Systemic and Radiation Therapy Approaches for Locally Advanced Non–Small-Cell Lung Cancer

The treatment for locally advanced non–small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non–small-cell lung cancer.

Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy

Background To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). Methods We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). Results A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552–2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621–5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139). Conclusions Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.

CTNI-19. CONCURRENT CHEMORADIATION AND TUMOR TREATING FIELDS (TTFields, 200 kHz) FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF DISTANT RECURRENCE

INTRODUCTION: Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) along with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. Secondary analysis of EF14 trial demonstrated TTFields treatment may increase the rate of distant recurrence. We report our experience evaluating areas of progression in our pilot clinical trial of concurrent chemoradiation with TTFields. METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from primary enhancing lesion. RESULTS: A total of 30 patients were enrolled on the trial. Twenty were male, and ten were female, with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 11.6 months (1.7-22.1 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Twenty patients (66.7%) had progression, with median PFS of 9.1 months (range 1.6 to 12.9 months). Five patients (26%) of patient presented with distant recurrence, with median distance from primary lesion of 5.1 cm (2.26-9.12 cm). One infratentorial progression was noted. Another patient transferred care and location of progression is unknown. CONCLUSIONS: Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may have increased incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding.

RADT-22. CONCURRENT TTFIELDS (200 KHZ) WITH CHEMORADIATION FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF PSEUDOPROGRESSION: ANALYSIS OF A PILOT CLINICAL TRIAL

OBJECTIVE The standard of care for the adjuvant treatment of glioblastoma is concurrent chemoradiation, maintenance temozolomide, and Tumor Treating Fields (TTFields). TTFields may reversibly impact the blood-brain barrier, most significantly at 100 kHz. We hypothesized that this may increase the rate of pseudoprogression (PsP) in patients who receive concurrent chemoradiation with TTFields (200 kHz). METHODS This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Patients with newly diagnosed glioblastoma, age ≥ 18 years, and KPS ≥ 60 were eligible. They received concurrent temozolomide (75 mg/m2), scalp-sparing radiation (60 Gy in 30 fractions), and TTFields (200 kHz). Radiation was delivered through the TTFields arrays. PsP was defined as radiographic progression of enhancing lesions without clinical decline that improved or remained stable upon subsequent imaging. The rate of PsP was determined by an evaluation of the 2nd MRI at our multidisciplinary tumor board after the completion of trimodality treatment. These findings were confirmed with official radiology reports. RESULTS 30 patients were enrolled. Of these, 29 had imaging available for evaluation. Male-to-female ratio was 20:10. Median follow-up was 11.6 months (1.6-22.4 months), median age was 58 years (19-77 years), and median KPS was 90 (70-100). 20 (66.7%) patients had unmethylated and 10 (33.3%) had methylated MGMT promotor. Median time from surgery to initiation of radiation was 34 days (26-49 days). Median time from completion of trimodality treatment to 2nd follow-up MRI was 90 days (29-109 days). 15/29 (51.7%) patients had PsP. Patients with methylated and unmethylated MGMT promotor had 50.0% (5/10) and 52.6% (10/19) rates of progression respectively. CONCLUSIONS 51.7% of the patients who received concurrent chemoradiation with TTFields demonstrated PsP. The incidence is greater than historical reports. However, these findings should be explored in larger cohorts as this study was limited by a small sample size.