bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of induction chemotherapy with cisplatin (Cis) and gemcitabine (Gem) followed by concomitant Cis-Gem and thoracic radiation (RTX) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC)
Authors: Driesen P. , Verbeke L. , Lonchay C. , Lambrechts M. , Mentens Y. , Carestia L. , Rosier J. , Colinet B. , Chouaki N. , Kraaij K. J. 
Published: August 2020

7550 Background: In the CALGB Study Cis with Gem followed by concomitant chemoradiation for inoperable LA-NSCLC was effective, however with significant toxicity (E. Vokes et al; JCO 20: 2002). The aim of this study was to improve tolerability by reducing the Gem dose during radiotherapy and adding one cycle of induction chemotherapy. Methods: Patients with histological proven stage IIIA and IIIB NSCLC were included in this study from 8/04 to 9/07. All patients were to receive 3 induction cycles (21 days) of Cis 80 mg/m2 d1 plus Gem 1250 mg/m2 over 30 minutes d1, 8. After a 3 weeks rest period, 2 cycles of concomitant chemoradiation Cis 80 mg/m2 d1, Gem 300 mg/m2 d1, 8 and RTX (about 60 Gy; 5 times 1,8 Gy fractions / week) were given. Results: A total of 49 patients, median age 63.4 yrs, 73.5% male, with Karnofsky performance status 80/85/90/100: 16.3% / 2.0% / 49.0% / 32.7% were entered. Disease stage IIIA/IIIB: 28.6% / 71.4%. Median dose intensity during chemoradiation Gem 98.4%, Cis 99.0% and radiation median total dose was 63 Gy. Number of grade 3/4 toxicities during induction chemotherapy (N=49): neutropenia 9/9, thrombocytopenia 4/1. Acute grade 3/4 toxicities during chemoradiation phase (N=31): neutropenia 4/0, thrombocytopenia 5/1, radiation esophagitis 4/0 and radiation pneumonitis 1/0. No toxic death. Tumor Response Rate of enrolled patients was 22 (44.9%) (95% CI: 30.7–59.8). Conclusions: Concurrent Cis Gem chemoradiation after Cis Gem induction is an active treatment for LA-NSCLC with managable toxicity. [Table: see text]
Involved-field radiotherapy for patients with limited small cell lung cancer: Patterns of local-regional failure and feasibility
Authors: Xia B. , Fu X. , Cai X. , Chen G. , Yang H. , Fan M. , Zhao K. 
Published: August 2020

7554 Background: To investigate the feasibility of the involved-field radiotherapy in patients with limited-stage small cell lung cancer (LSCLC) according to the patterns of local failure, focused on the first local-regional failure. Methods: Two clinical phase II studies for patients with LSCLC treated at our institute between 1997 and 2007 were reviewed. All patients received combined chemotherapy (CHT) with cisplatin and etoposide, and thoracic RT (TRT) was generally delivered sequentially following one to three cycles of CHT and consisted of either 56 Gy in 40 fractions for 4 weeks or 55 Gy in 22 fractions for 4–5 weeks. TRT fields encompassed primary tumor volume (post-CHT) and the involved nodal areas (pre- and post-CHT) without elective node irradiation. The local-regional failure was defined as failure within thoracic cavity and supraclavicular fossa except for pleural effusion, which was then divided into two subtypes: in-field and out-field failure according to the first occurred site in the planning target volume or not. Results: There were 89 patients completed the planed regimen and eligible for evaluating patterns of failure, 54 patients (57%) in 56 Gy cohort and 35 patients(43%) in 55 Gy cohort. The media cycles of CHT were 6 (4–8). The overall survival and local progression-free survival rates for 89 patients at 2 years were 56% and 71%, respectively, with a median survival of 25.6 months. 56 patients (63%) developed distant metastases and 21 patients (24%) developed local-regional failures: 12 in-field and 9 out-field. 8 out of 9 out-field failures occurred in the ipsilateral supraclavicular fossa, and the media duration to the end of TRT was 6 mouths (5–14). Comparing the 56 Gy and 55 Gy cohorts, the rates of any thoracic, in-field and out-field failures were no difference significantly. Conclusions: Thoracic radiotherapy using involved-field technique in patients with LSCLC resulted in a high failure rate of the supraclavicular fossa. Whether improving accuracy for the initial evaluation of clinical stage could reduce out-field failure in supraclavicular fossa need to be investigated. No significant financial relationships to disclose.
Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected stage I non-small cell lung cancer
Authors: Medford-Davis L. N. , Varlotto J. , Recht A. , Flickinger J. C. , DeCamp M. M. 
Published: August 2020

7583 Background: To examine the effects of different definitions of local recurrence on the reported patterns of failure and associated risk factors in patients undergoing potentially curative resection of Stage I non-small cell lung cancer (NSCLC). Methods: The study included 306 consecutive patients treated from 2000–2005 without radiotherapy. Local recurrence was defined as either: “radiation” (i.e., recurrences confined to the post-operative radiotherapy fields used in the Phase III trial of adjuvant radiotherapy by Trodella et al) (LRR), including the bronchial stump, staple line, the ipsilateral hilum, and ipsilateral mediastinum; or “comprehensive” (LRC), including these sites plus the ipsilateral lung and contralateral mediastinal and hilar nodes. Results: The median follow-up was 33 months. Proportions of LRC and LRR at 2, 3 and 5 years were 14%, 21% and 29%; and 7%, 12%, and 16%, respectively. Significant risk factors for LRC on multivariable analysis were diabetes, lymphatic vascular invasion and tumor size; significant factors for LRR were resection of less than a lobe and lymphatic vascular invasion. Distant (non-local) relapse proportions using these definitions at 2, 3 and 5 years were 10%, 12%, and 18%; and 14%, 19%, and 29%, respectively. Significant risk factors for distant failure were histology when using the LRC definitions and tumor size using the LRR definition. Conclusions: Local recurrence increased nearly two-fold when a broad definition was used, rather than a narrow one. The definition also affected which factors were significantly associated with both local and distant failure on multivariate analysis. Comparable definitions must be used when analyzing different series. No significant financial relationships to disclose.
Effect of lobectomy on survival in early-stage small cell lung cancer: A retrospective analysis
Authors: Varlotto J. M. , Recht A. , Flickinger J. C. , Dyer A. , Medford-Davis L. , DeCamp M. 
Published: August 2020

7585 Background: Small cell lung cancer (SCLC) rarely presents as I/II Disease. In order to assess the incidence, treatment and prognosis of this early-stage SCLC, we used the Surveillance, Epidemiology and End Results database. Furthermore, since some investigators are irradiating growing and/or PET Scan positive nodules without biopsy, presenting characteristics of surgically-resected Stage I SCLC were compared to those of non-small cell lung cancer (NSCLC). Methods: The SEER 17 Database from 1988–2003 was accessed for all patients with early-stage SCLC. Presenting characteristics of surgically-resected Stage I SCLC were compared to those of resected Stage I NSCLC using chi-square and Wilcoxon Rank Sum tests. The logrank test was used to compare the differences in Survival(S) resulting from the various treatments options for early-stage SCLC. Results: 1,615 patients were identified with early-stage SCLC with greater than 3 months of follow-up. The median S was 20 months for the entire group. Over the time period of our study, the incidence of early stage SCLC as a percentage of all SCLCs and all lung cancers (SCLCs and NSCLCs) remained stable and ranged from 3.00–4.96% and 0.09–0.16% respectively. Surgically-resected Stage I SCLC did not differ from NSCLC in regards to patient characteristics (age, sex, race) or tumor location, but SCLC was found to have significantly smaller tumor size (p< 0.0001). Lobectomy or greater resections without radiotherapy were associated with a greater median S than those treated with segmental/wedge resections and those treated with radiotherapy alone (44 vs 29 months, p=0.03 and 20 months, p <0.0001). Furthermore, when lobectomy or greater resection was performed, adjuvant radiotherapy was associated with a shorter, but not significantly different median S (32 vs 44 months, p = 0.17). Segmental/wedge resections without radiotherapy were associated with significantly better S than patients who received radiotherapy alone, but no difference in S was found with the use of adjuvant radiotherapy (29 vs 20 months, p =0.003, and 35 months, p=0.31). Conclusions: The incidence of stage I/II small cell lung cancer was stable over the years of our study. Anatomic lobectomy without adjuvant radiotherapy appears to be the optimal therapy for patients without mediastinal nodal metastases. No significant financial relationships to disclose.
Sublobar resection with I-125 brachytherapy for early-stage non-small cell lung cancer (NSCLC) using prefabricated mesh
Authors: Manning M. A. , Mohamed M. , Burney D. P. 
Published: August 2020

7586 Background: Lobectomy is standard of care for stage I NSCLC, but it reduces pulmonary reserve. Patients with pulmonary dysfunction may tolerate curative wedge resection with a permanent I-125 mesh implant. We report results using this technique with and without a novel prefabricated mesh device. Methods: Between 7/06 and 5/08, 56 patients with clinical stage I NSCLC had wedge resection and brachytherapy. All had PET-CT staging and were ineligible for lobectomy. Median age was 72 (48–87) and median FEV-1 was 1.3 liters (0.6–3.4 liters). At surgery, a significant proportion were upstaged. Pathologic staging confirmed 60.7% to be stage IA and 23.2% stage IB. Others were IIA (3.6%), IIB (5.4%), IIIA (1.8%), IIIB (1.8%), and IV (3.6%). All implants consisted of absorbable polyglactin mesh containing a median of 40 (30–50) I-125 seeds with a median seed activity of 0.536 mCi (0.47 - 0.63 mCi). Half of the patients received mesh prepared intraoperatively, while the second half received patient-specific prefabricated mesh (BrachyMESH - Oncura). Results: The median hospital stay was 5 days. All were immediately extubated. Common toxicities included air leak delaying chest tube removal, leukocytosis, paroxysmal atrial fibrillation, and increased secretions. Two required repeat chest tube placement for subsequent pneumothorax. Two patients with severe pre-op pulmonary dysfunction (pre-op FEV-1 of 0.6 and 0.68 liters) experienced respiratory failure and expired following prolonged hospital stays. With a median follow-up of 7 months (0–23 months), overall survival is 87.5% and disease free survival is 89%. The local control was 96.4% with the intraoperative mesh and 100% with the prefabricated mesh. Conclusions: Wedge resection with permanent I-125 mesh implant is a generally well-tolerated procedure leading to acceptable early local control in patients ineligible for lobectomy. This technique may not be suitable for patients with pre-op FEV-1 < 0.7 liters; but, it provides accurate surgical staging conferring a diagnostic advantage over non-invasive treatment modalities. The prefabricated device offers similar results to manually prepared devices. No significant financial relationships to disclose.
Intratumoral chemotherapy as an adjunct to endobronchial brachytherapy
Authors: Nader D. , Ketterl P. , Kelly D. , Flynn J. , Stark J. J. , Staren E. D. , Braun D. P. 
Published: August 2020

7591 Background: NSCLC patients (pts) with clinically significant endobronchial obstruction have a poor prognosis and quality of life in both locally advanced and metastatic stages of disease. Radiation therapy (RTx) in conjunction with chemotherapy (CTx) improves survival compared to either modality alone but produces greater toxicity and morbidity. Significant clinical benefit with respect to disease management and quality of life could be realized with improved methods for controlling obstructing endobronchial lesions. The hypothesis for this study is that optimal clinical control of endobronchial lesions can be achieved by intratumoral injection of a drug with both clinical activity against NSCLC and synergy with RTx. Cisplatin (CPt), an active agent in NSCLC and a known radiosensitizer is an ideal drug for this objective. Thus, the goal of this exploratory study was to determine the clinical efficacy and tolerance to intratumoral CPt injection in combination with HDR brachytherapy (BTx) in NSCLC patients with obstructing endobronchial lesions. Methods: NSCLC pts (n=16) with > 75% endoluminal obstruction of a main or lobar airway were evaluated. Intratumoral CTx consisted of CPt (1 mg/ml; 0.5–2.0 ml/session) injected into the entire visible tumor through a flexible 21 gauge needle through the bronchoscope. BTx was given as 500 cGy/session at one cm diameter for 4 sessions concomitant with CTx. Results: All pts completed the entire 4 sessions of planned local therapy. There was complete resolution of injected lesions in 14/16 pts confirmed bronchoscopically and cytologically. In the other 2 pts, necrotic tissue occupying < 10 and 20% of the airway, cytologically negative for tumor was seen. There were no adverse events or complications related to bronchoscopy or local CTx. Conclusions: The results of this study demonstrate that intratumoral administration of CPt, as an adjunct to endobronchial BTx for the management of endobronchial obstructing lesions in patients with NSCLC is safe and effective. This approach offers the possibility of superior local tumor control while reducing toxicity to normal lung and esophagus as compared to conventional external beam radiation therapy modalities. Further studies evaluating the impact of this approach on survival and quality of life are warranted. No significant financial relationships to disclose.
Vandetanib plus pemetrexed versus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer (NSCLC): A randomized, double-blind phase III trial (ZEAL)
Authors: De Boer R. , Arrieta Ó. , Gottfried M. , Blackhall F. H. , Raats J. , Yang C. H. , Langmuir P. , Milenkova T. , Read J. , Vansteenkiste J. 
Published: August 2020

8010 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. A phase I trial of vandetanib + pemetrexed (pem) supported further investigation of this combination (de Boer et al, Ann Oncol 2008). Methods: The primary objective was to determine whether vandetanib 100 mg/day + pem 500 mg/m2 every 21 days (max 6 cycles) prolonged progression-free survival (PFS) vs placebo + pem. Overall survival (OS), objective response rate (ORR), time to deterioration of symptoms (TDS, by Lung Cancer Symptom Scale) and safety were secondary endpoints. Efficacy and safety were assessed in females as a co-primary analysis population. Eligibility criteria included stage IIIB/IV NSCLC, PS 0–2, and previous 1st-line therapy. Results: Between Jan 07-Mar 08, 534 patients (mean age 59 yrs; 38% female; 21% squamous histology; 8% brain metastases; stage IV 84%; PS 0/1/2: 41%/53%/6%) were randomized 1:1 to receive vandetanib + pem (n=256) or placebo + pem (n=278). Baseline characteristics were similar in both arms. Median duration of follow-up was 9.0 months, with 83% patients progressed and 50% deceased. There were positive trends seen for vandetanib + pem for both PFS (hazard ratio [HR] 0.86, 97.58% CI 0.69–1.06; P=0.108) and OS (HR 0.86, 97.54% CI 0.65–1.13; P=0.219); similar advantages were observed for females. There were statistically significant advantages for ORR (19.1% vs 7.9%, P<0.001) and TDS (HR 0.61, P=0.004). The adverse event profile was consistent with previous studies of vandetanib: rash (38% vs 26%), diarrhea (26% vs 18%) and hypertension (12% vs 3%) being more frequent in the vandetanib arm. There was evidence of reduced pem toxicity with the addition of vandetanib: anemia 8% vs 22%, nausea 29% vs 37%, vomiting 15% vs 22%, fatigue 37% vs 45%, and asthenia 11% vs 17%. The incidence of protocol-defined QTc prolongation was <1%. There was no increase in bleeding or thrombotic events in the vandetanib arm. Conclusions: The combination of vandetanib + pem demonstrated evidence of clinical benefit in patients with pretreated advanced NSCLC, although the study did not meet the primary endpoint of statistically significant PFS prolongation vs pem alone. Vandetanib + pem was generally well tolerated. [Table: see text]
MO19390 (SAiL): Safety and efficacy of first-line bevacizumab (Bv)-based therapy in advanced non-small cell lung cancer (NSCLC)
Authors: Crino L. , Mezger J. , Griesinger F. , Zhou C. , Reck M. M. 
Published: August 2020

8043 Background: MO19390 (SAiL) is a single-arm, multicenter, international trial evaluating the safety and efficacy of first-line Bv in combination with a range of chemotherapy regimens in over 2,000 patients (pts). Methods: Primary endpoint was safety; secondary endpoints included time to disease progression (TTP) and overall survival (OS). Pts with untreated locally advanced, metastatic or recurrent non-squamous NSCLC (ECOG PS 0–2) received Bv (7.5 or 15mg/kg) with standard chemotherapy for up to six cycles, then non-progressors proceeded to receive Bv until disease progression. Results: This analysis (data cut-off July 2008) was based on 2,008 pts with a median age of 59. Pts (%) were: male 60.1; stage IIIB/IV 19.5/80.5 (no data 3 pts); adenocarcinoma/large cell/other 85.8/7.1/7.1; ECOG PS 0/1/2 38.1/56.1/5.8. Pts received a median of 6 Bv cycles and 4 chemotherapy cycles. 26.7% of pts experienced grade ≥3 serious adverse events (SAEs); 8.3% of pts experienced grade ≥3 SAEs related to Bv. Adverse events (AEs) of special interest (all grades) included bleeding (27.6%), hypertension (19.3%), proteinuria (14.6%), thromboembolism (8.6%), CHF (2.9%) and GI perforation (1.2%). The incidence of AEs of special interest (all grades) was comparable across the various types of chemotherapy regimens: carboplatin doublets (50.6%)/cisplatin doublets (49.9%)/non-platinum doublets (41.7%)/monotherapy (37.5%). No new safety signals were reported. Trial data were not deemed mature enough to provide efficacy results. Conclusions: SAiL confirms that Bv-based therapy has a well-established and manageable safety profile. Clinical outcomes obtained in this real-life population are consistent with those seen in the pivotal trials of bevacizumab (Avastin) in NSCLC (E4599 and AVAiL), and compare favorably with historical data. Updated efficacy results for 2,147 pts will be presented, based upon an additional 5 months’ follow-up. [Table: see text]
Docetaxel plus carboplatin with or without levofloxacin prophylaxis in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): The APRONTA trial
Authors: Schuette W. , Nagel S. , von Weikersthal L. Fischer , Pabst S. , Schumann C. , Salm T. , Roscher K. , Dickgreber N. 
Published: August 2020

8047 Background: Elderly pts receiving chemotherapy are more likely to have febrile neutropenia and infection than younger pts. Prophylactic fluoroquinolone during chemotherapy reduces the rate of infection and hospitalization vs placebo. The effect of prophylactic treatment with the fluoroquinolone, levofloxacin, on infection rates and survival during docetaxel plus carboplatin therapy was assessed in elderly pts with advanced NSCLC. Methods: In this randomized, double-blind, placebo-controlled Phase III study, eligible pts were aged ≥65 years with previously untreated, histologically/cytologically proven stage IIIB/IV NSCLC, and normal cardiac, renal, hepatic, and hematologic function. Active infection or antibiotics 72 hours before inclusion was not permitted. A planned sample size of 192 pts was considered sufficient for analysis. Pts were randomized to docetaxel (75 mg/m2 IV, Day 1) plus carboplatin (AUC 6 IV, Day 1) q3w, plus placebo or levofloxacin (500 mg po, once daily) on Days 5–11. Primary endpoint was grade 3/4 infection rate or systemic antibiotic therapy of grade 1/2 infection rate. Secondary endpoints were progression free-survival and overall survival. Between-group comparisons were performed using Fisher's exact test. Results: 192 pts (median age 70 years; ECOG PS 0/1/2 in 36%/55%/9%) were randomized to docetaxel plus carboplatin and levofloxacin (n=99) or placebo (n=93); 5 pts received no treatment and were excluded from the ITT population. Rate of grade 3/4 infection was 27.5% (95% CI: 19.3–39.0%) with levofloxacin vs 36.7% (95% CI: 27.1–48.0%) with placebo. Median progression-free survival (PFS) for patients in the levofloxacin arm was 165 days compared with 121 days in the placebo arm (p=0.22). Median overall survival was comparable between groups (307 vs 314 days, respectively; p=0.28). Conclusions: Levofloxacin prophylaxis reduces the rate of grade 3/4 infection compared with placebo. [Table: see text]
Phase II study of amrubicin (AMR) in patients (pts) with non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy: WJTOG0401
Authors: Hayashi H. , Kaneda H. , Okamoto I. , Miyazaki M. , Kudoh S. , Sawa T. , Takeda K. , Negoro S. , Iwamoto Y. , Nakagawa K. 
Published: August 2020

8059 Background: AMR is a totally synthetic 9-aminoanthracycline and a novel topoisomerase II inhibitor. AMR has shown promising clinical activity for advanced NSCLC as well as SCLC. This trial was conducted to evaluate the efficacy and safety of AMR for pts with NSCLC previously treated with platinum-based chemotherapy. Methods: Eligible pts had a performance status 0 to 1, previous treatment with one platinum-based chemotherapy for advanced NSCLC, and adequate organ function. Pts received AMR 40 mg/m2 intravenously on days 1–3 every 3 weeks. The primary endpoint was the objective response rate, which determined the sample size based on an optimal two-stage design. With the target activity level of 18% and the lowest response rate of interest set at 5%, 60 eligible patients were required with a 90% power to accept the hypothesis and a 5% significance level to reject the hypothesis. Results: Sixty-one pts (median age, 63 years; range 51–74 years) were enrolled. The median treatment cycles were 2 (range, 1–15). No complete responses and 7 partial responses were observed, giving an overall response rate of 11.5% (95% CI, 4.7–22.2%). Twenty patients (32.8%) had stable disease and 34 patients (55.7%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 44.3% (95% CI, 31.5–57.6%). The median overall survival and 1-year survival rate were 8.5 months and 32.0%, respectively. Grade 3/4 hematological toxicities were neutropenia (82%), anemia (27.9%) and thrombocytopenia (24.6%). Grade 3/4 non-hematological toxicities were anorexia (9.8%), febrile neutropenia (29.5%) and pneumonitis (1.6%). No treatment-related death and cardiac toxicity were observed. Conclusions: AMR exhibits significant activity with manageable toxicities as second-line therapy for advanced NSCLC. [Table: see text]