bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of prognostic factors with cervical squamous cell carcinoma after neoadjuvant chemotherapy
Authors: Hayashi S. , Fujii T. , Nakamura M. , Hirao N. , Nakagawa H. , Fukuchi T. , Kubushiro K. , Tukazaki K. , Aoki D.
Published: March 2020

15060

Background: The purpose of the study was to evaluate retrospectively the clinical effects of neoadjuvant chemotherapy (NAC) given to women with cervical squamous cell carcinoma using the response rates, prognostic parameters, and diagnostic imaging data (CT scan or MRI). Methods: Patients included in the study were 32 women with a mean age of 48.8 ± 10.6 who had stage Ib-IIIb cervical squamous cell carcinoma and was treated initially with platinum-based NAC prior to surgical intervention at our institution between 1994 and 2003. The response rates in these patients were assessed, and a statistical analysis was performed to evaluate the effects of NACT on survival rates and disease recurrence using the following 9 parameters: 1. clinical stage of cancer, 2. lymph node metastasis, 3. blood vessel invasion, 4. parametrial involvement, 5. depth of stromal invasion, 6. tumor diameter, 7. pre- and post-treatment serum levels of the squamous cell carcinoma antigen, 8. age, and 9. rates of response to NAC. CT scan or MRI obtained prior to and after NAC were compared and evaluated for any evidence of lymph node metastasis. Results: Five and 18 patients achieved complete response (CR) and partial response (PR), respectively, with a response rate of 71.8% for these CR and PR patients. A multivariate analysis revealed that lymph node metastasis was the only independent prognostic parameter for survival rates and disease recurrence. In 13 patients in whom lymph node metastasis was found by the was found by the CT scan or MRI prior to NAC, 8 (61.5%) still showed the evidence of metastasis after treatment. Among these, 7 (87.5%) actually had metastatic lymph nodes. In addition, the occurrence of lymph node metastasis was unrelated to rates of response to NAC. Conclusions: The rates of response to NAC dose not predict prognosis in patients with cervical squamous cell carcinoma. The occurrence of lymph node metastasis is unrelated to rates of response to NAC. If metastatic lymph nodes are suspected after NAC, appropriate treatment approaches should be well considered in such patients.

No significant financial relationships to disclose.
Borderline ovarian tumors: A study of 100 cases
Authors: Taner C. E. , Oztekin M. , Mun S. , Sehirali S. , Büyüktosun C. , Basogul O.
Published: March 2020

15069

Background: The purpose of the study was to evaluate the patients with borderline ovarian tumors. Methods: Clinical features, treatment and survival status of 100 patients with borderline ovarian tumors were retrospectively evaluated between 1998 and 2005. Results: Mean age was 37.75 (Range: 15–72) years. 22 cases were in postmenapausal status. Histopathological diagnosis was serous, musinous, endometrioid and clear cell in 54%, 41%, 2%, 3% of the patients, respectively. 19 cases underwent restaging laparotomy. In 52 cases fertility sparing surgery was performed. 70 patients had stage IA, 8 patients had stage IB, 16 cases had stage IC, 2 cases had stage IIIA, 3 cases cases had stage IIIB and a case had stage IIIC disease. 22 cases were administered chemotherapy because of advanced stage disease. All cases were alive. 5 year disease free survival of 51 cases was 100%. Conclusions: Borderline ovarian tumors have excellent prognosis and conservative surgery can be performed in young patients with early stage disease.

No significant financial relationships to disclose.
Early necrosis following concurrent temozolomide and radiotherapy in adult patients with glioblastoma
Authors: Chamberlain M. C. , Glantz M. J. , Chalmers L. , Van Horn A. , Sloan A. E.
Published: March 2020

1513

Background: Concurrent temozolomide (TMZ) and radiotherapy (RT) is the new standard of care for patients with newly diagnosed glioblastoma GBM). This report is a prospective observational study of surgically confirmed early necrosis in adult patients with GBM treated with concurrent TMZ and RT and post-RT TMZ. Methods: 52 consecutive patients (33 males; 19 females) ages 34 to 69 years (median 60), with newly diagnosed GBM were treated with surgery (complete resection in 40%, incomplete in 33%, biopsy in 27%) followed by concurrent TMZ and RT (median tumor dose 60Gy) followed by planned 6 cycles of monthly TMZ. TMZ was administered as 75mg/m2/day for 42 consecutive days with radiotherapy followed by 200mg/m2/day for 5 consecutive days every 28 days. Neurological evaluations were performed monthly and cranial MR bimonthly. Results: 26 patients (50%) manifested clinical and neuroradiographic evidence of tumor progression within 6 months of completing RT. 15 patients (28%) underwent reoperation with image verified complete resection. Histopathology was interpreted as necrosis without evidence of tumor in seven patients (13%). Conclusion: The patients in this study with early necrosis suggest a potential and perhaps significant chemo- radiosensitization effect in a subset of patients treated with this regimen of concurrent TMZ and radiotherapy that may predict for durable responses and contribute to the regimens observed benefit in patients with newly diagnosed GBM. Clearly, confirmation of this preliminary observation of unexpected and common early necrosis using concurrent TMZ and radiotherapy in a larger GBM population is required.

[Table: see text]
Evidence-based review of intrathecal chemotherapy in outcome of patients with leptomeningeal metastasis
Authors: Rogers L. R. , Chamberlain M. , Glantz M.
Published: March 2020

1529

Background: Intrathecal chemotherapy (ITC) is commonly employed to treat leptomeningeal metastasis (LM). An evidence-based literature review supporting this practice is lacking. We therefore searched the literature for evidence of efficacy of ITC on LM patient outcome in order to provide evidence-based treatment recommendations. Methods: Computer-assisted searches of the Medline and Cochrane Library databases were performed. Only prospective, randomized, controlled trials in which ITC chemotherapy was used to treat LM were selected. Study design, patient characteristics, interventions, and outcome measures were independently compiled by each of the authors using customized data extraction forms. Each article was assigned a class of evidence by each of the authors. Disagreements were resolved by consensus. Results: Five articles met the criteria. Four studies compared different ITC regimens. One compared ITC to controls who did not receive ITC. Study populations included solid tumors (3 [2 of these included lymphoma]), lymphoma only (1), breast cancer only (1). Positive CSF cytology was a requirement for study entry in three trials. In each trial patients were allowed to receive CNS radiation as needed and non-investigational chemotherapy to treat the underlying cancer. Outcome measures included neurological status (5), survival (5), toxicity (5), CSF cytology (4), cause of death (3), time to neurologic progression (3), and quality of life (2). All studies lacked masked outcome assessment, and some suffered from additional design flaws including insufficient size, inequalities in baseline characteristics, inadequate characterization of treatment arms, and poor choice or definition of primary endpoints. Consequently, all studies provided only Class III evidence. Conclusions: There is no Class I or II evidence that ITC improves outcome in patients with LM. Improved quality of life, survival, or time to neurologic progression in treatment responders vs. non-responders in some of these trials provides a weak suggestion that effective therapy improves clinical outcome. Well-designed, adequately powered studies are urgently needed to determine efficacy of ITC in LM.

No significant financial relationships to disclose.
Superiority of bi-dimensional measurements compared to RECIST in measuring response of metastatic brain tumors
Authors: Kilpatrick M. R. , Linn N. U. , Smith J. K. , Winer E. P. , Bullitt E. , Carey L. A. , Ewend M. G.
Published: March 2020

1542

Background: Criteria for measuring response rates of brain metastases are not well established. Unilateral (RECIST), and bilateral (WHO) criteria were developed to approximate tumor volume, which is the gold standard but difficult to measure. We compared WHO and RECIST criteria to volumetrics in patients with metastatic breast cancer lesions in the brain treated with lapatinib. Methods: MRI data from 20 patients enrolled in a prospective phase II study at UNC-Chapel Hill, the Dana-Farber/Harvard Cancer Center, and Georgetown were retrospectively analyzed. Post-gadolinium MRI images were analyzed at baseline and at 2 month intervals over a 7 month period. 196 lesions were analyzed for tumor size using one-dimensional (single greatest diameter), bidimensional (product of 2 longest diameters in perpendicular dimensions), and volume (calculated with an institutionally-derived software program) measurements. Tumor response was classified according to WHO and RECIST criteria. Progressive disease required a >20% increase, partial response >30% decrease, and stable disease for those in between. Similar definitions for volume measurements were used. Results: 3 of 20 patients were excluded as the diffuse metastatic nature of their tumors and small size prevented application of the RECIST or WHO measurement criteria. RECIST correctly predicted volumetric response or progression in 12/17 cases, but was delayed by either one or two scan cycles in reaching that conclusion in 3 of these 12 cases. WHO criteria correlated with volumetrics in 16/17 cases with a delay of one scan interval in a single case. The delay in correct identification of response category was particularly noticeable in identifying progressive disease with RECIST as compared to volumetrics. RECIST was only 50% specific for progressive disease at the time that progression was documented with volume. WHO was 90% specific. Both methods were sensitive to clinical benefit (SD + PR) (RECIST 86%; WHO 100%). Conclusions: For metastatic brain tumors that are large enough to be measured with linear criteria, WHO bidimensional criteria appear superior to unidimensional RECIST measurements in predicting volumetric response of tumors. Supported by EB000219-NIBIB and UNC Breast SPORE CA58223.

No significant financial relationships to disclose.
Spinal myxopapillary ependymoma outcomes in patients treated with surgery and radiotherapy at M. D. Anderson Cancer Center
Authors: Akyurek S. , Chang E. L. , Yu T. , Little D. , Allen P. K. , McCutcheon I. , Mahajan A. , Maor M. H. , Woo S. Y.
Published: March 2020

1547

Background: Myxopapillary ependymomas (MPEs) are a distinctive variant of ependymomas both clinicopathologically and genetically. These tumors usually occur in the lumbosacral/cauda equina region. Most spinal ependymoma series published in the literature included a few patients with MPEs. In this study, we report the outcomes from a single institutional experience with 35 spinal MPEs treated with either surgery alone or with adjuvant radiotherapy (RT). Methods: The medical records of 35 patients with MPE treated at The University of Texas M. D. Anderson Cancer Center between December 1968 and July 2002 were reviewed. The median age of patients in this series was 35 years (range, 14–63 years) and the male to female ratio was 2.5:1. Twenty-one patients (60%) underwent a gross total resection, 13 (37%) a subtotal resection, and 1 (3%) a biopsy only; 22 of these patients (63%) also received adjuvant RT. The endpoints analyzed were progression-free survival, overall survival, and local control. Results: The median follow-up was 10.7 years. The 10-year OS, PFS and LC rates for the entire group were 97%, 62%, and 72% respectively. Twelve patients (34%) had disease recurrence, all in the neural axis; 8 patients had treatment failure at the primary site only, 3 in the distant neural axis only, and 1 at the primary site and in the distant neural axis. Older patient age (≤35 vs. >35 years; p=0.002) and initial treatment modality (surgery vs. surgery + adjuvant RT; p=0.04) showed significant impact on PFS. Conclusions: The long-term patient survival duration for MPE managed with surgery and adjuvant RT is favorable. Regardless of the extent of resection adjuvant RT appears to significantly reduce the rate of tumor progression. Failures in this series occurred exclusively in the neural axis, mainly at the primary site.

No significant financial relationships to disclose.
Concurrent chemoradiotherapy (crt) with weekly docetaxel (d) for advanced head and neck cancer
Authors: López-Argumedo G. , López-Vivanco G. , Fernández R. , Díaz de Corcuera I. , Sancho A. , Rubio I. , Martínez-Bueno A. , Mañé J. , Muñoz A. , Barceló R.
Published: March 2020

15516

Background: Concomitant CRT has become a standard treatment for advanced head and neck cancer. The aim of this study was to evaluate the efficacy and toxicity of concurrent CRT with D in patients (pts) with advanced squamous cell carcinoma of head and neck (SCCHN). Methods: Patients with untreated and unresectable stage III or IV (M0) squamous cell carcinoma of head and neck were included. Treatment consisted of D 20 mg/m2 weekly with concomitant radiotherapy 70 Gy (2 Gy per day, 7 weeks). Results: From September 03 to October 05, sixty-four pts with advanced SCCHN, were recruited. Gender: 61 male, 3 female. Mean age: 56.5 years old (range 42–77). ECOG PS 0/1/2: 0/57/7. Primary sites of disease: oral cavity 8, oropharynx 26, hypopharynx 15 and larynx 15. Stage III 16 pts and stage IV 48 pts. Compliance: 393 administrations of D were given, median 6, mean 6 (range 1–8). Fifty-five pts (86%) completed the radiotherapy dose planned (mean dose of RT was 66 Gy). One refused more treatment with D after first administration. Nineteen pts required supportive percutaneous gastrostomy or nasogastric tubes previously or during therapy. Grade 2/3/4 toxicity per patient: anemia 4/2/0, mucositis 21/24/0, dermatitis 21/20/0. Neither thrombopenia nor neutropenia were observed. Four pts died of aspiration pneumonia during treatment, one of gastric perforation and two of unknown causes. Fifty-six pts were evaluable for response: CR 28 (44%), PR 23 (36%), SD 2 (3%), PD 3 (5%), with an overall response rate of 80%. Median overall survival was 74.86 weeks (95% CI: 40.40–109.32) and median progression free survival was 48 weeks (95% CI: 18.80–77.20). With a median follow up of 40 weeks 34 pts (53%) were alive and 21 of them (33%) remained free of disease. Conclusions: Concurrent weekly D with conventional radiotherapy showed a high response rate. Toxicity was manageable and allowed maintaining radiotherapy administration. Taking into account poor prognostic factors of our series, survival results seem promising.

No significant financial relationships to disclose.
A phase II trial of stereotactic radiosurgery boost following surgical resection for solitary brain metastases
Authors: Narayana A. , Chan K. , Brennan C. , Chang J. , Higgins V. , Lymberis S. , Yamada J. , Gutin P. H.
Published: March 2020

1552

Background: At present there is no standard of care for adjuvant therapy following resection of solitary brain metastases. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a surgery-stereotactic radiosurgery (SRS) combined therapy approach while avoiding upfront whole brain radiation therapy (WBRT). Methods: The eligibility criteria included radiologically proven solitary brain metastases, KPS≥70 and a neurologic function score of 0–2. Following the surgical resection, SRS was delivered to the surgical cavity 4–8 weeks later to a dose of 15–22 Gy in a single fraction using the BrainLAB linear accelerator system. Patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. Results: 25 out of 50 patients needed for the study have been accrued since it opened in August 2004. Four patients have failed locally, with a median time to local failure of 9.5 months. The one year local control at the site of original disease was 35%. Two of the four patients who had local recurrence at the time of relapse also had evidence of leptomeningeal disease. Six additional patients developed new brain metastases, resulting in a 1 year brain relapse free survival of 38% following the combined approach. The median overall survival was 12 months. One patient (4%) developed radiation necrosis that required surgical intervention 6 months following the procedure. Six patients (24%) needed WBRT, two patients (8%) needed further SRS and one patient (4%) needed surgery as salvage following development of new brain lesions with this approach. Conclusions: The preliminary results of surgery-SRS approach appear inferior to surgery-WBRT data for solitary brain metastases in terms of local control and development of new brain metastases. However, relapses can be subsequently managed with WBRT without adversely affecting the overall survival and the morbidity.

No significant financial relationships to disclose.
Phase I/II trial of induction chemotherapy in locally advanced head and neck carcinoma (LAHNC) and recurrent disease (RD) after surgery/radiotherapy with weekly docetaxel (D), tomudex (T) and cisplatin (P)—DTP
Authors: Johnson-Buarque E. J.
Published: March 2020

15536

Background: The role of neoadjuvant chemotherapy in LAHNC and treatment for RD have not been established yet. Infusional 5-FU combination with DP is one of the most active regimens for patients (pts) with LAHNC, at the same time is very toxic (hematological, gastrointestinal (GI) and cardiovascular). In order to reduce its toxicity we designed a novel weekly triple-drug scheme trying to reduce toxicity and mantain the high response rate. Methods: LAHNC and RD pts received D 35/mg/m2, T 1 mg/m2 and P 25 mg/m2 on days 1, 8 and 15. with one week rest. Some pts received only days 1 and 8 due to hematological toxicity (grade 2, 3 or 4). Planned treatment included 3 through 6 cycles (50% pts received 3 cycles). After neoadjuvant chemotherapy, pts with LAHNC were sent to their doctors to continue the treatment according to their own preference (surgery, RXT or RXT/QT). Results: Between november 2001 and may 2004, 24 pts (M = 17 F = 7) median age 61 (range 45–72) have been enrolled. 17 was LAHNC and 7 RD; tumor sites were: oral cavity 18 and oropharinx/larinx 6 pts. Response rate (RECIST) and toxicity (NCI) were avaible to all pts. 37.5% pts had grade 3/4 toxicity (hematological or GI) and these pts had a dose reduction. There was one febrile neutropenia and no deaths. The overall rate response was 91.6% (3 CR and 19 PR) in all sites of disease including lymphonodes. Conclusions: This scheme DTP has a high respose rate with low and manageable toxicity. It will be necessary to compare it with concurrent radiotherapy + dose reduction chemotherapy with or without cetuximab.

No significant financial relationships to disclose.
Recurrent/progressive oligodendroglial tumors: A phase II study with temozolomide as first line chemotherapy
Authors: Soffietti R. , Rudà R. , Guarneri D. , Laguzzi E. , Trevisan E.
Published: March 2020

1561

Background: There are few data regarding the efficacy of first line temozolomide in recurrent oligodendroglial tumors, and responses range from 17% to 54%. The objective of this phase II study was to investigate the efficacy and toxicity of temozolomide in the “standard schedule” in patients with oligodendroglial tumors at first relapse after surgery alone or surgery plus radiotherapy. Methods: The main inclusion criteria were as follows: age ≥ 18 yrs, Karnofsky ≥ 70; diagnosis of oligodendroglioma or oligoastrocytoma (grade II or III) according to WHO. Temozolomide was administered in the standard regimen up to 24 cycles in responding or stable patients or to unacceptable toxicity. Primary endpoint was response basing on Macdonald’s criteria, whereas secondary end-points were time to tumor progression and progression-free survival at 6 and 12 months. Results: Fifty patients are evaluable, with a median age of 50 (range 19–72). A median of 12 cycles (range 1–24) were administered. Responses were as follows: CR 8/50 (16%); PR 13/50 (26%); mR (minor response, a tumor volume reduction of 20–40%) 7/50 (14%); SD 18/50 (36%); PD 4/50 (8%). The overall response rate (CR+PR+mR) was 56%. The maximum tumor response was observed after 3 cycles in 9/28, 6 cycles in 10/28, 9 cycles in 6/28, 12 cycles in 1/28, 15 cycles in 2/28. Fourteen of 28 responding (CR+PR+mR) patients (50%) and 8 of stable patients (44%) displayed a reduction of seizures. Eighteen of 35 (51%) oligodendrogliomas responded, including 7 patients with CR (5 grade III tumors and 2 grade II), compared to 10/15 (67%) oligoastrocytomas. Twenty of 35 enhancing tumors responded (57%) compared to 8/15 non-enhancing tumors (53%) and 57% of grade III responded compared to 55% of grade II. Median TTP was 17 months (range 2–37), with a PFS at 6 months of 40% and at 12 months of 29%. Grade III-IV myelotoxicity accounted for 22%. Conclusions: Temozolomide shows activity as first line treatment in oligodendroglial tumors at first relapse. A long term treatment with temozolomide is well tolerated.

No significant financial relationships to disclose.
Survival study of RTA 744 (currently a single agent phase I study) alone and in combination with temozolomide in orthotopic model of glioma
Authors: Conrad C. A. , Meyer C. , Madden T. , Priebe W. , Lang F. F.
Published: March 2020

1577

Background: Treatment for high-grade gliomas represents an area of significant unmet medical need, largely because few agents cross the blood-brain barrier (BBB). RTA 744744 (WP744, 4’-O-benzyldoxorubicin hydrochloride) is a potent topoisomerase II poison and novel anthracycline screened for its ability to circumvent P-gp and MRP1allowing it to cross the BBB. To assess the drug’s potential in gliomas, RTA 744 was tested alone or in combination with temozolomide in an intracranial xenograft model of glioblastoma multiforme (GBM). It was hypothesized that a DNA repair inhibitor such as RTA 744 would enhance the effects of temozolomide. In vitro cell based assays confirmed this hypothesis and led to in vivo testing of this novel combination. Methods: U87MG cells were implanted into the right basal ganglia of nu/nu mice via an implantable screw system. In all studies, groups of 5 or 6 mice received PBS, temozolomide, RTA 744, or the combination of RTA 744 and temozolomide administered IP. PBS and temozolomide were given on a QDx5 schedule, and several schedules were tested for RTA 744. The primary endpoint in these studies was survival. Results: In the single agent study, by day 33, all 5 of the control animals had died compared with just one of the RTA 744-treated animals. Median survival for control animals was 28 days versus 37 for RTA 744-treated animals (T/C=132%). In the combination study, median survival was 30 days for controls, 40 days for temozolomide alone (T/C=133%), and 48 days for animals receiving the optimal combination of RTA 744 and temozolomide (T/C=160%). One animal in the combination group survived to day 78, whereas no control or Temodar treated animals survived past days 32 and 45, respectively. Conclusions: RTA 744 demonstrated potent single agent activity in a rigorous preclinical model of GBM. The combination of RTA 744 and temozolomide produced survival results significantly better than those from any chemotherapeutics tested in this model. This data supports the current Phase 1 trial of RTA 744 in patients with brain tumors as well as future trials testing the combination of RTA 744 and temozolomide.

[Table: see text]
Comparison of red blood cell transfusion rates of epoetin alfa and darbepoetin alfa in an inpatient oncology setting
Authors: Vekeman F. , McKenzie R. S. , Watson S. , Mody S. , Lefebvre P. , Piech C. T. , Duh M. S.
Published: March 2020

16002

Background: Epoetin alfa (EPO) and darbepoetin alfa (DARB) are used to treat cancer-related anemia and to reduce the requirements for blood transfusions. To date, limited information on the relative effectiveness of these agents in the inpatient setting is available. This analysis evaluated red blood cell (RBC) transfusion rates in cancer patients receiving EPO or DARB during hospitalization. Methods: An analysis of electronic inpatient hospital records from the Premier Perspective Comparative Hospital Database was conducted to compare RBC transfusion rates in cancer patients receiving EPO or DARB therapy. Study subjects were identified through hospitalizations recorded between 07/2002 and 03/2005 from over 500 hospitals nationwide. Patients were required to be ≥18 years old, have a primary admitting diagnosis of cancer and be treated with EPO or DARB during hospitalization. Patients who had received renal dialysis were excluded. To minimize effects of outliers, 5% of patients with extreme doses in each group were excluded from the dosing analysis. In addition to descriptive statistics on transfusion requirements, a multivariate logistic model was employed to isolate the effect of an individual erythropoietic agent on the risk of RBC transfusion after controlling for patient demographics, comorbidities, admission characteristics, use of IV or oral iron and hospitalization severity markers. Results: Among the 24,814 EPO and 2,990 DARB study patients, mean age and gender distribution at admission were similar (age: EPO 65.3 years, DARB 64.5 years; %women: EPO 53%, DARB 55%). Mean cumulative dose per inpatient stay was EPO 61,656 ± 50,274 Units and DARB 259 ± 340 mcg. RBC transfusions occurred in 37.9% of EPO patients compared to 39.8% of DARB patients (p=0.0404). Transfused EPO patients received a mean of 2.24 units versus 2.20 units for DARB patients (p=0.2111). After adjusting for covariates, the multivariate model confirmed that DARB treatment was associated with a higher risk of transfusion compared to EPO (odds ratio: 1.2, 95% CI: 1.1–1.3, p=0.0007). Conclusions: This analysis of inpatients with cancer indicates DARB treatment is associated with a higher risk of receiving RBC transfusion compared to treatment with EPO.

[Table: see text]
Human resource (HR) costs of chemotherapy infusion reactions (IR) in community oncology
Authors: Ogle J. , Fortner B. V. , Moore K. , Zhu L. , Schwartzberg L. S.
Published: March 2020

16013

Background: Chemotherapy IR are the dose limiting factor for many agents and have clinical consequences ranging from patient symptom burden to death. No work has been done to describe the provider burden of chemotherapy IR. The purpose of this analysis was to describe the clinical interventions associated with mild and severe IR and estimate the associated HR costs. Methods: Staff from a single, free standing, community oncology practice were surveyed regarding involvement in the management of mild and severe chemotherapy IR using a modified time and motion survey to identify tasks required to manage CIR and the HR time required. Mild and severe chemotherapy IR HR events were created. Salary averages for each type of staff were used to estimate HR costs. Results: 39 staff participated in the survey and were 85% (n = 33) female, average age 44, with M = 7.6 years experience. 21 distinct tasks (e.g. initial assessment, patient monitoring, infusion stopped, notify physician) were identified representing the management of the mild and severe chemotherapy IR. 11 types of staff indicated routine participation in ≥ 1 IR related task. Total HR time was 188 and 194 minutes for mild and severe IR respectively, resulting in HR cost of $124 and $187. Conclusions: The above methodology will be used in an expanded analysis of 20 outpatient practices. Recent changes in cancer treatment reimbursement have resulted increased interest in practice efficiency and provider cost. Definitions for quality care should consider minimization of unnecessary direct and indirect costs and maximization of practice efficiency. Models such as the one described are needed to understand provider costs. Clinical processes and chemotherapy agents that reduce rates and severity of CIR should reduce HR burden related to CIR.

[Table: see text]

[Table: see text]
Electronic medical record (EMR) in the oncology setting tested: A first hand experience
Authors: Hesita E. L.
Published: March 2020

16043

Background: Current data indicate that America’s medical system has been slow to embrace technology in relation to the use of the electronic medical record (EMR). The disruption caused by hurricane Katrina in the lives of cancer patients living in the city of New Orleans may prove to be an eye-opening experience that will persuade healthcare providers to change the traditional way of storing medical records. This study focuses on the experience of displaced New Orleans cancer patients. Methods: An anonymous validated questionnaire was completed by a random group of returning patients six weeks after the hurricane. This random group of patients evacuated to various states across the country. The focal questions asked were: the degree of difficulty in obtaining records, whether the alternate oncologist had to order further test(s), and whether the patients agree to having their medical records in an electronic format. Results: Of the total of 75 respondents, 93% are served by an institution in the New Orleans area that utilizes EMR while 7% are served by various institutions within the New Orleans area that do not have EMR. Overall, 81% stated ease in obtaining their records (within 1–4 days) while 19% stated difficulty (7 days or greater). Only 3% of the patients with EMR indicated difficulty while 100% of the non-EMR patients stated difficulty. For patients with EMR, 83% of the alternate oncologists did not order further tests, while 100% of the alternate oncologists ordered further testing for patients without EMR. In terms of patients’ sentiments regarding EMR, 76% agree to have EMR while 24% disagree. Conclusions: EMR in the oncology setting may prove to be an essential component in the delivery of quality patient care in terms of safety, cost effectiveness, and preservation of privacy. The majority of the patients surveyed agree to a form of electronic record-keeping based on their first-hand experience.

No significant financial relationships to disclose.
Reproducibility of diagnosis in patients with myelodysplastic syndrome
Authors: Burger J. A. , Borthakur G. , Pierce S. , Kantarjian H. , Estey E.
Published: March 2020

16506

Background: The myelodysplastic syndromes (MDS) have been considered notoriously difficult with regard to reliability of diagnosis and proper classification. The diagnosis and subclassification of MDS is based on hematopathology studies on the peripheral blood and marrow, along with cytogenetic and clinical information. Determination of single or multiple lineage dysplasia, percentage of myeloblasts, grading of cellularity, fibrosis, and iron content are essential for establishing the diagnosis of MDS. Methods: We reviewed the diagnosis of 112 patients who were referred to MD Anderson Cancer Center (MDACC) with an outside diagnosis of MDS. Results: Between July and December 2005, 112 patients were referred to MDACC with a diagnosis of MDS (bone marrow blast percentage <30%). Upon review of bone marrow studies performed at MDACC, diagnosis of MDS was confirmed in 83 patients. Acute myelogenous leukemia (AML) was diagnosed in 11 patients, and 3 patients were diagnosed to have myeloproliferative disorder (MPD) or chronic myelomonocytic leukemia (CMML). Alternate diagnosis offered in 18 patients included other cause of anemia (6), normal marrow (3), large granular lymphocyte leukemia (2), uncertain (2), immune thrombocytopenia (1), and multiple myeloma (1). Excluding 14 patients with AML or MPD/CMML (since they may represent natural progression of disease), diagnosis other than MDS was established in 15% (18/98) of patients. Conclusions: Upon review, diagnosis other than MDS is made in a significant percentage of patients referred with a diagnosis of MDS. As such, repeat blood and marrow workup and evaluation by more than one hematopathologist increases the accuracy of diagnosis in MDS and should be mandatory for clinical trials in MDS.

No significant financial relationships to disclose.
A prospective randomized phase II trial of splenic irradiation (SI) versus supportive therapy (ST) for patients (Pts) with hypersplenism (HS) secondary (2ry) to splenic periportal fibrosis (SPPF)
Authors: Eid S. , Elbeih E. , Hamid A. , Helal S.
Published: March 2020

16511

Background: HS 2ry to SPPF is a common problem in Egypt as a result of prevalence of bilharziasis. ST is the only option for the majority of pts who have poor performance status (PS) and cannot tolerate/refuse surgery. Methods: Aim of study was to evaluate the effect of SI versus ST on patients with HS 2ry to SPPF. Assessment of treatment was based on changes in Red Cell indices (RCI), Platelet indices (PI), splenic volume (SVol), and splenic vein diameter (SVD). In this study we had 19 evaluable Pts, 10 had SI and 9 had ST. Those who received SI had a twice weekly course of 1.5 Gy for a total of 3 weeks. RCI & PI were measured each visit, SVol & SVD (measured by duplex-Doppler US were measured initially, 3 & 6 months (mos) after treatment). Results: SVol & SVD increased significantly after 3 and 6 mos of ST, compared to insignificant decrease after 3 and 6 mos of SI. Platelet count (PC) significantly increased in all follow-ups (FU) after SI till 1.5 years compared to insignificant decreases in ST group after 3 and 6 mos. FU of mean platelet volume (MPV) and platelet distribution width (PDW) increased in ST group and decreased significantly in SI. Red blood cell (RBC) count and hemoglobin (Hb) levels increased significantly after SI till 6 and 9 mos respectively compared to insignificant decrease in RBC count and significant decrease in Hb level after 6 mos of ST. Changes in white blood cell counts were insignificant. After SI, changes in SVol showed significant positive correlations with changes in SVD and significant negative correlations with changes in PC. Changes in MPV showed significant positive correlation with changes in SVD. Side-effects (SE) seen with SI were moderate and transient. Conclusions: SI is a promising new modality of treatment with acceptable SE for pts with HS. Dose and schedule of SI should be modified according to pts PS. Changes in SVD are highly correlated with the degree of platelet and red cell turnover. Its predictive value for HS should be studied further.

No significant financial relationships to disclose.
Clinical characterization of first cycle reactions in patients with chronic lymphocytic leukemia treated with oblimersen
Authors: Kolibaba K. S. , Chanan-Khan A. A. , Bociek G. , Boyd T. , Moore J. , O’brien S.
Published: March 2020

16514

Background: Serious adverse reactions during the first treatment cycle characterize many drugs used for chronic lymphocytic leukemia (CLL), including rituximab, alemtuzumab, flavopiridol, lenalidomide, and oblimersen. Termed cytokine release reactions (CRRs), these events have occurred more commonly in pts with bulky disease and elevated leukocyte counts, and some have been fatal. Rapid increases in serum levels of tumor necrosis factor-α, interleukin-6, interleukin-2, interferon-γ, and other cytokines may result in symptoms including fever, chills, nausea, vomiting, hypotension, and dyspnea. Ex vivo treatment of CLL cells with oblimersen induce release of vasoactive interleukin-8. First cycle reactions, including tumor lysis syndrome (TLS), proved dose-limiting in a phase 1–2 trial of oblimersen in pts with relapsed or refractory CLL. To characterize these reactions, we evaluated data from this single-agent study and from a phase 3 randomized clinical trial of oblimersen with fludarabine and cyclophosphamide (Flu/Cy). Methods: Data on investigator assessment of CRR and TLS were obtained from both studies, which included 155 pts; 40 were treated with oblimersen alone (3–7mg/kg/d by CIV for 5–7 days) and 115 with oblimersen (3 mg/kg/d × 7 days) in combination with Flu/Cy. Results: Of 145 pts treated with oblimersen 3mg/kg/d, either alone or with Flu/Cy, 2 pts (1.3%) experienced CRR and TLS, respectively. Two CRRs occurred in 10 pts treated with 4–7mg/kg/d. Reactions typically began 24–48 hours after starting treatment. CCR was usually associated with spiking fever, nausea, dehydration, rigors, and back pain. Rarely pts developed hypotension, acidosis, or reversible renal insufficiency, usually with a reduction in WBC. Symptoms lasted 1 day to several weeks (1 pt). In most cases, reactions were reversible with intensive supportive care, including IV fluids, pressors, and antibiotics; 1 death from TLS and 1 from CCR occurred during cycle 1. There was no definitive correlation with baseline measures of disease burden. Conclusion: First cycle oblimersen reactions are uncommon but represent a risk. Early symptoms (fever, nausea, and dehydration) require aggressive treatment, which may prevent progression of the reaction.

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Gemtuzumab ozogamicin for treatment of relapsing/refractory acute myelogenous leukemia (AML)
Authors: Case D. C. , Boyd M. A. , Hedlund J. A. , Ervin T. J.
Published: March 2020

16531

Background: Gemtuzumab ozogamicin is a calicheamicin-conjugated anti-CD 33 monoclonal antibody studied and utilized in relapsed and refractory acute myelogenous leukemia. Methods: At our center we treated a series of refractory patients (<60 years old) and relapsed patients (>60 years old) with gemtuzumab ozogamicin over a 3 year period. We treated 20 patients: 14 males and 6 females with an age range of 21 to 77 years (median 64 years). Seven patients were refractory to multiple regimens (<60 years old) and 13 were relapsing from initial therapy (>60 years old). Cytogenetic analysis revealed 60% were intermediate-risk and 40% were poor-risk. The goal of therapy was complete remission (≤ 5% leukemia blast cells in the marrow. ≥ 9 g/dl hemoglobin, ≥1500/ul absolute neutrophil count, and platelet count ≥100,000/ul). Patients received gemtuzumab ozogamicin 9 mg/m2 I.V. days 1 and 5. All patients received at least one dose. Patients achieving complete remission were eligible to receive monthly doses of gemtuzumab ozogamicin after complete remission was obtained. Results: Of the 7 refractory patients (<60 years old), there were no complete remissions. Of 13 relapsing patients (>60 years old) there were 2 complete remissions. One patient was 64 and the other 67 years old. Both remissions lasted 2 months. All patients were treated in the hospital. Chills/fever with treatment occurred in 40% of patients. Fever/neutropenia was universal. Thirty percent had elevation of liver function tests. Conclusions: Gemtuzumab ozogamicin as a single agent is capable of producing complete remission in a small number of relapsing patients >60 years old. Remissions are short.

No significant financial relationships to disclose.
Fixed-dose single administration of pegfilgrastim vs daily filgrastim in patients with breast cancer and lymphoma undergoing autologous peripheral blood stem cell transplantation
Authors: Boy D. , Gonella R. , Barbero V. , Nencioni A. , Patrone F. , Ballestrero A.
Published: March 2020

16534

Background: Pegylated filgrastim is a new formulation of a granulocyte colony-stimulating factor that has a long circulating half-life, permitting a single dose of filgrastim per cycle of chemotherapy. Methods: To evaluate whether a single subcutaneous injection of pegfilgrastim (6 mg) is as safe and effective as daily filgrastim (5 mcg/kg/day), 40 consecutive autologous stem cell transplantations performed for breast cancer and lymphomas have been analysed. Median age was 47 yrs (20–61) and 48 yrs (30–63) in pegfilgrastim and filgrastim group, respectively. All patients had normal bone marrow biopsy. The first cohort of patients received 5 mcg/kg/day of filgrastim starting from day 5 post transplantation and the second cohort of patients received a single subcutaneous injection of 6 mg pegfilgrastim on day 5 after transplantation. Results: Median duration of grade 4 neutropenia in the pegfilgrastim and filgrastim groups was 7 (4–9) and 6 (5–9) days, respectively (P 0.29). Neutropenic fever incidence was significantly higher in filgrastim group, 9/20 vs 16/20 (P 0.048), the median duration was not significantly different, 1 (1–6) vs 3 (1–7) days. The grade 3–4 mucositis was higher in filgrastim patient group, 4/20 vs 13/20 in pegfilgrastim and filgrastim, respectively (P 0.009). The adverse events observed during post-transplant aplasia were attributable to complications arising from myelo-suppressive chemotherapy or the primary disease. The only occurring adverse event considered to be cytokine related was mild to moderate bone pain. The overall incidence of bone pain requiring non-narcotic analgesia was not statistically different, 20% (4/20) in pegfilgrastim patients and 40% (8/20) in filgrastim patients. The patients in filgrastim group received a mean of 9.8 daily injections. Conclusions: A single injection of pegfilgrastim administered at day 5 post transplant shows comparable safety and efficacy profiles to daily injections of filgrastim and may be cost-effective.

No significant financial relationships to disclose.
Complete 18FDG positron emission tomography (PET) response after induction chemotherapy (IC) is correlated with long survival in patients (pts) with locally advanced non-small cell lung cancer (LA NSCLC)
Authors: Schallier D. , Everaert H. , Neyns B. , Baelde N. , Meysman M. , Fontaine C. , De Grève J.
Published: March 2020

17004

Background: PET and computerized axial tomography scan (CT) are complimentary tools in the diagnosis and treatment of pts with LA NSCLC. Recent data have shown that response to IC as determined with PET has a better prognostic relevance for long term outcome than CT (Hoekstra et al JCO 2005;23:33:8362–70). Methods: PET and chest CT were performed before and after 3 cycles of IC in pts with LA NSCLC (D. Schallier et al, Suppl JCO 2005;23:165:7285, 6915). Response was defined according to WHO and EORTC criteria for CT and PET respectively (complete response: CR; partial response: PR; stable disease: SD; progressive disease: PD). PET images corrected for attenuation were acquired in 3D on a Siemens Accel camera starting 60 minutes after administration of 307–606 MBq 18FDG. The maximal standardized uptake value (SUVmax) within the tumor was measured and a SUVmax value ≥2.5 was used as a cut off. PET responses were classified either as complete (resolution of the enhanced uptake within the tumor) or non-complete. For each subgroup, classified according to CT and PET response, time to progression (TTP) and survival (S) was calculated and analysed statistically according to Kaplan-Meier and log rank test. Results: 21 pts were eligible for the PET and CT confrontation. Characteristics: 14 male, 7 female; median age 70 y (39–78); median KS: 90 (80–100); stage III A: 9; stage III B: 12; T1,2,3,4: 4/3/7/7; N0,1,2,3: 4/1/11/5. Response: CT: 12 PR; 9 SD; PET: 6 CR, 9 PR, 5SD, 1PD. Nine/12 PR on CT were also CR (5) and PR (4) on PET. Median TTP was correlated significantly with PR and CR (versus SD and non-CR) on CT and PET respectively (288 versus 606 days, p = 0.045 for CT and 299 versus median not reached p = 0.024 for PET); with a median follow up of 19+ month, median S was not significantly correlated with PR on CT but was highly significantly correlated with CR on PET (439 days versus median not reached p = 0.005). Conclusions: Assessment of response to IC using CT or PET largely overlaps. PET appears to be a more ‘sensitive‘ tool to measure response. CR on PET provides a better accuracy for determination of long term outcome than CT. The present results corroborate previously published results.

No significant financial relationships to disclose.
Lung cancer in never-smokers: A single institutional experience
Authors: Subramanian J. , Gao F. , Sainani N. , Viswanathan A. K. , Pillot G. A. , Baggstrom M. Q. , Sorscher S. , Govindan R.
Published: March 2020

17044

Background: Approximately 10% of patients (pts) with lung cancer do not have a history of tobacco smoking. The clinical presentation and outcomes of pts with LCINS have not been well characterized in the Western population. Methods: We reviewed our institutional tumor registry to identify patients with lung cancer from 1992 to 2002. Data regarding tobacco smoking, stage, histology and survival were collected. Results: Of the 5417 consecutive pts diagnosed with lung cancer, 254 were determined to be never-smokers with confirmed pathologic diagnosis of non-small cell lung cancer (NSCLC). The table below describes the patient demographics. The five-year survival for the entire population with LCINS was 22.56%, with 37 pts surviving beyond five years. The median overall survival for women was 21.08 months (95% CI 14.03–23.37) and for men 13.5 months (95% CI 8.5–32.492); p = 0.73. Among the different histologic subtypes, broncho-alveolar carcinoma was associated with better median overall survival of 61.67 months (p < 0.0001). The median overall survival by TNM stage: I (71 months), II (32 months), III (15 months), and IV (6 months). Conclusions: 1. LCINS affects predominantly women. 2. Adenocarcinoma is the most common histological type. 3. Brain and bone are the most common sites of metastases.

[Table: see text]

No significant financial relationships to disclose.
Multimodality treatment of non small cells lung cancer (NSCLC) brain metastases: Long term outcome
Authors: Cassano A. , Pompucci A. , D’Argento E. , Schinzari G. , Di Chirico A. , De Bonis P. , Quirino M. , Basso M. , Anile C. , Barone C.
Published: March 2020

17046

Background: Lung cancer is the most common cause of cancer deaths and has the highest incidence for brain metastases of all malignancies. The prognosis of these patients (pts) remain poor with a median survival of 4–5 months. Whole brain radiation therapy (WBRT) in inoperable brain metastases prolongs survival to 3–5 months. In pts with 1 or ≤ 3 brain metastases neurosurgical resection improves median survival to 3.5–8 months. The aim of this study was to evaluate the long-term outcome of patients with brain metastases from NSCLC treated with multimodal strategy, including systemic chemotherapy, neurosurgery and radiotherapy. Methods: From 1997 to 2005, 56 pts were considered. Inclusion criteria were: single or multiple NSCLC brain metastases suitable of surgery; Karnofsky performance status ≥ 70%; controlled extracranial disease with Cisplatin-based chemotherapy; life expectancy > 4 months. Surgery was followed by 40 Gy WBRT. Statistical analysis was performed using the Kaplan-Meier method and Cox-regression analysis. Results: The median age was 58.4 years. The histological types were adenocarcinoma in 35 pts (62.5%), squamous cell carcinoma in 11 pts (19.7%) and large cell carcinoma in 10 pts (17.8%). The lesions were single in 39/56 pts (69.6%) and multiple in the other pts (30.4%). Radical surgery was performed in 37 pts (66%), while surgical citoreduction was possible in 19 pts (34%). The median follow-up period was 22.12 months (range 2–90 months). Overall survival (OS) of the whole group was 12.8 months; OS of pts radically resected was 16.5 months while OS of pts partially resected was 7.2 months. Based on Cox-regression analysis, age < 65 years and radical resection were independent predictors of survival (respectively p = 0.004–95% CI 1.46–7.6 and p = 0.04–95% CI 1.03–4.97), while the number of lesions was not relevant in terms of OS. Conclusions: Analysis of long-term outcome seems to confirm that the combined treatment of NSCLC brain metastases is a primary therapeutic option. In our series of 56 patients, radical surgery, not the number of metastases, was related with prolonged survival. Further randomized studies comparing surgery+WBRT vs gamma-knife-radiosurgery could define the best therapeutic option in the different subsets of pts.

No significant financial relationships to disclose.