When controlling for tumor volume and/or dimensions and other independent prognostic factors, patients with locally advanced NSCLC who were not candidates for concurrent CRT benefited from a radiation dose > 66 Gy versus < 60 Gy with improved OS and reduced LF. An increased radiation dose did not appear to affect the incidence of DF.
Background
Radiation with platinum-based chemotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic mutations are associated with response to chemoradiation therapy.
Methods
We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing.
Results
110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between
AKT2
mutations and decreased local-regional tumor control and overall survival (hazard ratios [HR] 12.5 and 13.7,
P
= .003 and
P
= .003, respectively). Analyses restricted to loss-of-function mutations identified
KMT2C
and
KMT2D
deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0,
P
< .001 and
P
< .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32,
P
= .049).
Conclusions
This study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in
AKT2, KMT2C,
and
KMT2D
as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information.
46 patients (0.63%) received salvage surgery out of 7,290 patients underwent surgery for primary lung cancer at Median follow-up time was 24.5 months (range, 2-157.6). Of 46 patients evaluated, 30 (65.2%) were men, the median age was 64.5 years (range, 20-78 years), 22 (47.8%) underwent chemotherapy, 18 (39.1%) underwent resection after definitive chemoradiotherapy, 3 (6.5%) underwent resection after SBRT and 3 (6.5%) underwent resection after PBT. The number of patients undergoing salvage surgery has increased in recent years: 9 patients were between 2000 and 2009, whereas 37 patients were between 2010 and 2018. Method of surgical resection was as follows: 28 lobectomies (2 bilobectomy, 15 right upper, 1 right middle, 6 right lower, 2 left upper, 2 left lower), 10 pneumonectomies (left:right¼7:3). One patient received a wedge resection, and one recieved wedge resection with chest well resection, and 2 segmentectomy and lymphadectomy for residual lymph nodes respectively. A complete resection (R0) was achieved in 42 cases (91.3%). Postoperative complications were observed in 3 patients (6.5%): prolonged air leakage, bronchopleural fistula, and atrial fibrillation. There were no post-operative deaths within 30 days after surgery. The five-year progression free and overall survival rate after surgical resection was 39.1% (95% CI.: 19.9-57.9) and 64.1% (95% CI.: 39.3-80.9), respectively. Conclusion: The frequency of salvage surgery after initial treatment has been increasing possibly due to a better treatment course using novel medical and radiation oncology technique. Salvage pulmonary resections demonstrated acceptable morbidity and mortality with promising long-term efficacy in selected patients.
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