bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective review of stage III non-small cell lung cancer (NSCLC) patients treated with carboplatin/paclitaxel plus radiotherapy followed by docetaxel
Authors: Patel M. R. , Weidner M. , Lynch J. W. , Walden E. , George T. J.
Published: March 2020

18123

Background: Concurrent chemoradiotherapy is standard of care for unresectable patients and the most widely cited trials include the locally advanced multi-modality protocol (LAMP) study, SWOG S9019 and S9504. Our institutional approach represents a merger between the protocols utilized in two of these phase II studies: chemoradiotherapy from the LAMP study and consolidation therapy from SWOG S9504. Methods: We identified all stage III patients treated at the NF/SG VHS from Jan 2001 to Dec 2005. Eligible patients who had unresectable stage III NSCLC were included in the analysis. We treated 34 patients with weekly paclitaxel 45 mg/m2 plus carboplatin AUC 2 and concurrent TRT 63.0 Gy over 7 weeks. Four weeks after the completion of chemoradiotherapy, docetaxel 75 mg/m2 was given every 3 weeks for 21 days for 3 cycles as consolidation. Our primary endpoints were overall and progression free survival. The secondary endpoints were response rate and toxicity. Results: With a median age of 65 years and follow-up time of 25.9 months, median overall survival was 13.7 mos. Median progression free survival was 9.8 mos. The overall response rate was 68% including 5 CRs (15%). The most common grade 3/4 toxicities included pneumonitis (21%), esophagitis (21%), neutropenia (21%) [febrile neutropenia (9%)], neuropathy (18%), anemia (15%) and hypersensitivity to paclitaxel (9%). 62% of patients were able to complete the planned treatment. There were no treatment related deaths. At the time of this analysis, 9 patients were alive (26%) including 7 without progression (21%). Conclusions: Chemoradiotherapy with weekly carboplatin and paclitaxel followed by consolidation therapy with docetaxel is associated with comparable outcomes to other combined modality regimens. Given the advanced age and co-morbidities of our population, this regimen was generally well tolerated with the expected toxicities and can be considered as an option in the treatment of patients with unresectable stage III NSCLC.

No significant financial relationships to disclose.
Effects of dexamethasone (Dex) pretreatment on toxicity and efficacy of carboplatin and gemcitabine (Carbo/Gem) in patients with non-small cell lung cancer (NSCLC)
Authors: Leggas M. , Kuo K. , Cloud G. , Li M. , Wang H. , Zhang R. , Robert F. , Rinehart J. J.
Published: March 2020

18124

Background: Our preclinical data showed that treating mice with Dex 4 days prior to chemotherapy increased efficacy and decreased toxicity of Carbo/Gem in nude mice bearing human NSCLC by increasing drug concentration in tumors, and decreasing drug concentration in normal tissue without altering plasma pharmacokinetics (PK). Thus, we undertook a Phase I/II trial to determine the optimal dose of Dex, and the effect of Dex on Carbo/Gem plasma PK. Methods: Patients (n=30) with untreated, stage IV NSCLC and PS =2 received Gem, 1g/m2 days 1&8, and Carbo, AUC 5.5 on day 1. Patients were randomized (1:2:2) to receive no Dex (arm 1), or Dex at 8 and 16 mg bid po 4 days before and on day 1 (arms 2 and 3). Dex was administered in courses 2, 3, and 4 (only) to allow course 1 vs course 2 intra-patient toxicity and Carbo/Gem plasma PK assessment. Plasma samples were analyzed by HPLC for Carbo/Gem. Plasma PK analysis was performed with NONMEM v5 using a 5-compatment or 2-compartment structural models for Gem and Carbo. Results: Patients in arms 1, 2, and 3 were similar in PS, age, gender, and histology. In arms 1, 2, and 3, patients completing 4 planned courses of therapy: 1/6, 6/12, 9/12; partial responses (RECIST): 2/6, 7/12, and 8/12. Hematologic toxicity in arms 1 (no Dex), 2, and 3 (Dex) was compared. Platelet nadirs (course2÷course1): 0.6±0.2, 3.77±2.0, 3.4±0.72 (p<0.02); AGC nadirs: 1.1±0.3, 2.32±0.4, 4.95±1.04 (p< 0.01); Change in median time to recovery from day 1 (course 2-course 1) of AGC to 1,500 mm3 in days: +9, -15, -19; Change in median time to recovery of platelets to 100,000 mm3: +5, -1, -1.5. Comparison of nadir AGC and platelets between courses 2, 3, and 4 consistently demonstrated superiority of arm 3 over arm 2. No significant differences in non-hematologic toxicities were seen between arms 1, 2 and 3. Gem and Carbo clearance values were not significantly different among arms or courses. Area under the time-concentration curves (course2÷course1): 0.91±0.18, 0.77±0.15, 0.80±0.16. Conclusions: Dex pretreatment appears to reduce toxicity and improve efficacy of Carbo/Gem in NSCLC patients, with arm 3>2. These effects are not due to alteration of plasma PK since no significant decrease in chemotherapy exposure was observed in arms 2 and 3.

[Table: see text]
A combination phase I study of topotecan with carboplatin for relapsed small cell lung cancer: Results of West Japan Thoracic Oncology Group trial (WJTOG0202)
Authors: Kashii T. , Kurata T. , Takeda K. , Seki N. , Tsuboi M. , Miwa T. , Morinaga R. , Kobayashi M. , Satoh T. , Fukuoka M.
Published: March 2020

18126

Background: Topotecan is an active agent for relapsed or recurrent SCLC. Combination chemotherapy of topotecan and carboplatin for relapsed SCLC has not been fully evaluated. To determine the maximum-tolerated dose (MTD), a phase I study was conducted. Method: Patients with measurable disease and one prior chemotherapy regimen excluding topotecan were enrolled in this study. Topotecan was administered through days 1 to 5, whereas carboplatin was administered on day 5. Courses were repeated every 3 weeks. The starting doses of topotecan and carboplatin were 0.50 mg/m2/day and AUC=5, respectively. The dose levels examined are shown in the table below. Results: A total of 32 patients with relapsed SCLC have been enrolled. Patient characteristics are as follows: median age, 64 yrs (range 43–74); male/female, 23/9; ECOG PS 0/1, 15/17 patients. Dose-limiting toxicities (DLTs) were observed in 1 patient at dose level 1 (infection), level 3 (diarrhea), and level 5 (thrombocytopenia), respectively. Three of 6 patients have experienced DLTs at dose level 6 (thrombocytopenia). MTD of topotecan and carboplatin were determined to be 0.85 mg/m2 and AUC=5, respectively. Five of 29 (17 %) assessable patients have responded to treatment with a partial response (PR), and 13 (45 %) patients have had stable disease (SD) at best response. Conclusions: The recommended doses are 0.75 mg/m2 of topotecan and AUC=5 of carboplatin. The combination of topotecan and carboplatin shows an acceptable activity and toxicity profile in relapsed SCLC patients. Further study in the phase III setting is warranted.

[Table: see text]

No significant financial relationships to disclose.
Targeting Na+/K+-ATPase in non-small cell lung cancer (NSCLC)
Authors: Nilsson B. , Mijatovic T. , Mathieu A. , Roland I. , Van Quaquebeke E. , Van Vynckt F. , Darro F. , Kiss R.
Published: March 2020

18144

Background: Non-small cell lung cancer patients that present with grade IIIB or stage IV disease have a median survival of 5–7 months if left untreated. With modern chemotherapy overall survival may be 11–12 months, but still no patients are cured. We have investigated the impact of modulation of the a-1 subunit of Na+/K+-ATPase in NSCLC. Methods: Cancer tissue from 59 patients with NSCLC (30 adenocarcinomas and 29 squamous cell cancers) and 25 normal lung samples as well as four human NSCLC cell lines (A549, Cal-12T, NCI-H727, A427) were assessed with regard to expression of the a-1 subunit of Na+/K+-ATPase (sodium pump) by use of immunohistochemistry. In addition, A549 cells were transfected with specific a-1 siRNA for study of a-1 subunit expression and of cell proliferation and migration. Protein expression was analyzed by Western blotting. Cell proliferation was assessed by MTT and cell migration by video microscopy. Cell lines were exposed to varying concentrations of ouabain, digoxin, digitoxin and UNBS1450, a novel cardenolide targeting the a-1 subunit of Na+/K+-ATPase for study of proliferation, migration, and inhibition of the target. Results: Expression of the a-1 subunit of Na+/K+- ATPase was elevated in almost half of the tissue samples from patients with NSCLC compared to normal controls. The a-1 subunit was also overexpressed in A549, Cal-12T and NCI-H727 cells. Transfection of A549 cells with siRNA resulted in markedly decreased expression of the a- 1 subunit and also to reduced migration and proliferation of such cells. UNBS1450 at 10 and 100 nM for 72 hours reduced A549 cell migration and proliferation similar to that observed with anti- a-1 siRNA. Digoxin had no activity at these concentrations. Conclusions: Inhibition of the a-1 subunit of Na+/K+-ATPase is associated with significant decrease of cell migration and proliferation and has potential as a therapeutic strategy in NSCLC.

No significant financial relationships to disclose.
Gemcitabin (G) plus cisplatin (P) versus etoposid (E) plus cisplatin in advanced/metastatic non-small cell lung cancer (NSCLC): Preliminary results of a randomized monocentric study
Authors: Bousahba A. , Bereksi-Reguig F.
Published: March 2020

18155

Background: we performed a randomized monocentric study to compare the treatment response of two chemotherapy doublets EP versus GP. Survival rates and toxicity are the secondary endpoints. Methods: from December 2003 to October 2006, patients with non-operable stage IIIB /IV histological or cytological proven NSCLC, ECOG PS = 2, were randomized to: (A) gemcitabin 1250 mg/m2 on d 1, 8 plus cisplatin 80 mg/m2 on d1 q3w for 6 cycles or (B) cisplatin at same dose followed by etoposid 100 mg / m2 on d1, 2, 3 q3w. The sample size was estimated at 64 patients per treatment arm to provide a power of 0.80 to detect a 20% difference in response rate between the two groups at the 5% level. Results: one hundred thirteen chemonaïve patients were enrolled (A: 57, B: 56), median age 61 years (arm A) and 57.5 years (arm B), stage IIIB (42.1% A vs 41.1% B), two or more metastatic sites (34% A, 39% B), PS 1 (68.4% A, 69.6% B). 360 cycles were administered 187 (A) and 173 (B) with a median of 3 cycles per patient in each group. Two patients were excluded from analysis. One hundred one patients were evaluable for toxicity, 90 for response. 47 pts were evaluable in A and 43 pts in B with treatment response in intent to treat principle respectively: complete response (1.8% - 0%), partial responses (29.1% and 20.7%). The objective response rate was 30.9% (95% CI 18.8%-43.2%) in A, 20.7% (95% CI 9.8%-31.6%) in B, no change (36.4% and 37.7%) and progressive disease (18.2% and 22.6%). Median duration of objective response 8.2 months (A) and 8.3 months (B), median time to progression : 8.0 months (A) and 7.5 months (B). Incidences of grade 3–4 toxicities were respectively in arms A and B: nausea-vomiting (37%-12.5%), leucopenia (5.6%-14.6%), neutropenia (13%-37.5%), thrombopenia (0–2.1%), anemia (13%-6.3%). Febril neutropenia occurred in 1.9% (A) and 8.3% (B). One toxic death occurred in arm B. Conclusions: preliminary analysis indicates that GP had a more favourable toxicity profile and a higher activity is suggested for the GP regimen. The enrolment is continued.

No significant financial relationships to disclose.
A feasibility study of adjuvant carboplatin (C) plus gemcitabine (G) in completely resected stage IB-III non-small-cell lung cancer (NSCLC)
Authors: Horiike A. , Ohyanagi F. , Okano Y. , Satoh Y. , Okumura S. , Ishikawa Y. , Nakagawa K. , Horai T. , Nishio M.
Published: March 2020

18158

Background: In recent randomized phase III trials in early-stage NSCLC, cisplatin-based adjuvant chemotherapy resulted in a 4.1–15% 5-year survival benefit versus observation. However, only 56–74% of patients completed planned treatment, suggestive of poor compliance. C plus G (CG), one of the standard regimens for advanced NSCLC, is considered more tolerable than other platinum-based regimens because it is associated with less nausea/vomiting, sensory neuropathy, and alopecia. The objective of this study was to assess the feasibility and safety of adjuvant CG in patients with completely resected NSCLC. Methods: Eligibility criteria included histologically confirmed NSCLC, age 20–74 years, complete surgical resection, post-operative pathological stage IB-III, 4–8 weeks post-surgery, ECOG performance status (PS) 0–1, adequate organ function, and informed consent. Patients were treated with adjuvant CG (C, AUC=5 on day 1; G, 1,000 mg/m2 on days 1 and 8) every 3 weeks for 4 cycles. The primary endpoint was treatment compliance, and the planned sample size was 35 patients (Simon’s minimax design). Results: From October 2004 to July 2006, 35 patients (17 males, 18 females; median age, 64 years) were enrolled. All patients had PS=0. Histologic types included adenocarcinoma (n=27), squamous cell carcinoma (n=3), large cell neuroendocrine carcinoma (n=3), large cell carcinoma (n=1), and adenosquamous carcinoma (n=1). Pathological stages included stage IB (n=7), stage IIA (n=7), stage IIB (n=4), stage IIIA (n=13), and stage IIIB (n=4). Resection consisted of lobectomy (n=33) and pneumonectomy (n=2). All patients received =2 cycles of chemotherapy, with 29 patients (83%) completing 3 or 4 cycles. Primary G3/4 toxicities were leukopenia (51%), neutropenia (83%), thrombocytopenia (71%), and anemia (38%). Nonhematologic toxicities were very mild: 6% G3/4 febrile neutropenia, 3% infection, and 3% rash. No treatment-related deaths occurred. Conclusion: Adjuvant CG in patients with completely resected NSCLC is well tolerated, and treatment compliance is very good.

No significant financial relationships to disclose.
A phase II study of weekly docetaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer
Authors: Son C. , Kim K. , Lee K. , Yang D. , Lee S. , Choi P. , Cho S.
Published: March 2020

18174

Background: Combination chemotherapy has been shown to extend survival and improve symptoms for patients with advanced stage, unresectable non-small cell lung cancer (NSCLC). However, chemotheraputic agents sometimes show significant toxicities that restrict their usefulness and not well tolerated in elderly and/or poor performance status patients. Docetaxel has shown efficacy with manageable toxicities when used alone or in combination with a platinum compound in a sequential manner before localized radical radiotherapy in advanced stage NSCLC. We performed this study to explore the efficacy and safety of weekly docetaxel plus carboplatin in patients with advanced NSCLC aged 60 years or older. Methods: From January 2005 to August 2006, 45 patients with advanced NSCLC patients aged 60 years or older were enrolled in the study. Patients received docetaxel 25mg/m2 by IV infusion over 30–60 min and carboplatin, AUC = 2, infused IV over 15–30 min weekly. Treatment was continued until disease progression or unacceptable toxicity occurred, at which time the patient was taken off treatment. Maximum doses were 18 and evaluated the patients received at least 9 doses. Results: Of 45 patients, 24 patients received at least 9 dose of study drug. 21 patients stopped the treatment before the completion of 9 cycles; 9 (42.9%) due to poor general condition, 7 (33.3%) due to disease progression, and 5 (23.8%) due to volitional withdrawal. Of the 24 patients who received more than 9 cycles, final results were complete response in 1 (4.2%) patient, partial response in 16 (66.7%) patients, stable disease in 1 (4.2%) patient, and progressive disease in 6 (25%) patients. The most common hematological grade 3/4 adverse event was neutropenia(25%). There was no treatment-related death. Conclusion: Weekly docetaxel at low doses plus carboplatin in elderly patients with advanced non-small cell lung cancer provides acceptable response rate and toxicity. However, further study with large population will be needed to confirm its effectiveness and toxicity.

No significant financial relationships to disclose.
Clinical Responses to EGFr-TKI’s characterized by drug-induced cell death in human NSCLC primary cultures
Authors: Nagourney R. A. , Paulsen M. , Mc Connell D. , Shuman R.
Published: March 2020

18184

Background: Small molecule inhibitors of the EGFr have proven effective in advanced NSCLC but response rates in unselected populations remain low. Certain subsets of patients appear favored including females, non-smokers and Asians. Molecular profiles suggest that gene amplification or EGFr mutations (codons 19–21) may underlie responses. Our prior observations (Proc. AACR 2002, Abs.3902) indicated that gefitinib and erlotinib induced cell-death in human tumor microspheroids isolated from surgical specimens of some NSCLC patients, suggesting programmed cell death to be an important mechanism of action for these molecules. As part of an IRB-approved clinical trial, patients whose tumors were found sensitive to the EGFr-TKI’s by laboratory analysis, received 1st line single agent oral erlotinib at 150 mg/day. Methods: Following informed consent, NSCLC patients participating in the trial provided tissue for analysis as previously described (J Clin Oncol, 2000 18: 2245–2249). Dose response curves provided LC50 values by interpolation. Modified Z-score analysis identified patients sensitive to the EGFr-TKI’s by comparison with a database of over 900 EGFr-TKI analyses. Results: Three female caucasian patients were found more sensitive to EGFr-TKI’s than cytotoxic chemotherapy (2 non- & 1 former smoker). All 3 responded to erlotinib, 2 near-CR by PET, 1 lasting 19 months, the 2nd continuing at 10 months, with a 3rd patient in continuous PR at month 6. Toxicities have been moderate. One near-CR had virtually no skin rash. The molecular profile of 1 near-CR revealed no known gain of function mutation but instead a novel mutation in the EGFr domain. Conclusions: Exposure of human NSCLC microspheroids to EGFr-TKI’s in short term culture results in cell death events associated with clinical response, suggesting that programmed cell death is an important determinant of clinical response to these agents. This is consistent with the concept of oncogene addiction, in tumors driven by EGFr upregulation. Accrual to this trial continues. Supported by the Memorial Medical Center Foundation.

[Table: see text]
NETS of the lung (non SC): Experience of lung cancer working group E. Morelli Hospital Sondalo
Authors: Valmadre G. , Delfanti R. , Robustellini M. , Rossi G. , Della Pona C. , Epis R. , Pastorini A. , Buscemi A.
Published: March 2020

18191

Background: pulmonary NETS are typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNC), and SCLC. Purpose: to evalue prognosis of pulmonary NET (non SC) according by histotype, treatment and serum CgA. Methods: From 1996 to 2006 our lung cancer working group followed 42 pulmonary NETs, none carcinoid syndrome and 1 metastatic (CgA 100xN) at diagnosis. 39/42 underwent radical surgical resection with adenectomy. 2/42 TC had endobronchial laser, the metastatic any treatment. 31/42 (73.8%) are TC. 10/42 (23.8 %) are AC, 1/42 (2%) undetermined. Results: In dec 06 we reviewed 37/42 cases (20 clinical examination and 17 by phone). 2/5 missing were dead: 1 AC 7 years later with liver metastasis, high CgA without syndrome and 3 years of octreotide. 2 TC, 1 AC drop-out. Of 20 pts seen, 3 had high CgA, but Octreoscan negative. 32 pts (86.5%) had only surgery: 15 with more than 5 years DFS. 7 had preoperating CgA: 4 normal, 2 high (1 had hepatic metastasis, in 1 normalized and 36 months DFS), 1 ongoing. 2 pts without surgery are alive after 17 and 8 months. The metastatic pt has PR with octreotide. 1 TC had gastric carcinoma at 7 years. 3 TC had progressive disease. 1 TC (IA and high pre-lobectomy CgA), had persistent high CgA and positive octreoscan hepatic lesion 4 months later: PR after 6 months of octreotide. Another with normal pre-lobectomy CgA (TC IB) had carcinoid syndrome with high CgA and octreoscan positivity, 4 months later: negative restaging at 22 months with one-year of octreotide. A sixteen girl - TC IB - with high CgA (normal after pneumonectomy) developed octreoscan positive thoracic lesions, 18 months later. PR after 44 months with radiometabolic therapy. Conclusion: NETS are heterogeneous and with better prognosis (except SC) than other lung cancers. AC radically resected had good prognosis (1/10 metastasis ), sometimes TC gave metastasis and progression (2/31). For the 2 subtypes OS is high. Octreotide- and radiometabolic therapy can control the metastatic disease. CgA is not indicative of relapse but well correlates with the extension of metastatic disease. High CgA values are not predictive of carcinoid syndrome. It is important to evalue CgA before and 2–3 months after surgery. Carcinoid syndrome is rare in lung NET. We don’t have any LCNL.

No significant financial relationships to disclose.
Phase I study of cisplatin/carboplatin/irinotecan (CPI) regimen in patients with ED small-cell lung cancer
Authors: Ichiki M. , Yoshida Y. , Ishimatsu A. , Minami S. , Taguchi K. , Tachibana K. , Aizawa H.
Published: March 2020

18202

Cisplatin/irinotecan(IP) is standard regimen for ED-SCLC in Japan. Cisplatin (CDDP)-based treatment requires copious hydration, which can lead to a deterioration of outpatients’ quality of life. CDDP and carboplatin (CBDCA) have a common active form, but are associated with different adverse reactions. We considered that the combined use of these two agents could increase the dose intensity of active form platinum complexes without enhancing their toxicities. The IP was modified to nearly half the dose of CDDP/CBDCA to facilitate outpatient administration. We conducted a phase I study to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of this modified regimen for patients with ED-SCLC and stage IV NSCLC. Eligibility criteria included: PS 0–1, age <75 yrs, no prior therapy, measurable disease, adequate organ functions. DLT was defined as follows: 1) grade 4 neutropenia lasting 4 days or febrile neutropenia, 2) grade 4 thrombocytopenia, 3) prolongation of treatment due to toxicity, 4) grade 3 or worse non-hematological toxicity. Three patients were enrolled at level 1(CDDP/CBDCA: 25 mg/m2/AUC2), 3 patients at level 2 (25 mg/m2/AUC 2.5) and 3 patients at level 3 (30 mg/m2/ AUC 2.5), respectively. DLT was not observed at level 1, 2, 3. At dose level 4 (30 mg/m2/AUC3), two of three patients experienced DLT, suggesting this level to be the MTD. The recommended dose for phase II study is CDDP 30 mg/m2 on day 1, CBDCA AUC 2.5 on day 1 and irinotecan 60 mg/m2 on days 1, 8, 15. A phase II study of this regimen in ED-SCLC is ongoing.

No significant financial relationships to disclose.
Phase I study of amrubicin (AMR) for patients (pts) with previously treated small cell lung cancer (SCLC)
Authors: Katakami N. , Hata A. , Yoshioka H. , Higashi Y. , Nishimura T. , Sakaguchi S. , Hayashi M. , Tomii K. , Naya R. , Ishihara K.
Published: March 2020

18209

Background: Amrubicin, a totally synthetic 9-amino-anthracycline, has been demonstrated to have excellent antitumor activity against previously untreated SCLC. However, severe hematological toxicities were observed in previously treated SCLC when given at doses of 40 to 45 mg/m2, days 1–3. We sought to determine the maximum tolerable dose (MTD) and toxicity of amrubicin for pts with previously treated SCLC. Methods: Pts with confirmed SCLC, ECOG PS 0–1, and 20 to 74 years of age, with a history of receiving one or two regimens were eligible for the study. Pts were divided into two groups. Group R (-) consisted of pts without history of radiotherapy except prophylactic cranial irradiation. Group R (+) consisted of pts with history of irradiation up to two fields including thoracic radiotherapy. AMR was initially given at 35 mg/m2, iv, days 1–3, every 3 weeks in both groups. The dose was then increased to 40 and 45 mg/m2. Three pts were treated at each dose level in the absence of a dose limiting toxicity (DLT). All pts received prophylactic hG- CSF between days 8–13. DLT was defined as neutrophil nadir <500/μL lasting more than 4 days, neutropenic fever and neutrophil nadir <1000/μL, platelet nadir <20,000/μL or ≥ grade 3 non-hematologic toxicities. Results: Fourteen pts were enrolled, 10m/4f. The median age was 62 years (range 34–82). Two of 6 pts in the first cohort in group R (-) had dose-limiting neutropenia. The dose escalation is ongoing. Three pts in the first cohort in group R (+) had no dose-limiting toxicities. A subsequent 5 pts were treated at dose-level 2, and 3 pts had dose-limiting neutropenia. The MTD in group R (+) was 40 mg/m2. A response rate of 62% was observed. Median survival time was 12 months. No treatment-related death was observed. Conclusions: The MTD in group R (-) was not determined. The MTD in group R (+) was determined as 40 mg/m2. Further data will be presented.

No significant financial relationships to disclose.
Comparison of metabolic activity in mantle cell lymphoma at biospy site and other tumor sites using 18F-FDG PET
Authors: Chundru S. , Nguyen M. , Jaiyesimi I. , Wong O. , Douglas-Nikitin V. , Nadeau L. , Balon H. , Mardis N. , Fink-Bennett D.
Published: March 2020

18529

Background: Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin’s lymphoma (NHL) with a variable clinical course ranging from indolent to aggressive. Treatment for MCL is complicated by this variability, as systemic chemotherapy for NHL is directed by the aggressiveness of the lymphoma. Previous attempts have been made to correlate clinical outcome in MCL with histologic features. More recently, measurement of metabolic activity using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) was found to be highly correlative with the aggressiveness of NHL. Given the clinical heterogeneity of MCL, the search for the true metabolic status in MCL is important in prognostication and management. We propose to study the metabolic activity in MCL by comparing the maximum SUV at the site of biopsy with the highest SUV in other MCL areas of the body. Methods: 12 patients with newly diagnosed MCL and having staging by FDG-PET were identified. PET(CT) body scans were obtained in the usual fashion. The SUVs, defined as tumor activity divided by dose injected per lean body mass, from the PET and PET-CT cameras were cross validated to produce the same value in a given phantom and patient. Maximum biopsy SUV was measured by searching the maximum value within a volume of interest over the known biopsy site, and highest body SUV was similarly searched in known tumor sites in other body areas. Results: One patient was excluded because the tumor at the biopsy site had been completely resected. The remaining 11 patients (M:F=8:3, age=63±8 yrs) were analyzed. The SUV at biopsy sites ranged from 2.1 to 9.8 (mean=5.2±2.3). The SUV in other tumor sites ranged from 4.8 to 18.6 (mean=8.9±4.1), which was significantly higher when compared to the respective biopsy site (p=0.0036). Conclusions: As the SUV of MCL at the biopsy site may not represent the highest SUV, it is important to search other tumor sites in the body for the highest SUV to help in grading, managing, and subsequent monitoring of MCL. Perhaps FDG-PET can direct biopsies to tumor sites with the highest SUV and subsequently provide useful histologic detail for predicting clinical course. Future study is needed to correlate the maximal SUV of MCL with histology and clinical course.

No significant financial relationships to disclose.
Mutant P53 in non-Hodgkin lymphoma
Authors: El-Wahidy G. F. , Sharaf-eldin O. A. , Awad M. A. , Abdel Ghaffar H. A. , Salama M. S.
Published: March 2020

18537

Background: *Chromosomal aberrations are important events in the pathogenesis of lymphoma & leukaemias P53 belongs to class of genes whose functions involves negative regulation of cell growth through certain protein synthesis which leads to arrest of the cell cycle at growth phase. *Elucidate the nature of P53 in cases with Non Hodjkins lymphoma presented in our province (North east Mediterranean) and the impact of its mutation on known prognostic factors as well as on survival of patients receiving treatment by different chemotherapy protocols. Methods: Study done on 34 patients and 10 normal contorls Conclusions: *P53 +ve mutations in patients with lymphoma outnumbered those with −ve mutations. *Positivity degree is increased in higher grade than lower grade lymphoma. *Dfs is prolonged in those with −ve mutations than in subgroups with +ve mutations. *Subgroups with negative Exon mutations carry better survival than those with +ve mutations.

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No significant financial relationships to disclose.
Granulocyte macrophage colony stimulating factor as adjuvant therapy for resected stage III/IV melanoma: Retrospective review of a single institutional experience
Authors: Patel T. A. , Baweja M. , Maples W. , Markovic S.
Published: March 2020

19002

Background: Preliminary data suggesting positive clinical outcome in patients treated with adjuvant granulocyte macrophage colony stimulating factor (GM-CSF) following surgical resection of stage III/IV melanoma already exist (Spitler et al). A compassionate use protocol for the treatment of such patients with the “Spitler” regimen (GM-CSF administered at 250 mcg/day s.c. for 14 days of a 28 day cycle) has been ongoing at Mayo Clinic. Herein we present a retrospective review. Methods: Between 1998 and 2006, data was collected from 30 patients rendered disease free by surgery who received adjuvant GM-CSF. GM-CSF was administered per the “Spitler” regimen, although one patient received a reduced dose of 125mcg/day. The Kaplan-Meier approach was used to estimate relapse free survival. Results: Thirty patients (14 Female) with a median age of 53 and excellent performance status were evaluated. Most patients had resected stage III melanoma (Stage II/III/IV: 1/20/9). Median followup was 33 months (3–96). Twenty one patients were treated with GM-CSF for at least 12 months. Overall, relapse-free survival at 1 year was estimated to be 69% (95% confidence interval (CI) of 54% to 88%), reducing to 44% (95% CI of 29% to 67%) at 3 years. According to stage, relapse free survival at 1 year was 70% (III) and 63% (IV), and at 3 years was 54% (III), and 13% (IV). Among the 21 patients completing at least 1 year of therapy, relapse free survival at 3 years was 52%. Seventeen patients relapsed (III/IV: 10/7). Six of these patients were retreated and only two relapsed. Toxicities were grade 1 with most common being injection site rash (23%), asthenia (17%), myalgia (17%), and fever (7%). One patient required dose modification for elevated liver function tests. Conclusions: Although limited in scope, our data further support a potential beneficial effect of adjuvant GM-CSF in resected stage III/IV melanoma. Recurrences in the treated population were often localized and amenable to further surgical treatment. The clinical relevance of this strategy is currently being prospectively tested (E4697, now closed to accrual).

No significant financial relationships to disclose.
Assessment of cancer pain
Authors: Dugas A. F. , Murphy B. A. , Wells N. , Dietrich M. S. , Dwyer K.
Published: March 2020

19500

Background: This study investigates: 1) The concordance between patients and staffs’ standard use of the numerical rating scale (NRS) for pain, in which 1–4 is mild pain, 5–6 is moderate and 7 and above is severe; 2) The relative importance of functional impairment secondary to pain in patients’ pain ratings. Methods: Patients with cancer and current or previous pain (N=178) were asked to complete a fifteen minute interview with open-ended questions about their perception of pain. Results: When asked to define mild, moderate and severe pain according to the NRS, 65% of patients gave numbers that did not meet standard definitions as noted above. When asked to define mild, moderate and severe pain in general, 38% differentiated severity of pain based on its impact on their ability to fulfill activities of daily living (ADLs) and 39% differentiated it based on their emotional reactions. When asked to define tolerable pain, 28% described it in terms of its impact on ADLs, while 30% described it in terms of the NRS. For those patients who used a NRS, the mean value for tolerable pain was 4.9 (range 2–8) and the mean value for intolerable pain was 8.1 (range 5–10). 26% of patients defined satisfactory pain control based its impact on ADLs while only 2% defined it according to a NRS. 68% of patients reported that pain interfered with their ADLs, however only 33% reported that pain medication interfered. Conclusions: There is discordance between the standard definition of the NRS and patient perceptions of it, suggesting it should be supplemented by other types of pain assessment. Based on NRS, patients tolerate higher levels of pain than expected. Patient satisfaction with pain control is more dependent upon ability to complete ADLs than on a numerical rating of pain. Therefore, patients’ ability to function at an acceptable level should be part of the standard pain assessment.

No significant financial relationships to disclose.
Fitness and quality of life in endometrial cancer survivors and controls
Authors: Basen-Engquist K. , Lenihan D. , Carmack Taylor C. , Lu K. , Perkins H. , Hughes D. , McFalls K. , Shin K.
Published: March 2020

19502

Background: It has been suggested that sedentary behavior during cancer treatment or effects of the treatment itself may decrease cardiorespiratory fitness in cancer survivors. However, few studies have tested whether cancer survivors actually have impaired cardiorespiratory fitness compared to similarly aged individuals who have not had cancer. We investigated whether endometrial cancer survivors had poorer fitness than women of similar age and activity level with no cancer history. Methods: The sample included endometrial cancer survivors in a pilot exercise study; all had been diagnosed with Stage I-IIIa disease and were at least 6 months post- treatment. Controls were recruited from a local multi-speciality clinic. Both groups had no contraindications to exercise and were sedentary. Cardiorespiratory fitness was measured by predicted maximal myocardial oxygen carrying capacity (MV02 max) on a submaximal ramped cycle ergometer test. Quality of life was measured using the SF-36 (physical and mental component scores). Results: The study accrued 20 survivors (Mean age=58.6, SD=7.9; Mean BMI=30.5, SD=7.7) and 13 controls (Mean age=55.8, SD=7.6; Mean BMI=30.3, SD=7.0). In t-tests comparing survivors and controls, there were significant differences in predicted MV02 max (p=0.044) and physical aspects of quality of life (p=0.004), but not mental aspects of quality of life. After adjusting for age and BMI using ANCOVA, the p value for predicted MV02 max increased to 0.068, but differences in physical quality of life remained significant (see Table 1 ). Conclusions: Endometrial cancer survivors have diminished quality of life in the physical domain compared to women who have not had cancer; similar results were found for cardiorespiratory fitness, although the effect was attenuated after adjusting for BMI and age. The results suggest endometrial cancer survivors could benefit from exercise interventions to improve fitness and physical functioning. Table 1 : Fitness and quality of life of endometrial cancer survivors and controls.

[Table: see text]

No significant financial relationships to disclose.
Smoking cessation is challenging even after lung cancer surgery
Authors: Cooley M. E. , Sarna L. , Kotlerman J. , Lukanich J. M. , Jaklitsch M. , Bueno R.
Published: March 2020

19507

Background: It is recommended that patients undergoing lung cancer surgery quit smoking pre-operatively to reduce peri- operative complications. Smoking cessation after diagnosis is associated with improved clinical outcomes. Few studies have examined the behavior of surgical lung cancer patients who are smokers. We sought to 1) determine the smoking prevalence rate at diagnosis; 2) identify readiness to quit and cessation strategies, 3) describe patterns of smoking overtime, and 4) identify factors (demographic, tobacco-related, and health status) correlating with smoking relapse and/or continued smoking (SR) after surgery. Methods: Ninety-four patients were enrolled in a descriptive study. Data were collected through chart review and standardized tobacco and health status questionnaires. Smoking status was assessed through self-report and measurement of urinary cotinine. The primary endpoints were smoking status at 1, 2, and 4 months after surgery. Frequencies, t-tests, and chi-square were used for analysis. Results: Eighty-four patients (89%) were ever-smokers and 35 (42%) reported smoking at diagnosis. Twenty-nine (83%) current smokers attempted cessation at diagnosis and 18 (51%) received assistance with pharmacotherapy being the most common strategy. One month post-operatively, 20 (56%) self-reported smokers planned to quit within the following month. Fifty (60%) ever-smokers remained abstinent, 13 (15%) continued smoking, and 21 (25%) relapsed. Ten (48%) of those who relapsed were former smokers and had not smoked for at least a year before diagnosis. Factors significantly associated with SR included younger age, lower education and pain. Those who relapsed were on average 7 years younger (p=0.01). Those without high school education (HS) had a significantly higher rate of relapse as compared to those with at least HS (83% vs. 48%, p=0.04). Those with pain had a higher rate of relapse as compared to those who did not have pain (73% vs. 33%, p=0.03). Conclusions: Smoking relapse rates are high after lung cancer surgery even among those who previously quit. Former and current smokers are at high risk for relapse and will require smoking cessation programs incorporating symptom management and relapse prevention.

No significant financial relationships to disclose.
Oral chronic graft-versus-host disease symptom experience and cytokine correlates in survivors after transplantation for hematologic malignancies
Authors: Fall-Dickson J. M. , Ramsay E. S. , Imanguli M. , Guadagnini J. , Odom J. , Atlam N. , Pavletic S.
Published: March 2020

19510

Background: Oral chronic graft-versus-host-disease (cGVHD) is a frequent, clinically significant sequela of hematopoietic stem cell transplant (HSCT). No optimal treatment exists; molecular pathogenesis remains unclear. This descriptive study assessed stomatitis, oral pain, and dry mouth severity, and correlations with proinflammatory cytokine levels in stimulated submandibular saliva samples from cGVHD patients. Methods: Subjects were enrolled in the NCI sponsored cGVHD natural history protocol. Stomatitis severity was assessed with the Oral Mucositis Rating Scale (OMRS) (0–103); oral pain and dryness were self-reported via VAS (0–10). Saliva samples were collected on ice, stored at -80°C, centrifuged at 4000xg for 10 minutes at 4°C, and supernatant retained. Salivary TNFa, IL1a, and IL6 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) (R & D Systems, Minneapolis, MN). Results: Adult male and female subjects (N = 42) with cGVHD after HSCT primarily for hematologic malignancies were prescribed systemic (n = 34) and/or topical (n = 4) immunosuppressive agents, and opioids (n = 19). All subjects had mild to moderate stomatitis (OMRS mean = 18.38; range = 2.0 to 46) with erythema (n = 40), lichenoid (n = 32), and ulceration (n = 25). Mild to severe oral dryness (43%) (mean = 2.56; range 0 to 10) was more clinically significant than oral pain (8%) (mean = .13). Salivary cytokine concentrations were: TNFa (n = 32; mean = .31 pg/mL; range 0 to 2.8); IL1a (n = 29; mean = 85.23 pg/mL; range = 13 to 250), and IL6 (n = 29; mean = 2.48 pg/mL; range 0.100 to 10.00). Significant associations by Pearson Product Moment correlation were: TNFa and erythema (r = .34; p < .05); IL1a and oral dryness (r = .40; p < .05); IL6 and OMRS (r = .49; p < .01), erythema (r = .63; p < .001), and ulceration (r = .38; p < .05). Conclusions: Paucity of oral pain may be related to appropriate management. Moderate to strong correlations between salivary TNFa and IL6 and oral cGVHD severity, and IL1a and oral dryness suggest utility as correlates of disease severity and symptom, and monitors of therapeutic response to investigational agents.

No significant financial relationships to disclose.
Accuracy and usefulness of a clinical prediction rule and D-dimer testing in excluding deep vein thrombosis (DVT) in cancer patients
Authors: Carrier M. , Lee A. , Bates S. , Wells P. S.
Published: March 2020

19522

Background: Cancer patients frequently present with thrombotic complications and rapid, accurate diagnostic testing would reduce morbidity and mortality. Although the combination of a low clinical probability using clinical prediction rules (e.g. Well’s Score) and a negative D-dimer result have proven to be safe and reliable in ruling out DVT in the general population, the accuracy of such a strategy is less certain in cancer patients. Because cancer patients often have alternative reasons for leg swelling and pain, and because malignancy and chemotherapy can render the D-dimer test positive in the absence of DVT, we hypothesize that the Well’s Score and D-dimer testing are potentially less accurate and less useful in excluding DVT in patients with active cancer. Methods: We performed a retrospective analysis of 2 prospective studies to compare the diagnostic test characteristics of the Well’s Score and D-dimer testing between patients with and without cancer presenting with suspected DVT. Results: A total of 1630 patients were studied; 107 had cancer. DVT was confirmed in 39.3% of patients with and 13.7% of patients without cancer. In both patient groups, the proportions of patients with DVT were significantly different among the high-, moderate- and low-probability groups according to the Well’s score (P<0.001). However, significantly fewer cancer patients (19.6%) had a low-probability score compared to patients without cancer (47.5%) (P<0.001). Similarly, 36.4% of cancer vs. 60.4% of noncancer patients had a negative D-dimer result (P<0.001). In cancer patients, a low probability score alone had a sensitivity of 95.2% (95%CI 82.6%-99.2%) and a specificity of 29.2% (95% CI 18.9%-42.0%). In combination with D-dimer testing, the sensitivity improved to 100% (95%CI 31.0%-100%) but the specificity was reduced to 26.4% (95%CI 13.5%-44.7%). In contrast, the specificity in patients without cancer was preserved at 53.9% (95%CI 50.4%-57.3%). Conclusion: DVT can be ruled out in cancer patients with a low clinical probability of DVT and a negative D-dimer result. However, the low specificity of these tests excludes very few patients and thereby limits their clinical usefulness.

No significant financial relationships to disclose.
The use of complementary and alternative medicine in patients with terminal cancer in Korea: Nationwide cross-sectional study
Authors: Park J. , Chang Y. , Kang K. , Jeong H. , Moon D. , Kim S. , Yun Y.
Published: March 2020

19534

Background: Although the use of complementary and alternative medicine(CAM) is widespread among patients with chronic diseases including cancer, little is known about CAM use in terminal cancer patients. Methods: This study included 4,042 families of cancer patients who died at 17 hospitals in Korea between January and December 2004. We conducted with telephone survey to decedents’ families. The response rate was 41.1%. The questionnaire included whether cancer patients had used CAM during last one year before death, type of modality, motivation for use, attitudes to CAM, and consultation with doctors. Results: CAM use of cancer patients was reported by 36.3% (604 of 1,662) and the average rate of CAM cost was 32% of total medical costs during one year before patient’s death. CAM use was more likely to death at hospitals (adjusted Odds Ratio: 1.35, 95% Confidential Interval: 1.15–1.58), residence in rural (aOR:1.26, 95%CI:1.08–1.47), need consultations about care (aOR:1.65, 95%CI:1.30–2.09) and religious support (aOR:1.3, 95% CI:1.11–1.53), diagnosis except liver/gallbladder cancer (aOR:0.67, 95%CI:0.55–0.81), and longer disease period (aOR:1.85, 95% CI:1.5–2.2). Use was greatest for mushrooms (41.6%), vegetable juice (25.6%), ginseng (21.8%) and Chinese medicine (16.4%). The motivation for CAM use was the recommendations from family members or friends (83.5%) and internet or advertisement (16.1%) but physicians’ recommendation or education (1.4%) was rare. The 37.4% of families of CAM-used patients were satisfied with CAM because of but feeling better or comfortable (79.3%), not cure (5.4%). And otherwise, the 62.1% of them were unsatisfied with CAM because of no effect (87.3%). Only 41.7% CAM users consulted with their physician. Conclusions: This study revealed a high prevalence of CAM use among terminal cancer patients without recommendation from doctors. Medical staffs should evaluate patients’ CAM use and inform accurately about CAM to terminal cancer patients and family for quality of care improvement.

No significant financial relationships to disclose.
Neoplastic pulmonary lymphangitis: Symptomatic treatment and quality-of-life evaluation in a prospective palliative care series
Authors: Dettino A. A. , Pagano T. , Jardim C. , Takagaki T. , Deheinzelin D. , Okamoto V. N. , Bensenor I. , Teodoro A. L. , Serrano S. C. , Negri E. M.
Published: March 2020

19536

Background: Neoplastic lymphangitis, or lymphangitis carcinomatosa, is a rare and distressing form of lung metastasis, for which symptom improvement is strongly necessary. Since measuring quality of life is an important step toward improving symptom management in cancer patients, and dyspnea in pulmonary lymphangitis is a complex syndrome in end-of-life care, we focused on evaluating a cohort of those individuals. Methods: 52 consecutive patients with neoplastic pulmonary lymphangitis (NPL) were prospectivelly followed in 3 services, with quality of life (QoL) evaluation also, using Medical Outcomes Study 36-item Short-Form Health Survey (SF- 36) and Saint George's Respiratory Questionnaire (SGRQ). Results: 65% (34) of patients were female; age ranged from 37 to 84 years (median: 60). Primary tumor sites were: 28 lung (54%), 18 breast (35%), 5 digestive (9%) and 1 bone cancer. Histological findings were of adenocarcinoma in most cases (71%). Karnofsky performance scale ranged from 10 to 90% (median: 60%); 52% (27) patients had other comorbidities (Charlson index ranged from 6–10; median 7); 48% (25) were previous smokers; hemoglobin levels ranged from 4.9 to 16.7 g/dL (median: 12). We also evaluated 33 patients with echocardiography, and 13 (43%) of them had signs of associated pulmonary hypertension; ejection fraction ranged from 46 to 83% (median: 69%); diastolic dysfunction was present in 22 and pericardial effusion in 10 patients. At accrual, median QoL scores were of: 32% (range: 0–84%) for SF-36 (scale with 0 worst) and 66% (range: 0–100%) for SGRQ (scale with 100% worst). Treatment is showed in a table below. Median survival was of 4 months (range: 0.2–40+ months); 22 (42%) of the patients had an unusual longer survival of more than 6 months, still showing good QoL scores. Conclusions: Despite the fact that QoL is generally poor and survival is short for patients with NPL, some patients may have longer survival time and some improvement is possible with active palliative care.

[Table: see text]

No significant financial relationships to disclose.