bluuebunny/crossref_metadata_2025 huggingface dataset:
Plerixafor (P) plus G-CSF (G) in previous peripheral blood progenitor cell (HPC) mobilization failures (MF)
Authors: Van Rhee F. , Panozzo S. , Anaissie E. , Pineda-Roman M. , Waheed S. , Alsayed Y. , Nair B. , Cottler-Fox M. , Barlogie B.
Published: August 2020

7095

Background: Successful autologous stem cell transplantation (AT) requires harvesting sufficient HPC to ensure reliable engraftment, which cannot be accomplished in ∼10% of previously treated patients. Methods: MF was defined as the inability to collect at least 2 x106 CD34+ cells/kg with growth factor alone (GF) (n=38) or in combination with chemotherapy (GF-CT) (n=27). Of 65 patients reported here, 45 were enrolled in a compassionate use program and 20 were part of a clinical trial (AMD3100–2102); 55 had MM, 9 had lymphoma and 1 had primary amyloidosis. All patients had been treated previously and included prior AT in 26 patients, 15 of whom had 2 AT and 2 had ≥3 AT. The P+G regimen started with G (10 μg/kg) for 4 days, P (240 μg/kg) was added on the evening of day 4; both P and G were continued until completion of collection. In the case of MM, all collected products were analyzed for tumor contamination by DNA/cIg flow cytometry. Results: Of all 65 patients, 63 initiated apheresis which yielded a median 3.6x106 CD34/ kg (range, 0.3–17.8) during a median of 5 days (d) of collection (range, 2–7), with successive median daily CD34 yields of 1.1, 0.9, 0.6, 0.5, 0.3, 0.4 and 0.5 x106/kg. MM cells were mobilized in only 2/55 patients. Additional collection was undertaken in 25 patients, using GF or GF-CT in 19 (median, 3.2x106 CD34 cells; range, 0–8.5), further P+G in 5 (median, 1.7x106 CD34 cells/kg; range, 0.9–3.5), and 1 patient received P+G on a third occasion (2.2x106 CD34 cells /kg). Of 63 patients, 51 (81%) and 24 (38%), respectively, collected ≥2.0 and ≥5.0x106 CD34 /kg. AT was supported with P+G derived products in 43 patients including 7 who received 2 AT. With median infused CD34+cells of 3.6x106 / kg (range, 1.0–7.7), the median times to neutrophils > 500/μl and platelets >20,000/ μl were 14 d (range, 11–35) and 15 d (range, 9–253). Conclusions: P+G ensures collection of an adequate HPC product after MF in 81% that affords durable engraftment even though 40% had prior AT.

[Table: see text]
BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients
Authors: Kim J. , Kim E. , Sohn B. , Yoon D. , Yoo C. , Kim S. , Lee D. , Kim S. , Lee J. , Suh C.
Published: August 2020

7097

Background: The objective of this study was to compare the efficacy and toxicity of two high-dose regimens for autologous stem cell transplantation (ASCT) in patients with non-Hodgkin's lymphoma (NHL): BEAM (BCNU, etoposide, cytarabine, and melphalan) and BuCyE (busulfan, cyclophosphamide, and etoposide). Methods: We analysed 65 NHL patients, who underwent high-dose chemotherapy with BEAM (N=43) or BuCyE (N=22), followed by ASCT, at the Asan Medical Center. BEAM was used from February 2002 to October 2005, and BuCyE was used from November 2005 to April 2008. Results: Median age was 46 years (range: 15–68), and baseline characteristics, such as gender, International Prognostic Index (IPI), age adjusted IPI, stage and status of disease at ASCT, and median number of infused CD 34+cells/kg were well balanced between groups. The incidence of mucositis, nausea/vomiting, diarrhea and bleeding, and the number of events clinically important infections during ASCT did not differ between groups. Median follow-up for survivors was 49.3 months in the BEAM group and 21.5 months in the BuCyE group. Median overall survival (OS) was 30.6 months (95% confidence interval [CI], 8.19–53.0 months) and 22.6 months (95% CI, 12.1–33.1 months) and median event-free survival (EFS) was 16.1 months (95% CI, 0.0–53.6 months) and 11.2 months (95% CI, 0.0–22.5 months) in the BEAM and BuCyE group, respectively. There were no significant differences in OS (p=0.636) and EFS (p=0.575) between the two groups. Conclusions: In our analysis, BuCyE appeared to be not inferior to BEAM for survival. And we found that regimen-related toxicities did not differ significantly between the two groups.

No significant financial relationships to disclose.
Updated survival analysis of JBR.10: A randomized phase III trial of vinorelbine/cisplatin versus observation in completely resected stage IB and II non-small cell lung cancer (NSCLC)
Authors: Vincent M. D. , Butts C. , Seymour L. , Ding K. , Graham B. , Twumasi-Ankrah P. , Gandara D. , Schiller J. , Green M. , Shepherd F.
Published: August 2020

7501

Background: JBR.10 was one of a number of phase III trials that established adjuvant cisplatin based chemotherapy as a recommended treatment in completely resected NSCLC . Long-term follow-up of these trials is important to document persistent benefit and potential late toxicities of adjuvant therapy. We report the updated survival data for JBR.10 with more than 9 years median follow up. Methods: Patients with completely resected stage IB (T2N0) or II (T1–2N1) NSCLC were randomized to receive 4 cycles of vinorelbine/cisplatin or observation.. Kaplan-Meier curves were generated for overall (OS) and disease specific survival (DSS). Log-rank test was used to compare survival distribution and to test cause specific hazard. For the competing risk analysis, the Gray test was used to test the difference in cause specific incidences. All efficacy analyses were done on an ITT basis. Results: 482 patients were randomized. Data cut-off for this update was July 2008. Median follow-up is 9.3 years (3.2–13.8 y). 12 patients were lost to follow up, a median 4.9 years from randomization (1.5–12 years). 271 deaths have occurred, 73% due to lung cancer or its treatment. Survival analysis continues to show a benefit for chemotherapy: HR .78 (CI .61-.99, p=.04). The benefit appears to be confined to N1 patients: median OS 6.8 y versus 3.6 y, HR .68 (CI .5-.92, p=.01). N0 patients did not appear to benefit: HR 1.03 (CI .7–1.52, p=.87). Chemotherapy significantly prolonged DSS, HR.73 (CI .55-.97, p=.03) Competing risk analysis showed observation to be associated with significantly higher risk of death from lung cancer (p=.02) with no difference in incidences of death from other causes between arms (p=.62). Conclusions: Prolonged follow-up of patients in the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm.

[Table: see text]
Relationship of thymidylate synthase levels to outcome of malignant pleural mesothelioma patients treated with pemetrexed-based chemotherapy
Authors: Selvaggi G. , Righi L. , Ceppi P. , Bacillo E. , Billè A. , Pandiscia S. , Ardissone F. , Scagliotti G. V. , Papotti M.
Published: August 2020

7508

Background: Pemetrexed has shown activity in malignant pleural mesothelioma (MPM) but scanty data are available on the expression of thymidylate synthase (TS), its most important molecular target. Methods: From a database of 75 non-surgical, chemotherapy-naive MPM patients from our Institution in the period 2004–2008, 50 (male/female: 37/13, median age: 65 years) met the selection criteria i.e. epithelial type, availability of thoracoscopic tissue and outcome data. Pemetrexed was administered as single agent (14/50) or in combination with cisplatin or carboplatin (36/50). Retrospectively TS protein expression levels were evaluated by immunohistochemistry and quantified with H-score method. In addition, mRNA extraction was performed in 23 micro-dissected tissues and TS relative levels quantified by RT-PCR. Survival probability was assessed by Kaplan-Meier method and results compared by log-rank test. Cox multivariate analysis for survival was performed adjusting for clinical-pathological variables. Results: Thirty-two patients had progressive disease and 24 had died at the time of the analysis. Median time to progression (TTP) and median survival time (MST) were 11.6 and 20.9 months, respectively. Median TS H-score value was 90 (5–240). No correlation were found with sex, age, PS, stage and chemotherapy regimen. Patients with high TS H-score (4th quartile) had a significantly shorter MST (13.3 vs 21.1 months, p<0.01) and showed a trend for shorter TTP (8.3 vs 11.9 months, p=0.07). Median TS mRNA level was 1.88 (1–3.7 unit-less ratio) and a significant correlation between mRNA and protein expression (RS=0.67, p<0.0001) was found. Patients with high TS mRNA levels (4th quartile) had significantly shorter TTP (8.7 vs 14.7 months, p=0.019) and MST (11.7 vs 24.7, p=0.018). Multivariate analysis for survival indicated that TS protein levels were an independent prognostic factor (HR=2.17; CI 1.04–4.54; p=0.038). Conclusions: TS (protein and mRNA) levels predict outcome of epithelial MPM patients treated with pemetrexed-based chemotherapy. TS quantification, if confirmed in larger prospective studies, could be used to select those patients more likely to respond to chemotherapy.

[Table: see text]
Quality of surgical resection for non-small cell lung cancer (NSCLC) in a U.S. metropolitan area
Authors: Allen J. W. , Osarogiagbon R. , Farooq A. , Ninan M. , O'Brien T. F.
Published: August 2020

7512

Background: Curative treatment of early stage NSCLC requires good quality oncologic resection (GQR). For GQR, the National Comprehensive Cancer Network (NCCN) requires a minimum of segmentectomy, negative margins, lymph node (LN) sampling from stations 10–14 (level-1) and >2 mediastinal (level-2) stations. We reviewed details of consecutive resections for NSCLC to determine the proportion that met NCCN GQR criteria and the proportion who would have met eligibility for the RADIANT trial which requires >1 level-2 stations. Methods: Retrospective review of medical records of all patients who underwent curative- intent resection for NSCLC in the Memphis Metropolitan Area from 1/1/2004 to 12/31/2007. Resections for benign and metastatic disease were excluded. Death information was obtained from a national death index search. Categorical variables were compared by chi-square test or Fisher's exact test, survival curves by log-rank test. Results: 746 patients were eligible (Table). Median age was 67.7 (range, 36.5 - 89.4). 61/746 (8.2%) met NCCN GQR criteria. Black patients were more likely than whites to have GQR (P=0.022). No other patient demographic factor was associated with GQR. Three year survival was 72% in those with GQR versus 63% in those without GQR (P=0.50). There was a difference in achievement of GQR between the 3 major institutions where surgery was done (P=0.001) although it was low across the board. 77.9% of patients would have been disqualified from the RADIANT trial. Conclusions: Majority of surgical resections for NSCLC did not achieve GQR standards per RADIANT and NCCN. The greatest deficit is in surgical sampling of level-2 LNs, but evaluation of level-1 LNs is also frequently sub-optimal. Intervention is needed to improve current surgical and pathology practices in collection and examination of surgical specimens in order to achieve minimum standards for accurate staging, prognostication, determination of candidacy for post-operative adjuvant therapy, and eligibility for clinical trials.

[Table: see text]

[Table: see text]
Clinical impact of age on outcomes following anatomic lung resection for stage I non-small cell lung cancer
Authors: Schuchert M. J. , Pettiford B. , Kilic A. , Landreneau J. P. , Landreneau J. R. , Christie N. A. , Pennathur A. , Nason K. S. , Wilson D. O. , Luketich J. D. , Landreneau R. J.
Published: August 2020

7515

Background: There is an increasing body of evidence that anatomic segmentectomy may represent an equivalent approach compared to lobectomy in the management of stage I NSCLC. Comorbidities associated with age may result in improved survival with sublobar resection for stage I cancer in the elderly. We report our single institution experience with segmentectomy vs. lobectomy for stage I non-small cell lung cancer stratified by age. Methods: A total of 232 consecutive anatomic segmentectomies were performed for stage IA (n=137) or IB (n=95) NSCLC from 2002–2007. Lobectomy was performed in 594 patients for stage IA (n=297) and IB (n=295) during the same period. Results of segmental resection were compared with lobectomy, stratified by the following age groups: <60, 60–69, 70–79 and = 80. Primary outcome variables included complications, mortality, recurrence patterns, and survival. Statistical analysis included t-test and Fisher's exact test. Results: Mean age (69.9 vs. 68.2), gender distribution and tumor histology were similar between the segmentectomy and lobectomy groups. There was no significant difference in complications, mortality, recurrence, and overall survival in the younger age groups (Table). Segmentectomy was associated with reduced mortality (7.8% vs. 2.8%) and improved overall 3-year survival (p=0.02) in patients >80 years old. Conclusions: Anatomic segmentectomy can be performed with similar morbidity, mortality, recurrence, and survival compared to lobectomy in stage I lung cancer. This approach may be particularly advantageous in the elderly age group, achieving comparable oncologic outcomes with less mortality and improved overall survival.

[Table: see text]

No significant financial relationships to disclose.
Survival predictors after surgical resection of synchronous bilateral non-small cell lung cancers (NSCLC)
Authors: Tanvetyanon T. , Robinson L. , Sommers E. , Altiok S. , Haura E. , Kim J. , Bepler G.
Published: August 2020

7517

Background: Non-small cell lung cancer (NSCLC) that presents with bilateral lung lesions, but without extra-thoracic metastasis, is uncommon. Prognosis is typically poor: No long-term survivor is expected with systemic chemotherapy. However, small reports have suggested the feasibility of bilateral resections. To date, the predictors of survival following this treatment approach remain unknown. Methods: Our institutional tumor registry was searched for patients who underwent bilateral resections of NSCLC during 1998–2006. Patients with metachronous presentations (second lesion found ≥ 2 years afterward) were excluded. Kaplan-Meier survival estimate and Cox proportional hazards model were used to identify survival predictors. Results: Of the 2582 patients operated for NSCLC, 50 patients were included in this analysis. Median age was 69.2 years. Median tumor sizes were 2.0 cms; Adenocarcinomas were the most common (51%). Of 103 thoracotomies, pneumonectomy was performed in 3 patients. Overall peri-operative mortality was 1.9%. Median progression-free survival was 46.0 months (95% CI, 33.1–66.6); overall survival was 77.5 months (95% CI, 43.1–111.1). Performance status, presence of comorbidity, and pathological vascular invasion were important prognostic factors (Table). Risk score based on the sum of these factors (present =1; absent =0) was a strong predictor of survival. Patients with score ≥ 2 (N=11) had a median survival of 17.2 months, compared with 83.5 months among those with score ≤ 1 (HR 5.52, 95% CI 2.27–13.46; p=0.0002). Conclusions: In this largest series of surgery for synchronous bilateral NSCLC to date, the overall survival rate at 5 years is approximately 50%. Performance status, comorbidity, and vascular invasion are strong predictors of survival. Patients with vascular invasion are at an increased risk of progression or death and adjuvant therapy should be considered.

[Table: see text]

No significant financial relationships to disclose.
Baseline thymidylate synthase expression according to histological subtypes of non-small cell lung cancer
Authors: Scagliotti G. , Monica V. , Ceppi P. , Righi L. , Cambieri A. , Volante M. , Novello S. , Cappelletto E. , Papotti M.
Published: August 2020

7521

Background: In non-small cell lung cancer (NSCLC) baseline thymidilate synthase (TS) levels are higher in squamous cell carcinoma (SCC) compared to adenocarcinoma (AC) and randomized clinical trials have shown a selective benefit for patients with non-squamous histology treated with pemetrexed, a TS-inhibiting agent. TS expression in undifferentiated large cell carcinoma (LCC) is unknown. Methods: TS expression at both mRNA (using tissue microdissection and qRT-PCR) and protein (through immunohistochemistry, IHC) levels was tested in 34 surgically resected LCC (stage I=20,II=6,IIIa=8) and compared with TS expression in surgical cases of SCC (n= 31) and AC (n=40). In addition other comparisons were made: a) TS protein expression with Ki-67 index; b) TS mRNA and E2F1 transcription factor mRNA; c) in all histotypes TS protein level with desmocollin-3 (DSC-3) immunostaining, a marker of squamous cell differentiation. TS expression level was assessed in a group of patients (n=22) with cytological diagnosis of NSCLC-NOS (not otherwise specified) and compared with TS data in tissue specimens obtained through subsequent bronchial biopsy or surgical resection. Results: Significantly higher median TS levels in LCC compared to AC (p<0.001 for both mRNA and protein values) and SCC compared to AC (p=0.002 mRNA, p<0.001 protein) were detected. A strong correlation between TS mRNA and protein levels were found (p<0.001) in SCC and AC, but not in LCC. TS and both Ki-67 and E2F1 were significantly correlated in AC and SCC (p=0.003 and p=0.05, respectively), but in LCC no correlation was found. In LCC, significantly higher TS levels were observed in DSC3-positive compared to DSC3-negative tumors (p=0.02). A significant correlation between TS IHC scores in matched cytological and corresponding tissue specimens was observed (p<0.001). Conclusions: This study demonstrates and confirms the: a) differential expression of TS among the NSCLC histotypes; b) lack of DSC-3 immunoreactivity in LCC is associated with lower TS expression; c) assessment of TS by IHC in cytological specimens correlates with the corresponding tissue TS expression.

[Table: see text]
Prognostic significance of tumor size in patients with stage III non-small cell lung cancer: A SEER database survey
Authors: Waqar S. N. , Gao F. , Govindan R. , Morgensztern D.
Published: August 2020

7529

Background: Although tumor size is a known predictor of stage I and II non-small cell lung cancer (NSCLC) treated with surgery or radiotherapy, there is limited information regarding its prognostic significance in patients with mediastinal lymph node involvement. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with unresected NSCLC stage III, without malignant pleural effusion, aged 21 or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1–3 cm), S2 (3.1–5 cm), S3 (5.1–7 cm) and S4 (7.1–20 cm). Demographic variables included age, gender, race and histology. The Kaplan-Meier method was used to estimate the overall survival (OS) and disease-specific survival (DSS), and the Cox proportional hazard model to evaluate whether tumor size remained an independent risk factor after adjusting for stage and other demographic variables. Results: A total of 12,205 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were male (58.8%) and white (81.3%). Tumor size was a statistically significant predictor for both overall survival (p<0.0001) and disease-specific survival (p<0.0001) on multivariate analysis. Selected groups of patients with smaller stage IIIB disease had better OS compared to patients with stage IIIA, including; IIIBS1 vs. IIIAS3 (p=0.0005) or IIIA S4 (p<0.0001) and IIIBS2 vs. IIIAS4 (p=0.0001). Conclusions: Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC and should be considered in the stratification of patients treated in this setting.

[Table: see text]

No significant financial relationships to disclose.
Clinical factors predictive of overall survival (OS) and the identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801
Authors: Stinchcombe T. E. , Hodgson L. , Herndon J. E. , Kelley M. J. , Cicchetti M. , Ramnath N. , Niell H. B. , Atkins J. N. , Green M. R. , Vokes E. E.
Published: August 2020

7535

Background: CALGB 39801 was designed to test whether treatment with induction chemotherapy and concurrent chemoradiotherapy (arm B) would improve OS in comparison to identical chemoradiotherapy alone (arm A), and demonstrated no significant benefit in OS for induction therapy. The objective of this analysis was to identify factors predictive of OS, and to use relevant factors to dichotomize pts into prognostic groups. Methods: Between July 1998 and May 2002, 331 pts were studied and included in a Cox proportional hazard regression analysis investigating previously identified prognostic factors: age (< 70 vs. ≥ 70 years), gender, race/ethnicity, hemoglobin (hgb) (< 13 vs. ≥13), performance status (PS) (0 vs.1), pretreatment weight loss (wt loss) (<5% vs. ≥ 5%), and treatment arm. Results: Cox regression analysis identified weight loss ≥ 5%, age ≥ 70, PS of 1, and hgb < 13 as predictive of worse survival (p<0.05), but not treatment arm (p=0.55). The median survival for pts with 0 (n=66), 1 (n=100), 2 (n=100), or ≥ 3 (n=65) risk factors were 24, 18, 10, and 8 months, respectively (p=0.0001). The pts were dichotomized into “poor prognosis” (PP) defined as ≥2 factors (n=165) and “good prognosis” (GP) defined as ≤ 1 factors (n=166). The hazard ratio (HR) for overall survival for the PP in comparison GP was 1.88 (95% CI, 1.49 to 2.37; p-value < 0.0001); the median survival times (MST) observed were 9 and 18 months, respectively (p<0.0001). The reasons for discontinuing treatment, and the rates of hematologic and non-hematologic adverse events were similar between the two groups. In the PP group the OS was similar between arms A (n=82) and B (n=83) (HR=0.97, 95% CI, 0.70 to 1.4; p=0.34); MST of 8.7 and 9.5 months, respectively. In the GP the OS was similar between arms A (n=79) and B (n=87) (HR=0.86, 95% CI, 0.63 to 1.1; p=0.87); MST of 19.3 and 17.6 months, respectively. Conclusions: Factors predictive of OS can be used to dichotomize pts into prognostic groups. Induction chemotherapy was not beneficial in either prognostic group.

No significant financial relationships to disclose.
Clinical outcomes of elective nodal irradiation (ENI) compared with involved field radiotherapy (IFRT) in NSCLC
Authors: Fernandes A. , Faerber J. , Finlay J. , Shen J. , Lin L. , Evans T. , Stevenson J. , Langer C. , Glatstein E. , Hahn S. , Rengan R.
Published: August 2020

7541

Background: Local failure rates in patients treated with definitive radiotherapy for non-small cell lung cancer (NSCLC) remain high. IFRT allows higher radiation doses to the primary tumor with the goal of reducing local failure rates while minimizing toxicity. This approach, however, raises concern for increased nodal failures. Our retrospective analysis evaluates clinical outcomes of patients treated at our institution with ENI or IFRT. Methods: We assessed all patients (pts) with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy (RT) from January 1, 2003 to August 21, 2008. The decision to treat with ENI vs. IFRT was based on physician treatment philosophy. We compared baseline demographics in each group as well as toxicities and therapeutic outcomes. Involved nodal failures (INF) were defined as radiographic progression in lymph nodes that were initially involved at the time of treatment. Elective nodal failures (ENF) were defined as progression in initially uninvolved lymph nodes. Results: A total of 104 consecutive pts (56 ENI vs. 48 IFRT) were assessed. Pts in both groups had similar characteristics with respect to age, baseline KPS, and percentage receiving chemotherapy. The average RT dose was 6,345 cGy in the ENI group and 6988 cGy in the IFRT group. The median follow-up time was 8.4 mos (0.3–43.4) for all pts and 9.7 mos (1.5–40.1) for survivors. The results follow in the table below. Conclusions: Our data suggest that IFRT does not result in increased nodal failures or decreased survival compared to ENI, and may result in increased local control. The majority of patients who experienced a local failure also experienced nodal failure, suggesting that local relapse may be linked to subsequent nodal failure. This may explain the increased nodal failure rates in patients treated with ENI. Decreased esophagitis rates in patients treated with IFRT may allow the integration of concurrent, full dose systemic therapy in a greater proportion of patients, as well as higher RT doses.

[Table: see text]

No significant financial relationships to disclose.
S-1-based concomitant chemoradiotherapy for locally advanced non-small cell lung cancer: Two phase I trials from Okayama Lung Cancer Study Group (OLCSG)
Authors: Fujiwara Y. , Kiura K. , Takigawa N. , Hotta K. , Kishino D. , Nogami N. , Gemba K. , Takemoto M. , Tabata M. , Tanimoto M.
Published: August 2020

7547

Background: Chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), but the treatment outcomes have remained unsatisfied. Thus, more effective and feasible CRT is urgently needed to improve their survival. S-1 is a newly developed oral 5-fluorouracil derivative and has synergistic effects with radiation. However, the role of S-1 in CRT for LA-NSCLC has been undetermined. Methods: We conducted two phase I trials to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of S-1-based chemotherapy when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) for LA-NSCLC. OLCSG 0501 was designed to evaluate the two cycles of combination of S-1 (days 1–14) and cisplatin (days 1 and 8) for patients aged 75 or younger. S-1/cisplatin dosages (mg/m2) were escalated as follows: 60/30, 60/40, 70/40, 80/40, and 80/50. The other trial, OLCSG 0502, recruited patients aged 76 or older and evaluated S-1 alone. S-1 dosages (mg/m2) were increased as follows: 60, 70, and 80. Results: A total of 44 previously untreated LA-NSCLC patients were enrolled (22 in both trials). The MTDs for S-1/cisplatin and S-1 alone were determined to be 80 mg/m2/day / 50 mg/m2 and 80 mg/m2/day, respectively. In the OLCSG 0501, DLTs included febrile neutropenia, thrombocytopenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced grade 3 or more acute radiation pneumonitis and only one patient experienced grade 3 radiation esophagitis. In the OLCSG 0502, the DLTs were febrile neutropenia, stomatitis and delayed second cycle of chemotherapy. The overall response rates in OLCSG 0501 and OLCSG 0502 were 86.4% and 59.1%, respectively. Conclusions: These results indicate that S-1-based concomitant CRT would be a feasible treatment option and further phase II trials are currently under way.

No significant financial relationships to disclose.
A phase I trial of concurrent chemoradiotherapy (cCRT) with the conventional administration of docetaxel (D) and cisplatin (P) for dry-stage III non-small cell lung cancer (NSCLC) (JCOG9901DI)
Authors: Hida N. , Tsujimura S. , Fujii T. , Naoki K. , Kunikane H. , Okamoto H. , Shimizu T. , Watanabe K.
Published: August 2020

7549

Background: In cCRT for locally advanced NSCLC, full dose chemotherapy with a new agent plus a platinum doublet is considered to have unacceptable toxicities. Consequently, weekly or split chemotherapy doses are often used. However, cCRT plus conventional regimens are expected to enhance systemic effects. This phase I trial aimed to establish the MTD of cCRT plus conventional administration of DP (conv-DP). Methods: Unresectable stage III NSCLC patients (pts) (<70 years) with ECOG performance status 0–1 and adequate organ function were eligible. Pts received 60 Gy in 30 fractions by once daily radiotherapy. Concurrent P (day1; 60 mg/m2 at levels 1–3, 80 mg/m2 at level 4) and D (day1; 30 mg/m2 at level 1, 40 mg/m2 at level 2, 50 mg/m2 at levels 3–4) were given every 4 weeks for at least 2, and up to 4 courses. DLT was defined as either Gr3/4 febrile neutropenia, Gr4 neutropenia lasting ≥ 4 days, Gr4 thrombocytopenia, Gr2 pneumonitis or any Gr3 non-hematological toxicities except for nausea, vomiting and alopecia. Results: Eighteen pts were enrolled from 06/1999 to 05/2006: 6 pts at levels 2 and 4, 3 pts at levels 1 and 4; 13 males; median age 60 years (range 43–70); stage IIIA/IIIB 5/13; histology Ad/Sq/Large 9/7/2. DLTs were observed for 3 pts at level 2 (D40/P60): Gr4 pneumonitis at level 3(D50/P60), Gr3 cerebral infarction and Gr3 atrial fibrillation. Although 3 cases were added at these levels, tolerability for each level was cleared, as DLTs occurred for ≤ 2 pts among 6. MTD was not detected, even at the highest dose (D50/P80). However, dose escalation was stopped, as D60/P80 was the recommended dose for chemotherapy alone in Japan. Radiotherapy (60 Gy) was completed for 15 pts. Seventeen pts received more than 2 courses of chemotherapy. No Gr3/4 esophagitis or severe hematologic toxicities were observed. Objective response rate was 89% and 1-yr survival rate was 55%. Conclusions: The recommended dose in this regimen was D50/P80, which was near the full dose for conv-DP. Based on these promising results, we are planning a phase II trial to evaluate the efficacy and toxicity of this cCRT with conv-DP therapy.

No significant financial relationships to disclose.
A phase I/II trial of perioperative paclitaxel (P), carboplatin (C), and erlotinib (E) with concurrent accelerated hyperfractionated radiation (HFRT) followed by maintenance E for stage III non-small cell lung cancer (NSCLC)
Authors: Pennell N. A. , Videtic G. M. , Murthy S. , Mason D. , Rice T. W. , Mazzone P. , Samsa J. , Rich T. , Shapiro M. , Mekhail T.
Published: August 2020

7557

Background: Concurrent chemoradiotherapy (CRT) is standard treatment for stage III NSCLC, although the management of resectable patients (pts) remains controversial. We report an open-label phase I/II trial of the epidermal growth factor receptor inhibitor E added to perioperative CRT for resectable stage III NSCLC pts, followed by maintenance (m) E. Methods: Eligible pts had stage IIIA/B NSCLC, PS 0–1, and were resectable as determined by a thoracic surgeon. Pts received weekly P (50 mg/m2), and C (AUC 2) with daily oral E for 28 days concurrent with twice daily thoracic radiation (1.5 Gy/fraction) to 30 Gy, followed by restaging. Non-progressors underwent resection followed by the same CRT regimen and 2 years of mE (150mg). The primary endpoint of the phase I portion was the maximum tolerated dose (MTD) of E given with CRT; and for the phase II was safety and tolerability. Secondary endpoints were pathologic complete response (pCR) rate, pathologic downstaging of mediastinal nodes, progression free survival (PFS), and overall survival (OS). Results: 9 pts were enrolled in the phase I trial. The MTD of E was150mg, which was the phase II dose used. 25 pts were treated in the phase II component: median age 60, 92% stage IIIA, 64% female, 72% PS 0, 64% adenocarcinoma, and 16% never smokers. The median duration of mE was 5.5 months, with the most common reason for discontinuation being pt preference. There was no grade 4 toxicity. Grade 3 toxicity seen in >5% of pts: rash (12%), diarrhea (9%), nausea (9%), and encephalopathy (6%). The most common toxicities during mE: grade 1/2 diarrhea (72%), rash (61%), fatigue (56%), nausea (22%), and dry eyes (17%).1 pt (4%) had a pCR after neoadjuvant CRT, and 46% were downstaged to pN0–1 at surgery. At a median follow-up of 36.5 mos the median PFS is 41.8 mos (95% CI 9.3-not yet reached). The median OS has not been reached. 3 year survival is 69%. Pts downstaged to pN0–1 vs those with persistent pN2–3 had a median PFS of 41.8 vs 18.1 mos (p=0.11). Conclusions: Perioperative P, C, and E given concurrently with HFRT was well tolerated and showed promising efficacy, while compliance was poor with maintenance E.

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Comparative use of perioperative chemotherapy (CT) in non-small cell lung cancer (NSCLC) between 2004 and 2007
Authors: Le Naour B. , Mauguen A. , Fabre D. , Pignon J. , Planchard D. , Soria J. , Dartevelle P. , Besse B.
Published: August 2020

7564

Background: Adjuvant (ADJ) platinum-based CT has become a new standard of care for patients (pts) with resected stage II and III NSCLC, and is discussed in selected stage IB pts. Impact of positive randomized trials which showed significant survival improvement (first published in 2004) on the use of ADJ CT has been poorly studied to date. Methods: A retrospective study of consecutive pts with NSCLC who underwent curative surgery during the first half of year 2004 and 2007 in the surgical center Marie Lannelongue (France) was conducted. Logistic regression models were employed to identify cofactors associated with the use of ADJ CT (excluding stage IV). Odds ratio (OR) > 1 corresponds to a more frequent use than in reference group. Results: A total of 240 pts (116 in 2004, 124 in 2007) underwent curative surgery for NSCLC (11% IA; 30% IB; 27% II; 27% III; 5% IV). Among all pts, 12 % received neoADJ CT (less in 2007, 8% vs 16% p=.04), 35% ADJ (4% both). Reasons for not receiving ADJ CT included stage I (34%), death (11%), comorbidities (10%), poor performance status (10%), advanced age (8%), post-operative complications (7%), patient refusal (3%). More ADJ CT was prescribed in 2007 (41% vs 30% in 2004, p=.009). Overall, 45% of pts with stage II-III received ADJ CT in 2004 versus 69% did so in 2007. In multivariate analysis (194 pts), ADJ CT was associated with the year of inclusion (OR=2.67 p=.009), stage (stage II, OR=6.77, stage III, OR=16.85; p<.0001), serious medical history (OR=.41 p=.01) and salvage surgery (OR=.26 p=.03). Cisplatin was the preferred platinum compound in 76% of neoADJ regimens (mostly cisplatin-docetaxel), and 70% of ADJ CT (mostly cisplatin-vinorelbine). Conclusions: The presentation and publication of “positive” ADJ CT trials had significantly increased prescription of ADJ CT in pts with stage II-III NSCLC. Nevertheless 31% of the stage II-III did not received CT mostly because of comorbidities, highlighting the need of a personalized CT.

No significant financial relationships to disclose.
Pemetrexed in combination with cisplatin or carboplatin as adjuvant chemotherapy in early-stage NSCLC
Authors: Schmid-Bindert G. , Chemaissani A. , Fischer J. R. , Schütte W. , Mazières J. , Viñolas N. , Wolf M. , Thareau Vaury A. , Leschinger M. , Reck M.
Published: August 2020

7565

Background: Platinum based chemotherapy after complete resection of stage I-IIIa non-small cell lung cancer (NSCLC) has improved 5-yr survival by 4–15%. Pemetrexed (P) in combination with cisplatin (C) or carboplatin (Carb) has shown to be effective and safe in first-line Tx of advanced NSCLC, thus being a promising option in the adjuvant setting. Methods: Multicenter, open phase 2 in pts with resected stage Ib/II NSCLC. Pts were randomized to P (500 mg/m2)+C (75mg/m2) or P (500 mg/m2)+Carb (AUC5) d1 q3 wks, for 4 cycles; adequate organ function and ECOG PS 0–1 required. Primary endpoint was feasibility of the regimen defined as compliance to 4 Tx cycles with ≥ 95% of planned dose without ≥ Grade 3 toxicities (tox) at 30 d after last infusion. A regimen was deemed feasible if the rate (feasible pts/total pts) was >60%. Results: Please see Table for results. Conclusions: According to the strict definitions in this protocol neither regimen was feasible. The reason was poor compliance with at least one of the components that defined feasibility, but dose intensity and % pts completing cycle 4 was notably high, compared to other adjuvant trials. P+C was the more favourable regimen concerning feasibility and tolerability. In terms of tolerability pemetrexed could be combined with either platinum compound.

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Predictive role of 18F-FDG-PET/CT 1 month before and after hypofractionated stereotactic body radiation therapy for stage I non-small cell lung cancer
Authors: Song S. , Ryu J. , Lee S. , Ahn S. , Kim J. , Lee J. , Park C. , Choi E.
Published: August 2020

7569

Background: To know the predictive role of 18F-FDG-PET/CT 1month before and after stereotactic body radiation therapy (SBRT) to stage I non-small cell lung cancer (NSCLC). Methods: Between 2004 and 2007, 20 patients received SBRT with 48 Gy for 4 consecutive days and checked two times of FDG- PET/CT and chest CT with contrast-enhancement at 1 month before and after SBRT. Change of maximal SUV (SUVmax) on FDG-PET/CT and the longest tumor diameter on chest CT before and after SBRT was measured. Patients only with high FDG uptake, SUVmax 3.0 or above, on FDG-PET/CT before SBRT and tumor diameter below 5 cm were analyzed in this study. Change of tumor diameter was classified to PR (partial response), SD (stable disease), and DP (disease progression) as RECIST criteria and change of SUVmax was described as % change. Chest CT was checked at every 3 or 6 months during follow-up. Results: Mean time intervals from SBRT to FDG-PET/CT and chest CT were 32 and 30 days respectively. Mean longest tumor diameter was changed from 2.59 cm (1.36–3.93) to 2.17 cm (1.18–3.41), and its reduction rate was -16.2%. By RECIST criteria, 4 patients showed PR, 15 patients showed SD, and other 1 patient showed DP. Mean decrease rate of SUVmax on FDG-PET/CT was -52.1% and its mean value was changed from 7.1 (3.2–13.1) to 3.4 (0.3–9.8). Median follow-up time was 16 months. Local tumor progression developed in 2 (10%) patients and time to progression was 3.4, 6.1 months. Tumor responses on post-SBRT chest CT were PR in 1 and SD in the other 1 patient, and SUVmax changes were -31.9%, -25.5% in each. Most of patients showing no response, SD or DP, didn't recur after SBRT, and so chest CT at 1 month could not predict actuarial tumor response. On the contrary to chest CT, no patients showing SUVmax decreases over 40% experienced tumor progression after SBRT. High decrease rate of SUVmax over 40% decrease on FDG-PET/CT 1 month after SBRT could warrant good actuarial local tumor control earlier. Conclusions: Change of SUVmax on FDG-PET/CT 1 month before and after SBRT could predict actuarial local tumor control of stage I NSCLC earlier and 1 month after SBRT was adequate timing for the earlier evaluation of tumor response.

No significant financial relationships to disclose.
Value of FDG-PET/CT findings revised using an anthropomorphic body phantom for the evaluation of tumor malignancy grade in small-sized lung adenocarcinomas: A multicenter study
Authors: Nakayama H. , Kato Y. , Tsuboi M. , Okumura S. , Daisaki H. , Uehara H. , Adachi S. , Yoshimura M. , Okada M.
Published: August 2020

7573

Background: The malignant behavior of small lung adenocarinomas (AD), which have been detected with increasing frequency recently, has not yet been clearly evaluated, and an understanding of this biological characteristic is vital for selecting the appropriate therapeutic strategy. We examined the malignancy grade of small lung ADs using FDG-PET/CT (PET), in addition to high-resolution CT (HRCT) and pathologic evaluation in a multicenter setting. Methods: A total of 204 patients with cT1N0M0 AD underwent PET and HRCT, followed by complete resection with lymph node dissection. The associations between components of bronchioloalveolar carcinoma (BAC) on pathologic examination and maximum standardized uptake value (maxSUV) on PET, ground-glass opacity (GGO) ratio and tumor disappearance rate (TDR) on HRCT were examined, and these findings were analyzed in relation to pathologic features and surgical outcomes. To reduce the errors in PET machines used for this analysis, maxSUV data were adjusted using an anthropomorphic body phantom of the NEMA standards (corrected maxSUV). Results: Examination of tumor aggressiveness based on the presence of lymphatic, vascular and pleural invasion, and of nodal metastasis, showed that maxSUV, BAC ratio, TDR, and GGO ratio, in the order, can reflect the malignancy grade. MaxSUV and BAC ratio were also valuable prognostic predictors of the disease-free survival. There were no significant differences in the values between maxSUV and corrected maxSUV. Although BAC ratio was significantly associated with maxSUV, GGO ratio and TDR (all p<0.0001), the degree of association with maxSUV (R2=0.2533) was weaker than that with GGO (R2=0.5843) ratio or TDR (R2=0.5123). Conclusions: A higher maxSUV reflects an aggressive malignant behavior of cT1N0M0 ADs, independently of BAC component. Assessment by PET in addition to HRCT is useful for selection of the appropriate treatment strategy for small lung AD.

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No significant financial relationships to disclose.
The impact of length of hospitalization following surgical resection of stage I non-small cell lung cancer on long-term survival
Authors: Kilic A. , Schuchert M. J. , Landreneau J. R. , Landreneau J. P. , Oostdyk A. , Wilson D. O. , Luketich J. D. , Landreneau R. J.
Published: August 2020

7584

Background: The aim of this study was to evaluate the impact of length of hospital stay (LOS) following surgical resection of stage I non-small cell lung cancer (NSCLC) on long-term survival. Methods: We reviewed the records of patients undergoing surgical resection for stage I NSCLC at our institution between 1990–2003. Patients not surviving hospitalization related to their surgery were excluded from analysis. Multivariate analysis was utilized to evaluate the impact of age, gender, tumor histology, tumor stage, LOS, and type of operation (lobar or sublobar) on long-term (>5 year) survival. As a secondary analysis, Kaplan-Meier survival curves of patients stratified according to LOS were compared using the log-rank test. Two-tailed p-values less than 0.05 were considered statistically significant. Results: A total of 730 patients underwent lobectomy (n=518) or sublobar resection during the study time period. There were 18 (2.5%) operative or in-hospital mortalities. Median LOS was 6 (range 1–81) and 7 (range 1–46) days in the lobar and sublobar cohorts, respectively. Patients with a longer hospital stay (≥14 days) had significantly worse 5- and 10-year overall survival rates as compared to those with a shorter hospitalization (lobectomy: 5-year- 60.3% vs 33.8%; 10-year-27.3% vs 8.4%; p<0.001; sublobar: 5-year-44.3% vs 11.7%; 10-year-9.9% vs 0%; p=0.006). There were 171 patients with extended clinical follow-up who had survived at least 5 years (mean follow-up = 88.1 ± 2.0 months). Multivariate analysis demonstrated that LOS predicted long-term survival independent of patient age, gender, tumor histology, tumor stage, and type of operation (p=0.013). Conclusions: LOS following surgical resection of stage I NSCLC is an independent predictor of long-term survival. These survival differences related to hospital stay may be related to underlying medical co-morbidities important to the decision making regarding therapy of patients with otherwise resectable stage I lung cancer. Prospective assessment of medical co-morbidities may be an important initiative for future treatment planning of early stage lung cancer patients.

No significant financial relationships to disclose.
Assessment of the safety and efficacy of percutaneous cryoablation for lung tumors
Authors: Yamauchi Y. , Izumi Y. , Tsukada N. , Asakura K. , Inoue M. , Yashiro H. , Nakatsuka S. , Kawamura M.
Published: August 2020

7592

Background: Percutaneous cryoablation using high resolution fluoroscopic CT guidance under local anesthesia offers a potential tool for local control of lung tumors in combination with systemic treatments. In this study, we retrospectively analyzed the safety, and efficacy of percutaneous cryoablation for lung tumors (PCLT). Methods: This study was approved by the institutional review board. From October 2002, PCLT was performed in patients who either did not oncologically fulfill the indications for resection, or refused resection. CT scan was examined every 3 months after PCLT. >20% increase in the treated lesion size was diagnosed as local failure. Survival analysis was done by Kaplan-Meier. Results: There were 147 patients (95 male, 52 female, mean age 60, 20 primary lung cancer, metastases; 29 of lung cancer, 35 of colorectal cancer, 63 of other sites). 251 sessions were done for 462 tumors. Mean tumor diameter was 18.3mm. PCLT was well tolerated in most patients. In 1 case, broncho-thoracic fistula occurred in the treated region which lead to empyema. Other complications were pneumothorax (153 sessions, 61%, chest tube required in 23 sessions), pleural effusion (160 sessions, 64%), and transient hemoptysis (82 sessions, 33%). Overall one- and two-year local control rates were 81.0% and 59.1%, respectively. Overall one- and two-year survival rates were 80.0% and 54.5%, respectively. In the 1–20 mm sized (n=362) vs. over 21mm sized (n=100) lesions, the local control rates at one year were 84% vs. 56% (p=0.0007), and at two years were 63% vs. 35% (p=0.017), respectively. There were no differences in local control between primary and metastatic tumors, carcinomas and sarcomas. Survival of patients whose lesions were limited to 1–20mm (n=89) was prolonged vs. those who had at least one over 21mm lesion (n=58) (p=0.01). However, one, and two-year survival rates did not differ significantly between these groups (one-year; 85.5% vs. 71.7% (p=0.07), two-year; 60.7% vs. 46.5% (p=0.16)). Conclusions: PCLT was minimally invasive and safe. 1–20mm tumors were good candidates. Contribution of PCLT to survival was not clear in this mixed patient population. To improve local control in over 20 mm tumors, we are computer simulating freezing kinetics to optimize the number and the positioning of the probes.

No significant financial relationships to disclose.