bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase III trial of carboplatin, paclitaxel, and thoracic radiation therapy with or without thalidomide in patients with stage III non-small cell carcinoma of the lung (NSCLC): E3598
Authors: Schiller J. H. , Dahlberg S. E. , Mehta M. , Johnson D. H.
Published: August 2020

7503

Background: Thalidomide (T) is an oral angiogenesis inhibitor with anti-tumor activity in hematological malignancies. Given that antiangiogenic drugs such as bevacizumab have proven activity in advanced NSCLC, ECOG conducted a phase III study to compare the effects of the addition of thalidomide to paclitaxel/carboplatin/radiation therapy (PC/RT) on overall survival (OS) in pts with newly diagnosed stage III NSCLC. Secondary endpoints included time to progression (PFS) and toxicity. Methods: Pts were required to have inoperable stage IIIA or IIIB (no pleural effusion) NSCLC and a PS of 0 or 1. Pts were randomized to receive 2 cycles of P (225 mg/m2)+ C (AUC=6) every 3 wks or PC + thalidomide starting at 200 mg daily with the possibility of dose escalation. This was followed by weekly C (AUC=2), P (45 mg/m2) and concurrent RT (60 Gy) ± T. Pts on PC/RT + T continued thalidomide for 24 mo. or until disease progression. Results: 277 eligible pts were randomized to PC/RT and 272 pts to PC/RT + T. Median age was 63; 61% of pts had stage IIIB disease, 35% had squamous histology, and 46% were PS 0. The third planned interim analysis was conducted with 403 of 506 planned deaths (73.9%) for full analysis and the trial was stopped early by the ECOG Data Monitoring Committee for futility. The median overall survival for the no T arm was 15.3 mo. (12.4–20.2 mo.) compared to 16.0 mo for the T arm (14.4–18.3 mo.); hazard ratio = 0.985 (0.81–1.19); p = 0.88. Median PFS for the no T arm was 7.6 mo. (6.6–8.7 mo.) compared to 8.0 mo. for the T arm (7.1–9.1 mo.), p>0.05. The most common toxicity on both arms was myelosuppression. 11% of pts on the T arm had a grade 3–5 thrombosis/embolism, compared to <3% on the no T arm. Conclusions: The addition of thalidomide to PC/RT in pts with stage III NSCLC does not provide a clinically significant benefit.

[Table: see text]
Verification of the newly proposed T category (7th edition of the TNM classification) from a clinicopathologic viewpoint in non-small cell lung cancer
Authors: Yano T. , Morodomi Y. , Ito K. , Miura N. , Takenaka T. , Kawano D. , Shoji F. , Maehara Y.
Published: August 2020

7533

Background: The proposed revision of the TNM classification by the International Association for the Study of Lung Cancer (IASLC) has been determined and validated based on the overall survival data. In the present study, we verified the T classification, which was the major point of revision regarding the newly proposed TNM classification, from a viewpoint of the clinico-pathologic findings at the primary tumor site. Methods: The medical records of 621 patients with primary non-small cell lung cancer (NSCLC) who underwent a complete resection at our institution from 1990 through 2003 were reviewed for the clinico-pathologic variables. The patients ranged in age from 31 to 87 years old with a mean of 66.4. The male:female ratio was 382:239. The adenocarcinoma:non-adenocarcinoma ratio was 449:220. Results: According to greatest dimension of the primary tumors, the 5-year postoperative survival was 77.8% for T1a (2cm>; n=168), 63.3% for T1b (3cm>; n=169), 46.4% for T2a (5cm>; n=205), 38.8% for T2b (7cm>; n=48), and 21.4% for T3 (7cm<; n=31) (p<0.001). The incidence of lymphatic permeation within the primary tumor was 12.5% for T1a, 17.2% for T1b, 29.8% for T2a, 35.4% for T2b, and 32.3% for T3 (T1b vs. T2a p<0.05). The incidence of vascular invasion within the primary tumor was 17.8% for T1a, 24.9% for T1b, 35.3% for T2a, 54.2% for T2b, and 64.5% for T3 (T1b vs. T2a, T2a vs. T2b, p<0.05). On the other hand, the incidence of pleural invasion of the primary tumor was 18.1 % for T1a, 29.4% for T1b, 49.3% for T2a, 47.3% for T2b, and 87.5% for T3 (T1a vs. T1b, T1b vs. T2a, T2b vs.T3, p<0.05). Significant differences were observed among the newly revised T subsets in at least one incidence of lymphatic permeation, vascular invasion or pleural invasion. Conclusions: The newly revised T classification, which is based mainly on the tumor dimension, is therefore considered both effective and appropriate for the pathological findings of the primary tumor.

No significant financial relationships to disclose.
Erlotinib as maintenance therapy after concurrent chemoradiotherapy in patients (p) with stage III non-small cell lung cancer (NSCLC): A Galician Lung Cancer Group phase II study
Authors: Casal J. , Vázquez S. , León L. , Lázaro M. , Fírvida J. L. , Amenedo M. , Alonso G. , Santomé L. , Afonso F. J.
Published: August 2020

7537

Background: Combination of platinum-based chemotherapy and radiotherapy is the standard treatment for p with unresectable stage III NSCLC, but considering the high rates of recurrence, it is necessary to improve these results. Erlotinib is an EGFR TKI that prolongs survival in p with recurrent and metastatic NSCLC. In this study, we aim to evaluate the role of erlotinib as maintenance therapy after a standard concurrent chemo-radiotherapy regimen in p with stage III NSCLC. Methods: P with unresectable stage IIIA/IIIB—without malignant effusions—NSCLC who had received a standard concurrent chemo-radiotherapy regimen and had no evidence of tumor progression were enrolled in this single arm, open-label phase II study and received erlotinib 150 mg/day po for 6 months. Main eligibility criteria were: PS 0–2, adequate bone marrow, hepatic and renal function and measurable disease by RECIST criteria. Primary endpoint was the percentage of p without evidence of disease progression after 6 months of erlotinib therapy and secondary endpoints were: PFS, OS, ORR and safety profile. Results: 49 p have been included in the study and data from 37 p are presented in this analysis. Baseline characteristics: median age 62 years (range 41–76); male 94.6%; caucasian 100%; smokers/never smokers (%) 97.3/2.7; ECOG PS 0/1/2 (%) 18.9/75.7/2.7; adenocarcinoma/squamous cell carcinoma/large cell carcinoma (%) 16.2/75.7/5.4; stage IIIA/IIIB (%) 16.2/83.8. Most common previous chemo-radiotherapy regimen is cisplatin/docetaxel/RT (83.8%). 27 p were evaluable for tumor response: CR 22.2%; PR 12.8%; SD 55.6%; PD 7.4%. Median TTP was 7.3 months (95% CI 5.8–16.9) and median OS was 18.7 months (95% CI 11.8-NA). Most common adverse events related to erlotinib were rash 30.6% (3 p gr. 3) and diarrhea 16.7%. Conclusions: Erlotinib as maintenance therapy is an active and well tolerated treatment after concurrent chemo- radiotherapy in p with stage III NSCLC. In spite of the majority of patients are caucasian, males, smokers with squamous cell carcinoma, maintenance with single agent erlotinib reached a promising median OS of 18.7 months. Updated data will be presented.

No significant financial relationships to disclose.
A multinational phase III randomized trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small cell lung cancer (CCheIN): Interim analysis
Authors: Park K. , Ahn Y. , Chen M. , Cho E. , Kim J. , Min Y. , Kim H. , Zhu G. , Heo D. S. , Wu Y.
Published: August 2020

7538

Background: Currently, the recommended treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). The efficacy of consolidation chemotherapy after CCRT needs to be confirmed. The aim of this phase III randomized trial is to determine the efficacy of consolidation chemotherapy with docetaxel (D) and cisplatin (P) following definitive CCRT with the same agents in stage III inoperable NSCLC. Herein we report the pre-planned interim analysis. Methods: Patients with inoperable stage III NSCLC were randomized to either CCRT alone (observation arm) or CCRT followed by consolidation chemotherapy (consolidation arm). N2 or N3 disease was confirmed by PET and/or pathology. CCRT with D (20 mg/m2) and P (20 mg/m2) was administered every week for 6 weeks with a total dose of 66 Gy of thoracic RT as 33 fractions. In the consolidation arm, patients were further treated with 3 cycles of D and P (35 mg/m2 each on day 1 and 8, every 3 weeks). The primary endpoint is time to progression (TTP). Total target number of patients is 458. Results: From Oct 2005 to Mar 2008, 233 patients were enrolled and 226 were randomized (observation 112; consolidation 114). Patients’ characteristics were similar in both arms. In the consolidation arm, 83 patients (73%) received consolidation chemotherapy, of whom 52 (45%) completed 3 planned cycles. Grade 3–4 neutropenia occurred in 5.4% of 203 consolidation cycles. Common non-hematologic toxicities of all grades during consolidation were anorexia (47%), nausea (37%), vomiting (16%), fatigue (35%) and esophagitis (31%). At the time of this analysis, there were 40 and 41 deaths in the observation and consolidation arms, respectively. Treatment-related mortality rates were similar. With a median follow-up of 28.2 months, the median TTP was 9.0 months in the observation arm and 13.9 months in the consolidation arm (P=0.19). Median overall survival was 20.7 and 21.2 months, respectively (P=0.49). Conclusions: This interim analysis suggests that consolidation chemotherapy with DP after CCRT with weekly DP is feasible and relatively well tolerated. Patient enrollment is ongoing.

No significant financial relationships to disclose.
A fractionated schedule of oral vinorelbine (NVBo) with cisplatin (CDDP) concomitantly with radiotherapy (RT) after induction chemotherapy (CT) in locally advanced (LA) non-small cell lung cancer (NSCLC): Safety and efficacy results of a phase II trial
Authors: Lerouge D. , Gervais R. , Dansin E. , Dujon C. , Chouaid C. , Riviere A. , Precheur-Agulhon B. , Piolat V. , Zalcman G. , Lartigau E.
Published: August 2020

7539

Background: NVB+CDDP as induction and concomitant regimen with RT is a recognized treatment in LA NSCLC (Vokes, J Clin Oncol. 2002). The oral formulation of NVB may simplify the administration and a new fractionated schedule may further improve the results during CT-RT. Methods: Non operable stage IIIA-IIIB NSCLC patients (pts) received an induction CT of 2 cycles of NVBiv 25 mg/m2 + CDDP 80 mg/m2 on D1 and NVBo 60mg/m2 on D8 every 3 weeks. Non progressive pts received 2 additional cycles of fixed dose NVBo of 20 mg on D1, D3 and D5, + CDDP 80 mg/m2 on D1 every 3 weeks, combined with a conformal RT at 66 Gy. Results: Between October 05 and May 08, 70 pts were enrolled (68 evaluable for the safety, 64 for response) : 28% stage IIIA, 72% IIIB; 44 % squamous, 30 % adenocarcinoma; 85% male; median age 61 years (range 41;73); median KPS 90%. After induction CT, OR was 42% (PR), Disease Control (DC) = 87%. 4 pts were down-staged and underwent surgery. After CT-RT completion, OR was 55% (CR = 7%), DC = 88%. Main Toxicities (G3–4, % of pts) were: neutropenia (19%), N/V (1%), radic pneumopathy (1%), anorexia (7%). Oesophagitis was recorded in 42% of pts with no G3–4 : G1 (26%), G2 (16%). Conclusions: This new schedule provides a disease control in 88% of pts with 55% OR. Given the optimal tolerance profile of this fractionated administration of NVBo+CDDP, 72% of pts could complete the planned treatment. Furthermore, NVBo taken at home at D3 and D5 reduces the organizational constraints linked to CT-RT. This new scheme offers a well tolerated and efficient therapeutic option in the treatment of non operable IIIA-IIIB NSCLC. Further follow-up is required in order to assess time to progression and survival.

[Table: see text]
Pulmonary functional map on V/Q SPECT and TGFβ1 during radiotherapy and post-treatment lung function in patients with non-small cell lung cancer
Authors: Yuan S. , Frey K. A. , Gross M. D. , Ramnath N. , Ten Haken R. K. , Cai X. , Hayman J. A. , Kong F.
Published: August 2020

7543

Background: Current research focus on the TGFß1 and pulmonary perfusion (Q) SPECT pre or post-treatment to predict lung toxicity in patients with non-small-cell lung cancer (NSCLC). However, ventilation (V) is also important, while the change of V/Q SPECT map and TGFβ1 during radiotherapy (RT) maybe more predictive for the lung function post-treatment. Methods: Patients with stage I-III NSCLC undergoing radiation based treatment were included and V/Q SPECT-CT, circulating TGF ß1 and carbon monoxide diffusing capacity (DLCO), as the key parameter of pulmonary function test, were assessed pre-, during- and 3 months post-RT. Patients were treated with conformal radiation therapy of more than 60 Gy, with or without chemotherapy per standard of care based on their stage of disease. The defects of V/Q SPECT images were defined by semi-quantitive method. Results: Total 45 patients with stage I-III NSCLC undergoing radiation (>60 Gy) were enrolled. All patients had functional defects (V, or Q or both) at or adjacent to the tumor and the V/Q defects were mismatched in 40%, 50% and 23% patients, pre-, during- and post-RT, respectively. After 45 Gy, the V and Q defects improved remarkably in 38.4% and 34.6% patients respectively, and the V scores were also improved significant during-RT (p<0.01). The Q scores of ipsilateral lung and V score of both lungs during-RT were correlated with DLCO 3 months post-RT margin-significantly (p=0.07) and significantly (p=0.02). The TGFß1 level decreased significantly during-RT and TGFß1 ratios (over the pre-RT level) at 4- and 6-week during-RT correlated with DLCO 3 months post-RT significantly (p=0.05). Conclusions: The V/Q SPECT map and TGFß1 level change during RT, and these changes are predictive for the lung function post-treatment in patients with NSCLC.

No significant financial relationships to disclose.
Impact of positron emission tomography (PET) in stage III non-small cell lung cancer (NSCLC): A prospective randomized trial (PET START)
Authors: Ung Y. , Sun A. , MacRae R. , Gu C. , Wright J. , Yu E. , Darling G. , Leighl N. , Evans W. , Levine M.
Published: August 2020

7548

Background: Patients with stage III NSCLC are potentially curable using combined modality therapy (CMT) with chemotherapy and radical radiation (RT). The use of PET-CT rather than conventional imaging (CI) may better identify patients for CMT by enhanced tumor staging and improved definition of RT treatment volumes. Methods: Patients with stage III NSCLC (based on histology/cytology, brain CT/MRI, CT thorax, CT/US abdomen, and bone scan) who were considered candidates for CMT were randomized to either PET-CT or CT for RT treatment planning. The primary outcome was the proportion of patients who did not receive CMT because their tumor was upstaged to Stage 4 or their intrathoracic tumor was too extensive for radical RT. Overall survival (OS) and alteration of RT treatment planning volume were secondary outcomes. Target sample size was 400 patients based on a hazard rate reduction of 30% in OS at 2 years in favor of PET-CT with 2-sided alpha = 0.05 and 80% power. We also postulated that 200 patients would be required to detect a 20% difference between arms for the primary endpoint. 5 centers in Ontario participated. Results: The trial commenced in August 2004. In November 2008 after a planned interim analysis for the primary outcome, the Data Safety Monitoring Board recommended stopping recruitment because of superior efficacy with PET-CT. 304 patients were randomized and 289 had analyzable data. 25 patients were unsuitable for CMT: 21 in the PET-CT arm (16 upstaged to Stage 4 and 5 unsuitable for radical RT) and 4 in the CT arm (unsuitable for radical RT). Thus, 21 of 140 (15%) patients in the PET-CT arm achieved the primary outcome compared with 4 of 149 (2.7%) in the CT arm, P= 0.0002. Conclusions: This is the first randomized trial in stage III NSCLC showing that PET-CT is superior to CT planning alone in selecting appropriate patients for CMT. Longer patient follow-up will determine potential impact on OS.

No significant financial relationships to disclose.
Chemoradiation therapy in patients (pts) with small cell lung cancer (SCLC) with pericardial effusion but no distant metastasis
Authors: Niho S. , Kubota K. , Yoh K. , Goto K. , Ohmatsu H. , Saijo N. , Nishiwaki Y.
Published: August 2020

7555

Background: Our previous retrospective analysis demonstrated that the survival of the limited-disease (LD) SCLC pts with ipsilateral pleural effusion was intermediate between those of LD pts without ipsilateral pleural effusion and extensive-disease (ED) pts, and that long-term survival was achieved by LD-SCLC pts with ipsilateral pleural effusion who successfully underwent chemoradiotherapy (CRT) (J Thorac Oncol 2008;3:723–7). We retrospectively investigated the clinical course and outcome in pts with SCLC with pericardial effusion but no distant metastasis and examined the overall survival in pts who received chemotherapy and definitive thoracic radiotherapy (TRT). Methods: The medical records of SCLC pts who received treatment at the National Cancer Center Hospital East between July 1992 and December 2007 were reviewed. During this period 767 pts were newly diagnosed as having SCLC. Four-hundred seventeen pts had no distant metastasis. Ninety-six of those 417 pts (23%, 95% confidence interval (CI): 19–27%) had pleural or pericardial effusion or disseminated pleural nodules, and were included in this study. The 96 pts were divided into two groups: group A included pts with pericardial effusion (n=33), and group B included pts who had pleural effusion and/or disseminated pleural nodules, but did not have pericardial effusion (n=63). Sixteen pts had both pleural and pericardial effusion. Results: All but one patient received systemic chemotherapy. A remaining patient with pleural effusion received only best supportive care. In group A, 19 pts received chemoradiotherapy. TRT was conducted concurrently with 3 or 4 cycles of chemotherapy in 12 pts and sequentially in 7 pts. The response rate for first-line chemotherapy was 79%. In group B, 26 pts received chemoradiotherapy. Survival data were shown as below. Conclusions: Long-term survival was seldom achieved by SCLC pts with pericardial effusion but no distant metastasis, even if they underwent chemoradiotherapy.

[Table: see text]

No significant financial relationships to disclose.
Phase III study of induction chemotherapy (docetaxel and carboplatin) with or without radiotherapy followed by surgery in patients with stage IIIA (pN2) non-small cell lung cancer (NSCLC): WJTOG9903
Authors: Tada H. , Tanaka M. , Katakami N. , Kurata T. , Mitsudomi T. , Negoro S. , Kudoh S. , Nishiyama H. , Nishimura Y. , Nakagawa K.
Published: August 2020

7556

Background: Standard treatment of resectable N2 disease is not yet established. To gain insights on significance of preoperative chemoradiotherapy, we tried to evaluate feasibility and efficacy of induction chemotherapy with or without radiotherapy followed by surgery in patients with stage IIIA NSCLC with mediastinal lymph node metastases. Methods: Patients with histologically proven N2 disease were randomized either to receive induction chemotherapy (taxotere 60 mg/m2 and carboplatin AUC 5x2 cycles) with concurrent radiation therapy of 40Gy/20fr (CRS group) or without it (CS group). Patients subsequently underwent pulmonary resection if the tumor was judged resectable. Original sample size was 180 to detect a 20% of survival difference (2 sided P=0.05) with a power of 0.8. The primary endpoint was overall survival. Results: Between Jan. 2001 and Dec 2005, 60 patients were randomized Because of poor accrual of the patients, the study was prematurely terminated. Two patients assigned to CRS group were ineligible due to staging misconducts. Median age was 57 years (range 34–70 years), and 66% were male. Two groups were well balanced with regard to age, gender, histology, and operative procedures. Induction therapy was well tolerated, and there was no treatment related death. Grade 3 and 4 neutropenia occurred in 74 and 89%, respectively. Objective response rate was 25% for the both groups. Surgical resection was performed in 86% and 89%of the patients in CS and CRS groups, respectively. There have been 37 deaths to date. Event free survival at 3 year was 18% and 32% for patients in CS and CRS group, respectively (HR=0.64; 95% CI: 0.36–1.17, P=0.15). Overall survival at 3 year was 44.4 %. and 52.7% (HR=0.84; 95% CI: 0.44–1.62, P=0.62), respectively. Conclusions: Because of small sample size, there was no statistically significant difference. However, our study suggested that addition of radiotherapy to induction chemotherapy could potentially prolong survival of NSCLC patients with N2 disease.

[Table: see text]
Response, time to progression, and overall survival of patients with stage III lung cancer in a minority-based cohort
Authors: Kouz R. , Sreenivasappa S. , Adab K. , Ciobanu B. , Ofori S. , Shah M. , Kassem M. , Hussein L. , Lad T.
Published: August 2020

7558

Background: Lung cancer is the leading cause of cancer death. Response and survival of patients (pts) with stage III lung cancer in minority population is not well studied. Methods: 79 pts treated between 2001 and 2006 were studied as a retrospective cohort. Clinical and survival data were analyzed using fisher's test, chi square test, Kaplan Meier analyses. Results: 33 Pts had Stage IIIA; Median age at diagnosis was 58 yrs (37–75). 14 were males (42.4%) 19 females (57.6%) 26 African American (78.8%) and 7 Caucasians (21.2%). Median number of co morbidities 2 (0–4). Mean follow up was 25 months (mo) (2 - 93), 19 had surgery (12 Lobectomy (36.4%), 7 Pneumonectomy (21.2%)) and 14 were unresectable (42.4%). All pts received adjuvant chemotherapy. Unresectable pts received chemotherapy and radiation, 8 carboplatin and gemcitabine and 6 cisplatin and etoposide. Median time to progression in resectable IIIA was 23 mo (2- 67), unresectable IIIA was 12 mo (3–93). Median survival in pts with resection was 26 mo (2 - 67), unresectable was 12 mo (5 - 93). Overall survival and time to progression was not influenced by sex, race, tumor type. 46 pts had stage IIIB, median age at diagnosis 57.5 yrs (40–68). 31 were males (67.4%) 15 females (32.6%) 29 African Americans (63%) 11 Caucasians (23.9) 3 Asians (6.5%) and 3 Hispanics (6.5%). Median follow up was 10 mo (3–97). All pts received chemotherapy and radiation. 23 received cisplatin and etoposide (50%), 14 carboplatin and gemcitabine (30%), 5 carboplatin and etoposide (9%), 5 carboplatin and paclitaxel (9%). 13 had complete response (28.3%), 15 partial response (32.6%), 2 stable disease (4.3%) and 10 Progression (21.7%). Median time to progression was 9 mo (3–97). Median overall survival was 10 mo (3–97). Overall survival and time to progression was not influenced by sex, race, tumor type, chemotherapy regimen. Conclusions: In this minority based cohort response, time to progression, overall survival in both IIIA and IIIB pts is much lower then historical controls. The overall survival and time to progression in both IIIA and IIIB is not influenced by race, sex, tumor type and type of chemotherapy regimen. Further investigations of disease and healthcare disparities in the underserved minority population, are warranted.

No significant financial relationships to disclose.
Adjuvant chemotherapy in completely resected stage III-N2 non-small cell lung cancer
Authors: Wang S. , Ou W. , Sun H. , Yang H. , Ye X. , Fang Q.
Published: August 2020

7563

Background: We evaluate effect of postoperative adjuvant chemotherapy on overall survival after complete resection of stage III-N2 non-small-cell lung cancer. Methods: From Jan.1999 to Dec. 2003, a total of 150 stage III-N2 non-small cell lung cancer patients randomly received four cycles of chemotherapy (NVB25mg/m2, D1,D5 or paclitaxel 175mg/m2, D1 / carboplatin AUC=5, D1) or observation after operation. Results: The median survival for the 150 patients was 879 days, with a 1-year survival rate of 81%, 3-year survival rate of 43%, and 5-year survival rate of 28%.There was significant difference in median survival between chemotherapy and control group (897 days vs 821 days p=0.04), and also there was significant difference in 5-year survival rate (30% vs 24% p<0.05). The most common site of recurrence was brain. 26% (39/150) of patients recurred in the brain as their first site, 22% (18/79) for chemotherapy group, 29% (21/71) for control group. The median survival time for brain metastasis patients between chemotherapy and control group is no difference (812 days vs 512 days, p=0.122), but there was significant difference in 2-year survival rate (66.71% vs 37.6% p<0.05). Conclusions: Postoperative adjuvant chemotherapy dose significantly improves median survival among completely resected stage III-N2 non-small-cell lung cancer patients, and significantly improves 5-year survival rate. It dose not decrease incidence of brain metastasis but postpone the time of brain metastasis in chemotherapy group.

No significant financial relationships to disclose.
Impact of revised lymph node measurement rules in the new RECIST version 1.1 on the tumor response evaluation in patients with advanced lung cancer
Authors: Endo M. , Watanabe H. , Yamamoto S. , Yamamoto N. , Ohe Y. , Tamura T.
Published: August 2020

7567

Background: The new RECIST ver. 1.1 was published in a special edition of the European Journal of Cancer in the first quarter of 2009 (EJC 2009;45:228). The major change involves the rules for lymph node measurement, which is to measure SHORT axis in stead of the longest diameter of lymph node. To be considered pathologically enlarged and measurable, a size of lymph node must be at least 15mm in short axis when assessed by CT scan. Lymph nodes that are at least 10mm but less than 15mm in short axis may be pathologic and can be considered as non-measurable/non-target lesions (not measured). The purpose of our study was to evaluate the response assessment using RECIST ver. 1.1. in comparison with that using ver. 1.0 in patients with advanced lung cancer. Methods: Two radiologists independently reviewed the objective tumour response of 305 patients (pts) with advanced lung cancer who had primary lesion and lymph node metastases as target lesions measured more than 10 mm in the longest diameter. According to ver. 1.1, only the short axis will be measured both at baseline and at follow-up. The response rates were calculated according to both the versions of RECIST. The tumor responses were divided into four categories (CR, PR, SD, PD), following proportion of agreement and estimation of kappa statistics between two the criteria as agreement measure. Results: The best overall responses as assessed by RECIST ver. 1.0 and ver. 1.1 are shown in the table. Out of the 108 pts with PR by ver.1.0, 8.3 % were downgraded to SD and 1.0 % was categorized as PD by ver.1.1. On the other hand, out of the 190 pts with SD by ver.1.0, 6.3 % were upgraded to PR and 8.9 % were downgraded to PD by ver.1.1. The proportion of agreement was 86.2 % (263/305, 95% CI: 75.8 - 96.6) and the kappa coefficient was 0.734 (95% CI: 0.662 - 0.806). Conclusions: No significant impact was observed for the revised lymph node measurement rules in the new RECIST ver. 1.1 on the response evaluation in pts with advanced lung cancer registered in this analysis.

[Table: see text]

[Table: see text]
11C-PD153035 PET/CT molecular imaging of EGFR for evaluation of advanced non-small cell lung cancer (NSCLC) to EGFR-targeted therapy
Authors: Meng X. , Yu J. M. , Yang G. R. , Zhao S. Q. , Sun X. D.
Published: August 2020

7576

Background: Our previous study suggests that 11C-PD153035, a specific and potent inhibitor of EGFR tyrosine kinase (EGFR-TKI), is a novel PET radiotracer and 11C-PD153035 PET/CT is a promising non-invasive method for in vitro and vivo imaging of EGFR in NSCLC. We report a pilot study evaluating the efficacy of 11C-PD153035 PET/CT imaging as a “molecular fingerprint” to the EGFR-TKI in advanced NSCLC (stage IIIB/IV). Methods: Patients with pathologically proved advanced NSCLC were enrolled. 11C-PD153035 PET/CT was performed before (PET/CT 1) and 4 weeks after (PET/CT 2) received EGFR-targeted therapy (erlotinib) with assessment of maximum standardized uptake values (SUVmax) for correlation with response. Treatment response was also expressed as CT results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Image fusion and calculation of tumor subvolumes was performed on Xeleris workstation. Radioactivity concentrations, derived from regions of interest, were analyzed to the SUVmax. Results: 12 patients (5 men, 7 women; age range, 60–79 years) have been enrolled in this study from August 2008, including 3 cases of squamous cell carcinoma, 1 case of large cell carcinoma, and the other of adenocarcinoma. Tumor uptake of 11C-PD153035 before received therapy was observed in 8 patients and SUVmax ranged from 3.1 to 5.9. There was significant difference in SUVmax (p < 0.01) between tumor and normal tissue. Tumor/lung ratio at 20 min was 4.14 ± 1.80. The SUVmax did not correlate with tumor marker before therapy in our limited data. After 4 weeks therapy, a total of 7 patients underwent the 11C-PD153035 PET /CT again and 5 patients only received CT scanning. Tumor responders had a higher baseline pre-therapy SUVmax than nonresponders (p < 0.01). However, there was no significant difference between pre- and post-therapy SUVmax among 7 patients (p > 0.05). Conclusions: Our data indicated that 11C-PD153035 PET/CT before therapy may play a vital role for identification of patients that could be suitable for EGFR targeted therapies. Thus, it offers opportunities to individualize and optimize target therapy for NSCLC patients.

No significant financial relationships to disclose.
The role of extrapleural pneumonectomy in the management of pleural cancers
Authors: Sugarbaker D. J. , Tilleman T. R. , Swanson S. J. , Jaklitsch M. T. , Mentzer S. J. , Mujoomdar A. A. , Bueno R.
Published: August 2020

7577

Background: We report our experience with EPP for non-mesothelial malignancies. Methods: A retrospective chart review, from June 1994 to October 2007. For all cases, the site of disease involved a single pleura. Results: Sixty-five patients underwent EPP for cancers other than mesothelioma over a 13-year period at our institution. Of these, 32 patients had mediastinoscopy negative T4 lung cancer, 11 had metastases to only one pleura from extrathoracic sites, 10 had unilateral lung sarcomas involving the pleural envelope, 8 had thymomas metastatic to a pleural space, 2 were preoperatively diagnosed as mesotheliomas but at final pathology were determined to be small cell lung cancer and sarcomatoid carcinoma, and 2 represented primary mucoepidermoid and neuroectodermal malignancies. Twenty-eight patients had stage IIIB (T4-N0–1) lung adenocarcinoma representing the largest homogeneous group of patients by cell type and stage. Overall perioperative mortality was 4.6% (3/65). Postoperative morbidity was 44.6% (29/65) with the most common being arrhythmia (n=15), vocal cord paralysis (n=7), and respiratory failure (n=5). Overall survival after surgery was 15.7 months for all the patients. Survival was significantly higher for NSCLC patients with N0 (n=9) on final pathology versus any other nodal status (N1/N2), 52.1 months versus 14.1 months (p=0.0003). Median survival for stage IIIB NSCLC was 16.7 months. Seven of the 8 thymoma patients were alive at last follow-up (median follow-up 22.8 months). Median survival for patients with sarcoma (n=10) or pleural metastases from extrathoracic sites (n=11) was 3.7 and 4.2 months, respectively. Recurrence at follow-up was documented in 21 patients with only 2 (9.5%) occurring in the ipsilateral hemithorax. Conclusions: EPP can be a safe treatment option for some cancers that involve a unilateral pleura. Patients with stage IIIB (T4, N0–1) NSCLC confined to a single pleural cavity or patients with thymoma involving one pleura may benefit from multimodality treatment including EPP. Absence of residual nodal disease at resection is positively correlated with survival in the stage IIIB NSCLC group. Patients undergoing surgical resection for pleural metastases of primary sarcomas or extrathoracic metastasis, however, do not appear to benefit from EPP.

No significant financial relationships to disclose.
Feasibility and safety of detection of sentinel node in lung cancer
Authors: Barcelo-Galindez R. , Uribe-Etxebarria N. , Viteri A. , Genollá J. , Jimenez-Maestre U. , Lorenzo-Martín M. , Rios G. , Rojo-Marcos R. , Rumbero-Sanchez J. , Pac-Ferrer J.
Published: August 2020

7587

Background: Sentinel node (SN) can be detected in the drainage of many primary cancers and is considered a standard procedure in some tumors. For resectable lung cancer its study has began recently and its detection has not yet been standardized. Objective: To study the feasibility and safety of SN detection during surgery for lung cancer. Methods: Patients with non-small cell lung cancer, clinical stage I, amenable to surgery were eligible. Written informed consent was obtained in each patient before the procedure. Technique, as described by Liptay et al, consisted of four injections of albumin labelled with Technetium99, 0,25 mCi each peritumorally, and five minutes later, lobectomy and lymphadenectomy were associated with detection of SN (both in vivo and ex vivo). Results: From Jan 2006 to Nov 2008, the first 37 patients were included. In 35 patients one SN was detected, and in 2 there were two SN. SN was found in the lymphatic stations 10 or 11, except for tumors located in the left upper lobe, where two cases of a SN were found in station 5 and 6 each. In 23 cases of 37, both SN and lymphadenectomy were free of tumor. In seven of 37, SN was positive (in one, micrometastasis was detected with haematoxilin-eosin), and the rest of the nodes were free of tumor. In five of 37, SN and another node were positive. In two of 37, SN was falsely negative as one peribronchial node was positive but masked by radioactivity in the injected lung, one in right lower lobe and another in left lower lobe. Accuracy was 94,6%, sensibility 86%, specificity 100%, positive predictive value 100% and negative predictive value 92%. No relevant prolongation of surgery time was observed (5–15 minutes), and no morbidity or mortality related to this technique were seen. The cost of the materials used was 100 Euro per patient. Recruitment is ongoing. Conclusions: SN can be detected with a very high accuracy in lung cancer. This technique is feasible and safe, and does not add excessive cost or difficulty to the surgery of lung cancer. Modifications of the technique, using metabolic isotopes or new portatil 3D gamma detectors can be incorporated. Its final role in the staging and treatment of lung cancer is still unknown. Supported in part by a grant of the FIS (Fondo de Investigaciones Sanitarias), Spain.

No significant financial relationships to disclose.
Gemcitabine-capecitabine in platinum-refractory patients with thymic epithelial tumors
Authors: Palmieri G. , Merola C. , Petillo L. , Merola G. , Federico P. , Leopardo D. , Marino M. , Montella L.
Published: August 2020

7590

Background: Platinum based combination chemotherapy is the actual standard of care for advanced and recurrent Thymic epithelial tumours-TET (thymoma and thymic carcinoma). Additional agents are needed in this setting. We have designed a pilot study, phase II multicenter, to evaluate the efficacy and safety of no tested schedule gemcitabine-capecitabine in patients refractory to platinum based chemotherapy. Methods: Eligible patients had pathologically confirmed TET and were treated with at least 2 lines of chemotherapy, one of this being a platinum based schedule. From January 2007 to September 2008 twelve pts were enrolled. Treatment Schedule: Gemcitabine 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks plus oral capecitabine 650 mg/m2 twice daily on days 1 to 14. Response was evaluated at 3 and 6 cycles. Results: Pts Characteristics: 12 pts (7 M-5F, Median Age 51,3 yrs,range 27–76). 7 pts had received Thymectomy and 4 of this had received also surgery for metastatic disease. 5 pts have received only thymic biopsy. Performance status sec. Karnofsky was 90% (range 80–100). Site of disease: liver, lung, bone, nodal, pleural and pericardium. All pts were staged IVB sec. Masaoka. Tumors were classified by WHO classification as follows: 4-B2, 8-B2/B3. All pts were evaluated as concerns performance status and all had Karnofcky 90% (range 80–100). Sites of metastatic disease were: liver,lung,bone,nodal, pleural and pericardium. Associated paraneoplastic syndromes were: myasthenia in 7 pts, B-lymphopenia 11 pts. The minimum number of cycles administered on study was 3 (range 3–8).Among the 12 enrolled pts there were 10 objective response: 2 CR, 8 PR. 2 pts had SD. Prolonged maintenance of absence of disease was obtained in the 2 pts reporting a CR (more than 6 months in 1 patient). Treatment was well tolerated, no grade 4 toxicities was registered. Conclusions: The combination schedule gemcitabine-capecitabine have an high activity in Thymic malignancies in pts heavily pretreated with advanced recurrent TET and appears to be a safe option in platinum-refractory TET pts. This schedule must be proposed to be used also in randomized clinical trial compared with platinum based treatment.

No significant financial relationships to disclose.
Prognostic value of microRNAs (miRNAs) profiling in early-stage squamous cell lung cancer (SqCLC)
Authors: Skrzypski M. T. , Szymanowska A. , Jassem E. , Rzepko R. , Pawlowski R. , Wyrwicz L. , Goryca K. , Marjanski T. , Rzyman W. , Jassem J.
Published: August 2020

7594

Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable clinical factors to select high risk pts for adjuvant chemotherapy. miRNAs profiling is expected to indicate pts with aggressive disease and to provide prognostic information. Confounding effect of NSCLC pathology heterogeneity justifies searching for prognostic miRNAs separately in SqCLC and adenocarcinoma. Methods: Fresh frozen tumor tissue was obtained from 30 SqCLC stage I-II pts during curative pulmonary resection. Of those, 15 pts developed distant metastases and 15 had no relapse after a median follow-up of 5.4 years (range, 3.1–6.9 years). RNA was isolated from tumor sections containing ≥60% of tumor cells per section. Expression of 380 miRNAs was analyzed by RT-PCR arrays (TLDAs-Appliedbiosystems). Raw data were normalized vs. the expression of U6 RNA and calibrated by ΔΔCt method. Results: Expression of 300 miRNAs was detected in tumor tissues. Expression of three miRNAs (193a[5p], 146b[5p] and 10b) differed between groups with and without metastases (t-Student test, p<0.05). Due to the limited number of samples, proportional hazard regression for survival (Cox analysis) could not be performed on the full data set of 300 variables. Cox analysis performed for the top 5 miRNA identified with t-Student test showed significant correlation for 10b (p<0.02). The internal consistency of data sets was tested using PCA, and three samples were excluded. In this modified test set, the top 10 miRNAs (ranked according to p-value of t test) revealed two significantly correlated miRNAs in Cox analysis: 484 and 146b (5p). Similar results were obtained for miRNAs expression defined as continuous or categorized variables. Conclusions: Four miRNAs: 10b, 146b, 193a(5p) and 484 are potentially related to high metastatic propensity of early stage SqCLC. Further validation is necessary to confirm their prognostic relevance in this tumor.

No significant financial relationships to disclose.
A randomized placebo-controlled phase III study of docetaxel/carboplatin with celecoxib in patients (pts) with advanced non-small cell lung cancer (NSCLC): The NVALT-4 study
Authors: Groen H. , Hochstenbag M. M. , van Putten J. W. , Vincent A. , Dalesio O. , Biesma B. , Smit H. J. , Termeer A. , van den Borne B. E. , Schramel F. M.
Published: August 2020

8005

Background: Cox-2 is overexpressed in NSCLC tumors and has a negative impact on survival. It is involved in proliferation and angiogenesis. The hypothesis is that celecoxib by inhibiting Cox-2 enzyme will prolong survival and may increase response to chemotherapy. Methods: We performed a phase III study with planned sample size of 540 pts. Included were pts with pathologically proven NSCLC, no prior chemotherapy, PS=0–2, measurable disease, adequate organ functions. Excluded were pts with CHF NYHA class II-IV, atherosclerotic diseases, gastrointestinal bleeding, symptomatic brain metastases and chronic use of NSAIDs (defined as 1 wk for >3 wks per yr or more than 21 days throughout the year). Acetylsalicylic acid (ASA) ≤ 150 mg/d was allowed. Pts were treated with docetaxel 75 mg/m2;, carboplatin (AUC = 6 mg/ml.min) every 3 wks for 5 cycles and randomized for celecoxib (cel) 400 mg bd, starting on day 1 for 3 years or placebo (plac) 400 mg bd. Stratification was by WHO PS (0–1 vs. 2), stage (IIIB vs. IV), ASA (yes vs. no) and hospital. Primary endpoint was overall survival. Results: From July 2003 until Dec 2007 561 pts were randomized (cel 281 pts, plac 280 pts). Median follow-up was 36 months (mo). Median (range) age 61 yrs(33–84), M/F 63/37%, PS 0/1/2 45/48/6%, adeno/large cell/squamous/other 48/27/18/7%, stage IIIB/IV 17/83%, 11% of pts used acid ≤ 150 mg/day. Reason to end treatment (cel/plac arm) was therapy completed (51/45%), PD (17/22%), adverse events (8/10%), death (8/8%). Toxicity was mild and no increase in cardiovascular events were observed in cel arm. CR, PR, SD, PD in cel/plac arm was 0/1%, 33/26%, 35/40%, 14/19%, respectively. Response rate in evaluable pts was better in the cel arm (p=0.05). Median PFS (95% CI) was 5,5 mo ( 4,3 - 6,8), OS was 8,3 mo (7,5 - 8,8), not different for both arms. HR stratified by ASA and PS for PFS and OS was 0,94 (0.79–1.13) and 0.95 (0.79–1.15), respectively. Conclusions: Addition of celecoxib to first line chemotherapy improves response rate but not progression-free interval or overall survival.

No significant financial relationships to disclose.
A phase II trial of salirasib in patients with stage IIIB/IV lung adenocarcinoma enriched for KRAS mutations
Authors: Johnson M. L. , Rizvi N. A. , Ginsberg M. S. , Miller V. A. , Kris M. G. , Pao W. , Riely G. J.
Published: August 2020

8012

Background: KRAS mutations are present in 30% of lung adenocarcinomas and are associated with primary resistance to erlotinib and gefitinib. Salirasib severs RAS proteins from the membrane, decreasing function of all RAS isoforms. Salirasib inhibits KRAS-dependent growth in cell lines and xenograft models. This phase II study was designed to determine the activity of salirasib in patients (pts) with advanced NSCLC enriched for KRAS mutations. Methods: Two cohorts of pts with stage IIIB/IV NSCLC were eligible. Group A: pts with KRAS mutations previously treated with chemotherapy. Group B: previously-untreated pts with ≥15 pack-year smoking history. Salirasib was given orally, for days 1–28 of a 35 day cycle, with response assessment on day 28, day 63, and every 10 weeks (wks) thereafter. The primary endpoint was rate of RECIST non-progression at 10 wks. Secondary endpoints were response rate (RR), time to progression (TTP), overall survival (OS) and toxicity. Results: From August 2007-December 2008, 33 pts were enrolled (20 women); median age 68 (range 46–79). Pts in Group A had received a median of 2 lines of prior chemotherapy. All 23 pts in Group A and 7/10 pts in Group B had KRAS mutations. Of the 30 pts with KRAS mutations, 7 were never smokers or smoked ≤15 pack-years. Three pts withdrew due to drug-related diarrhea in the first 10 wks of therapy. Four pts have not reached 10 wks of therapy. After 10 wks of salirasib, 5/18 (28%) previously treated pts with KRAS mutations and 3/8 (38%) previously untreated pts showed no progression. The RR in pts was 0/18 for Group A and 0/8 in Group B. For all pts with KRAS mutations, the RR was 0/23. The median TTP was 1 month (mo) and 2 mo in Groups A and B, respectively. The median OS was 13 mo for Group B and not reached in Group A (median follow-up 3 mo). Grade 3 diarrhea and fatigue were the most common toxicities. Conclusions: After 10 wks of salirasib, 28% of previously treated pts with KRAS mutations and 38% of untreated pts had stable disease. No partial or complete responses were seen in pts with KRAS mutations. The successful enrollment over 15 months of 29 pts with tumors with known KRAS mutations demonstrates that trials of a KRAS-specific genotype in lung cancer are feasible, and should be standard in future studies targeting the KRAS pathway.

[Table: see text]
Biomarker analyses from the phase III placebo-controlled SATURN study of maintenance erlotinib following first-line chemotherapy for advanced NSCLC
Authors: Brugger W. , Triller N. , Blasinska-Morawiec M. , Curescu S. , Sakalauskas R. , Manikhas G. , Mazieres J. , Whittom R. , Rohr K. , Cappuzzo F.
Published: August 2020

8020

Background: The SATURN (BO18192) study investigated whether erlotinib maintenance therapy improved PFS in patients (pts) with advanced NSCLC who had obtained clinical benefit from 1st-line chemotherapy. This study included a prospective analysis of the prognostic/predictive value of several molecular markers. Methods: 889 pts with advanced NSCLC whose disease had not progressed following 4 cycles of 1st-line platinum-doublet chemotherapy were randomized to erlotinib 150 mg/day or placebo. Mandatory tumor specimens were collected at baseline and tested for EGFR protein expression using immunohistochemistry (IHC), EGFR gene copy number using fluorescent in-situ hybridization (FISH), and EGFR and KRAS somatic mutations using DNA sequencing. Pts were stratified according to EGFR IHC status (any membranous staining in ≥10% tumor cells used as cut-off); the co-primary endpoint was PFS in EGFR IHC+ pts. Baseline whole blood samples were obtained for genotyping of EGFR (intron 1 CA-repeat polymorphisms). Results: In the overall population, erlotinib significantly prolonged PFS vs placebo (HR 0.71, p<.0001; primary endpoint). The co-primary endpoint was also met, with erlotinib significantly improving PFS in the EGFR IHC+ group (HR 0.69, p<.0001). Many tumor samples were assessable for molecular marker status (see table). Biomarker data suggest that patients derived a PFS benefit with erlotinib irrespective of EGFR FISH or EGFR intron 1 CA-repeat status. The magnitude of benefit with erlotinib was similar in both KRAS-mutant and KRAS wild-type pts. Conclusions: This is the largest biomarker analysis performed for erlotinib in a randomized, placebo-controlled setting, and answers key scientific questions regarding the prognostic and predictive value of potential biomarkers of efficacy. Full data will be presented.

[Table: see text]

[Table: see text]