bluuebunny/crossref_metadata_2025 huggingface dataset:
18F-FDG uptake on positron emission tomography in gefitinib-treated non-small cell lung cancer patients
Authors: Na I. , Byun B. , Kang H. , Cheon G. , Kim C. , Koh J. , Choe D. , Ryoo B. , Lim S. , Lee J. , Yang S.
Published: March 2020

18136

Background: This study evaluated the clinical significance of 18F-fluoro-2-deoxy-glucose (FDG) uptake on positron emission tomography (PET) in gefitinib-treated non-small-cell lung cancer (NSCLC) patients. Method: We retrospectively analyzed PET scans of 66 NSCLC patients with stage IIIB-IV and its association with gefitinib responsiveness. Response rate and time-to- progression (TTP) were analyzed according to the maximum standardized uptake value (SUV) at presentation. Cut-off vale of SUV was obtained from receiver operating characteristic analysis. Univariate and multivariate analyses were performed. Results: According to smoking history and pathology, different response rates were observed (P = 0.012 and 0.048, respectively). Thirteen patients were categorized into low SUV group. Patients with low SUV showed higher RR compared with those with high SUV (46% vs 13%, P = 0.007). In univariate analysis, prolonged TTP was observed in never-smoker (P = 0.007). Low SUV was associated with prolonged TTP (P = 0.010). Multivariate analysis confirmed that low SUV and never-smoker remained favorable prognostic factors (P = 0.046 and 0.043, respectively). Conclusion: These results suggest that FDG uptake may be predictive of outcome in gefitinib-treated non-small-cell lung cancer patients.

No significant financial relationships to disclose.
Improvement in symptoms and quality of life (QoL) for patients (p) with non-small cell lung cancer (NSCLC) treated with erloninib: TargeT study
Authors: Alberola V. , Gallego O. , López-Vivanco G. , Mesía C. , Oramas J. , Trigo J. M. , Virizuela J. A. , Camps C. , Regueiro P. , Massutí B.
Published: March 2020

18140

Background: Erlotinib is an EGFR TKI that is effective in the treatment of advanced NSCLC, in terms of longer survival, better quality of life and delayed symptom progression.We present here the outcome of a group of p from the TargeT study, whose QoL was assessed by the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire and the Lung Cancer Subscale (LCS). Methods: TargeT study was a multicenter, single-arm phase II study evaluating efficacy, safety, and tolerability of erlotinib (150 m/day) in p with stage IIIB or IV NSCLC, in 1st, 2nd and 3rd line treatment. Primary end-point was time to progression. QoL was a secondary end point as assessed monthly by the Functional Assessment of Cancer Therapy-Lung questionnaire (FACT- L) and its Lung Cancer Subscale. Physical and functional aspects of the QoL were measured by the Trial Outcome Index (TOI), which is the sum of the physical well being, functional well-being and LCS scores from the FACT-L questionnaire. Results: Data from 91 pts were available. QoL analysis showed that 53% of the p (95% IC 37–58%) had improvement in FACT-L or TOI. Similarly, 45% (95% IC35–56%) of improved their symptoms from baseline. Improvement was observed for each individual LCS item and specifically in the pulmonary items. In symptomatic p, shortened of breath was 17,6% at baseline vs 2.2% after treatment (p<0.001) and cough was 24.7% vs 8.8 % (p<0.001) after treatment. Those improvements in symptoms were rapid and, 73% of the patients who improved showed that recovery in the first cycle of treatment. In terms of association between efficacy of erlotinib and QoL, there is a statistically significative relationship between objective response and improvement in TOI or FACT-L (p<0.02). Conclusions: This QoL analysis confirms that erlotinib improves both symptoms and functional aspect of patients with NSCLC. The improvement in QoL is related with objective response.

No significant financial relationships to disclose.
A single institution experience of lung cancer treatment in octogenarians
Authors: McCormack S. , Pleister A. , Young D. , Confer P. , Otterson G. A.
Published: March 2020

18141

Background: In the NCI’s SEER database nearly 15% of NSCLC patients were = 80 years during the years 1973–2003. As the “elderly” population increases, the percentage of octogenarians with NSCLC will increase. To better understand this population we investigated the patient and tumor characteristics and treatment modalities by stage in octogenarians with NSCLC over a recent 5 year period at The Ohio State University Medical Center. Methods: Patients aged 80 years and older with biopsy-proven NSCLC seen between 1998–2003 were included in the analysis. 74 patients met criteria for study. Data was gathered from the cancer registry and chart reviews. Characteristics included stage, histology, treatment, and co-morbid conditions (pulmonary and non-pulmonary co-morbidities, weight loss, and ECOG PS). PS was either explicitly stated or inferred from the records, or recorded as “unknown” when PS could not be determined. Results: The 74 patients averaged 82.8 years of age (range 80–91), with 53% males and 47% females (83 years of age with 56% males and 44% females from the SEER database). 46% of patients had “surgical” disease (Stage IA, IB, and IIB), 20.3% had stage III disease, 29.7% had stage IV disease, and 4.0% had indeterminate staging. 82.4% of “surgical” disease patients received some variety of treatment (70.6% surgery[S], 23.5% radiation[RT], and 12.5% chemo[Ch]); 80% of stage III patients received treatment (53.3% S, 40% RT, and 33.3% Ch); 50% of stage IV patients received treatment (0% S, 31.8% RT, and 40.9% Ch). Patients with an ECOG PS of 0–1, 2, 3–4, or “unknown” equaled 44.6%, 20.3%, 16.2%, and 18.9% respectively with 81.8%, 100%, 41.7%, and 78.6% of these patients receiving treatment. Conclusions: There is little data on treatment of the ‘extreme elderly.‘ Our analysis of this subset of the elderly reveals that most octogenarians seen at a referral center can receive treatment. The majority of “surgical” disease octogenarians received surgical resection of their primary tumor and the majority of all patients received some treatment. Further studies of outcomes based on staging, co-morbidities, and PS will be important in this population. Additional studies of this population in non-referral centers are of interest.

No significant financial relationships to disclose.
Gemcitabine and radiotherapy: Analysis of safe use
Authors: Czarnecki A.
Published: March 2020

18146

Background: Radiation in combination with chemotherapy offers a significant survival advantage. Preclinical and clinical data indicate that gemcitabine (GEM) is a potent radiosensitizing agent in numerous cancer types used subsequently with radiation given in different doses and techniques. We compared safety/toxic effects of GEM with GEM plus radiation. Methods: Lilly Safety Database was searched for all reports where patients received radiation before, during and after GEM therapy. The string search for ‘radio’, ‘radia’ and a search for MedDRA terms covering possible radiation recall and typical recall phenomena were conducted. Cases were reviewed by a physician and allocated to one of the categories: ‘concurrent’ (radiation and GEM was given at the same time or 7 days apart), and ‘non-concurrent’ (treatment was given more than 7 days apart). Results: In one third of cases who received concurrent treatment the toxicity reported was higher in 3 System Organ Classes (SOC): ‘Injury’, ‘Gastrointestinal disorders’ (GI), and ‘Respiratory’ in comparison to non radiation treated patients: 4.1%, 16%, 14.8% versus 1.4%, 11.2% and 10.5% respectively but toxicity was lower for ‘Blood and lymphatic disorders’ and ‘General disorders’. In cases with ‘non-concurrent’ treatment the results were similar to ‘concurrent’ treatment for the Injury, Respiratory and Blood SOCs but GI toxicity was only 60% of the one seen in non radiation treated patients. In patients with reported radiation recall the most frequent were skin reactions, pneumonitis and myositis. Radiation injury mainly affected targeted tissue organs exposed to direct radiation e.g eosophagitis and pneumonitis for chest irradiation, GI effects for abdominal irradiation. In Non-concurrent administration no correlation between GEM dose and toxicity could be established. In Concurrent cases, treatment dose and technique of radiation, target tissue and volume were factors together with dose and frequency of GEM administration. Conclusions: Review of adverse drug reactions for GEM and radiation treatment reported from estimated GEM exposure of nearly 1.1 million patients suggests that any increase in GEM toxicity in non- concurrent combination regimen other than radiation recall is due to typical radiation toxicity and mainly affects directly irradiated tissues.

No significant financial relationships to disclose.
Lipoplatin monotherapy: A phase II trial in second line treatment of metastatic non-small cell lung cancer
Authors: Ravaioli A. , Papi M. , Pasquini E. , Marangolo M. , Rudnas B. , Fantini M. , Nicoletti S. V. , Drudi F. , Possenti C. , Tamburini E. , Gianni L.
Published: March 2020

18160

Background: Lipoplatin is a liposome encapsulated form of cisplatin. Phase I studies on lipoplatin showed an excellent toxicity profile of the compound. Therefore we performed a phase II trial in pre-treated patients with advanced non-small cell lung cancer (NSCLC). Methods: Nineteen patients with stage IV NSCLC pre-treated with first line chemotherapy were enrolled in our study. Patient selection criteria included: histologically confirmed malignancy type or cytological confirmation of advanced NSCLC, at least one measurable bi-dimensional lesion outside an irradiation field, stage IV disease, a life expectancy of more than 3 months, previous chemotherapy regimens, PS 0–2, age between 18 and 75, good bone marrow function (peripheral absolute granulocyte count of > 2,000/mm3 and platelet count of 100,000/mm3) and liver function (bilirubine less or equal to 1,5 mg/dl). Patients with symptomatic brain metastases or other severe illnesses were excluded from the study. Written informed consent was required from each patient prior to inclusion. The protocol was approved by the Local Ethical Commitee. We administered lipoplatin at the dose of 100 mg/m2 every fourteen days as second line chemotherapy. Primary endpoint was response rate. Results: We enrolled 19 patients, median age 64, with stage IV NSCLC. This was an open label single-arm trial. Statistical analysis was performed with the SPSS statistical program (version 11.0). Survival curves were estimated by the Kaplan-Meier method. All of the patients completed at least 6 cycles and were evaluated for response and toxicity. After 19 patients were treated we obtained only one partial response (5.2%) and three stable diseases (15.9%) and the study was stopped. Median time to progression was four months and median survival time was 7 months. Conclusions: In this study lipoplatin as second line drug demonstrated a lower activity in comparison to other drugs used in second line treatment. Nevertheless at the light of the excellent safety profile shown we think that the possibility to increase the dose in a new phase I-II study with escalation of the dosage should be considered.

No significant financial relationships to disclose.
Phase II trial of bevacizumab plus pemetrexed and carboplatin in previously untreated advanced nonsquamous non-small cell lung cancer
Authors: Dalsania C. J. , Hageboutros A. , Harris E. , Krieger K. , Vora C. , Stevenson J.
Published: March 2020

18163

Background: A randomized phase III trial has demonstrated the efficacy and safety of high dose bevacizumab (15 mg/kg) with carboplatin and paclitaxel in previously untreated advanced nonsquamous NSCLC (Sandler et al, NEJM 2006). Pemetrexed has also shown significant activity in advanced NSCLC. Clinical investigation of combination bevacizumab (BEV), pemetrexed (PEM) and carboplatin (CARBO) is therefore of interest in this population. Methods: Phase II, open label study in stage IIIB/IV NSCLC: eligible patients have non- squamous histology and no prior chemotherapy, brain metastasis, gross hemoptysis, tumor proximity to major vessels, uncontrolled hypertension or anticoagulation. All patients receive PEM (500 mg/m2), CARBO (AUC 6) and BEV (15 mg/kg) every 21 days. Patients are pretreated with vitamin B12 1,000 mcg every 9 weeks and folic acid 1 mg daily. Responses are assessed every 2 cycles. Patients with CR, PR or SD receive maximum of 6 cycles followed by BEV (15 mg/kg) maintenance. Our primary objective is to determine time to progression and secondary objectives include response rate, overall survival, and safety of the combination. Results: 14 patients (9 female/ 5 male; median age 62 years; range 34–77; 2 stage IIIB/12 stage IV, all ECOG PS 0 or 1) have been entered. Median number of cycles received is 5.5 (range 2 - 15). 12 patients are evaluable for response. 9 patients continued to have disease control at a median duration of 20.2 weeks (range 5–52) with 6 PRs and 3 SDs (response rate 60%; disease control rate 75%). 5 patients proceeded to BEV maintenance with 2 still ongoing. Overall survival data is immature to date. Toxicity data is available for all patients. Grade 3/4 toxicities have included neutropenia (4), nausea/vomiting (2), BEV related allergic reaction (1) and epistaxis (1). Conclusions: Combination BEV, PEM and CARBO is safe, well tolerated and shows promising activity to date. The regimen is not associated with alopecia, neuropathy or arthralgias/myalgias, and is conveniently administered. Enrollment continues and updated results will be presented.

No significant financial relationships to disclose.
Phase II study of irinotecan based fourth-line chemotherapy for gefitinib therapy-failed non-small cell lung cancer (NSCLC)
Authors: Lee S. , Lee K. , Lee E. , Lee S. , Kim J. , Shin C. , Jung K. , Shim J. , In K. , Kang K. , Yoo S.
Published: March 2020

18164

Background: Despite the undoubted gains from EGFR TK inhibitor therapy as 2nd or 3rd line chemotherapy, most of them will relapse during treatment. Among these patients, they might be young, with good performance status, and their disease is expressed with only minor symptoms. The objectives of this study were to evaluate the antitumor efficacy and safety of irinotecan based regimen as 4th line therapy for refractory or recurrent to gefitinib treatment. We report our experience with irinotecan-based 4th line chemotherapy. Methods: Eligibility required proven NSCLC refractory or recurrent after 3rd line chemotherapy(gefitinib), measurable lesions by RECIST, and ECOG PS 0–1. Irinotecan (60mg/m2, day 1,8,15) and/or cisplatin (60 mg/m2, day 1) were administered every four week for at least 2 course. We analyzed for time to tumor progression (TTP) for first, response rates and toxicities. Results: Since June 2004, 17 patients (consisting of 9 with squamous cell, 7 with adeno-, and 1 with NSCLC not further specified) with a median age of 61 years were enrolled, with 1 drop out during treatment. Chemotherapy was administered for a median 2 courses (range 2–6). Median TTP was 91 (range 35–210) days. Two pts achieved a PR and 5 pts a SD. Disease control rate was 41.2%. Response rate was 11.8%. Toxicity of grade 3 or 4 consisted of neutropenia (35.3%), anemia (29.4%), thrombocytopenia (17.7%), nausea (17.6%), and diarrhea (23.5%). There were no treatment related deaths. Conclusions: This irinotecan based chemotherapy for EGFR TK inhinbitor therapy failed NSCLC patients showed promising efficacy with tolerable toxicity. Irinotecan based chemotherapy may be considered a potential therapeutic option for 4th line chemotherapy in well selected patients.

No significant financial relationships to disclose.
Low SER versus high SER thoracic radiotherapy in the management of limited-stage small cell lung cancer
Authors: Lee K. , Lee S. , Lee S. , Kim J. , Shin C. , Shim J. , In K. , Kang K. , Yoo S.
Published: March 2020

18170

Background: Patients with small-cell lung cancer account for about 20% of all lung cancer patients, with only one third of the patients presenting with limited disease. Although the combinations of chemo and radiation therapy have improved the prognosis substantially, the optimal chemoradiotherapy remains controversial in LD-SCLC. There are many reports that the overall duration of the chemoradiotherapy package is the most relevant predictor of the outcome. Therefore we tested SER beginning with the start of any treatment until the end of radiotherapy in patients with LD-SCLC. Methods: We enrolled the patients who were diagnosed as SCLC histologically in Korea University Medical Center from 2003 to 2006. All of them presented with limited disease. We divided them into two groups; the low SER (within 60 days of SER) and the high SER group (over 60 days). The patients were treated with thoracic radiotherapy and platinum based topoisomerase inhibitor. Overall survival was analyzed with a Cox model adjusted for performance and the chemotherapy regimen. Results: Of 29 patients, 16 patients were in low SER and 13 patients were in high SER. Low SER, as compared with high SER, significantly prolonged survival rate (p=0.028). We evaluated the radiation effect by the time between the start of chemotherapy and the start of radiotherapy, below 30 days and above 30 days, but there were no statistically comparable difference in there survival time between the two groups (p=0.176). The survival times of the patients were increased by 3.094 times in the low SER (95% C.I, 1.083 to 8.840, p=0.028) and by 6.901 times in ECOG groups 0 or 1 compared with group 2 (95% C.I, 1.563 to 30.468, p=0.018). There were no statistically significant increases in the side effects: pneumonitis, esophagitis, and BM suppressions. Conclusions: The cumulative survival of the patients in the low SER group is higher than for patients in the high SER group. The SER may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.

[Table: see text]

No significant financial relationships to disclose.
Phase II study of weekly docetaxel plus cisplatin as first-line therapy in advanced or metastatic non-small cell lung cancer (CHN TAX-206)
Authors: Chu D. , Li J. , Zhang X. , Liu J. , Chen Z. , Lin Y. , Wang Y.
Published: March 2020

18173

Background: There has been increasing interest in the use of weekly administration of docetaxel as a way of reducing its hemotologic toxicity. Weekly docetaxel plus cisplatin has also shown promising efficacy and well tolerability for first-line treatment of advanced or metastatic NSCLC in our previous phase I study (2002 ASCO, abstract No 2744). We conducted this phase II trial to further evaluate this regimen’s efficacy and toxicity. Methods: Patients with histologically confirmed stage IIIB or IV NSCLC were treated with docetaxel (35 mg/m2, 30 min. iv. infusion) on days 1, 8, 15 and cisplatin (75 mg/m2, 30 min. iv. infusion) on day 1 repeated every 4 weeks for up to 6 cycles. Pts received oral dexamethasone 7.5 mg twice daily from the day before chemotherapy and consecutive two days thereafter. The primary endpoint of this phase II study is efficacy of the regimen. Results: A total of 83 patients were enrolled from July 2002 to June 2004, 75 patients were evaluable for response and 83 for safety. Median age was 55 years (range 29–70 years); and 69.9% were male; adenocarcinoma/squamous cell carcinoma/others (65/12/6); stage IIIB /IV( 47/36); ECOG PS 0/1(52/31). Median number of chemotherapy cycles was 3(1–5). One CR (complete response) and 22 PR (partial response) were achieved with an ORR of 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3–34 months). Neutropenia was the most common adverse event, though most were mild; Grade III/IV toxicities per patient were: Neutropenia (15.6%), asthenia (11%), skin/nail toxicity (10.8%) and vomiting (9.6%). Febrile neutropenia was not observed. Conclusions: In the present study, the combination of weekly administration docetaxel combining with cisplatin appears well tolerated with very low frequency of severe hematologic toxicity and similarly efficacious as 3-weekly docetaxel in NSCLC pts.

No significant financial relationships to disclose.
Retrospective analysis of pulmonary neuroendocrine/carcinoid tumors at Ohio State University
Authors: Ort E. M. , Confer P. , Otterson G. A.
Published: March 2020

18176

Background: Neuroendocrine tumors are a unique malignant neoplasm which can arise from the respiratory tree. Bronchial neuroendocrine tumors account for 25% of all neuroendocrine tumors, but only about 1–2% of all lung cancers. The epidemiology, clinical behavior, treatment, and prognosis of carcinoid tumors differ from other lung malignancies in significant ways. Located most often in the major bronchi, these tumors secrete neuroendocrine granules such as serotonin, histamine, and prostaglandins. Classic carcinoid syndrome (diarrhea, flushing, palpitations, wheezing), however, is rare in these patients. Treatment is primarily surgical resection for cure. The purpose of our study was to identify the experience with these malignancies at our institution and compare it to other series. Methods: A total of 64 patients were identified using diagnostic codes via our institutional cancer registry from 1980–2006. Poorly-differentiated neuroendocrine tumors and small cell lung cancer cases were excluded from analysis. Data collected included survival after diagnosis, staging, epidemiologic characteristics, and treatment. Additional variables included smoking history, laterality, and tumor staging. Results: The patient age distribution ranged from 17 years old to 82 years old, with a median age of 57 years old. Most of the patients were female (73%). Tobacco use is variable in carcinoid - 54% of our patients were never smokers, whereas 17% were previous smokers, 20% were current smokers, and history was unknown in 7%. Staging was unknown in over half of the patients. Treatment was generally surgical; lobectomy (40%) was the most common intervention, followed by wedge resection (17%), radiation therapy (14%), bronchial sleeve resections (3.5%), and pneumonectomies (3.5%). Survival was generally good - at the time of last contact, 50 patients (78%) were still alive with a median follow up of 39 months since diagnosis. Conclusion: Neuroendocrine tumors of the bronchial tree remain a unique and uncommon malignancy among lung cancers. The findings at our medical center are consistent with reported series as far as epidemiologic characteristics, treatments, and outcomes. The future direction of non-surgical therapy in this malignancy remains investigational.

No significant financial relationships to disclose.
Multi-institutional phase II study of carboplatin-gemcitabine combination chemotherapy in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Sasaki J. , Uramoto H. , Kashiwabara K. , Kishi H. , Moriyam E. , Ushijima S. , Fujii S. , Senba H. , Okamoto I.
Published: March 2020

18179

Background: Because elderly pts may tolerate platinum-based combination chemotherapy poorly, single-agent chemotherapy is selected for the treatment regimen. However, retrospective subgroup analyses have consistently indicated that elderly pts indeed benefit from platinum-based combination chemotherapy as well as their younger counterparts. This phase II study evaluated the efficacy and safety of carboplatin-gemcitabine combination chemotherapy in elderly pts with advanced NSCLC. Methods: Fifty-four pts aged more than 70 years old (median, 77; range, 70–88) with previously untreated advanced NSCLC were enrolled on this trial. Additional criteria included the presence of measurable lesions, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Pts received carboplatin at an area under the curve of 4 mg/ml/min on the first day and gemcitabine at 1000 mg/m2 on the first and eighth day of consecutive 3 week periods. The primary endpoint was to determine the objective response rate of this platinum-doublet regimen. The RECIST criteria were used to measure response. Results: Enrolled pts included 15/39 with stage IIIB/IV diseases. Fifty-one out of enrolled pts were eligible for efficacy and safety analyses. The median number of treatment cycles was 4 (range, 1–7). Fifteen partial responses (response rate: 29%) were obtained. The median TTP was 118 days. Hematological toxicities of grade 3/4 included leukopenia (46%), neutropenia (72%) and thrombocytopenia (50%). Non-hematological toxicities of grade 3/4 included nausea (6%), appetite loss (7%), fatigue (7%) and infection (9%). Conclusions: The combination carboplatin-gemcitabine at these doses has shown activity with a favorable toxicity profile for fit elderly pts with advanced NSCLC.

No significant financial relationships to disclose.
Expression of Bax and Bcl2 proteins in small cell lung cancer (SCLC)
Authors: Badzio A. , Krajewska M. , Elsaleh H. , Kowalczyk A. , Kurowski K. , Jassem J.
Published: March 2020

18189

Background: Bax and Bcl2 proteins are members of Bcl-2 family which plays a critical role in the regulation of apoptosis. There are few data on the occurrence and clinical relevance of these proteins in SCLC. Methods: We have analyzed expression of Bax and Bcl2 in 86 SCLC patients. All patients had limited disease and were treated with surgery followed by chemotherapy between 1982 and 2001 (median follow up 2 years). In all cases the diagnosis of SCLC was established only after the examination of surgical specimen. This series included 59 males and 22 females, 11 T1, 46 T2, 13 T3 and 11 T4 tumors, 41 N0, 15 N1, 24 N2 and 1 N3. Expression of both proteins was evaluated by immunohistochemistry and scored, taking into account proportion of cells with positive staining and staining intensity. H-score was calculated as a proportion of positive cells times staining intensity. Continues data on H-score were used to assess relationships with clinical data. Results: Median H-scores for Bax and Bcl2 were 70 (range 0–300) and 90 (range 0–300) respectively. The positive immunostaining rates (cut-off point of 10%) for Bax and Bcl-2 in the entire group were 81% and 79% respectively. Bax and Bcl-2 expression did not correlate with any clinicopathological parameters such as age, tumor size, lymph node involvement and stage of the disease. Survival was not influenced by expression of Bax (p=0.6) or Bcl2 (p=0.86). There was a significant positive correlation between Bax and Bcl2 expression rates (p=0.018, regression coefficient 0.23). Conclusions: Bax an Bcl2 proteins are commonly overexpressed in SCLC, with tendency for co-expression. Clinical relevance of these markers is questionable in this patient cohort.

No significant financial relationships to disclose.
What is the place of clinical variables in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy?
Authors: Berhoune M. , Fabre-Guillevin E. , Banu E. , Scotte F. , Bonan B. , Medioni J. , Cojocarasu O. , Rideller K. , Ayllon J. , Levy E.
Published: March 2020

18197

Background: Chemotherapy (CT) has shown its effectiveness in symptom control and quality of life improvement in advanced NSCLC patients. The therapeutic strategy and some clinical variables could have a major impact on outcome. Methods: Our retrospective analysis evaluated the impact on overall survival (OS) of the clinical benefit (CB), ECOG performance status (PS) and toxicity, function of treatment. CB was defined as disease-related symptoms improvement according to hospitalization report. Only grade III-IV CTC-NCI version 2 toxicities have been considered. OS was calculated between start of CT and death or last follow-up. Multivariate Cox regression analysis including CB, PS, toxicity and age, stratified by AJCC initial stage was used. Results: Data of 68 consecutive stage IIIB-IV patients treated in a single French centre were analyzed. Chemotherapy was platinum-salt based in 88, 45 and 25% of pts for the first, second and third-line, respectively. Median age was 61 years, 37% were women. More than half (66%) were metastatic and 14% were previously irradiated. Median survival was 14 months (95% CI, 6.1–21.8), 53 % of patients are dead. The risk of death PS-related was multiplied by 2.3, 2.4 and 5.3 for the first, second and third-line of CT, respectively. PS and CB were initially associated with OS (first and second-line CT), but after the third-line of CT only PS was significantly related with OS. The risk of death reduction induced by a CB was 59, 82 and 29%, respectively. Less toxicities during CT were associated with a better OS (an unsignificant 20- 30% risk of death reduction), independently of the chronology of CT. Older pts >70 years have a higher risk of death (HR=1.87), independently of the CB and treatment-related toxicities in the multivariate analysis (P=0.18), sex-adjusted. Conclusions: No matter how many lines of CT are used for a specified patient, the ECOG PS was a patient-related variable with a dominant impact on the outcome. CT must be less toxic in order to achieve a CB and ameliorate the PS.

No significant financial relationships to disclose.
Targeting the therapy: Octreotide in thymoma relapse
Authors: Zampa G.
Published: March 2020

18199

Background: Thymomas are rare slowly growing neoplasms, associated with myasthenia gravis, hypogammaglobulinemia and pure red-cell aplasia. About 40% of thymomas are invasive and some well encapsulated tumor recur years after surgical resection. 5 years survival rate in patients with noninvasive thymomas is 70 - 85% and decreases at 50 - 67% for invasive thymomas with the worst trend for stage IV (23%). Recurrence rate is 2% for stage I thymomas while for stage II and III is 28% and it decreases to 5% when thymectomy is followed by RT. Thymomas have a high content of somatostatin receptors and show high Indium-labeled octreotide (111In-DTPA- D - Phe - octreotide) uptake when octrescan is performed. Methods: From 1997 to 2006 we treated 45 consecutive patients, age ranged from 19 to 84, with tymoma histological diagnosis. 12 patients had miastenia gravis, 1 SLE and 1 autoimmune pericarditis. In our series 36 pt performed toracotomy, 28 underwent chemotherapy and 23 underwent radioterapy. 25 patients (89%) chemotherapy treated showed stable disease at CT examination while 3 of 28(11%) cases who underwent chemotherapy showed progression disease. The chemotherapy schedule was PAC used both in neoadjuvant than in adjuvant setting. On the basis of positive octreotide uptake, after the patients’ informed consent had been obtained, we treated, 14 of 20 pt resulted scintigraphically positive, with octreotide (20 mg) every 2 weeks. Six of them refused treatment. Treatment was well tolerated and no side effects were reported.We monitored CgA and NSE. Results: At CT and Octreoscan examination, after octreotide treatment, 5 (35.7%) patients showed stable disease and also CgA and NSE decrease. In 2 (14.2%) cases we observed progression disease and in 4 (28,5%) cases partial response (decrease of mediastinic masses evaluated at previous CT examination). Conclusions: Treating thymoma recurrences or residual disease with octreotide seems to be feasible and safe. All pts treated showed good compliance. Positive scintillography gives the oncologist the possibility to address a new target, the somatostatin’s receptor, through the octreotide.

No significant financial relationships to disclose.
Topoisomerase-II, c-erb B2, c-kit and bcl-2 expression in non-small cell lung cancer treated with docetaxel and gemcitabine based threapy
Authors: Kara I. O. , Erkisi M. , Gumurdulu D. , Sahin B. , Zeren H.
Published: March 2020

18212

Background: This study was conducted to determine the expression of the topoisomeras-II, c-erb B2, c-kit and bcl-2 in patients with non-small cell lung cancer (NSCLC). Material-methods: These factors expression were identified by immunohistochemical method in 62 NSCLC patients pathologically verified on before therapy. Results: 3 patients were in stage-II, 10 in stage-IIIA, 21 in stage-IIIB and 28 in stage-IV. 14 patients had refused therapy, 12 were undergone to surgery alone and 36 recieved multimodality therapy. 27 patients recieved docetaxel-cisplatin therapy and 7 had recieved gemcitabine-cisplatin therapy. Of those docetaxel treated patients 14 received radiation therapy and others undewent surgery in combination therapy. In 31 patients topoisomerase-II was +2 (50%), +1 in 3 patients, +3 in 27 patients and in 1 patient the expression was negative. c-erb B2 was negative in 1, +1 in 2, +2 in 14 and +3 in 45 patients. bcl-2 was negative in 9, +1 in 16, +2 in 22 and +3 in 15 patients. c-kit was negative in 9, +1 in 26, +2 in 15 and +3 in 12 patients. Statistical analysis was done by SPSS- 14 software program. The disease stage, received therapies and the expression of the these proteins was correlated, median survival time and possible prognostic factors were identified. There were statistically significant between stage and patient status (P=0.000), either with therapy or no therapy (p=0.003), bcl-2 (p=0.09) and c-kit (p=0.022), respectively. There were statisticaly significant between stage and bcl-2 (p=0.023), bcl-2 and c-kit (p=0.001), respectively. At the end of the follow-up time, 38 (61.3%) patients were alive. The median survival was 37.2 months. There were not any prognostic values for topoisomerase-II (p=0.7), c-erb B2 (p=0.6), bcl-2 p=0.15) and c-kit (p=0.118) expression. Conclussion: In conclussion, we suggested that the treatment modality of patients with NSCLC should be combination therapy. The patients received docetaxel based therapy had long median survival time. In addition there was no prognosticeffect of the expression of the topoisomeras-II, c- erb B2, c-kit and bcl-2 in patients with non-small cell lung cancer (NSCLC).

No significant financial relationships to disclose.
Breast radiation dose estimates compared to measured doses from involved field radiotherapy (IFRT) or mantle fields for early stage Hodgkin lymphoma (ESHL)
Authors: Wirth A. , Wittwer H. , Kron T. , Sullivan K.
Published: March 2020

18503

Background Breast cancer risk after mantle irradiation has prompted concern regarding the use of IFRT for ESHL. As breast cancer risk is radiation dose related, reliable estimates of breast radiation dose from IFRT might aid individual patient risk assessment. However, estimates of breast dose from radiation scatter/leakage beyond the involved field, using standard computer algorithms, are of uncertain accuracy. The aims of this study were to compare computer estimates with measured breast dose, and to compare breast dose from mantle and neck IFRT. Methods A phantom with breast tissue equivalent was used to determine breast dose using computerized treatment planning (CMS XiO), and to perform measurements within the phantom breast tissue using thermoluminescent dosimetry (TLD). These measurements were made for mantle fields and (neck) IFRT. Results Computer estimates and TLD measurements of breast dose in centigray (cGY) are shown for IFRT and mantle treatment, for a prescribed dose of 3000cGy, using 6MV X-rays from a Varian 21eX linear accelerator. Conclusions Breast dose from neck IFRT was lower than from mantle treatment by an order of magnitude, but being well outside the treatment field, was not accurately estimated by our computer algorithm. Work in progress will examine breast dose from mediastinal IFRT and involved node irradiation. Modifications to the planning algorithm may improve accuracy of dose estimates at a distance from the primary field, allowing routine breast dose estimates for patients. Ultimately, utilisation of dose-risk data may allow risk modelling and risk-benefit analysis of IFRT for ESHL in individual patients.

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No significant financial relationships to disclose.
Phase I study of vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients (pts) with non-Hodgkin lymphoma (NHL) in Japan
Authors: Tobinai K. , Watanabe T. , Kobayashi Y. , Yamasaki S. , Morita-Hoshi Y. , Yokoyama H. , Morishima Y. , Kato H. , Frankel S. R. , Otsuki T.
Published: March 2020

18521

Background: Vorinostat (Zolinza™), a potent histone deacetylase inhibitor, has demonstrated clinical activity in pts with cutaneous T-cell lymphomas (CTCL) and other NHL subtypes. However, the clinical activity and PK profile in Japanese pts with NHL was unknown. Methods: Japanese pts with NHL were sequentially enrolled in two dose levels ranged from 100 (Level 1) - 200 mg (Level 2) BID, PO for 14 consecutive days every 3 wks. Higher doses were not tested as other phase I studies had established that 300 mg BID for 14 consecutive days every 3 wks exceeded the MTD. PK profiles were analyzed in serum and urine samples. Response was also evaluated according to the international workshop criteria. Results: Ten pts were enrolled: 9 were evaluable for toxicity. One was excluded due to noncompletion of the 1st cycle. All were evaluable for PK. Median age was 60 yrs (range 52–74). Four pts had follicular lymphoma (FL), 2 mantle cell lymphoma (MCL), 2 diffuse large B-cell lymphoma and 2 CTCL. Median no. of prior regimens was 3 (1–4). In the 1st cycle, none of 3 pts at Level 1 and 1 of 6 pts at Level 2 developed DLTs (anorexia and hypokalemia of grade 3), indicating Level 2 to be the MTD in this setting. PK was not greatly affected by multiple doses. Intact drug was hardly excreted in urine (<1% of dose). PK profile is similar to that established in US pts. As of Dec 2006, 4 pts were continuing treatment (median 5 mos [1–15]). Two pts with FL showed PR for 8+ and 2+ mos, respectively, and the remaining 1 pt with FL and 1 of 2 pts with MCL showed tumor reduction greater than 30%. Conclusions: Oral vorinostat was well tolerated up to 200 mg BID for 14 consecutive days every 3 wks in Japanese pts with NHL. Preliminary observations of clinical efficacy warrant further investigations for NHL focusing on FL and MCL.

No significant financial relationships to disclose.
Bleomycin dose modification in Hodgkin disease (HD) treated with ABVD: Patient characteristics, treatment outcomes, and association with mixed cellularity (MC) histology
Authors: Iqbal U. , Radhakrishnan N. , Kaufman M. , Thomas A. , Patel D. , Mehrotra B. , Roy R.
Published: March 2020

18525

Background: Bleomycin used in the ABVD regimen is associated with a risk of pulmonary toxicity (10 - 19%). Pts with early signs of suspected bleomycin toxicity are often treated with modifications of the regimen. We conducted a retrospective study of patients with HD at our institution in whom bleomycin dose was modified or discontinued during their course of therapy with ABVD. Their response to modified therapy and possible predisposing factors were analysed. Methods: IRB approval was obtained for this study. Tumor registry data for adult pts diagnosed with HD between 2004 and 2006 were analysed for age, stage, sex, histology, smoking history, reduction in bleomycin dose and outcomes. Results: 38 pts were diagnosed with HD at our institution during this time period. Histology: NS: n=15(39.4%), MC: n=16(42.1%), NLP: n=2(5.2%), LR: n=2(5.2%). Histology NOS: n=4(10.5%). 8 pts with bleomycin dose modifications were identified. Pt. characteristics : Med.age 46 yrs (28- 64 ), M:F3:5; 7 of 8 were newly diagnosed and one pt had recurrent HDs. Stages: Stg I: n = 1; Stg II: n= 3; Stg III: n = 3, Stage IV: n= 1, B symptoms : n = 3. Histology: MC (n = 6), NS (n = 1). Unk n=1. 4 of 8 pts were ex-smokers. One patient never received bleomycin due to initial poor PFTs. 7 pts had bleomycin discontinued due to symptoms and decrease in DLCO during their treatment. One patient was continued on 50% reduced dose bleomycin for 2 cycles prior to discontinuation of bleomycin. The distribution of the number of patients discontinuing bleomycin by cycle of treatment is as follows: C#2: n=1; C#3: n=2; C#4: n=1; C#5: n=2. The complete response rate was 100% in this group despite bleomycin dose modification. There were no relapses after a median follow up of 18 mos (range: 8- 33). One patient treated for recurrent HD had severe pulmonary toxicity and did not receive any further treatments. All other patients completed their intended cycles of treatment. Conclusions: Despite bleomycin modification in this small series of pts treated initially with ABVD, DFS remains excellent with no noted relapses at this early follow up. Majority of pts requiring dose modifications had MC histology. Further trials are needed to evaluate the role of bleomycin in the ABVD regimen.

No significant financial relationships to disclose.
Analysis of competing risks of causes of death and their variation over different time periods in Hodgkin disease
Authors: España P. , Sanchez A. , Espinosa P. , Massip V. , Perez-Maestu R. , Yebra M. , Hurtado A. , Hurtado A. , Maximiano C. , Salas C. , Provencio M.
Published: March 2020

18528

Background: Hodgkin’s disease is put forward as a model of curable illness. However, long-term studies show an excessive mortality in relation to the general population. The only way for detecting these causes are the long-term follow-up clinical studies, even these long-term follow-ups may not be fully representative of current causes of death. Methods: All patients diagnosed with HD at the University Hospital “Clínica Puerta de Hierro” between 1967 and 2003 were included. The competing risks of causes of death and the vital situation were examined in three time periods. Three cohorts were compared: cohort A with patients treated before 1980, B with those treated 1981–1986 and C from 1986 on. Results: We studied 534 patients, with a median follow-up time of 9.1 years for the whole cohort. The 5, 15 and 20-year Kaplan-Meier survival estimates for all patients were 81%, 72% and 65%, respectively. At the close of the study, 337 (63.1%) were alive and 170 (31.8%) had died. In general, the most common cause was the progress of Hodgkin’s disease, followed by deaths due to a second tumor. By time periods, we found statistically significant differences between cohort A and the other two cohorts, with less LD and MC histology, fewer advanced stages and fewer combined treatments in the latter. Between cohorts B and C there were only differences in the histological results, with less LD and MC and increased NS in the latter. Survival was significantly worse in the first period than in the other two (p<0.001) and in the three periods the main cause of death was tumor progression. Conclusions: The progression of Hodgkin’s disease is the main cause of death in all the periods studied. Over time a clear reduction in death related to the toxicity of treatments was seen. In the light of our results, the question is posed as to whether the survival and causes of death series for those patients treated since the 1970s are telling us about a real situation. Patients die now for reasons that are different from in the 1970s and this is important when planning preventive and clinical research activity.

No significant financial relationships to disclose.
R-CHOP compared with CHOP in patients with diffuse large B-cell lymphoma (DLCL): Russian experience
Authors: Poddubnaya I. , Osmanov E. , Babicheva L. , Tumyan G. , Sorokin E. , Stefanov D.
Published: March 2020

18536

Background: R-CHOP is regarded as the best available treatment for untreated patients with aggressive and indolent B- NHL. Methods: 184 previously untreated patients with DLCL were included in retrospective study: 92 patients were treated by CHOP, 92 patients were treated by CHOP plus rituximab ( R-CHOP ). Age of patients ranged 16–87 years (median 50 years). The median follow- up was 18 months. Compared groups were balanced in all parameters. The advanced stage of disease (III-IV) at diagnosis had 66% patients treated with CHOP and 67,5 % patients treated with R-CHOP. =2 extranodal zones were initially revealed at 35% in CHOP group vs 47% in R- CHOP group. PS of 25 % patients in R-CHOP group and 30% patients in CHOP group was regarded as appropriate 3–4 degrees on ECOG. Increased LDH level was marked at 60% in CHOP-group vs 54% in R-CHOP. 29% patients in R-CHOP group and 21% patients in CHOP group had B-symptoms at diagnosis; bulky disease took place in 53% cases in R-CHOP group and 62% cases in CHOP. High IPI score had 47 % patients in CHOP-group vs 48 % in R-CHOP. Results: Complete response was achieved in 74% of the patients treated with R- CHOP, as compared to 56% of those treated with CHOP alone (p<0,05). Disease progression during treatment was reported in 25% of patients in CHOP group and 18,5% in R-CHOP group. Median overall survival in patients treated with R-CHOP was NS, in patients treated with CHOP alone was 16 months. With a median follow-up of 18 months, 29 (31,5%) events (progression - 18,5%, relapse - 10%, death - 3% ) were observed in the R-CHOP group and 48 (52%) events ( progression - 25%, relapse - 20%, death - 7%) in the CHOP group (p<0,05). Median event-free survival and relapse-free survival in the CHOP group was 12 months, in R-CHOP group NS. Toxicity was equivalent in both groups. Conclusions: We have established better direct efficiency and outcome of R-CHOP in any age of pts.

No significant financial relationships to disclose.
Biopsychosocial problems identified by women with breast cancer
Authors: Loscalzo M. , Clark K. , Mortimer J.
Published: March 2020

19514

Background: It is frequently assumed that women with breast cancer have higher levels of distress and psychosocial problems than women with other malignancies. We compared the biopsychosocial needs of breast cancer patients with women with non-breast malignancies. Methods: A biopsychosocial screening tool was developed from clinical practice, focus groups, and the administration of questionnaires to over 3,000 patients. The refined 36-item self-administered questionnaire was completed by all new patients evaluated in the Moores Cancer Center. The severity of each problem was scored from 1 (not a problem) to 5 (the worst problem I could have). Problems scored as 3 or above were identified to be clinically significant. The screening results from women with breast cancer were compared with those of women with non-breast malignancies. Results: Between December 2005 and December 2006, 2063 patients completed screening questionnaires. Complete information, including staging, is available on 299 women, 155 of whom were diagnosed with breast cancer and 144 with non-breast malignancies. The two groups were comparable with respect to age, ethnicity, and the number of significant problems reported. The 5 most common problems identified to be significant by breast cancer patients included: fatigue, sleeping, being dependent on others, feeling depressed, and pain. The non-breast cancer women identified a greater number of significant problems overall with the 5 most significant being: fatigue, sleep, controlling my fear and worry about the future, being dependent on others, and pain. Getting medications and recent weight loss were more commonly identified in the non-breast cancer patients (p<0.05). Conclusions: Our data suggest that breast cancer patients identify similar biopsychosocial needs as women with other primary malignancies.

No significant financial relationships to disclose.