Local-regional control (LRC) rates for non-small cell lung cancer after chemoradiotherapy were studied (using two different definitions of LRC) for the association between LRC and survival.
Seven ...legacy Radiation Therapy Ooncology Group trials of chemoradiotherapy for locally advanced non-small cell lung cancer were analyzed. Two different definitions of LRC were studied: (1) freedom from local progression (FFLP-LRC), the traditional Radiation Therapy Oncology Group methodology, in which a failure is intrathoracic tumor progression by World Health Oorganization criteria; and (2) response-mandatory (strict-LRC), in which any patient not achieving at least partial response was considered to have failure at day 0. Testing for associations between LRC and survival was performed using a Cox multivariate model that included other potential predictive factors.
A total of 1390 patients were analyzed. The LRC rate at 3 years was 38% based on the FFLP-LRC definition and 14% based on the strict-LRC definition. Performance status, concurrent chemotherapy, and radiotherapy dose intensity (biologically equivalent dose) were associated with better LRC (using either definition). With the strict-LRC definition (but not FFLP-LRC), age was also important. There was a powerful association between LRC and overall survival (p, 0.0001) on univariate and multivariate analyses. Age, performance status, chemotherapy sequencing, and biologically equivalent dose were also significantly associated with survival. Histology and gender were also significant if the strict-LRC model was used.
LRC is associated with survival. The definition of LRC affects the results of these analyses. A consensus definition of LRC, incorporating functional imaging and/or central review, is needed, with the possibility of using LRC as a surrogate end point in future trials.
12011 Background: NRG-CC003, a phase II/III study, randomized 393 patients with small cell lung cancer to prophylactic cranial irradiation (PCI) with or without Hippocampal Avoidance (HA). ...“Hopefulness” is a cognitive construct based on 3 components: goals; pathways to reach those goals; and agency (i.e., motivation to embark on the pathway). Hope can be measured with validated instruments. Since hope is cognitive in nature, the existence of a “hope center” in the brain -- most likely in the hippocampus -- has been hypothesized. One exploratory objective of NRG-CC003 posited that if hope levels (measured pre- and post-PCI) were better maintained in patients randomized to PCI+HA (in comparison to patients treated by PCI without hippocampal protection), then the hippocampus would, indeed, be implicated as part of the mechanism of hopefulness. Methods: In both arms, PCI consisted of 10 fractions of 2.5 Gy. The Adult Hope Scale (AHS) was administered at time-zero and at 6-months. With regard to patient reported outcome (PRO) measures, the EORTC QLQ-C30 was administered at baseline and then at 3, 6-, 12-, 18- and 24-month intervals. Comparisons of AHS scores by arm were made using Wilcoxon-Mann-Whitney tests, and correlation of AHS with EORTC QLQ-C30 by Pearson correlation coefficients. Results: Approximately 95% of patients completed the AHS at baseline and 67% filled out the questionnaire at 6-months which paralleled the completion rates of the conventional tools for QOL and neurocognition that were employed in the study. When comparing hope levels (change from baseline to 6 months) there was no significant difference (p > 0.05) between the two arms of the trial (PCI vs PCI + HA). There was a significant correlation for the components of hopefulness with QOL; specifically, between change in agency score and QLQ-C30 global health status (p < 0.0001) as well as between change in pathways score and QLQ-C30 global health status (p = 0.022). Conclusions: It is feasible to study hopefulness in the context of prospective trials conducted within the NCTN. The hippocampus could not be implicated as a critical structure in a central pathway that coordinates hopefulness. Whether these data categorically refute the “hope-hippocampal hypothesis” will be discussed vis-à-vis several caveats (e.g., selection of AHS; presence of sufficient cognitive reserve post-irradiation; adequacy of the dose-delta between the 2 arms to cause differential levels of damage to the purported hope center). For the first time, a validated tool prospectively established a relationship between hope and quality of life among patients with cancer. Given previous NRG studies correlating QOL with oncologic endpoints (e.g., local control and survival), modelling will be carried out to determine if hope mediates, results from, or is associated with these endpoints. Clinical trial information: NCT02635009 .
Abstract
PURPOSE
Previous analysis of NRG-CC001 suggested pre-treatment WMI volume was a significant imaging-biomarker predictor of post-treatment neurocognitive decline at 4-and 12-months following ...HA-WBRT+Memantine. This suggested patients with greater pre-treatment WMI were more susceptible to neurocognitive decline, specifically when undergoing HA-WBRT, but not standard-WBRT. The current analysis examined the relationship between changes in MR-determined WMI and NCF 6-months following WBRT+memantine+/-HA.
METHODS
NCF-testing was performed at baseline, 2, 4, 6, and 12 months post-WBRT, and included Hopkins Verbal Learning Test–Revised (HVLT-R), Trail Making Test (TMT) Parts A and B, and Controlled Oral Word Association (COWA). Pre-treatment WMI was measured by FLAIR-volume corrected for whole brain volume and corrected for the FLAIR volume associated with metastases (met vol) (FLAIR-volume/(whole brain volume–met-vol). Pearson correlation coefficients were used to assess the correlation between pre-treatment WMI and change from baseline to 6-months for each standardized NCF score.
RESULTS
Of the 518 randomized patients, 443 (217 patients WBRT+Memantine and 226 HA-WBRT+Memantine) had WMI data available at baseline, and of those, 162 patients (89 patients WBRT+Memantine and 73 HA-WBRT+Memantine) had both baseline and 6-month imaging available. For these patients, there was only a trend toward significance for change in corrected FLAIR-volume from baseline to 6-months (p = 0.174) but no significant change in met-vol (p = 0.438) or whole brain volume (p = 0.977). The change in standardized TMT Part A and B and the change in composite 6-month change scores were moderately correlated with change in corrected FLAIR volume adjusted for met-vol but only in the WBRT+Memantine arm (rho=-0.35, -0.34, -0.39 and p-value = 0.003, 0.006, 0.001).
CONCLUSIONS
Despite an increase in post-WBRT MR-WMI at 6-months, analysis did not show strong correlation between NCF and MR-WMI as determined by FLAIR-volume change between baseline and 6-months. Similar analyses are underway for the NRG-CC003 imaging data.
5533
Background: NRG-RTOG 1203 reported that intensity-modulated radiation therapy (IMRT) reduced patient-reported GI and GU toxicities in cervical/endometrial cancer patients receiving adjuvant RT, ...as compared to standard whole field pelvic RT (WPRT). We conducted a secondary analysis of patient-reported sexual function (PR-SF) to compare this endpoint among treatment groups and identify factors associated with sexual dysfunction. Methods: Patients on NRG-RTOG 1203 were randomly assigned to WPRT vs. IMRT and completed the PRO-CTCAE for GI toxicity and the cervical cancer FACT-Cx at baseline, week 5 of RT, and at 4-6 weeks, 1-year, and 3-years post-RT. Patient responses to FACT-Cx sexual function questions were analyzed. The between arm frequency and severity of responses were tested using chi-square. PR-SF was compared with PRO-CTCAE GI toxicity using chi-square. A repeated measures logistic regression model was used to determine the impact of clinical/treatment factors on sexual function by dichotomizing the responses. Results: Of the 279 patients included for primary analysis, 236 (85%) completed PR-SF questions; 125 (53%) in the WPRT arm and 111 (47%) IMRT. There were no significant differences in PR-SF between treatment groups (p>0.05). PR-SF improved for both groups post-RT, except responses to “my vagina feels too narrow or short” worsened (Table). Women without abdominal pain interference at 4-6 weeks post-RT were less likely to fear sex (74.2% vs. 25.8%, P=0.03) and more likely to like their body appearance at 1 year (95.7% vs. 4.3%, P<0.01) compared to women with interference. Women liked the appearance of their body less during RT vs. at baseline (OR 1.95, 95% CI 1.04-3.64, P=0.04). Women were less interested in sex during RT in both arms (WPRT: OR 3.61, 95% CI 1.40-9.34; IMRT: OR 3.96, 95% CI 1.02-15.34) and at 4-6 weeks post-RT for IMRT (OR 3.16, 95% CI 1.14-8.72) vs. at baseline. Conclusions: PR-SF was similar between treatment groups. PR-SF during and post-RT was not significantly reduced compared to baseline with the exception of patients with abdominal pain interference, who had significantly worse PR-SF at 4-6 weeks and 1-year post-RT. Clinical trial information: NCT01672892 . Table: see text
Reply to T. Sio et al Bezjak, Andrea; Paulus, Rebecca; Gaspar, Laurie E. ...
Journal of clinical oncology,
10/2019, Letnik:
37, Številka:
29
Journal Article
Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic ...radiation for resectable N2+ stage IIIA non–small cell lung cancer.
Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non–small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here.
One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9).
Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.
8513
Background: In advanced non-small cell lung cancer (NSCLC), high Programmed-Death-1 Ligand (PD-L1) (>50%) expression demonstrate superior response and survival with immune checkpoint inhibitors ...compared to chemotherapy. We hypothesize that it is safe and feasible to substitute durvalumab instead of chemotherapy concurrently with radiotherapy (RT) in patients with Locally Advanced-NSCLC (LA-NSCLC) and high PD-L1. Methods: NRG-LU004 (NCT03801902) is a Phase I study for patients with stage II-III unresectable or inoperable, LA-NSCLC with PD-L1> 50% (Dako 22C3 or Ventana SP263) expression. There were safety and expansion phases with a primary endpoint of safety. Patients started with 1500 mg durvalumab Q4 weeks and thoracic RT within 2 weeks from 1
st
infusion. Durvalumab continued once a month up to 1 year. In the safety cohort, 6 patients in cohort 1 were treated with accelerated fractionated RT (ACRT) to 60 Gy in 15 fractions, followed by a required safety hold for 90 days. During cohort 1 safety hold, cohort 2 patients were treated with conventional RT 60 Gy in 30 fractions (CONV) followed by a 60-day safety hold. A cohort advanced to the expansion phase to enroll 6 more patients if safety criteria (0-1 patients with a dose limiting toxicity DLT) were met. If both cohorts were deemed safe, patients would be randomized 1:1 to ACRT or CONV with safety defined as < 4 of 12 evaluable patients per arm experiencing a DLT. Feasibility was defined as at least 80% of patients in each arm receiving at least 80% of the planned dose of durvalumab during the first 8 weeks. Results: 24 evaluable patients enrolled between January 2019 and June 2021. No DLTs were reported in cohort 1, and 1 (unrelated bronchopulmonary hemorrhage leading to discontinuation of durvalumab) in cohort 2. Both safety cohorts advanced to the expansion phase. All but one patient (CONV) received RT per protocol/with an acceptable variation. At the time of analysis, 24% had received all 13 cycles of durvalumab. For the ACRT cohort, there were 4 grade 3, 1 grade 4 (lymphopenia), and 1 grade 5 AE (lung infection, assessed as unrelated to therapy). For CONV, there were 8 grade 3, 0 grade 4, and 1 grade 5 AE (respiratory failure, unrelated to therapy). For feasibility, 10 of 12 (85%) patients in the ACRT cohort received the second dose of durvalumab (2 not received due to shingles and unrelated death), while 9 of 12 (75%) of the CONV cohort received the second dose (reasons for not receiving: viral hepatitis, bronchopulmonary hemorrhage, and respiratory failure, all assessed as unrelated to therapy). Conclusions: Chemotherapy-free thoracic RT approaches (ACRT or CONV RT) are safe, when given with concurrent durvalumab in patients with PD-L1 high LA-NSCLC. A trial to compare immunoradiotherapy and consolidation durvalumab to standard chemoradiation and consolidation durvalumab is planned. Clinical trial information: NCT03801902.
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