bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of the Inuit oncology patients treated at the Ottawa Hospital Cancer Centre.
Authors: Febbraro Michela , Spaans Johanna , Alvarez Gonzalo G , Asmis Timothy R.
Published: March 2020

e17563

Background: Cancer is a major health concern among Canada’s northern Inuit population. Limited Inuit specific data exists on the geographical isolation and the effect on treatment outcomes of Inuit referred to urban hospitals for cancer treatment. Methods: A retrospective chart review of all Inuit referred to the Ottawa Hospital Cancer Centre from Nunavut, Canada (distance: 1298 miles) between 2001-2011 was conducted. Demographic, diagnostic and treatment related information was collected on all patients, including the number of visits made by each Inuit patient from Nunavut to OHCC for treatment. Results: 234 Inuit (male: 74, female: 160) were referred to OHCC with a diagnosis of cancer. Mean age at diagnosis was 58.5 years (sd 14.61). Over half the patients were current smokers (54%) and 39% of patients had a history of tuberculosis (TB). Among Inuit men, lung (n=32, 43%), colorectal (n=11, 14%) and nasopharyngeal (n=9, 12%) cancer were the most common diagnosis. Among Inuit women, the most common cancers were lung (n=72, 45%), colorectal (n=32, 20%), breast (n=21, 13%), cervical (n=11, 7%) and nasopharyngeal (n=7, 4%). Metastatic disease at presentation was common (n=76, 38%). Primary cancer was amenable to surgery in n=57 patients. An equivalent number of patients (n=82) received adjuvant/definitive radiation therapy (RXT) and adjuvant chemotherapy, with n=52 receiving chemoradiation. Palliative RXT and chemotherapy was received by 64 and 51 patients, respectively. Among patients receiving chemotherapy, there were no cases of TB reactivation and no treatment related serious adverse outcomes or deaths. Average number of trips made to Ottawa for treatment was n=7 (sd 7.90) with the upper quartile averaging n=10 trips. Conclusions: Lung, colorectal and nasopharyngeal cancers are over-represented among Canadian Inuit, who often present with advanced disease. Travel burden is significant among patients receiving treatment. Improved cancer screening and oral molecularly targeted therapies that can be delivered in remote northern communities are likely to improve the experience and treatment outcomes among Canadian Inuit.
Effects of prospective review of medical oncology treatment plans (TPs) on quality of care, payer denial, and cost.
Authors: Flood William A. , Yedwab Erik , Alley Evan W. , Gilman Paul , Frick Kevin D. , Forastiere Arlene A.
Published: March 2020

e17565

Background: Retrospective review of chemotherapy TPs for compliance with expected care presents financial and quality risks to providers, patients and payers. Prospective assessment of TPs before oncology care is delivered may limit these risks. Methods: Through the eviti web-based decision support platform, oncologists/staff submit TPs for review. The eviti Evidence-Based Library incorporates all recognized guidelines (ASCO, NCI, ASTRO, NCCN and others), the supporting literature and NCI registered clinical trials. Evidence-based treatments are approved while unexpected variances are not reported to the payer until medical record review and peer to peer (P2P) discussion when records are insufficient. The eviti data base was queried for all off-study treatment plans submitted by medical oncology providers in a single state from January 2011 through October 2012. The nature of variation, results of P2P discussion and final recommendation to the payer were then determined. Net cost differences between the proposed and expected care were calculated using ASP+6% in November 2012. Results: Of a total of 202 TPs submitted on 116 individual patients, 89 TPs (44%) included 92 unexpected variations of care at initial submission, 11 of which (12%) presented safety issues documented in the peer reviewed literature and guidelines. The total net cost difference for one cycle of the proposed care and expected standard was $304,055. Of these 92 unexpected variations, only 29 (32%) of the variations could not be unjustified and referred for probable denial by the payer. After review of medical records, 21 (23%) were referred to the payer as medical justified variations (MJV), while after P2P 17 (18%) were considered MJV’s and 25 (27%) were modified to fit expected patterns of care. Additional analysis by drug classes and cost will be presented. Conclusions: In this TPs set, prospective review of treatment plans decreased the incidence of non-EBM care, the rate of potential denials, and the cost of care. Prospective TPs review can limit risk to all parties in cancer care.
A national survey on patients’ enrollment rate in oncology clinical trials: The French experience.
Authors: Pauporte Iris , Thibaudeau Valerie , Calvo Fabien M. , Buzyn Agnes
Published: March 2020

e17567

Background: The rate of patients enrolled in clinical trials (CT) is one of the main indicators of clinical research and care activity. The successive French Cancer Plans (2003-2007 and 2009-2013) aimed at quantifiable targets of patients to be enrolled in high-quality clinical trials. To help investigators achieving this objective, a substantial financial support for clinical research associates (CRA) recruitment was given to University Hospitals (UH), Comprehensive Cancer Centers (CCC) and public or private community hospitals (CH). In the meantime, significant public investment was allocated to competitively selected academic projects through the Clinical Research National Program. Methods: From 2006 to 2011, we carried out annual national surveys on clinical research activities in oncology in France. A questionnaire was sent to cancer care institutions. Number of CT open for enrolment, number of CT sponsored by the institution, number of patients enrolled and human resources (CRA) were collected. Academic and industry-sponsored trials were analyzed separately. Results: We showed that the number of patients enrolled in CT increased continuously over this period: from 21,500 in 2002 to 35,400 in 2011 (+47%). Based on these figures and assuming that there were 420,000 to 472,000 patients eligible for CT over this period, the enrolment rate for patients in CT is estimated to be 7.5 to 8.5% in 2011 versus 5.8 to 6.7% in 2003. Nearly 80% of all enrolled patients were recruited in academic CT; over 75% of patients in therapeutic trials. UH and CCC equally contributed for 80% of enrolment, CH for the residual 20%. At last, the number of CT increased by more than 35% over the same period, while the number of CRA was multiplied by 3 over the French territory. Conclusions: Our results show that public intervention for improving enrolment to cancer CT seems to be efficient. Other types of intervention are being considered, i.e., targeted on investigators, on patients, or on both. Future work should also consider the impact of CT enrolment on patients’ outcome.
Efficacy and safety of balugrastim in chemotherapy-induced neutropenia: Integrated analysis of two randomized phase III studies.
Authors: Gladkov Oleg , Volovat Constantin D. , Barash Steven , Buchner Anton , Avisar Noa , Bias Peter , Mueller Udo W.
Published: March 2020

e17572

Background: Balugrastim is a recombinant fusion protein composed of human serum albumin and human granulocyte colony-stimulating factor, which allows for once-per-chemotherapy cycle administration. We present a combined analysis of two double-blind, randomized Phase III studies comparing efficacy and safety of balugrastim vs pegfilgrastim in breast cancer patients receiving myelosuppressive chemotherapy (CTx). Methods: All patients were treated with doxorubicin 60 mg/m2 followed by docetaxel 75 mg/m2 administered by i.v. infusion on Day 1 of a 21-day cycle for up to 4 cycles. For each cycle, patients received a single s.c. injection of balugrastim approximately 24 hours after administration of CTx. The primary endpoint for both studies was duration of severe neutropenia (DSN) in Cycle 1. Safety of balugrastim was assessed by evaluating the type, frequency, and severity of adverse events (AEs); changes in laboratory parameters and vital signs, and immunogenicity over time. Analyses were performed in the per-protocol population. Results: A total of 469 patients were randomized to receive balugrastim 40 mg (N=235) or pegfilgrastim 6 mg (N=234). Mean DSN in Cycle 1 was 1.1±1.11 days in patients receiving balugrastim (n=236) and 1.0±1.14 days in patients receiving pegfilgrastim (n=234). Non-inferiority was demonstrated by statistical analysis for balugrastim vs pegfilgrastim for reduction in DSN across studies. Patients treated with balugrastim had a significantly shorter time to ANC recovery in Cycle 1 vs pegfilgrastim (2.0 vs 2.3 days; P=0.015). No other significant differences were seen between treatment groups in either study for any other secondary endpoints in Cycles 1–4. The safety profile was similar for both drugs, with the incidence of AEs consistent with the underlying medical condition and administration of myelosuppressive CTx. Conclusions: In both Phase III studies, non-inferiority was clearly demonstrated for balugrastim 40 mg vs pegfilgrastim 6 mg. Balugrastim is a safe and effective alternative to long-acting pegfilgrastim for reducing DSN in breast cancer patients receiving myelosuppressive chemotherapy. Clinical trial information: 2010-019001-42.
Dosing of chemotherapy for solid tumors based on ideal body weight versus actual body weight: Review of a military oncology clinic’s practice.
Authors: Miller Lonnie D. , Henderson Aaron , Vietor Nicole , George Benjamin Jacob
Published: March 2020

e17575

Background: Dose-reductions or “capping” of the body surface area (BSA) at 2.0m2 for chemotherapy due to obesity has been widely practiced throughout oncology due to the concerns about AE in obese patients. In 2012 ASCO published guidelines recommending that full weight-based dosing of chemotherapy be used. This retrospective review was undertaken to evaluate the dosing practices at a major U.S. Army oncology clinic. Methods: Retrospective, random sampling of patients with breast, lung, gastrointestinal and testicular cancer and lymphoma treated at a tertiary military medical center within the last three years. Basic demographic data, cancer type, stage, actual and ideal BSA , incidence of dose-reduction, hematologic data before and after cycle 1, incidence of grade 3-4 toxicity and use of granulocyte-colony stimulating factor was recorded. Results: 231 patients (61.9% female, 38.1% male) were included in the analysis (breast 36.4%, lung 19.5%, GI 21.2%, testicular 6.5%, lymphoma 16.5%). The majority of patients were white, 70.6%, with asian, black, hispanic and other making up 2.6%, 13.4%, 1.7% and 11.7% respectively. Seventy-eight had a BSA >2.0m2. No incidences of dose-reduction were identified. Analysis did not show a correlation between differences in actual vs. ideal BSA and toxicity. When other variables were considered, there was a statistically significant inverse relationship between age and grade 3-4 toxicity (p=0.02) although this was deemed clinically insignificant (coefficient of determination <0.25). Conclusions: In a retrospective review of chemotherapy dosing practices in a major military medical center, we found no cases of dose-reduction based on obesity. There was also no significant increased toxicity when patients were dosed according to actual vs ideal body weight in keeping with previously published literature. There was a significant inverse relationship between age and grade 3-4 hematologic toxicity.
Effect of availability of oral iron chelation therapy (ICT) on initiation, duration, and dose adequacy in patients with myelodysplastic syndromes (MDS) and transfusional iron overload (TIO).
Authors: Gore Steven , Davidoff Amy J. , Hendrick Franklin , Duong Vu , Stuart Bruce C. , Baer Maria R. , Shenolikar Rahul , Zeidan Amer
Published: March 2020

e17584

Background: Most patients with MDS do not receive ICT despite evidence of TIO. Till 2005, the only approved ICT was Deferoxamine (DFO), a drug which requires daily prolonged parenteral administration. In addition to therapeutic equipoise of its efficacy, the logistics of administration of DFO may limit ICT use in MDS. We sought to assess whether the approval of an oral ICT (Deferasirox, DFX) in November 2005 has changed ICT use rates, dose adequacy and adherence in MDS patients with TIO. Methods: Using 100% Medicare enrollment and claims data from 2005-2008, we selected beneficiaries with MDS who were enrolled in Medicare Parts A, B, and D and were ICT-eligible based on RBC transfusions ≥ 20 units. Cox proportional hazard models examined the effect of time period relative to DFX market entry on the probability of ICT initiation and the effect of DFX vs. DFO use on duration and dose adequacy. Results: Of 3,843 ICT-eligible patients, 13.8% received ICT, with 81.6% of those receiving DFX, and 29.5% receiving DFO. Relative to the latter half of 2005, the probability of ICT initiation increased beginning in 2007, with a hazard ratio of 1.793 (CI,1.13-2.84; P=0.012) associated with cohort entry in the latter half of 2008. Treatment duration was longer for beneficiaries using DFX (mean 29.7, median 22 weeks) compared to DFO (mean 19.43, median 9 weeks). Only 7.1% of DFO-users received an adequate dose, compared to 72.8% of DFX-users. Conclusions: Use of oral ICT (DFX), following its approval, was associated with increased use, duration and dose adequacy of ICT, compared to DFO, among Medicare beneficiaries with MDS and TIO. The dramatic increase in use associated with availability of an oral formulation may have implications for other new oral chemotherapy and supportive care drugs.
Awareness of HPV and its vaccine among lesbian, gay, bisexual, transgender, and queer (LGBTQ) populations.
Authors: Ong Caroline , Winer Joel , Margolies Liz , Dai Feng , Patridge Eric , Chagpar Anees B.
Published: March 2020

e17597

Background: HPV is a sexually transmitted virus that is known to cause of a number of malignancies, including anorectal and oral cancers. However, there is a paucity of data regarding the knowledge of HPV and its now FDA-approved vaccine amongst LGBTQ populations. We sought to compare awareness of HPV and the vaccine in an LGBTQ sample to the general population. Methods: An anonymous electronic survey was conducted through well-known LGBTQ organizations. The survey was designed to replicate verbatim questions regarding HPV fielded in the 2010 National Health Interview Survey (NHIS) Cancer Supplement. Data from the LGBTQ survey was compared to the nationally representative population surveyed in the NHIS. Results: A total of 323 LGBTQ people responded to the survey; 148 were female (90 lesbian, 25 bisexual, and 33 queer/other), 158 were male (141 gay, 5 bisexual and 12 queer/other), 13 were transgender and 4 identified themselves as other/queer in gender. The median age of the cohort was 34.4 (range; 16-74). Of this population, 297 (92.0%) had heard about HPV (vs. 61.5% in the general population in NHIS). Both LGBQ men and women were equally likely to have heard about HPV (92.4% and 91.3%, respectively), whereas knowledge regarding HPV was more disparate between men and women in the general population (47.2% and 75.6%, respectively). Of the 11 transgender people who responded to the questions regarding HPV, all had heard about the virus. 88.5% of the LGBTQ cohort had heard about the vaccine; compared to 51.3% in the general population in NHIS. Again, there was less of a gap in knowledge between men and women in the LGBQ community (90.6% and 87.3%, respectively) than there was in the general population (68.1% and 34.0%, respectively). 10 of the 11 transgendered people who responded to questions regarding HPV (90.9%) were aware of the HPV vaccine. Conclusions: The LGBTQ community appears well-educated regarding HPV and its vaccine, compared to the general population. These findings are gratifying given the potential increase in risk of HPV-related malignancies in these populations, but further work is needed to explore whether this increased awareness translates into increased HPV-vaccination rates.
Efficacy of the hypomethylating agents as frontline, salvage, or maintenance therapy among older adults with acute myeloid leukemia (AML).
Authors: Tawfik Bernard , Sliesoraitis Sarunas , Klepin Heidi D. , Lawrence Julia , Isom Scott , Ellis Leslie R. , Lyerly Susan , Manuel Megan , Dralle Sarah , Berenzon Dmitriy P. , Powell Bayard L. , Pardee Timothy S.
Published: March 2020

e18002

Background: The hypomethylating agents, azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the use of these agents in the treatment of AML is currently evolving. Methods: We retrospectively examined 76 consecutive AML patients ≥60 years old treated with hypomethylating agents at Wake Forest from 2002-2009 as either 1st-line therapy (n=35), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charleston Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Results: In the front line setting 11.4% of patients received azacitidine (AZA), 34.3% received 5 days of decitabine (5DD) and 54.3% received 10 days (10DD). In the salvage cohort 3.6% received AZA, 42.8% received 5DD and 53.6% received 10DD. In the consolidation cohort 18.2% received AZA and 81.8% received 5DD. Response rates (CR+CRi) were reduced in the salvage cohort compared to frontline (3.6% versus 25.7%, p=0.033). Despite the reduced response rate, overall survival in the two cohorts was similar when survival was calculated from time of hypomethylating agent (8.2 [CI 4.8-10.3] vs. 3.1 [CI 1.9-12.0] months, p = 0.2967). In the salvage cohort overall survival from the time of relapse was similar to the overall survival of those treated in 1st consolidation (18.3 [CI 15.1 -23.5] vs. 13.7 [CI 8.0 – 21.6] months, p= 0.3346). This suggests that hypomethylating agents given in first remission did not improve survival over patients who received them only after relapse. Comorbidity burden (by the CCI) showed a non-significant trend with prognosis (p= 0.0667). Conclusions: These data suggest prior cytotoxic therapy decreases marrow response rates to hypomethylating agents but not survival. Furthermore, use of hypomethylating agents for consolidation did not result in an increase in median overall survival when compared to their use in salvage.
Imatinib dose hike in suboptimal response and failure in CML CP: Results from a developing nation.
Authors: Gullipalli Muralidhar , Linga Vijay Gandhi , Kota Rajesh , Kalpathi Krishnamani , Maddi Rahul Narayan , Goteke Vamshi Krishna Reddy , Arigela Ravi Sankar , Nasaka Srividya , Ganta Ranga Raman , Gundeti Sadashivudu , Digumarti Raghunadharao
Published: March 2020

e18003

Background: As perEuropean Leukemia Net (ELN) guidelines Imatinib 400mg/day is the standard of care in CML-CP. Options for patients with suboptimal response and failure are dose hike or change to second line TKIs. In resource poor countries where second line TKIs are expensive, dose hike of Imatinib may be an alternative. Methods: We retrospectively analyzed all CML - CP patients requiring dose hike at our centre from 2003-2009. Mutational analysis could not be performed. The trigger for dose hike to 600mg was suboptimal response or failure as per ELN 2010 guidelines. Event free survival (EFS), transformation free survival (TFS), and overall survival (OS) were analysed. EFS was defined as time from dose escalation to transformation to BC/AP or lost to follow up or death due to any cause. OS was defined as time from dose escalation to death. TFS was defined as progression to BC/AP from dose hike. Cytogenetic response was evaluated. Statistical analysis is done using Graphpad Prism. Results: There were 76 patients with a median age of 35 years (range, 13-68) and M: F ratio of 1.8:1.Trigger for dose hike was failure in 56 patients (73%) and suboptimal response in 27%. In failure group, after dose hike, complete cytogenetic response (CCR) was achieved in 41/56 (73%), partial (PCR) 4/56(7%), minor 5/56(9%), nil cytogenetic response in 6/56(10%). In suboptimal group CCR were seen in15/20(75%). Five year EFS, TFS and OS in both the groups together were 64.3%, 91.9%, and 94.7% respectively. The five year EFS, TFS and OS in failure group were 63.4%, 93.3% and 95.1% respectively. Five year EFS, TFS and OS in suboptimal group were 62.8%, 88.5% and 94.4% respectively. There was no significant difference between suboptimal and failure groups (p values for EFS-0.8414, TFS- 0.446,OS-0.7368). 75% patients experienced manageble toxicities. Conclusions: Dose hike to 600mg is still one of the viable options in CML CP patients with suboptimal response or failure in resource limited countries with an acceptable toxicity profile.
The outcome of acute biphenotypic leukemias in childhood: A single center experience.
Authors: Zulfikar O. Bulent , Cakir Betul , Koc Basak
Published: March 2020

e18006

Background: Acute biphenotypic leukemias is a rare type of leukemia in childhood, expressing both myeloid and lymphoid markers. We evaluated 22 patients having biphenotype leukemia to document the characteristics and outcome. Methods: We reviewed the files of the children with acute leukemia referred to Istanbul University Oncology Institute between May 2000 – May 2011. Results: There were 21 (22%) patients, 11 girls and 10 boys, having biphenotypic features among 93 acute leukemia patients. Of these, 15 were B-lymhoid/myeloid, 6 were T-lymphoid/myeloid patients. Genetic analysis was performed in 18 patients. Two had t(12;21) positivity; philadelphia chromosome or myeloid translocations including 16 inv., t(8;21), t(15;17) were negative. Median follow up time was 65 months (21-109). All the patients were treated with COG high risk acute lymphoblastic leukemia protocols and achieved remission except 2 patients who required myeloid induction treatment (MRC 10 Protocol). Two of the patients relapsed at 30th and 34th months of follow-up. Conclusions: In our series, all the patients are in remission including two relapsed patients who are disease free with stem cell transplantation. The outcome of biphenotypic leukemia patients treated with lymphoblastic leukemia protocols were not lower than acute lymphoblastic leukemia patients. These patients need special care and prompt approach due to their problems during treatment.
Combination HDACi and mTOR inhibitor therapy in poor-risk de novo and refractory elderly patients with AML.
Authors: Sandilya Vijay Krishna , Ghai Vikas , Sharma Kamal , Abbi Kamal Kant Singh , Epner Elliot E
Published: March 2020

e18012

Background: Valproic acid (VPA, 2-propylpentanoic acid) is a histone deacetylase inhibitors (HDACi), which has in vitro activity against Acute Myeloid Leukemia (AML) blasts. HDACi produce epigenetic modifications, and may have antineoplastic effects in AML by activating transcriptional silenced genes. The mammalian target of rapamycin (mTOR) pathways constitutive activation has been involved in the pathogenesis of various cancers, including AML. We present a series of two cases of poor risk de novo and refractory elderly AML patients treated with a combination of HDACi VPA and mTOR inhibitor sirolimus (S). Methods: This is a retrospective chart review garnered data on two patients with de novo AML and refractory AML who were treated with a combination therapy of VPA 500 mg three times a day with sirolimus 1 mg by mouth daily. Patients continued to receive treatment until disease progression. Results: Patient 1 achieved transfusion independence and a 6 month CR with ECOG PS 1 without hospitalizations. Repeat BM demonstrated no morphologic or immunophenotypic evidence of AML. Persistent disease was still detectable by FISH. Patient 2 was started on the regimen after persistent disease was detected by day 14 bone marrow, post standard 7 + 3 induction. Repeat bone marrow after 23 days of treatment with VPA and Sirolimus showed no immunophenotypic, morphological or cytogenetic evidence of AML. The patient remained in remission for 9 months on therapy with normal blood counts. Conclusions: We postulate that the use of VPA with sirolimus, is an active combination therapy for elderly, poor risk AML patients who may not otherwise tolerate intensive chemotherapy. The mechanism of action may involve activation of the mTORC2 pathway by HDAC1. Given our observations, further studies are warranted to better define the activity of this or similar combination therapies in elderly AML patients. [Table: see text]
Infection profile in patients developing febrile neutropenia after high-dose chemotherapy and stem cell transplantation.
Authors: Ozaydin Sukru , Ozturk Mustafa , Eser Mithat , Karadurmus Nuri , Erdem Gokhan , Arpaci Fikret
Published: March 2020

e18016

Background: Febril neutropenia is absorved in all patients after stem cell transplantation (SCT) antibiotic and antifungal prophlaxis is recommended to patients after the transplantation. The aim of this study was to evaluate the infection agents in patients developing febrile neutropenia after high dose chemotherapy (HDC) and SCT. Methods: Patients who underwent HDC and auto- and allogenic SCT between 2003-2012 in the GATA medical oncology department were investigated for infection agents. After the development of fever in the neutropenic period of SCT blood and urine cultures were taken and antibiotics was started. Data of 278 patients were reached who were eligible for evaluation. Of these 67 patients cultural examination were positive. 8 allogeneic SCT, 59 autologous SCT patients consisted of NHL (n=20), testicular cancer (n=11), multiple myeloma (n=10), Hodgkin Lymphoma (n=9), AML (n=4), ALL (n=2) and other diognosis (n=11). Results: When the agents identified according to standart blood culture examinations 44.5 % were coagulase neg. staph, 24% were gram neg. bacils and 15% consisted of candidas. When the results of urine culture was observed: 66.8% were gram neg. bacils, 11.1% were coagulase neg. Staph and 5.5% consisted of candidas. Gram neg. bacilli growth was present in 80% of the blood cultures of Hodgkin’s Lymphoma patients and coagulase neg. Staph growth were observed in 20% of the patients. Coagulase neg. Staph consisted 66.8% of the catheter culture results, 13.2% consisted of Acinetobacter beumonii and 6.6% consisted of enterococci. Conclusions: Physicians who are working in SCT area should be aware of different kind of infections, which is reported in this study. [Table: see text]
Does anatomic segmentectomy have better outcomes than wedge resections in stage I NSCLC patients treated by sub-lobar resection?
Authors: Lim Bora , Ali Suhail M. , Varlotto John M. , Higgins Kristin , DeCamp Malcolm M. , Recht Abram , Flickinger John Charles , Reed Michael , Toth Jennifer , Kelsey Christopher Ryan
Published: March 2020

e18506

Background: As compared to wedge resection (WR), anatomic segmentectomy (AS) may result in a more thorough resection because it allows bronchial and vascular dissection in a manner similar to a lobectomy and greater access for lymphadedectomy. The purpose of our study is to assess if AS allows for lower loco-regional (LR)/distant (DR) recurrences, improved overall survival (OS), and greater ability to resect lymph nodes as compared to WR. Methods: A multi-institutional database of consecutive patients undergoing surgical resection with negative margins for Stage I NSCLC FROM 1998-2009 was used. 2,300 patients had stage I NSCLC(<4cm) underwent surgical resection from which 267 received either AS or WR and were investigated. Variables studied to assess their impact on LR, DR, and OS included age, sex, surgical procedure, hilar node (N1) sampling, histology, LVI, tumor size, tumor grade, and visceral pleural involvement. Cox proportional hazard modeling was used for multivariate analysis. Results: Median follow-up was 188 weeks. The frequency of AS and WR were 3.3% and 12.7%, respectively. We compared LR and DR. There were higher numbers of N1 and N2 removed nodes in patients who underwent AS (p<0.05). There was no significant difference in rates of LR (p=0.58), DR (p=0.4), or OS (p =0.24) between WR and AS in multivariate analysis. Conclusions: Despite more extensive lymphadenectomy, AS is associated with similar rates of LR, DR and OS as WR. [Table: see text]
Determination of thresholds for the assessment of response to therapy relying on volume-based tumor burden in pulmonary CT images.
Authors: Beaumont Hubert , Labatte Jean Marc , Souchet Simon , Iannessi Antoine , Wormanns Dag
Published: March 2020

e18508

Background: Image-based biomarkers play an increasing role in the assessment of response to therapy. The widely adopted Response Evaluation Criteria in Solid Tumor (RECIST) mainly rely on the assessment of the Longest Axial Diameter (LAD) of tumors. A growing community suggests that quantifying the tumor volume addresses some of the RECIST limitations. However no consensus has yet emerged regarding the applicable thresholds classifying volume-based response. This study aims at determining such threshold values for tumors observable in pulmonary CT images. Methods: Our study is based on published data from the Quantitative Imaging Biomarker Alliance (QIBA) which reports a 15% variability in measuring the tumor volume. We analyzed additional clinical data in a retrospective study involving 10 patients with Non-Small Cell Lung Cancer (NSCLC), followed over 7 time points in average with CT. 2 expert radiologists and 5 imaging scientists measured the volume of each tumor at each time point. Response evaluation was modelled according to statistical inference of the ratio of two longitudinal measurements by the Geary-Hinkley (GH) transformation. We hypothesised a normal distribution of the measurements. Results: The study confirmed the previously published 15% variability in measuring tumor volume. From our data, the GH transformation appeared suitable to infer the evaluation while considering a normal distribution of the variability.We found that, using the volume of lesions, a tumor burden reduction corresponds to a decrease of at least -35 %, whereas a tumor burden growth is associated with an increase of at least +55%. These thresholds featured a 5% type I error. Applying the model to clinical data, we confirmed the impact on inter-reader agreement. Conclusions: Based on a well established evaluation of the variability of measurement and relying on an analytical model, we determined thresholds required to classify patient’s response to treatment when monitoring the volume of lesions. Our approach provides a couple of threshold values for given precisions of measurements and Type I error, making our approach generic and applicable to other longitudinal evaluations.
Survival results and prognostic factors in T4 N0-3 non-small cell lung cancer patients according to the AJCC 7th edition staging system.
Authors: Arslan Deniz , Bozcuk Hakan Sat , Tatli Ali Murat , Gunduz Seyda , Uysal Mukremin , Goksu Sema Sezgin , Koral Lokman , Coskun Hasan Senol , Savas Burhan
Published: March 2020

e18517

Background: In our study, we evaluated the survival results and prognostic factors among T4 local advanced non-small cell lung cancer (LA-NSCLC) patients in a large heterogeneous group, in accordance with the new staging system. Methods: We retrospectively evaluated the files of LA-NSCLC patients who have been treated at two centers between November 2003 and June 2012. One hundred twenty two T4 N0-3 M0 LA-NSCLC patients, identified according to the new staging system, were included in the study. Results: Median OS was 18.3 months, 1 year overall survival (OS) rate was 72%, 5 year OS rate was 28%. The median follow-up period was 17.4 months. Statistically significant predictors of survival were (p<0.20) ECOG-PS, age, subgroups of T4 factor, stage and primary treatment in OS univariate analysis. It was found that the statistically significant variables in multivariate analysis of OS rate were ECOG-PS (p=0.001), diagnostic stage (p=0.021), and primary treatment (p=0.004). In the group given non-curative treatment, the median OS was 11.0 months, 19.0 months in the definitive RT group as for 26.6 months in the curative treatment group. While there was a significant difference between the non-curative group and the groups which had definitive RT and curative operations (respectively p<0.001 and P=0.001) in terms of OS, no statistically significant difference (p=0.22) was found between the groups which had definitive RT and curative operations. Median EFS rate was 9.9 months, 46% in 1 year EFS rate, 19% in 3 years and 15% in 5 years. In univariate analysis of EFS rate with ECOG-PS, weight loss and staging, statistical significances were found only in PET-CT use, stage and primary treatment (p<0.20). In multivariate analysis with EFS, only the primary treatment was statistically significant (p=0.001). In the group that was approached with non-curative treatment, the median EFS was 10.5 months and in the curative operation group it was 14.7 months. Conclusions: Independent prognostic factors among this heterogeneous group of T4 N0-3 M0 122 LA-NSCLC patients were diagnosis age, ECOG-PS, stage and primary treatment. Primary treatment was a significant prognostic indicator of EFS rate.
Repopulation of tumor cells after neoadjuvant chemotherapy in non-small cell lung cancer and head and neck cancer: A neglected factor.
Authors: Xu Shanlin , Yue Jinbo , Liu Jing , Yang Jia , Sun Jujie , Mu Dianbin , Yu Jinming
Published: March 2020

e18533

Background: Neoadjuvant chemotherapy (NAC) has been widely used to patients with locally advanced Non-Small Cell Lung Cancer (NSCLC) or Head and Neck Cancer(HNC).Less is known about repopulation in human cancer after chemotherapy. It is hypothesized that NAC might be the preceding stimulus to activate the epidermal growth factor receptor (EGFR), which may trigger cellular repopulation. We aim to ananlyze whether NAC could trigger repopulation of surviving cells and evaluate the potential role of EGFR in molecular mechanisms that underlie accelerated repopulation after chemotherapy. Methods: Fifty-two patients with locally advanced NSCLC (28 cases) and HNC(24 cases) were studied. received platinum-based NACImmunohistochemical expressions of ki67 and EGFR were measured from biopsy before NAC and surgical specimens after NAC. Spearman rank correlation analysis and Chi-square test was used to determine whether pretreatment clinicopathological characteristics and time between last day of last chemotherapy and surgery are predictive of tumor cells repopulation. Results: The median duration between the last day of last chemotherapy and surgery was 15 days (range, 1–53 days).Twenty-one (40%) of fifty-two patients showed an increased Ki67 proliferative index PI after chemotherapy.The increased PI were significantly associated with poor clinical response and longer interval between last chemotherapy and surgery. No significant relationship was found between the change of Ki67 and clinicopathological characteristics including the location of the tumor, clinical stage, and histological grade,as well as the change of EGFR expression. A delay greater than 14 days produced greater increases in Ki-67 change ( p =0.028) than lesser delays. Conclusions: Our results suggest that tumor cell repopulation may frequently occur in patients with longer interval,especially greater than 14 days between the last day of last chemotheraoy and surgery. Our results did not suggest a higher EGFR expression lead to increased proliferation.
Feasibility of using the drug-induced apoptosis assay (MiCK assay) in mesothelioma as compared to non-small cell lung cancer (NSCLC).
Authors: Wigle Dennis A. , Hallquist Allan , Presant Cary , Molina Julian R.
Published: March 2020

e18538

Background: The drug-induced apoptosis MiCK assay has been predictive of outcomes in acute myelocytic leukemia, ovarian cancer, and a variety of solid tumors including breast cancer (Cancer Research 2012; 72:3901). We compared MiCK assay results in mesothelioma patients (pts) with NSCLC pts. Methods: Specimens from tissue or effusions were submitted to a central lab, processed to purify neoplastic cells, and a MiCK assay was performed as described (Cancer 2012; 118: 4877). Best chemotherapy regimens are defined as drugs/combinations with highest kinetic units (KU) of apoptosis +/- 1 SD compared to other drugs (this definition was predictive of outcomes in ovarian cancer). Active drugs have results over 1.0 KU of apoptosis. Results: 10 specimens have been submitted and 7 have been successful. Mean age was 69 and mean number of prior lines of therapy were 0.7 in 3 mesothelioma pts and 2.0 in 4 NSCLC pts. Mean number of drugs or combinations assayed successfully were 41 in mesothelioma and 20 in NSCLC. In mesothelioma, best active chemotherapy regimens (>1.0 KU) have been pemetrexed+doxorubicin, epirubicin, idarubicin, cyclophosphamide, ifosfamide, and dactinomycin. In NSCLC, best active regimens have been doxorubicin+cisplatin, irinotecan, and cyclophosphamide+doxorubicin+vincristine. In mesothelioma pts, the assay has been able to identify unexpected significant activity of several drugs: epirubicin, idarubicin, daunorubicin, dactinomycin, bendamustine, melphalan, vincristine, topotecan, azacytidine and bortezomib. Conclusions: Use of the MiCK assay in mesothelioma is at least as successful in the laboratory as it is in NSCLC. Unexpected new leads for innovative therapeutic strategies have been identified by the in vitro results. This feasibility study justifies a prospective controlled trial of the MiCK assay in mesothelioma and NSCLC pts. Clinical trials of drugs with unexpected activity are warranted in mesothelioma pts. Clinical trial information: NCT 01770665.
Efficacy and safety of oral etoposide maintenance therapy following cisplatin plus etoposide in advanced small cell lung cancers (Study of the Anatolian Society of Medical Oncology).
Authors: Urakci Zuhat , Kaplan Muhammet Ali , Unal Olcun Umit , Kucukoner Mehmet , Sevinc Alper , Oztop Ilhan , Suner Ali , Eren Tulay , Inanc Mevlude , Koca Dogan , Yazici Omer Kamil , Isikdogan Abdurrahman
Published: March 2020

e18546

Background: Small cell lung cancers (SCLC) constitute a mean of 15% of lung cancers and present with advanced disease at time of diagnosis in 60% of cases. Cisplatin plus etoposide schedule is the standard treatment in these patients , whereas the role of maintenance therapy is debated. We assessed the efficacy and safety of oral etoposide maintenance therapy following cisplatin plus etoposide in advanced SCLC. Methods: Demographic features, treatment response, survival rate, and toxicity rate were assessed in our patients who were followed up for advanced SCLC between 2006 and 2012, had a ECOG performance status of 0-1, and were given oral etoposide maintenance therapy (50mg/day, given 14 days of a 21-day cycle, a total of 6 cycles) following 6 courses of cisplatin (75 mg/m2, 1 day) and etoposide (100mg/m2, 3 days). Results: A total of 51 patients were studied, 46 (90.2%) of whom were male; the mean age was 59 (28-78) years at diagnosis. Forty-four (86.2%) patients had partial remission while 7 (13.7%) had complete remission. Nine (17.6%) developed neutropenic fever while grade 3-4 toxicities, neutropenia, anemia, thrombocytopenia, neuropathy, diarrhea, nausea and vomiting were present in 39.2%, 9.8%, 5.9%, 1.9%, 3.9%, 3.9%, and 1.9% respectively. Chemotherapy was postponed in fourteen (27.4%) patients due to toxicity. Six (11.7%) patients taking oral etoposide developed febrile neutropenia and 3 (5.9%) developed grade 3-4 thrombocytopenia. Chemotherapy was postponed in 5 (9.8%) patients due to toxicity while no toxic death was observed. After a median follow-up of 19 months, 32 (62.7%) patients experienced progression of disease and 29 (56.8%) died. Median progression free survival was found 11.6 months (%95 CI; 10.2-12.9 months) and median overall survival was found 15.6 (%95CI; 11.5-19.7 months) months. Conclusions: Our results were similar with the previous literature. Oral etoposide maintenance therapy following cisplatin plus etoposide therapy in advanced SCLC is effective and tolerable. Further randomized studies are needed in this topic.
Cisplatin, gemcitabine, and vinorelbine (PGV) compared with cisplatin and etoposide (PE) in the first-line treatment of extensive-stage small-cell lung cancer: Two Brazilian institution experience.
Authors: Pereira Augusto Akikubo Rodrigues , Assis Ronnei J F , Pereira Emiliano da Costa , Lima Vladmir C. , Nugue Pedro B. , Pereira Jose Rodrigues
Published: March 2020

e18548

Background: The standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) has been cisplatin plus etoposide (PE). Phase II studies showed comparable outcomes and less toxicity with platinum-doublets containing gemcitabine or vinorelbine. Aiming to improve response rates without increasing toxicity, we evaluated the combination of cisplatin, gemcitabine plus vinorelbine (PGV) in comparison to PE. Methods: Patients with ES-SCLC, ECOG 0-1, admitted from January 2002 to January 2011 in two brazilian institutions were analyzed. We compared patients treated with PE (cisplatin 80 mg/m2 D1 and etoposide 100 mg/m2 D1-D3 every 3 weeks for up to 6 cycles) versus modified PGV (cisplatin 80 mg/m2 D1, gemcitabine 1500 mg/m2 D1 and vinorelbine 30 mg/m2 D1 every 3 weeks for up to 6 cycles). Results: Of 69 patients analyzed, 29 were treated with PGV and 40 with PE. Clinical characteristics were comparable in both groups, except for adrenal metastases that were more frequent in PE group (20% vs. 0%; p=0,02). Overall response and complete response rates with PGV and PE were 75.9% vs. 65.0% (p=0.33) and 6 (20.7%) vs. 3(7.5%) (p=0.15), respectively. Median progression-free survival for PGV and PE was 6.47 and 5.06 months (p=0.37). Median overall survival for PGV and PE was 10.94 months versus 9.65 months (p=0.76). Severe neutropenia was higher with PE versus PGV (57.1% vs. 23.1%; p=0.01). Severe vomiting (38.5% vs. 17.2%; p=0.07) and peripheral neuropathy (15.4% vs. 5.3%; p=0.37) were more common with PGV than PE, although without statistical significance. Conclusions: Modified PGV presented comparable efficacy to standard PE in the first-line treatment of ES-SCLC. Response rates were higher with PGV, but without statistical significance. PGV showed less severe neutropenia than PE, but higher non-significant severe vomiting and neuropathy. Prospective studies with a large number of patients should be provided to confirm these results.
Expression of FLI-1 and the proliferation and survival of small cell lung cancer cells.
Authors: Song Wei , Cui Jiuwei , Li Wei , Wang Guanjun , Li Yan
Published: March 2020

e18550

Background: Small cell lung cancer (SCLC) exhibits aggressive behavior, rapid growth, early spread to distant sites. Over the last few decades, prognosis for patients with SCLC has changed little and there remains an critical need for evaluating novel agents. Here, we report that Fli-1 (Friend leukemia virus integration 1), a transcription factor and member of the Ets family, has an essential role in SCLC progression and may be a promising target for therapy. Methods: Immunohistochemical staining was used to investigate the expression level of Fli-1 in 25 patients with SCLC, including 12 patients in limited stage and 13 patients in extensive stage. The growth, apoptosis assay and molecular mechanism of Fli-1 in SCLC cell line (NCI-H446) was studied by down-regulating Fli-1 expression through RNA interference. Results: It was shown that expression level of Fli-1 was significantly up-regulated in SCLC tissues compared with adjacent tissues (p=0.0002). Its staining was found specifically in the nuclei of cancer cells. Expression level of Fli-1 was higher in extensive stage disease than that in limited stage disease (p=0.0045). Down-regulation of Fli-1 expression by RNA interference in NCI-H446 was found to strongly decrease cell growth, promote cell apoptosis and reduce metastasis. Importantly, when Fli-1 was down-regulated in NCI-H446, epidermal growth factor (EGF)-induced Akt activation was dramatically decreased. It was implied that Fli-1 was involved in the Akt regulation passway. It was also confirmed that the apoptosis induced by decrease of Fli-1 expression via down-regulation of its target regulation gene, bcl-2. Conclusions: The novel mechanistic insight into a critical role of Fli-1 in SCLC progression was shown in this study. Fli-1 overexpression promotes SCLC aggression partly via activating Akt phosphorylation. We propose that Fli-1 is a new powerful predictor for SCLC progression, and is also a new potential target for SCLC treatment.
Efficacy results of first-line chemotherapy re-challenge in sensitive small cell lung cancer (SCLC): A retrospective multicenter analysis.
Authors: Genestreti Giovenzio , Tiseo Marcello , Burgio Marco Angelo , Monti Manuela , Scarpi Emanuela , Carloni Federica , Verlicchi Alberto , Casanova Claudia , Dazzi Claudio , Amadori Dino
Published: March 2020

e18561

Background: Response and duration to initial chemotherapy are important factors used to classify SCLC patients into two groups. The first group comprises sensitive disease that responds to initial chemotherapy and relapses after more than 3 months and for which disease control could be obtained by re-challenging with first-line chemotherapy. The second group comprises refractory disease that progresses at the end or within 3 months of finishing first-line chemotherapy and for whom second-line chemotherapy represents the gold-standard. Methods: We reviewed clinical data from 4 Oncology Departments on sensitive SCLC treated with a first-line chemotherapy re-challenge in order to evaluate its activity and efficacy. Results: Of 211 SCLC patients diagnosed from January 2007 to December 2011, 25 (12%; 20 males, 5 females) had sensitive disease of whom 13 (52%) limited disease (LD) and 12 (48%) extended disease (ED). Median interval between the last day of chemotherapy and the onset of disease progression was 205 days (95% CI 169 – 279; range: 90 – 665). Chemotherapy consisted of etoposide + carboplatin in 15 (60%) patients or cisplatin in 10 (40%). On average 3-4 (range: 1-6) chemotherapy courses were administered, producing 8 (32%) partial responses, 3 (12%) stable disease, 10 (40%) progressive disease and 4 (16%) non evaluable disease. Further-line chemotherapy, mainly topotecan, was administered in 13 (52%) patients. Median overall survival produced by all treatments was 19.6 months (95% CI 16.5 – 27.6). Conclusions: In our experience, sensitive SCLC treated with first-line platinum/etoposide re-challenge produced interesting results in terms of activity and efficacy. Prospective randomized trials are warranted to investigate whether this strategy produces better results than standard second-line chemotherapy.