bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of induction and adjuvant bevacizumab in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) receiving induction docetaxel and cisplatin
Authors: Price K. , Kris M. G. , Rusch V. , Finley D. J. , Azzoli C. G. , Downey R. J. , Bains M. S. , Miller V. A. , Rizk N. , Rizvi N. A. 
Published: August 2020

7531 Background: VEGF supports growth of NSCLC and is blocked by bevacizumab. Bevacizumab with chemotherapy is an established treatment for advanced NSCLC. We conducted this study to assess the efficacy and toxicity of induction bevacizumab (Bev) with cisplatin (C) and docetaxel (D) in patients with resectable NSCLC. Methods: All patients (pts) had resectable Stage IB-IIIA NSCLC and received up to 4 cycles of D 75 mg/m2 and C 75 mg/m2 followed by surgery. Pts with non-squamous NSCLC also received 3 cycles of Bev 15 mg/kg along with induction DC (Bev-DC). Bev was not given in pre-operative cycle 4. Pts with squamous or central tumors or hemoptysis received 4 cycles of DC only (DC). All resected pts were eligible for adjuvant Bev 15 mg/kg q3 weeks for 1 year. The primary endpoint was rate of downstaging from pre-operative clinical stage to pathologic stage. Results: From Aug 2005 - Nov 2008, 47 pts were enrolled: 27 women; median age 62; Stage 1B -15%, Stage II-17%, Stage IIIA-68%. Of 36 pts given Bev-DC, 15/30 (50%) who have completed surgery were downstaged. Of 11 pts given DC, 3/11 (27%) were downstaged. In Bev-DC group, 22/33 (67%) completed all 4 cycles of DC without a dose reduction and 28/33 pts (85%) completed all 3 planned cycles of Bev. Pts received <3 cycles due to: hemoptysis (n=3), consent withdrawal (n=1), hypertension (n=1), and sepsis (n=1). For DC, 6/11 pts (55%) completed all 4 cycles of DC without a dose reduction. 42/43 patients were resected. R0 resection rate: 29/31 for Bev-DC and 9/11 for DC. Grade 3/4 surgical complications were seen in 5/31 pts (16%) in Bev-DC and 1/11 (9%) in DC. Only 17/41 (41%) who completed surgery received adjuvant bev (median 6 cycles), and 7/41 (17%) completed all adjuvant Bev. Pts did not receive adjuvant Bev due to: POD prior to adjuvant Bev (n=9), POD during adjuvant Bev (n=6), toxicity (n=4), consent withdrawal (n=1), RT for unresectable disease (n=1), surgical complications (n=4), chemotherapy complications (n=4). No treatment related deaths. Conclusions: Induction chemotherapy with Bev-DC in NSCLC is feasible and is associated with an improved rate of downstaging compared with historical controls (33%). In patients treated with DC-Bev, grade 3/4 surgical complications were increased by 7%. [Table: see text]
Third-generation drugs in the chemoradiation of stage III non-small cell lung cancer (NSCLC): A meta-analysis of efficacy and toxicity parameters
Authors: Aydiner A. , Can G. 
Published: August 2020

7536 Background: The role of third generation drugs (paclitaxel, docetaxel, gemcitabine and vinorelbine) in the chemoradiotherapy to maximize survival and decrease toxicity in NSCLC is unclear. We performed a meta-analysis of published randomized controlled trials (RCT) comparing third generation drugs. Methods: We searched MEDLINE, EMBASE, CENTRAL, proceedings of ASCO and other Cancer Congresses to December 08 for RCTs comparing chemoradiation treatment (CRT) including any type of third generation drugs in stage III NSCLC patients who had not been treated surgically. Standard meta-analysis techniques, using random effects model, were used to compare study arms with regards to treatment response, survival and toxicity data. For treatment response odds ratio (OR), to reach complete response and overall response were calculated. For survival data, hazard ratios (HR) and confidence intervals (CI) of individual studies were calculated based on survival curves-published in the manuscript (Parmar MKB, 1998). Basically two types of comparisons were performed: (1) subgroups defined by the type of CRTs, (2) subgroups defined by the type of drugs administered. Results: We found 18 RCTs including 2725 patients. Concurrent CRT was superior to the pool of other types of CRT (overall survival [OAS] HR 0.76, 95%CI 0.6–0.96, p=0.021) and sequential CRT (OAS HR 0.59, 95%CI 0.39–0.88, p=0.01). CRT with paclitaxel was superior to CRT without paclitaxel or with another type of third generation drug with regard to complete response (OR 1.93, 95%CI 1.02–3.67, p=0.044), with no significant difference in OAS (HR 0.94, 95%CI 0.56–1.57, p=0.799). CRT with paclitaxel was less toxic to CRTs without paclitaxel or with another type of third generation drug with regard to the incidence of grade III and IV anemia (OR 0.1, 95%CI 0.03–0.36, p<0.001) and febrile neutropenia (OR 0.22, 95%CI 0.1–0.49, p<0.001). Conclusions: Paclitaxel has less haematologic toxicity when compared with the other drugs without any significant survival difference. No significant financial relationships to disclose.
Topotecan consolidation after etoposide platinum for limited stage small cell lung cancer patients who do not receive prophylactic cranial irradiation
Authors: Ross H. J. 
Published: August 2020

7553 Background: Small cell lung cancer (SCLC) accounts for approximately 15% of new lung cancer diagnoses in the US and about one third of patients present with limited stage (LD-SCLC). Concurrent chemoradiotherapy followed by prophylactic cranial irradiation (PCI) is standard and produces long-term survival in up to 25% of good performance status (PS) patients. Some patients refuse or are ineligible for PCI resulting in poorer outcome. Topotecan is active against SCLC and crosses the blood brain barrier suggesting that it might reduce brain metastases in this group. This phase II trial was designed to explore that possibility. Methods: Eligible patients had declined or were ineligible for PCI after completing standard platinum etoposide chemotherapy with concurrent radiotherapy for LD-SCLC with at least a partial response (PR), had recovered from toxicity with PS 0–1, and had no evidence of brain metastases. Patients received 1.5 mg/m2/day topotecan IV for 5 consecutive days every 21 days for four cycles. Primary endpoint was incidence of brain metastases with secondary endpoints overall and progression-free survival and toxicity. Results: Twenty patients enrolled between November 1999 and May 2006. 17 patients (85%) completed 4 cycles of topotecan. Brain metastases developed in 6 patients (30%) at a mean of 5.3 months (range 84–324 days). Median survival was 25.9 months with median PFS 462 days. At final data analysis, eight patients (40%) were alive without evidence of disease at 19 to 92.6 months. Topotecan was well tolerated with grade 3/4 hematologic toxicity in 13 patients (65%) and neutropenic fever in 2 patients. One patient had radiation pneumonitis. One patient died with progressive disease and pneumonia after two cycles of topotecan. Conclusions: Adjuvant topotecan was well tolerated. The 30% rate of brain metastases suggests the possibility that topotecan was active in the brain. Overall and progression-free survivals are promising. Additional study of adjuvant topotecan in LD-SCLC patients who do not receive PCI may be warranted. No significant financial relationships to disclose.
A randomized phase II trial of adjuvant chemotherapy with docetaxel (DOC) plus cisplatin (CIS) versus paclitaxel (PAC) plus carboplatin (CAR) in patients with completely resected non-small cell lung cancer (NSCLC): Safety and feasibility data from trial TORG 0503
Authors: Kubota K. , Kunitoh H. , Seto T. , Shimada N. , Tsuboi M. , Okamoto H. , Masuda N. , Maruyama R. , Shibuya M. , Watanabe K. 
Published: August 2020

7561 Background: Adjuvant chemotherapy is standard of care for patients with completely resected stage IB, II and IIIA NSCLC. However, the optimum chemotherapy regimen has not been determined. TORG 0503 was conducted to evaluate platinum-based third generation regimens in this clinical setting. Methods: Patients with completely resected stage IB, IIA, IIB or stage IIIA NSCLC were stratified by stage (IB/IIA vs. IIB/IIIA) and institution and randomized to receive 3 cycles of DOC (60 mg/m2, day 1) plus CIS (80 mg/m2, day 1) or 3 cycles of PAC (200 mg/m2, day 1) plus CAR (AUC 6, day 1). Both regimens were repeated every 3 - 4 weeks. Other eligibility criteria included ECOG PS 0–1, age ≥20, and =<70 years old, adequate organ function, no prior chemotherapy or radiotherapy. Patients who underwent pneumonectomy were excluded. The primary endpoint was 2-year relapse free survival (RFS), and secondary endpoints were overall survival (OS), quality of life (QOL), feasibility and toxicity. Results: 111 patients were randomized between April 2006 and July 2008, 58 patients to DOC+CIS (DC) and 53 to PAC+CAR (PA). Patients’ demographics (DC/PA): median age 63/59 years, 60%/66% male, 17%/22% PS 1, 79%/73% adenocarcinoma, 40%/40% of patients were stage IB/IIA, 60%/60% IIB/IIIA. Feasibility: 93% (54/58) of patients allocated to DC and 92% (49/53) patients in the PA arm completed 3 planned cycles of chemotherapy. Toxicities: DC vs. PA: Grade (G) 3/4 neutropenia (86%/75%), G3/4 anemia (2%/0%). G 3 febrile neutropenia (10%/4%), G2 ALT (0%/10%), G2 creatinine (17%/0%), G2–4 allergy (0%/4%), G2 alopecia (43%/47%), G2/3 fatigue (5%/10%), G2/3 anorexia (43%/22%), G2/3 nausea (47%/22%), G2/3 vomiting (31%/12%), G2 diarrhea (12%/8%), G2 constipation (2%/4%), G2/3 sensory neuropathy (3%/33%), G2/3 arthralgia (0%/31%), G2 myalgia (2%/8%). No treatment related deaths were observed in either arm. Conclusions: Both docetaxel plus cisplatin and paclitaxel plus carboplatin are safe and feasible regimens as adjuvant chemotherapy. [Table: see text]
Usefulness of 18FDG-positron emission tomography (FDG-PET) for early prediction of erlotinib (Eb) treatment outcome in non-small cell lung cancer (NSCLC) patients: Results of a pilot study
Authors: Soto Parra H. J. , Ippolito M. , Tiseo M. , Cosentino S. , Ardizzoni A. , Latteri F. , Pumo V. , Cordio S. , Bordonaro R. , Spadaro P. 
Published: August 2020

7568 Background: FDG-PET could be useful for early evaluation of tumor response to tyrosine kinase inhibitors (TKI). Glucose metabolic activity seems to closely reflect response to epidermal growth factor receptor (EGFR) TKI in vivo and in vitro (Su H et al, Clin Cancer Res 2006;12:5659–67). Thus, we attempted to assess the clinical value of FDG-PET for early prediction of tumor response to Eb an EGFR-TKI. Methods: Pts with NSCLC stage IV in progression after at least one line of chemotherapy and PS 0–1 were treated with Eb (150 mg orally once daily). FDG-PET was performed on days 0 and 2, after administration of 3 daily doses. FDG uptake was evaluated as the maximum standardized uptake value in the tumor (SUVmax). SUVmax was divided by SUV of the background region (liver) to produce the tumor:nontumor ratio (TNT). FDG-PET responses were evaluated by quantitative changes on TNT and classified according to the EORTC PET study group. PET response were compared with radiographic tumor response (RECIST criteria) assessment based on CT scan at baseline and on day 45. Results: From May 2007, 27 pts were enrolled and 23 were evaluable (4 not-evaluable: 2 BAC PET negative, 2 violations). FDG-PET revealed a metabolic partial response (PR) in 8 pts; subsequent CT scan assessment evidenced 4 PR and 4 long lasting stable disease (SD), respectively. Seven pts had metabolic progressive disease (PD) at PET scan and 8 had SD, all of them presented PD at CT scan. Metabolic PR was associated with a longer median progression-free survival (152 vs 45 days, p = < 0.0001) and longer overall survival (323 vs 128 days p=0.15). For radiological PD pts who presented metabolic SD or PD, survival time was respectively 220 and 117 days. EGFR gene mutation, gene copy number and protein expression are ongoing. Conclusions: FDG-PET using changes on TNT can very early predict (already 2 days after initiation) Eb treatment outcome. Particularly, pts with early metabolic PD are unlikely to benefit from Eb. Therefore, evaluation of the early metabolic response holds promise for assessment of pts selection. The two different behavior of FDG-PET observed on refractory pts, deserve biomolecular analysis for understanding mechanism of resistance. No significant financial relationships to disclose.
FDG-PET/CT imaging for staging and definition of tumor volumes in radiation treatment planning in non-small cell lung cancer
Authors: Xu Y. , Ma S. , Yu D. , Wang J. , Zhang L. , Di X. 
Published: August 2020

7574 Background: 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) /computed tomography (CT) has a potential improvement for staging and radiation treatment (RT) planning of various tumor sites. But from a clinical standpoint, the open questions are essentially the following: to what extent does PET/CT change the target volume? Can PET/CT reduce inter-observer variability in target volume delineation? We analyzed the use of FDG-PET/ CT images for staging and evaluated the impact of FDG- PET/CT on the radiotherapy volume delineation compared with CT in patients with non-small cell lung cancer (NSCLC) candidates for radiotherapy. Intraobserver variation in delineating tumor volumes was also observed. Methods: Twenty-three patients with stage I-III NSCLC were enrolled in this pilot study and were treated with fractionated RT based therapy with or without chemotherapy. FDG-PET/CT scans were acquired within 2 weeks prior to RT. PET and CT data sets were sent to the treatment planning system Pinnacle through compact disc. The CT and PET images were subsequently fused by means of a dedicated radiation treatment planning system. Gross Tumor Volume (GTV) was contoured by four radiation oncologists respectively on CT (CT-GTV) and PET/CT images (PET/CT-GTV). The resulting volumes were analyzed and compared. Results: For the first phase, two radiation oncologists outlined together the contours achieving a final consensus. Based on PET/CT, changes in TNM categories occurred in 8/23 cases (35%). Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in 12/20 patients (60%) by comparison with CT targeting. The most prominent changes in GTV have been observed in cases with atelectasis. For the second phase was four intraobserver variation in delineating tumor volumes. The mean ratio of largest to smallest CT-based GTV was 2.31 (range 1.01–5.96). The addition of the PET data reduced the mean ratio to 1.46 (range 1.12–2.27). Conclusions: PET/CT fusion images could have a potential impact on both tumor staging and treatment planning. Implementing matched PET/CT reduced observer variation in delineating tumor volumes significantly with respect to CT only. [Table: see text]
PET-CT compared to invasive mediastinal staging in non-small cell lung cancer (NSCLC)
Authors: Darling G. , Maziak D. , Inculet R. , Gulenchyn K. , Driedger A. , Ung Y. , Miller J. , Gu C. , Evans W. , Levine M. 
Published: August 2020

7575 Background: In patients with NSCLC, preoperative staging tests including mediastinoscopy (M) are important in defining which patients are surgical candidates. 18FDG PET-CT is useful in identifying patients with mediastinal disease not evident by CT. Alternatively, M may not be required if PET-CT is negative. We have previously reported reduced rates of unnecessary thoracotomy (T) in the PET-CT arm of a trial which compared staging with PET-CT versus conventional imaging (bone scan and CT liver and adrenals) in patients with clinical stage I, II, or IIIA NSCLC being considered for surgery (J Clin Oncol 26 May 20 suppl: abstr 7502). Methods: In this analysis, we determined the accuracy of PET-CT in mediastinal staging compared to invasive surgical staging either by M alone or by M and T. Patients in the PET-CT arm had invasive mediastinal staging either by M or mediastinal nodal sampling at T. PET-CT was considered positive if N2 or N3 nodes exhibited increased 18FDG uptake. Results: M was performed in 81 of 143 patients in the PET-CT arm; the remainder had mediastinal nodal staging at T. Combining M with T, the sensitivity and specificity of PET-CT were 0.70 [95% CI: 0.48–0.85] and 0.94 [95%CI: 0.89–0.97], respectively. Of 21 patients with a positive PET-CT, 7 did not have tumor. The positive predictive value (PPV) and negative predictive value (NPV) were 0.67 [95% CI: 0.45–0.83] and 0.95 [95% CI: 0.90–0.98], respectively. The results for PET-CT versus M alone were: sensitivity, 1.0 [95% CI: 0.76–1.0]; specificity, 0.88 [95%CI: 0.79–0.94]; PPV, 0.60 [95%CI: 0.39–0.78]; NPV, 1.0 [95% CI: 0.94–1.0]. Based on PET-CT alone, 7 patients would have been denied T if PET-CT abnormalities had not been evaluated with invasive mediastinal staging. Conclusions: Mediastinal abnormalities on PET-CT should be confirmed by invasive mediastinal staging because of the risk of a false positive test. Patients should not be denied potentially curative therapy based on PET-CT alone. If PET-CT is negative in the mediastinum, the likelihood of occult metastatic disease in the mediastinum is very low and invasive staging may not be required depending on the clinical context. No significant financial relationships to disclose.
A multicenter phase II study of pemetrexed (P), cisplatin (C), and bevacizumab (B) in patients (pts) with advanced malignant mesothelioma (MM)
Authors: Dowell J. , Taub R. , Lan C. , Xie Y. , Dunphy F. , Blake V. , Kindler H. 
Published: August 2020

7578 Background: Vascular endothelial growth factor (VEGF) is a key growth factor for MM. In pre-clinical models, anti-VEGF antibodies inhibit MM proliferation. Standard chemotherapy for MM, pemetrexed + cisplatin, yields a response rate of 41%, progression-free survival (PFS) of 5.7 months (mo) and median overall survival (OS) of 12.1 mo. We added the anti-VEGF antibody B to PC in an ongoing phase II multi-center study in MM pts. Methods: Eligible pts have unresectable, histologically-confirmed MM, no prior chemotherapy, and PS 0–1. Pts receive C 75 mg/m2, P 500 mg/m2 and B 15 mg/kg Q21 days for 6 cycles, then B Q21 days until progression. CT scans are obtained Q 2 cycles. Primary endpoint: Progression-fere survival (PFS). Correlative studies include IHC for the VEGF/KDR complex and PCR for simian virus 40 (sv40) T antigen. Results: 43 pts enrolled at 4 centers from 3/06 to 12/08; currently, 34 are evaluable for PFS and 36 for toxicity. Pt characteristics: male 88%; median age 66 (range 24–81); histology: epithelial 62%, sarcomatoid 15%, biphasic 20%, unknown 3%; site of origin: pleural 85%, peritoneal 12%, tunica vaginalis 3%; PS 0 32%, PS 1 68%; thrombocytosis (>400) 32%. Cycles administered 229 (median 4, range 1–18). Grade 3/4 toxicity (%pts): neutropenia 8%; anemia 0%; thrombocytopenia 3%; thrombosis 11%; hypertension 8%; vomiting 8%; mucositis 6%; CVA 3%; proteinuria 0%; perforation 0%. Partial response: 41%, stable disease: 35%. Median PFS: 5.6 mo (95% CI: 4.1, 7.2). Median OS 11.5 mo (95% CI: 9.4, 24). Conclusions: These data suggest that the addition of B to PC does not improve PFS when compared with historical controls of PC in advanced MM pts. Correlative studies evaluating the VEGF/KDR complex and sv40 T antigen are pending. [Table: see text]
Precision pulmonary trans-arterial chemoembolization (PPTACE) plus percutaneous RFA for unresectable lung neoplasms: Initial experience in twelve cases
Authors: Gadaleta C. , Catino A. , Rubini G. , Ranieri G. , Fazio V. , Gadaleta-Caldarola G. , Vinciarelli G. , Armenise F. , Gaudiano A. , Mattioli V. 
Published: August 2020

7593 Background: The study aimed to evaluate the feasibility and safety of precision pulmonary arterial chemoembolization (PPTACE) followed by percutaneous RFA in patients with unresectable lung neoplasms Methods: From November 2007 to October 2008, twelve patients (5 male, 7 female, median age 57) and 20 nodules were treated in 14 sessions. Patients had lung metastases from the following tumors: uterine cancer (2), colorectal carcinoma (7), breast carcinoma (1) and two patients had primary unresectable NSCLC. Median diameter of neoplasms was 2 cm. Both RFA and pulmonary TACE were performed under general anesthesia. Two patients underwent two sessions of treatment due to bilateral disease. After subclavian vein puncture and mapping of arterial vascularization of the segment including the tumoral nodule, antiblastic agents loaded on microspheres (Hepasphere, 50–100 micron in diameter) were selectively perfused in a subsegmental sector. Doxorubicin was used in 3 sessions, as well as mitomycin C, while irinotecan was administered in six cases and cisplatin in one case (one session was performed only with microspheres). Percutaneous CT-guided RFA of lung nodules was performed 2–7 days after PPTACE. Pretreatment work-up included: contrast-enhanced CT-scan, (18-F)Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) and Ventilation Lung Single Photon Emission Tomography (VL-SPET). Results: The treatment was well tolerated; pneumothorax, requiring chest- tube placement, occurred in two sessions (14%). Technical success was achieved in all treated nodules. In all cases, the impedance during RFA decreased from 30 to 50%, with an increase of the delivered energy (expressed by Watts). Morphological response showed a necrotic area, without contrast-enhancement at CT scan, including the neoplasm plus a large safety zone. VL-SPET showed a wide area without ventilation in lung parenchyma submitted to PPTACE and extending over it; the changes on alveolar ventilation detected by VL- SPET after PPTACE could explain the better heat conduction during RFA. Conclusions: Lung RFA after pulmonary TACE is feasible and safe. These preliminary data deserve further investigation. No significant financial relationships to disclose.
Comparison of gefitinib and docetaxel in patients with pretreated advanced non-small cell lung cancer (NSCLC): Meta-analysis from four clinical trials
Authors: Shepherd F. A. , Douillard J. , Fukuoka M. , Saijo N. , Kim S. , Cufer T. , Sellers M. V. , Armour A. A. , Kim E. S. 
Published: August 2020

8011 Background: Four open-label, randomized trials evaluated gefitinib (G) vs docetaxel (D) in unselected patients with pre-treated advanced NSCLC: INTEREST (Lancet 2008; 372: 1809), V-15–32 (J Clin Oncol 2008; 26: 4244), ISTANA (J Clin Oncol 2008; 26: Abs 8025), SIGN (Anticancer Drugs 2006; 17: 401). Reported here is a meta-analysis using the patient data from each of these trials. Methods: The meta-analysis compared efficacy of G (250 mg/day) and D (75 mg/m2 [V-15–32 60 mg/m2]) using appropriate analysis populations from INTEREST (1466 patients randomized), V-15–32 (489), ISTANA (161) and SIGN (141). Meta-analyses (unadjusted and adjusted for covariates) were performed by Cox proportional hazards for OS and PFS, and by logistic regression for ORR. Results: G demonstrated similar OS and PFS and superior ORR to D in the primary analyses. Secondary analyses demonstrated similar results. Conclusions: Results were consistent with those of the individual studies. Given the similar/superior efficacy demonstrated by G, its favorable tolerability profile, quality of life benefits and oral administration, G has a favorable benefit-risk profile compared with D in a broad pre-treated advanced NSCLC patient population. [Table: see text] [Table: see text]