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R.U. Komaki
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GR 03 - Extensive Small Cell with Excellent Response to 1st Line Rx (PCI, Chest and/or Oligomet RT) and Second Line and Treatment of Thymic Malignancies (ID 16)
- Event: WCLC 2015
- Type: Grand Rounds
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:B.E. Johnson, B. Kavanagh, P. Kosmidis, E. Ruffini
- Coordinates: 9/09/2015, 14:15 - 15:45, 102+104+106
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GR03.01a - SCLC Therapy (ID 1838)
14:20 - 14:40 | Author(s): R.U. Komaki
- Abstract
- Presentation
Abstract:
The incidence of lung cancer has been declining since the advent of tobacco cessation efforts, and screening has improved 5-year overall survival rates among smokers to some extent. Nevertheless, about 13% of lung cancers are of the small cell subtype (SCLC), and many such cases present as extensive disease. Outcomes for patients with extensive SCLC remain poor, with median times to progression of 4–6 months, median survival times of 7–11 months, and 2-year survival rates of <5%.[1] Chemotherapy has been the cornerstone of treatment, with the current standard being 4–6 cycles of platinum-based chemotherapy. Other approaches involving other chemotherapeutic agents, molecular targeted drugs, or maintenance chemotherapy have not led to improvement. A notable exception, however, is prophylactic cranial irradiation (PCI) for patients who experience a complete response after induction chemotherapy. PCI has been shown to eliminate the progressive increase in the risk of brain metastasis that accompanies extended survival in patients with SCLC, and in that context is important for maximizing the probability for cure for such patients.[2] Indeed, PCI has led to extended survival among patients with limited-stage SCLC and some patients with extensive SCLC. A randomized phase III trial of patients with extensive SCLC reported by Slotman et al.[3] showed that PCI reduced the incidence of symptomatic brain metastases (15% versus 40% in a no-PCI control group) and increased the 1-year overall survival (OS) rate from 13% to 27%. However, a benefit of PCI for patients with extensive SCLC has not been noted consistently. A multicenter trial from Japan (UMIN000001755, reported in abstract form at ASCO 2014)[ 4] was terminated early because the futility boundary was crossed for OS. That study indicated that receipt of PCI after response to chemotherapy for extensive SCLC reduced the risk of developing brain metastases but had a negative effect on OS (median OS time 10.1 months for PCI vs. 15.1 months for observation, HR=1.38, 95% CI 0.95-2.01, stratified log-rank test P=0.091). Differences between that study and the phase III trial reported by Slotman included the use of magnetic resonance imaging to rule out brain involvement at enrollment, use of only platinum-based doublet chemotherapy, and use of a single PCI schedule (25 Gy in 10 fractions). Another multicenter study involving PCI, RTOG 0937, was also closed early for crossing a survival futility boundary. Further, although the Japanese study showed no difference between the PCI vs. observation groups in terms of incidence of grade >2 adverse events, a disproportionate distribution of grade 4 and 5 events in RTOG 0937 between groups (PCI with or without consolidative extracranial irradiation) also contributed to the early closure of that trial. In addition to PCI, thoracic radiation therapy can improve local control and extend survival for patients with limited-stage disease and possibly for some patients with extensive disease. Controlling intrathoracic tumors remains problematic in SCLC, as such disease remains after induction chemotherapy in most patients and progresses in nearly all patients within the first year after diagnosis. Evidence of benefit for patients with extensive disease includes a single-institution trial of patients with a complete response to induction chemotherapy at distant disease sites, and a complete or partial local response, who received additional low-dose chemotherapy with or without thoracic radiotherapy; that study showed significant improvements in local control and survival after thoracic radiotherapy.[5] Other evidence of benefit comes from two retrospective analyses,[6,7] one non-randomised phase II trial,[8] and a recent phase III multicenter trial of thoracic radiotherapy with PCI for patients with extensive SCLC that had responded to chemotherapy.[9] The latter study involved 247 patients who received thoracic radiation and PCI and 248 who received PCI only after responding to chemotherapy. Although OS at 1 year was no different between groups (33% [95% confidence interval {CI} 27–39] thoracic vs. 28% [95% CI 22–34] control), a secondary analysis showed that the 2-year OS rate was better (13% [95% CI 9–19] vs. 3% [95% CI 2–8], P=0.004) and progression was less likely in the group that received thoracic radiotherapy (hazard ratio 0.73, 95% CI 0.61–0.87, P=0.001). These findings, in combination with low rates of severe toxic effects (no grade 5; grade 3-4 in 26 thoracic and 18 control patients), led the authors to recommend that thoracic radiotherapy be considered, in addition to PCI, for all patients with extensive SCLC who respond to chemotherapy. References 1. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the Surveillance, Epidemiology, and End Results database. J Clin Oncol 2006;24:4539–44. 2. Komaki R, Cox JD, Whitson W. Risk of brain metastasis from small cell carcinoma of the lung related to length of survival and prophylactic irradiation. Cancer Treat Rep 1981;65(9-10):811-814. 3. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007;357:664–672. 4. Seto T, Takahashi T, Yamanaka T, et al. Prophylactic cranial irradiation has a detrimental effect on the overall survival of patients with extensive disease small cell lung cancer: results of a Japanese randomized phase III trial (abstract). J Clin Oncol 2014;32:5s (suppl; abstr 7503). 5. Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: a randomized study. J Clin Oncol 1999;17:2092–2099. 6. Giuliani ME, Atallah S, Sun A, et al. Clinical outcomes of extensive stage small cell lung carcinoma patients treated with consolidative thoracic radiotherapy. Clin Lung Cancer 2011; 12: 375–379. 7. Zhu H, Zhou Z, Wang Y, et al. Thoracic radiation therapy improves the overall survival of patients with extensive-stage small cell lung cancer with distant metastasis. Cancer 2011; 117: 5423–5431. 8. Yee D, Butts C, Reiman A, et al. Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer. Radiother Oncol 2012;102:234–238. 9. Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet 2015;385:36–42.
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MINI 02 - Immunotherapy (ID 92)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:P. Forde, S.J. Antonia
- Coordinates: 9/07/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
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MINI02.04 - Sequential Assessment of DNA Damage Response and PD-L1 Expression in Circulating Tumor Cells of Lung Cancer Patients during Radiotherapy (ID 2511)
11:00 - 11:05 | Author(s): R.U. Komaki
- Abstract
- Presentation
Background:
Recent evidence suggests that PD-L1 expression can be induced with radiotherapy and may be a mechanism for resistance to radiotherapy and immunotherapy. Sequentially assessing PD-L1 expression on cancer associated cells in circulation during treatment regimens may be a way to assess the efficacy of radiotherapy and immunotherapy in clinical trials. For this feasibility study, we evaluated the association of RAD50 induction, and PD-L1 expression, on CTCs and Cancer Associated Macrophage-Like Cells (CAMLs) in lung cancer patients (pts) before and during radiotherapy to determine expression changes of these markers.
Methods:
Eleven pts with stage I-IV lung cancer were included in this pilot study. Three pts received Stereotactic Body Radiation Therapy (SBRT) for stage I disease and 8 other pts received chemoradiation for stage II-IV disease. Baseline blood samples (7.5 ml) were drawn prior to the start of radiotherapy (T0) and a second blood sample was drawn at a follow up visit during radiotherapy; or for three pts, after completing SBRT (T1); for a total of 22 samples. Blood was processed using CellSieve™ microfiltration (Creatv Microtech), stained for cytokeratin 8, 18 & 19 and CD45, and imaged. Using the QUAS-R (Quench, Underivatize, Amine-Strip and Restain) technique to remove fluoresce signal, all cells were restained for RAD50-AlexaFluor550 and PD-L1-AlexaFluor 488, along with DAPI nuclear stain. The RAD50 foci numbers within nuclear regions were quantified. PD-L1 pixel intensity was measured by the ZenBlue software and grouped into 4 IHC groups: 0-negative (pixel average 0-215), 1-low (pixel average 216-300), 2-medium (pixel average 301-750), and 3-high (pixel average 751+).
Results:
There was at least one cytokeratin positive cell (i.e. CTC or CAMLs) found in each of the samples. Specifically CTCs were found in 82% of T0 and 64% of T1 samples, and CAMLs were found in 91% of T0 and 100% of T1 samples. RAD50 foci ranged from 0-16 per cell, with an average of 0.69 at T0 that increased to 3.46 at T1 (p=0.002) during radiotherapy. Distinctively, there were 6 pts with greater than 2 fold RAD50 foci increase at T1 and 5 pts with ≤ 2 fold induction. PD-L1 expression ranged from 34-2004 pixel intensity, with an average of 170 at T0 and 336 at T1 (p=0.08). Interestingly, 4 pts had no PD-L1 expression at T0 but an increase to 2 to 3+ at T1, 4 pts with low/no PD-L1 expression remained low at T1, and 3 pts had high PD-L1 expression that remained high or decreased at T1. There was no correlation between RAD50 induction and PD-L1 expression.
Conclusion:
Both RAD50 foci and PD-L1 expression were quantifiable in both CTCs and CAMLs, and had variable responses to radiotherapy +/- chemotherapy. These data suggest that sequential tracking of CTCs or immune-related cells from the primary lung tumor is feasible using microfiltration and potentially can serve as predictive biomarkers for cancer therapy.
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MINI 07 - ChemoRT and Translational Science (ID 110)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:D. Raben, B. Kavanagh
- Coordinates: 9/07/2015, 16:45 - 18:15, 201+203
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MINI07.04 - Dynamic Changes in Cell-Free Circulating Tumor DNA to Track Tumor Response and Risk of Recurrence in Stage III Non-Small Cell Lung Cancer (ID 2499)
17:00 - 17:05 | Author(s): R.U. Komaki
- Abstract
- Presentation
Background:
While the curative management of unresectable stage III non-small cell lung cancer (NSCLC) is definitive chemoradiotherapy, clinical outcomes remain poor. Cellular heterogeneity in tumors is correlated with therapeutic resistance and poor prognosis. We hypothesize that tumor-specific mutant allelic frequency in cell-free DNA from plasma quantifies tumor heterogeneity and that tracking allelic evolution via blood from patients during and after treatment can serve as a non-invasive means to monitor treatment response and recurrence.
Methods:
Between 2009-2013, 156 patients with unresectable NSCLC who received definitive radiotherapy or chemoradiotherapy were consented to have blood drawn at baseline before starting radiotherapy, once or twice during treatment, and once or twice during follow up visits. Cell-free plasma DNA was sequenced using a cell-free circulating tumor DNA (ctDNA) next generation sequencing (NGS) assay (Guardant360) that uses digital sequencing to report single nucleotide variants (SNVs) in 68 genes and amplifications in 16 genes. This ctDNA assay has high sensitivity (detects 85%+ of the SNVs detected in tissue in advanced cancer patients) and analytic specificity (>99.9999%). Over 670 serial samples were collected from these patients. Here we report the initial analysis of the first 26 patients of this ongoing study.
Results:
Among this initial cohort, 23 (88%) had a recurrence (PFS ranged from 1.2 – 27.9 months) and three (12%) had no evidence of recurrence as of last contact (32.8 – 42.8 months post-radiotherapy completion). Twenty-one patients (81%) had ctDNA alterations present pre-radiotherapy, of which six had a classic driver mutation: KRAS G12F x2; KRAS G12S; PIK3CA E545K x2; PIK3CA H1047R. These six patients had significantly shorter PFS compared to patients without a driver mutation present pre-radiotherapy: average PFS of 4.2 months (1.2 - 8.3) vs. 18.6 months (4.4 - 42.8) respectively (p=0.002). All six had the driver mutation disappear during radiotherapy, four had new alterations appear during and/or post-treatment. One patient had the driver mutation reappear in ctDNA post-radiotherapy and had the shortest PFS (1.2 months) of all patients. Ten patients (38%) had no ctDNA alterations present in the post-radiotherapy blood sample and a trend was observed of improved PFS among patients without ctDNA alterations post-treatment (average PFS 52.3 vs. 75.5 months respectively) however this was not statistically significant (p=0.1). Of note, the three patients without evidence of recurrence as of last contact had no ctDNA alterations identified in the post-treatment sample. This trend is anticipated to become significant with larger sample size.
Conclusion:
In this interim analysis, we found that the dynamic alterations of specific mutant alleles strongly correlated with clinical response and that persistence of ctDNA mutant allele concentrations post-definitive treatment is likely a marker of early metastatic recurrence. Undetectable ctDNA in post-treatment sample was seen in the three patients with approximately three years of PFS. These initial results suggest that serial ctDNA analysis may be useful to monitor treatment response and identify patients at high risk for early recurrence who may benefit from additional systemic therapy.
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MINI 37 - SCLC Therapy (ID 165)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:D. Ettinger, G.R. Simon
- Coordinates: 9/09/2015, 18:30 - 20:00, 605+607
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MINI37.10 - Factors Associated with Severe Pneumonitis for Limited Stage Small Cell Lung Cancer (ID 1714)
19:25 - 19:30 | Author(s): R.U. Komaki
- Abstract
- Presentation
Background:
Pneumonitis is a major side effect for the treatment of limited stage small cell lung cancer with concurrent chemotherapy and radiotherapy (CChRT). Prevention is more important than treatment when patients develop grade 3-5 severe pneumonitis (SP). We investigated factors causing SP among patients with limited stage small cell lung cancer (SCLC) treated by CChRT.
Methods:
This is a retrospective analysis of 559 patients with limited-stage SCLC treated at a single institution from 1986-2009 with definitive CChRT to a total dose of 45-70 Gray (Gy). Candidate variables included tumor size, year of diagnosis & treatment period (1986-1999 vs. 2000-2009), gender, age, Karnofsky’s Performance Status (KPS), ethnicity, radiation dose, cycles of induction chemotherapy, use of intensity-modulated-radiation-therapy (IMRT) and fractionation. CTCAE v2 before 2003 and CTAE v3 in 2003-2009 were used to evaluate SP Grade 3-5 which were similar. Chi-square test was used for between group comparisons for categorical variables and the median test was used for between group comparisons for continuous variables. Kaplan-Meier estimates were constructed for overall survival (OS), disease-free survival (DFS), local-recurrence-free survival (LRFS), distant metastasis-free survival (DMFS). Analysis was performed using Logistic regression analysis with SP as the primary endpoint.
Results:
Of the 559 patients included in this analysis, tumor size was available for 520 patients. Median follow-up was 21.2 months (range 1.2-240.8). Thirty-five (6.2%) patients developed SP (26 Grade-3, 8 Grade-4 & 1 Grade-5). 2D or 3DCRT was used before 2000 and IMRT was usually used for small cell lung cancer in 2000-2009. Univariate analysis (UVA)showed that SP was associated with treatment given in 2000-2009 ( OR 3.93, P<001) ,age ≥ 60 (OR 7.72, P=0.001) ,KPS < 90 (OR 2.22, P=0.02), IMRT (OR 2.3, P= 0.026) and twice daily fractionation( OR 2.38, P=0.03).Induction Chemotherapy reduced SP (OR 0.39, P= 0.023) compared to immediate CChRT. Tumor size (at cut points 3 cm & 5 cm) did not make significant difference regarding SP. Multivariate analysis (MVA) has shown that significantly higher SP was associated with treatment given in 2000-2009 (OR 3.42, P=0.006), age ≥ 60 (OR 7.77, P= 0.001), male (OR 2.12, P=0.047)and twice daily RT (OR 2.45, P=0.026) . OS was significantly reduced among SP group vs. Pneumonitis ≤ Grade 2 (MST 17.9 vs.25 months, P= 0.038) (5-year OS 16 % vs. 27%), respectively. SP were not significantly correlated with DFS, LRFS and DMFS.
Conclusion:
Significantly higher SP was seen among patients with limited stage small treated in 2000-2009, age ≥ 60, male and twice daily RT. OS was significantly reduced SP. UVA showed IMRT causing significantly higher SP. MVA did not show IMRT was a significant factor for SP. Tumor size did not show significant difference regarding SP.
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.06 - Outcomes of Intensity Modulated and 3D-Conformal Radiotherapy for Stage III Non-Small Cell Lung Cancer in NRG Oncology/RTOG 0617 (ID 938)
11:28 - 11:39 | Author(s): R.U. Komaki
- Abstract
Background:
Intensity modulated radiation therapy (IMRT) has the potential to improve target coverage and spare toxicity in locally-advanced non-small cell lung cancer (NSCLC). However, the effect of IMRT on outcomes for NSCLC has not previously been assessed in a large prospective cooperative group clinical trial.
Methods:
A secondary analysis was performed in patients with stage III NSCLC in NRG/RTOG 0617, a randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) chemoradiotherapy +/- cetuximab. Radiotherapy (RT) technique was stratified by IMRT and 3D-conformal radiotherapy (3D-CRT). Baseline prognostic and RT dosimetric parameters were compared between IMRT and 3D-CRT after adjusting for RT dose levels and cetuximab use. The prognostic value of RT technique with respect to toxicity and efficacy was assessed through multivariate logistic regression (MVA) and Cox proportional hazards model after controlling for RT dose level, cetuximab use and other factors.
Results:
Of the 482 eligible patients treated with RT, 53% and 47% were treated with 3D-CRT and IMRT, respectively. The IMRT group had more stage IIIB (38.6 vs. 30.3%, P = 0.056), larger PTVs (mean 486 vs. 427 mL, P = 0.005), and larger PTV:lung ratio (mean 0.15 vs. 0.13, P = 0.013). In spite of larger PTV volumes, IMRT was associated with lower lung V20 (P = 0.08), and lower heart doses (V5, V20, V40) than 3D-CRT. In turn, IMRT was associated with a lower rate (3.5 versus 7.9%) of Grade 3+ pneumonitis (P = 0.0653). On MVA, the lung V20 significantly predicted grade 3+ pneumonitis, while the lung V5 and mean lung doses did not. Larger heart V40 was associated with worse OS (HR=1.013, P < 0.001), and the heart V40 was significantly lower in patients treated with IMRT. Patients treated with IMRT were also more likely (37 versus 29%) to receive full doses of consolidative chemotherapy (P = 0.05).
Conclusion:
Although IMRT was used to treat larger and less favorable tumors in RTOG 0617, it was associated with reduced risk of Grade 3+ pneumonitis and higher likelihood of receiving full doses of consolidative chemotherapy. The heart V40, shown to be highly prognostic for survival, can be substantially reduced with IMRT compared to 3D-CRT.
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P2.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 210)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.02-032 - Phase II Clinical Trial of Stereotactic Ablative Radiotherapy (SABR) in Surgically Operable Stage I Non-Small Cell Lung Cancer (STARS) (ID 1254)
09:30 - 09:30 | Author(s): R.U. Komaki
- Abstract
Background:
Standard therapy for operable clinical stage I non-small cell lung cancer (NSCLC) is lobectomy with sampling or dissection of mediastinal lymph nodes. Stereotactic ablative radiotherapy (SABR) has produced local control rates in excess of 95% and has become standard care for medically inoperable stage I NSCLC. However, the role of SABR in operable stage I NSCLC remains controversial due to concerns about the risk of local or nodal recurrence after SABR, either of which could lead to worse OS than that after standard surgery. We report here the preliminary outcome using SABR in clinically operable stage I NSCLC.
Methods:
Patients with clinical T1A(<3 cm)N0M0 biopsy proven operable NSCLC who meet criteria for lobectomy are being enrolled. All patients are staged with chest CT, PET/CT imaging, and EBUS. 54 Gy in 3 fractions was used for peripheral lesions and 50 Gy in 4 fractions for central lesions, respecting critical normal tissue dose volume constraints. SABR plans are typically optimized by using 6 to 12 coplanar or non-coplanar 6-MV photon beams (3-D CRT or IMRT) or Cyberknife or one to three arcs (VMAT). Daily CT-on-rail or a cone-beam CT scans or tumor tracking was used during each radiotherapy fraction.
Results:
Enrollment was started in September 2009, temporally closed in 2013 with 20 patients and re-opened in 2014. The study is ongoing and 58 patients have been enrolled up to date. The median follow-up time for the first 20 patients was 40 months; for all patients, median follow up was 7 months (range 0.8-49.6 months, interquartile 4.7, 22.8 months). No deaths have occurred to date. There was one local failure in the treated lobe that was salvaged with lobectomy. There were 5 cases of regional mediastinal lymph node progression treated with concurrent chemo/radiotherapy. Three of these cases had suspicious lymph nodes by CT and PET before SABR but were enrolled because EBUS was negative. One patient developed distant metastasis and was treated with chemotherapy. No one had grade 3-5 toxicity. Six patients had grade 2 chest wall pain (10.3%) and three patients developed grade 2 pulmonary toxicity (5%).
Conclusion:
SABR is well tolerated with minimal toxicity and promising local control and survival. More stringent mediastinal staging is recommended in the future.
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P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.07-014 - Does Prophylactic Cranial Irradiation Improve Overall Survival of Elderly Patients with Limited-Stage Small Cell Lung Cancer? (ID 2967)
09:30 - 09:30 | Author(s): R.U. Komaki
- Abstract
Background:
Prophylactic cranial irradiation (PCI) has led to improved overall survival (OS) for patients with small cell lung cancer (SCLC) that has responded completely to chemotherapy and thoracic radiotherapy. However, whether PCI is indicated for elderly patients remains unclear.
Methods:
We reviewed 658 patients with limited-stage SCLC treated in 1986-2009 at a single institution with definitive concurrent chemoradiation to a total radiation dose of 45-70 Gy. Variables investigated for possible association with OS included patient sex, age, ethnicity, Karnofsky performance status (KPS) score, year of diagnosis and treatment period (1986-1999 vs. 2000-2009), tumor size, radiation dose, cycles of induction chemotherapy, use of intensity-modulated-radiation-therapy (IMRT), and fractionation. Groups were compared with chi-square tests for categorical variables or medians tests for continuous variables. Kaplan-Meier estimates were constructed for overall survival (OS), disease-free survival (DFS), local-recurrence-free survival (LRFS), distant metastasis-free survival (DMFS).
Results:
Among 658 patients, 507 patients were <70 years old (Group A) and 151 patients were ≥70 years old (Group B). Median survival time was significantly longer in the younger group (25.6 months vs. 20.3 months, P=0.007), but no differences were found in DFS, LRFS, or DMFS time by age. Of the 151 patients aged ≥70 years (54 of whom received PCI and 89 did not), those treated in 2000-2009 (vs. 1986-1999) had better brain MFS than those treated in 1986-1999 (P=0.048); those who received PCI had better brain MFS than those who did not (P=0.033). Multivariate analysis showed that among patients aged ≥70, receiving PCI, not receiving induction chemotherapy, and local-regional control were associated with fewer brain metastases (for PCI, subdistribution hazard ratio [SHR]=0.40, 95% confidence interval [CI] 0.17-0.95, P=0.037; for induction chemotherapy, SHR=0.43, 95% CI=0.19-0.96, P=0.039; and for local-regional failure, SHR=0.996, 95% CI=0.993-0.998, P=0.001). Among patients ≥70, receipt of PCI seemed to have been associated with better OS for those with small-volume disease (primary+nodal disease <5 cm, P=0.0545) but not for those with larger-volume disease (P=0.7387).
Conclusion:
Patients aged ≥70 years with small-volume limited-stage SCLC seemed to show a benefit in OS from the use of PCI, but those with larger-volume disease did not. Improved brain MFS was associated with use of PCI, no induction chemotherapy, and locoregional control.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-065 - PET Tumor Response by PERCIST Predicts Local-Regional Control in Locally Advanced NSCLC after Concurrent Chemoradiotherapy with Erlotinib (ID 1242)
09:30 - 09:30 | Author(s): R.U. Komaki
- Abstract
Background:
Assessing response of locally advanced non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy by computed tomography (CT) can be complicated by treatment-related pneumonitis or fibrosis. Hypothesizing that measurements of tumor response by [18]F-fluorodeoxyglucose standardized uptake values (SUVs) on positron emission tomography (PET) are more reliably associated with treatment outcomes than those by CT, we compared outcomes and responses according to PET SUV vs. CT among patients in a phase II study of erlotinib+chemoradiation for stage III NSCLC.
Methods:
Trial 2005-1023 enrolled 46 patients in 2007–2010; patients received 63 Gy in 35 fractions over 7 weeks with daily erlotinib and weekly paclitaxel-carboplatin. Tumor response was assessed on diagnostic CT scans with contrast or CT from PET-CT and scored according to RECIST 1.1. Tumor response was also assessed by PERCIST 1.0 (based on SUV) as follows: complete response (CR), disappearance of all measurable tumors; partial response (PR), ≥30% reduction in the sum of SUVs of target lesions; progressive disease (PD), ≥30% increase in the sum of SUVs of target lesions; and stable disease (SD), insufficient change in SUV to qualify for PR or PD. The longest diameter of measurable primary lesions and the short axis of measurable lymph nodes were measured. All non-target lesions were also measured. Two-sided Pearson’s chi-square tests were used to assess frequency associations. Overall survival (OS) and local-regional control (LRC) rates were assessed from treatment start by Kaplan-Meier analysis and log-rank tests; P≤0.05 indicated significance.
Results:
One patient did not have CT and PET after treatment. For the 45 evaluable patients, best response by PET-CT at 6 months after treatment was CR for 15 patients (33%), PR for 19 (42%), SD for 0, PD for 4 (9%), and not available due to did not have baseline or post treatment PET for 7 (16%). Best response by CT at 6 months was CR for 11 (24%), PR for 27 (60), SD for 3 (7%), and PD for 4 (9%) (P<0.001). The 3 patients with SD by CT all died within 7 months after treatment; the 4 patients with PD had new distant metastases. Four-year OS was associated with best overall response on both PET and CT at 6 months (P<0.05) and at 1 year (P<0.05). LRC was associated with best overall response on PET (P<0.01) and best primary tumor response on PET (P<0.05) at 6 and 12 months. Lymph node response was not associated with OS or LRC by PET or CT.
Conclusion:
The CR rate was higher with PET than with CT. Tumor response at 6 months by PET or CT predicted treatment outcomes after chemoradiotherapy for stage III NSCLC. The best overall and primary tumor response by PET within 6 months after treatment was more reliably associated with LRC than was response on CT because of difficulty to assess response due to pneumonitis/lung fibrosis.
