 7 pts had salvage surgery and neck dissection. Toxicity was assessed in all pts: 12 grade 3 events (44%; nausea 7, mucositis 4 (15%) and dermatitis 1). There have been no hematological grade 3 or 4 toxicities. The 3-year overall survival and laryngeal preservation rate were 88% and 65%, respectively. Conclusions: In this ACR trial, the rate of mucosal toxicity was equivalent to or less than those with radiotherapy alone, and the laryngeal preservation was equivalent to CCR in spite of 60% glottic carcinomas.
Feasibility of 6 months of maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck (HNC).
Authors: Matuschek Christiane , Boelke Edwin , Debus Jürgen , Belka Claus , Welz Stephan , Henke Michael , Wendt Thomas , Ohmann Christian , Stegmaier Petra , Bamberg Michael , Wiegel Thomas , Budach Volker , Schipper Joerg , Budach Wilfried
Published: March 2020

e16033

Background: The prognosis for HNC patients (pts) after surgical treatment and adjuvant chemoradiation (CRT) is unsatisfactory in case of close resection margin <5 mm (CM) or extra capsular extent at the lymph nodes (ECE). Therefore we conducted a multicenter phase II study to investigate the toxicity and efficacy of adjuvant radiotherapy (RT) in combination with concurrent cisplatin, 5- fluorouracil (5FU), and cetuximab (CTX) followed by maintenance therapy with CTX for 6 months. Here, we present the preliminary results on feasibility and toxicity. Methods: HNC pts after primary surgery were eligible for the study, if a CM or ECE was detected. Cisplatin [20 mg/m2 d1-5 and d29-33] and 5-FU (CI 600 mg/m2 d1-d5 + d29-33) were given concurrently to postoperative RT using an integrated boost IMRT-technique (1.8/2.0/2.2Gy QD) to a total dose of 61.6 Gy. CTX started 7 days prior CRT with a loading dose of 400 mg/m2 followed by weekly CTX (250 mg/m2) during CRT. Maintenance CTX started after completion of CRT plus CTX with 500 mg/m² every 2 weeks over a 6-month period. Results: 55 of 80 planned pts (46 male, 9 female, mean age 55.6, range 29-70 years) have finished CRT, 50 are evaluable for toxicity. Concurrent CRT plus CTX was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reaction outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). CTX was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts CTX was discontinued during the last 2 weeks or at the end of CRT. Of those pts embarking on maintenance therapy, 80% were still on CTX after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant CRT in combination with CTX followed by maintenance CTX is feasible with toxicity in the expected range. Compliance to maintenance CTX was satisfactory during the first 3-5 months.
Phase II study of postperative radiotherapy (RT), cisplatin (Ci), and cetuximab (Ce) in resected bad prognostic head and neck squamous cell carcinoma (HNSCC): Toxicity analysis.
Authors: Benezery Karen , Righini Christian , Chamorey Emmanuel , Lallemant Benjamin , le Caer Herve , Darloy Franck , Guelfucci Bruno , Dupuis Charlotte , Dassonville Olivier , Peyrade Frederic
Published: March 2020

e16051

Background: Despite toxic multimodal about 60% of resected HNSCC relapse. The addition of both Ce or Ci to RT improved overall survival of patients with HNSCC. Consequently, we designed a prospective phase II study, to evaluate the feasibility and efficacy of concomitant RT-Ci and Ce in bad prognostic resected HNSCC. Methods: Patients have resected HNSCC of the oral cavity , oropharynx, larynx or hypopharynx, and at least one of the following adverse prognostic factors: microscopically incomplete resection, >2 metastatic lymph nodes and/or >1 lymph node with extracapsular spread, vascular and/or lymphatic emboli, >2 perineural invasion, positive margins and pT4. All patients received: RT 70-72Gy in 7 weeks concurrent with Ce 250mg/m² weekly (6-7 weeks), after a loading dose of 400mg/m², and Ci 75mg/m² every 3 weeks x3 cycles. The primary endpoint is the 2 years disease-free survival. Results: 45 patients (35 Male) were enrolled, and 44 were evaluable for toxicity. Median age was 56 years (27-70). The tumor site was oral cavity (21), oropharynx (17), hypopharynx (3) and larynx (4). 39% of the patients had stage T2, 14% stage T3 and 27% stage T4. The nodal status was 0-2b in 80% of cases. The main adverse prognostic factors were the nodal involvement and microscopical positive resection (80% of patients). The RT-Ce-Ci regimen was discontinued in 11 cases including 7 due to toxicity. Among the 352 cycles (ie Ce+/-Ci) initially planned, 301 were delivered. Cutaneous and mucosal toxicity were the most common grade 3/4 side effects, accounting for 35% and 33%, respectively, and remained manageable. Grade 3 lymphopenia has been noted in 25% of cases. No treatment-related death was recorded. Conclusions: The triple association of RT-Ce-Ci appears to be safe and feasible in patients with bad prognostic resected HNSCC. The toxicity profile is comparable to that reported for RT-Ci or RT-Ce alone. Longer follow-up is required to evaluate the impact of addition of Ce to RT-Ci on survival.
Prospective analysis of qol in patients undergoing concurrent chemotherapy and radiation therapy for locally advanced head and neck cancer.
Authors: Blakaj Dukagjin , Godoy-Scripes Paola , Skinner William Kempton , Viswanathan Shankar , Haynes Hilda , Eng Yoko , Sarta Catherine , Haigentz Missak , Schiff Bradley A. , Smith Richard V. , Guha Chandan , Kalnicki Shalom , Garg Madhur
Published: March 2020

e16058

Background: This is a prospective analysis of quality of life (QoL) in patients undergoing concurrent chemotherapy and IMRT for locally advanced head and neck cancers. Methods: In a prospective IRB approved study, patients undergoing concurrent chemotradio therapy for head and neck cancers at AECOM/MMC completed a QoL survey (EORTC QLQ-C30 and QLQ-H&N 35) pretreatment, during radiation therapy, and at 1, 3 and 6 months after completion. The patients were re-simulated for adaptive planning midway through their treatment. Patients were treated to 66-70Gy (2-2.12 Gy/Fraction) to the primary and 54 to 60Gy (1.64-1.8 Gy/fraction) to the subclinical and high risk areas. Swallowing complex (SC) (base of tongue, constrictor muscles, proximal esophagus and oral cavity) were contoured as avoidance structures along with other critical structures. QoL scores were correlated with radiation dose to swallowing complex to evaluate relationships. Results: The Global Heath Status and Physical Functioning scores fell (mean 58.33 SD 35.36) during the first week of therapy before recovering at the end of second week. There is a 2nd dip in functioning scores at 4th week subsequent to which the scores rise and stabilized. The nausea/vomiting scores correlate with the timing of chemotherapy whereas the pain scores are highest at the second week mark before declining gradually. The mean swallowing specific score is worst at 5 weeks (61.11 SD 31.43) and recover gradually thereafter to level better than pre-RT score at 6-months follow-up. Conclusions: Most studies have reported QoL changes before and after treatment and have not looked at the changes during RT. One would imagine that QoL scores would gradually deteriorate throughout radiation therapy and should be the worst towards the end. In our experience, most of the QoL scores stabilize during the latter half of radiation therapy. This may be a result of multidisciplinary patient care, adaptive radiation therapy as well as tumor response to chemo-radiation therapy. Matched pair analysis is underway to compare dosimetric data and correlate this with QoL results.
Disparities in quality-of-life outcomes in immigrant cancer patients.
Authors: Goldstein David , Sze Ming , Bell Melanie , King Madeleine , Jefford Michael , Eisenbruch Maurice , Girgis Afaf , Vaccaro Lisa , Butow Phyllis Noemi
Published: March 2020

e16507

Background: Immigration is increasing world-wide. We explored disparities in quality of life outcomes for immigrant (IM) versus Anglo-Australian (AA) cancer patients having anti-cancer treatment. Methods: In a cross-sectional design, cancer patients were recruited through outpatient Oncology clinics in New South Wales, Victoria, and the Northern Territory in Australia. IM participants, their parents and grand parents were born in a country where Chinese, Greek, or Arabic is spoken and spoke one of those languages. AAs were born in Australia and spoke English. All were diagnosed with cancer < 1 year previously. Questionnaires (completed in preferred language) included the Hospital Anxiety and Depression Scale (anxiety/depression), FACT-G (quality of life) and the Supportive Care Needs Survey (unmet needs). Adjusted regression models comparing AA and IM groups included age, gender, socio-economic status, education, marital status, religion, time since diagnosis, and cancer type (colorectal, breast, lung, other). Results: There were 910 participants (response rate 57%). IM were similar to AA, except that IM were more likely to be married (76 vs 67 %, p = 0.01) and in the low and the highly educated groups (p < 0.0001). In adjusted analyses, IMs had clinically significant higher anxiety, greater unmet information and physical needs and lower quality of life than AAs (see table). The possible ranges are 0-21 for anxiety and depression, and 0-100 otherwise. Conclusions: In this hospital-based study with a high rate of advanced disease, immigrants with cancer experienced poorer quality of life outcomes, even after adjusting for socio-economic, demographic, and disease variables. Interventions are required to improve their experience of cancer care. Results highlight areas of unmet need that might be better addressed by the health system (particularly with regards to provision of information and meeting support and physical needs). [Table: see text]
Did FDA safety warnings and CMS coverage restrictions improve guideline adherence for ESA use for patients with myelodysplastic syndromes?
Authors: Hendrick Franklin , Baer Maria R. , Gore Steven , Weiss Smith Sheila , Davidoff Amy J.
Published: March 2020

e16519

Background: ESAs are used to treat anemia associated with MDS as an off-label indication. Our prior research demonstrated poor adherence to MDS treatment guidelines in US Medicare-insured patients. Concerns of adverse events including tumor progression led the FDA to release safety alerts and mandate label changes in early ‘07. In a rare move, CMS implemented a National Coverage Determination (NCD) in August ‘07, dramatically restricting ESA coverage based on specific clinical parameters (e.g. baseline hemoglobin). As MDS patients were not directly targeted by the NCD, we sought to examine if ESA use changed following these actions. Methods: We selected Medicare beneficiaries with MDS diagnostic codes and receiving a bone marrow aspirate based on 100% enrollment and claims data from 2004-2008. Patients were observed from diagnosis until death or end of study. Through procedures codes on claims we determined the receipt of any ESA within 6 months of diagnosis, whether serum EPO level was measured prior to ESA initiation, whether treatment was of therapeutic duration (>=8 weeks), and whether patients had low transfusion needs (defined based on a measure of transfusion dependence) at ESA initiation. Logistic regression models tested the effect of time (half-year increments pre-post the August ‘07 CMS NCD implementation), controlling for demographics, health status, and supplemental insurance Results: The sample included 36,537 MDS patients; 23,351 (64%) with ESA use. Regression results indicate that relative to Jan-June 2005, ESA use increased through ‘06 (OR 1.22, 95% CI 1.12, 1.33), and declined beginning in August ‘07 (OR 0.71,CI:0.65,0.77). Assessment of serum EPO levels increased beginning in January ‘06, preceding the FDA/CMS actions, ESA use increased among transfusion-users throughout the study period (Jan-June ’08 OR 1.59; CI 1.43, 1.77) though the proportion of patients receiving therapeutic-duration episodes began declining in Jan ‘07 (OR 0.82; CI 0.73-0.91). Conclusions: These results suggest a mixed pattern of change in the face of the FDA safety warnings and CMS NCD in MDS.
Treatment of diseased quality of life in specific dimensions: Effectiveness of quality-of-life diagnosis and treatment in a community-based RCT in women with breast cancer.
Authors: Klinkhammer-Schalke Monika , Koller Michael , Steinger Brunhilde , Lindberg Patricia , Hofstädter Ferdinand , Lorenz Wilfried
Published: March 2020

e16520

Background: Many studies described deficits in quality of life (QoL) in cancer patients. We developed a new pathway with QoL diagnosis and treatment which was implemented as complex intervention with theory building, modeling, exploratory trial and RCT, integrated in a population based (2.1 mio) Tumorcenter. Methods: We conducted a two-armed, randomized clinical trial with 200 breast cancer patients.QoL was measured prospectively in 10 specific dimensions in first year after surgery. Along new QoL pathway patients in intervention group (IG) received QoL diagnosis and treatment consisting of 5 therapeutic options (eg physiotherapy, psychotherapy, social counseling). Members of control group (CG) received standard postoperative care. Primary endpoint was rate of patients with diseased QoL (<50 points on at least one scale with 0=bad, 100=good QoL). χ2-tests were performed to compare rates of diseased QoL (Klinkhammer-Schalke et al, BrJCancer, 2012). Results: At begin of study there were no significant differences in both groups considering QoL. 6 months after surgery rate of patients with diseased QoL was significantly lower for emotion in IG (19.8%) vs CG (38.4%, p=.007), and for global QoL almost reached significance in IG (17.6%) vs CG (29.8%, p=.064). For other dimensions (except family life) there was a trend showing better QoL in IG, but results were not significant. Rates of patients with diseased QoL in 10 dimensions 6 months after surgery in intervention group [%] vs control [%]: Global QoL 17.6% vs 29.8%!, Physical functioning 4.7% vs 5.7%, Role functioning 26.4% vs 29.9%, Arm symptoms 13.8% vs 23.3%, Body image 13.8% vs 22.1%, Pain 19.5% vs 24.4%, Emotion 19.8 %vs 38.4%xx, Concentration, remembering 10.5% vs 17.4%, Fatigue 37.9 %vs 46.5%, Family life, social encounters 17.4% vs 16.3% (χ2-test: p<.10!, p<.01xx). Conclusions: Results confirm effectiveness of QoL pathway: 6 months after surgery IG showed better QoL in 2 important dimensions. Lower rates of diseased QoL in other dimensions support the result. Cancer patients will benefit from the QoL system implemented in clinical routine (long term implementation).
Evaluating the impact of a trial in breast cancer tumor markers: A value of research analysis.
Authors: Thariani Rahber , Blough David K , Barlow William , Henry Norah Lynn , Gralow Julie , Ramsey Scott David , Veenstra David L
Published: March 2020

e16524

Background: Despite not being recommended by clinical guidelines, the tumor markers carcinoembryonic antigen (CEA), cancer antigen (CA)15-3, and CA 27.29 are used by some clinicians to screen for increased risk of breast cancer recurrence. Although additional research may be warranted to evaluate the benefits and risks of breast cancer tumor marker tests, clinical trials would likely need to involve thousands of women and would take many years to complete. We conducted an analysis to assess the societal value of a prospective randomized clinical trial (RCT) for breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors Methods: We used value of information techniques to assess the benefits of reducing uncertainty of using breast cancer tumor markers. We developed a decision-analytic model of biomarker testing in addition to standard surveillance at follow-up appointments every 3-6 months for five years. Expected value of sample information (EVSI) was assessed over a range of trial sizes and assumptions. Results: The overall value of research for an RCT involving 9,000 women was $166 million (EVSI). The value of improved information characterizing the survival impact of tumor markers was $81 million, quality-of-life $38 million, and test performance $95 million. Conclusions: Our analysis indicates that substantial societal value may be gained by conducting a clinical trial evaluating the use of breast cancer tumor markers. The most important aspects of the trial in our analysis were information gained on survival improvements as well as quality-of-life parameters associated with testing and test sensitivity and specificity. Our analysis indicates that smaller randomized trials, as well as adding quality of life instruments to existing trials, retrospective, and observational trials can also generate valuable and relevant information.
Impact of computerized provider order entry on medication errors in chemotherapy administration.
Authors: DeMoor Patricia A , Bazhenova Lyudmila
Published: March 2020

e16535

Background: Computerized provider order entry (CPOE) reduces medication errors (ME) in ambulatory prescriber and hospital settings. We conducted a study to assess the effect of CPOE on ME in an outpatient NCI designated academic infusion center (IC). Methods: Both actual and prevented ME were reported by clinical staff as part of IC Standard Operating Procedure using the electronic Quality Variance Reporting (eQVR, Incident Reporting 2.0, University of California) system. Reported ME from 10/2007 to 03/2011 were reviewed by 2 investigators and classified into categories by consensus: wrong medication given (WM), medication missed (MM), wrong timing/rate (T/R), wrong dose (WD), unmet chemotherapy parameters (UP) and other (O). Classifications were further categorized by preventable or facilitated by CPOE. We compared ME 18 mo. pre and post implementation. The 6 month go live period was reviewed separately to examine ME related to a learning curve (LC). Results: 40,366 patients were seen pre-implementation, 47,460 post, and 14,343 during go live. The total ME per pt was similar pre and post (see table). There were dramatic rate differences in WM and MM, but no effect on T/R, WD, UP. In the pre period 66% of ME were felt preventable by CPOE. In turn 35% of ME were facilitated by CPOE. Preventability rates differed between categories. During go live 100% of CPOE facilitated ME were related to user and designer LC. Post implementation 58% of CPOE facilitated ME were still accounted by LC with the rest felt related to the complexity of CPOE. Conclusions: ME are rare in our outpatient oncology IC. CPOE did not change the total number of ME but significantly decreased the rate of WM. Complexities of CPOE resulted in increased MM. LC related errors still occur 24 mo. after implementation of CPOE and require constant monitoring and education. CPOE increased the rate of serious ME felt due to the change in workflow and adding an extra layer of complexity. Human errors cannot be fixed with CPOE and generally encompassed the ME in T/R, WD, and UP classifications. [Table: see text]
The incremental economic burden of clostridium-difficile associated diarrhea among hospitalized immunocompromised patients undergoing chemotherapy.
Authors: Quimbo Ralph A. , Palli Swetha , Strauss Marcie , Thomas Sheila
Published: March 2020

e16542

Background: Hospital-acquired Clostridium-difficile associated diarrhea (CDAD) results in an estimated $1.3 billion in excess costs in the US. Patients undergoing chemotherapy are at elevated risk of CDAD due to diminished immune response and increased exposure to health care facilities. This study describes the incremental economic burden of CDAD in hospitalized immunocompromised (IC) patients. Methods: IC cases (undergoing chemotherapy or other qualifying conditions) hospitalized with a diagnosis of CDAD having ≥12 months of prior health plan eligibility and age ≥18 years between 1/1/2005 and 10/31/2010 were identified from the HealthCore Integrated Research Database (HIRDSM). Cases were matched to hospitalized IC controls without CDAD diagnosis based on: age±10 years, gender, selected preceding/in-hospital comorbidities and use of antibiotics. Incremental hospital length of stay (LOS) and costs were calculated between matched cases and controls via multivariate methods using a Gamma distribution. Covariates were determined from post-match univariate analysis of baseline characteristics. Results: 3,586 cases were matched to 10,758 controls. Chemotherapy occurred among 91.3% of cases and controls. While age (65±15), gender (53% female), and selected comorbidities were balanced between cases and controls, post-match disparities persisted (p<.001): geographic region (37% vs. 32% Midwest), type of health plan (24 vs. 18% HMO), overall comorbidity burden (6.0±3.6 vs. 6.5±3.7 Deyo-Charlson Comorbidity Index). Cases had a lower incidence of mortality during their index hospitalization (6.7% vs. 7.8%; p<0.0001). Adjusted hospital LOS was significantly greater for cases vs. controls (22.1 days (20.61 to 23.69) vs. 13.67 days (12.74 to 14.67); p<.0001). Incremental hospitalization costs indicated a significantly greater economic burden among cases vs.controls (Δ = $32K ($29K to $35K); p<0.0001). Conclusions: This study indicates that the acquisition of CDAD among immunocompromised patients, of which chemotherapy recipients represented the majority, presents significant incremental economic burden within the hospital setting.
Performance teamwork training in ambulatory oncology.
Authors: Gross Anne , Mann Susan , Kalfin Michael , Lane Sharon , Weingart Saul , Bunnell Craig A.
Published: March 2020

e16559

Background: Increasingly complex diagnostic and multimodality treatment algorithms have yielded superior outcomes, but also magnified the risk for adverse events precipitated by failures of communication and coordination. We implemented team training principles in 14 outpatient oncology practices across 3 campuses (community and academic) to reduce the risk of errors and increase operational efficiency and quality. Methods: Over 950 physicians, nurses, pharmacists, and staff were trained in evidence-based concepts of teamwork. Intervention included 1) baseline data collection regarding key clinical processes, (e.g. non-communication of same-day chemotherapy order changes); 2) observations/interviews with care team members; 3) process meetings to identify vulnerabilities and develop agreements and tools to support them; 4) Train the Trainer methodology; 5) staff training; 6) post-training data collection. Results: Despite the infrequency of non-communicated same-day changes in chemotherapy orders at baseline (~2%), a trend toward improvement was seen (chi-square p=0.068). The incidence of missing chemotherapy orders for infusion visits not associated with an MD visit decreased significantly. Staff reported improved practice efficiencies and a more respectful, safer environment. Press Ganey patient-reported perceptions of teamwork improved significantly. Conclusions: Team training improved communication, task coordination, perceptions of efficiency, quality, safety and interactions among team members, as well as patient perception of teamwork in both community and academic environments of a comprehensive cancer center. [Table: see text]
Intervention to increase site activations for multicenter trials to improve accrual.
Authors: Massett Holly , Jaeckle Kurt A. , Hopkins Jenny R , Mann Bhupinder Singh , Denicoff Andrea , Dilts David M.
Published: March 2020

e16569

Background: The National Cancer Institute’s (NCI) Cancer Trials Support Unit (CTSU) provides access to NCI-sponsored trials. To participate in a multi-center trial, sites must first complete the trial’s Protocol Specific Requirements (PSRs); interested sites are listed as “pending” in the CTSU database until all PSRs are completed. The aim of this investigation was to examine site activation delays for a study with multiple start-up steps and evaluate an intervention directed at helping sites more rapidly open it to patient accrual. Methods: NCCTG N0577, an anaplastic glioma trial named CODEL, was identified as a slow accruing trial with many sites listed as pending activation in the CTSU’s database (>85%; n=227 pending). Most N0577 pending sites had 1-2 incomplete PSRs (with 75% requiring only a neurocognitive certification), and we suspected that sites were not aware of these requirements. To accelerate site activation for N0577, we created an intervention using Awareness Theory. First, N0577 was amended to streamline the neurocognitive certification process. We then generated email lists of the 227 pending sites’ PIs (n=21; note: many were PIs of multiple sites) and their respective administrators (n=46), and created tailored email notices by PSR category explaining the necessary steps to complete N0577 activation at their site or to report their site as not planning to participate. Emails were sent to sites via the CTSU. Results: 31 sites (14%) registered activity for N0577 within 3 weeks of the intervention. Of these, 22 changed status to “approved,” 2 were disapproved, 1 withdrew, and 6 made changes but remained pending. This represents a marked increase (+520%) in site activity of the CTSU Regulatory Support Service (RSS) for N0577, compared with the monthly average (5 events/mo) during the preceding 6 months. Accrual is being monitored to observe for any increases and will be reported. Conclusions: Complicated and incomplete PSRs delay site activation of multi-center trials and may impact accrual. Streamlining PSR processes and early monitoring of CTSU site activation with notifications to sites of outstanding PSRs for trials can increase the timeliness of sites opening trials, with the potential to improve accrual.
A case report of long-term complete remission following cessation of romiplostim dosing in a previously severe ITP patient.
Authors: Baxley Allison Ashley , George James N , Terrell Deirdra , Moorman Meredith , Holter Jennifer L.
Published: March 2020

e17001

Background: Primary Immune thrombocytopenia(ITP) is a chronic autoimmune disorder characterized by low platelet counts and bleeding complications. Platelet destruction together with insufficient platelet production occur through an antibody-mediated process and early treatment options revolve around targeting antibodies and immunologic pathways. Such therapies may not produce long-term responses and may be accompanied by considerable adverse effects which can lead to complications and/or drug discontinuation. Romiplostim is a thrombopoietic agent that stimulates platelet production and offers an alternative method for treatment of patients with ITP. In clinical trials, patients have achieved durable platelet count responses without clinically important side effects. Methods: We report the case of a 44 year-old female with refractory ITP who has achieved successful remission following treatment with romiplostim. Results: As previously described in Haematologica (2008;93:1445) this patient presented with purpura, menorrhagia, and a platelet count of 7,000. Throughout 2005 she had only transient responses to high dose dexamethasone, intravenous immunoglobulin, rituximab, and splenectomy. She was placed on romiplostim in August 2005 as part of a clinical trial and received a dose of 7 mcg/kg/week for approximately 50 weeks. She was able to tolerate dose reductions and by May 2007 her dose had been de-escalated to 3 mcg/kg/week, which she continued through 2009 as part of an open-label continuation study. In January 2010, after completion of the clinical trial, she began receiving romiplostim by prescription. She was able to gradually tolerate extended dosing intervals due to sustained platelet response. Her last dose was administered on October 27, 2010 and she has maintained a platelet count above 197,000 without further therapy. Conclusions: This case represents, to our knowledge, one of the longest maintained durable responses to romiplostim therapy. Romiplostim provides an alternative approach of treatment for ITP, and as evidenced by this case report, in some patients it may also lead to disease remission and eliminate the need for further treatment.
Phase II trial of daily pulse interleukin-2 (IL-2) therapy during marrow recovery in patients with acute myeloid leukemia (AML) NCT#01289678.
Authors: Kamdar Manali K. , Asch Adam Steven , Unger Jackie , Walker Paul R.
Published: March 2020

e17008

Background: Therapeutic advances in treating AML have been limited in the past two decades. Allogeneic stem cell transplant (Allo-SCT) can cure patients with relapsed and high-risk AML with a graft versus leukemia immune effect. IL- 2 promotes the proliferation and activity of cytotoxic T cells, natural killer cells and lymphokine activated cells. IL-2 has been shown to abrogate the clonogenic leukemic blasts in murine leukemias and has achieved complete remissions in relapsed AML. Early absolute lymphocyte recovery after induction chemotherapy predicts a superior survival in AML suggesting a critical role of early immune recovery. (Behl et al Leukemia 2006) Stimulated LAK cells by IL-2 during this critical early lymphocyte recovery period may enhance a graft versus leukemia immune effect and potentially improve the outcome of first-line AML treatment. Methods: 12 adult patients with de novo or secondary AML were consented to receive IL-2 during induction and/or post-remission treatment marrow nadir recovery. The eligibility criteria included a rising WBC count >500mm3, supported platelet count >20,000 and hemodynamic stability. IL-2 18 million IU/m2 was administered over 15-30 minutes daily for 5 days within 7 days of a WBC rising above 500mm3. Primary end point overall survival (OS). Median age 52 yrs. (range 33-72). Results: 3 pts. received IL-2 during induction recovery; 3 during re-induction recovery, 3 during consolidation recovery. 1 pt. subsequently underwent an Allo-SCT in remission. Median OS 25 months. With a median followup of 36 months (range 12-60 months), 5 of 9 (55%) treated pts. and 4 of 8 (50%) pts. without an Allo-SCT, are alive and leukemia free. Of the 5 alive, 3 are over the age of 60 and 2 had complex cytogenetics. Expected toxicities with IL-2 included grade 3 fever/chills (77%) but there were no respiratory or hemodynamic complications requiring ventilator support. Conclusions: IL-2 therapy administered during marrow/lymphocyte recovery after standard induction/consolidation chemotherapy in first-line AML treatment achieved a 50% 3-year overall and leukemia free survival without an Allo-SCT.
Hypoplastic MDS with PNH clone treated successfully with eculizumab.
Authors: John Sonia , Parekh Hiral D. , Qubaiah Osama M. , Selby George Basil , Holter Jennifer L.
Published: March 2020

e17010

Background: Myelodysplasia (MDS) is a myeloid clonal disorder characterized by dysplastic and ineffective hematopoiesis. Hypoplastic MDS is a rare variant found in <15 % of MDS patients.Severe aplastic anemia (SAA) is defined as <10% marrow cellularity associated with pancytopenia. Paroxysmal nocturnal hemoglobinuria (PNH) an acquired clonal hematopoietic disorder presenting as chronic intravascular hemolysis, venous thrombosis, deficient hematopoiesis and can be found in both SAA and MDS. PNH can be diagnosed by measuring the surface markers for phosphatidylinositolglycan (PIG),CD59, CD55 and CD14. In clinical practice, these three diagnoses have significant overlap with unclear thresholds for the level of clone for which therapy should be directed. Methods: We present a 69 year old patient who was found to have hypoplastic MDS/SAA by bone marrow biopsy and flow cytometry with no chromosomal abnormalities.Treatment with Anti-thymocyte globulin (ATG) and cyclosporine (CSA) was initiated. He achieved transfusion independence and was in complete remission for 6 months. He developed recurrent thrombocytopenia and was retreated with ATG & CSA with minimal improvement. He remained transfusion dependent.Repeat BM biopsy showed persistent hypoplastic MDS/SAA. PNH evaluation showed a small clone of PIG deficient cells quantified as 0 % red cell, 2% granulocytes and 0.9% monocytes which was negative at initial diagnosis. Eculizumab was instituted weekly for the last 18 months.Transfusion independence was obtained within 2 months with significant improvement in all cell lineages. BM biopsy performed 4 months after therapy showed hypercellular marrow. Patient continues to be treated with eculizumab and has maintained a complete remission for over 18 months. Results: The diagnosis hypoplastic MDS/aplastic anemia is usually highly sensitive to therapy with ATG and CSA. Although our patient initially responded to ATG, retreatment was not successful. Eculizumab has documented a significant and sustained response in this patient’s treatment. . Conclusions: We report a patient with less than 1% PNH clone that achieved complete transfusion independence with eculizumab and full resolution of hypoplastic MDS/SAA by marrow histology.
Allogeneic hematopoietic stem cell transplantation to improve survival in acute myeloid leukemia patients with FLT3 internal tandem duplication.
Authors: Lin Po-Han , Yang Hwai-I , Bai Li-Yuan , Yeh Su-Peng , Chiu Chang-Fang
Published: March 2020

e17014

Background: Fms-like tyrosine kinase (FLT3) gene with internal tandem duplication (ITD) is a poor prognostic factor in patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) is considered as an effective treatment for AML patients with poor risk. However, the efficacy of allogenic HSCT in the treatment of AML patients with FLT3-ITD was not clear. Methods: A total of 122 patients, who were newly diagnosed as de novo AML and received intensive chemotherapy at China Medical University Hospital between 2003 January and 2010 December, were retrospectively analyzed. At diagnosis, all patients received French-American-British (FAB) classification, cytogenetic analyses and immunophenotyping. The HSCT was performed on the basis of the consensus of the hematologists in this institute, mainly according to the two factors: unfavorable karyotype and suitable donor availability. The FLT3-ITD was detected by polymerase chain reaction and confirmed by direct sequencing. The Cox proportional hazards regression analysis was used to estimate the hazards ratios of the overall survival and corresponding 95% confidence interval (CI) for various combinations of FLT3-ITD and HSCT status. Results: An FLT3-ITD was detected in 34 patients (27.9%). The allogeneic HSCT was performed in 39 patients; 29 patients with wild type (wt)-FLT3 and 10 patients with FLT3-ITD. The number of death/number of patients (medium overall survival) of wt-FLT3/HSCT(+), wt-FLT3/HSCT(-), FLT3-ITD/HSCT(+) and FLT3-ITD/HSCT(-) was 12/29 (53.4 months), 25/59 (40.7 months), 3/10 (medium not reached) and 17/24 (12.0 months), respectively (p=0.014). Comparing with wt-FLT3/HSCT(-) patients, the hazard ratio (95% CI) of overall survival for wt-FLT3/HSCT(+), FLT3-ITD/HSCT(+) and FLT3-ITD/HSCT(-) was 1.39 (0.61-3.18), 0.40 (0.11-1.49), and 3.57 (1.58-8.09), respectively, after adjustment of age, sex, WBC, LDH, karyotype and FAB classification. Conclusions: AML patients without FLT3-ITD had better survival than those with FLT3-ITD regardless of the allogeneic-HSCT. The allogeneic HSCT may improve overall survival in AML patients with FLT3-ITD.
Clinicopathologic and survival analysis of patients with lung cancer treated at a tertiary care centre in India.
Authors: Raina Vinod , Malik Prabhat Singh , Mohanti B. K , Sharma Mehar C , Mohan Anant , Deo S. V. S , Shukla N. K
Published: March 2020

e17505

Background: Lung cancer ranks among the most common and lethal malignancies worldwide and also in India. There are geographic and ethnic variations in incidences, clinical and pathological profile of lung cancer. There is paucity of data of changing trend of pathological and clinical profile from this part of the world. Methods: A total of 434 patients with lung cancer were analyzed who were registered at All India Institute of Medical Sciences, over a 3 year period, from July 2008 till June2011, based on information in hospital records. Survival analysis was performed on 310 patients who have received at least one modality of treatment. Results: Median age of the whole cohort was 55 years (23-84 years). There were 357 (82.26%) males and 77 (17.74%) females, 295(69.91%) smokers and 127 (30.09%) non smokers. 370 (85.25%) patients had NSCLC and 64 (14.74%) had SCLC. Among NSCLC, adenocarcinoma was the commonest histology (45.41%) followed by squamous cell carcinoma (29.46%) and unclassified NSCLC (20.54%). Majority (66.13%) of the diagnosis were based on biopsy (needle or bronchoscopic). Among NSCLC, 26.3% patients were of stage 1-3A and 73.7% were of stage 3B and 4. Among SCLC 25% patients were of limited stage and 75% patients were of extensive stage. 73.18% of NSCLC patients received chemotherapy, 19.15% received TKI and 5.75% received RT as first line treatment modality. Among SCLC 93.88% received chemotherapy and 6.12% received RT as first line treatment. Median PFS and OS of patients with NSCLC were 7.8 months and 13.2 months respectively while that of SCLC were 6.1 months and 9.2 months respectively. Conclusions: Pathological profile of lung cancer has changed in India. Adenocarcinoma has become the commonest histology, contrary to the older reports when squamous cell carcinoma was more common. Majority of the patients are diagnosed in advanced stage and survival of these patients remains poor.