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PACIFIC: shifting tides in the treatment of locally advanced non-small cell lung cancer.

ABSTRACT: The treatment paradigm of stage III, unresectable non-small cell lung cancer (NSCLC) has had few advancement since concurrent chemoradiotherapy was established as standard of care treatment. Despite modifications to radiotherapy, chemotherapy and surgical approaches, loco-regional and distant relapse remain high, which unfortunately has translated to poor survival outcomes. The PACIFIC study introduced immunotherapy to the domain of stage III NSCLC and has emerged as the fourth pillar in cancer treatment for these patients. The positive results of the study have excited both the radiation and medical oncology communities, demonstrating improvements in overall and progression-free survival (PFS). In this review, we discuss the details and impacts of the PACIFIC study, as well as the future implications for the treatment of stage III NSCLC.

SUBMITTER: Bang A

PROVIDER: S-EPMC6795572 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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PACIFIC: shifting tides in the treatment of locally advanced non-small cell lung cancer.

Bang Andrew A Schoenfeld Jonathan D JD Sun Alexander Y AY

Translational lung cancer research 20190901 Suppl 2

The treatment paradigm of stage III, unresectable non-small cell lung cancer (NSCLC) has had few advancement since concurrent chemoradiotherapy was established as standard of care treatment. Despite modifications to radiotherapy, chemotherapy and surgical approaches, loco-regional and distant relapse remain high, which unfortunately has translated to poor survival outcomes. The PACIFIC study introduced immunotherapy to the domain of stage III NSCLC and has emerged as the fourth pillar in cancer ...[more]

PMID: 31673518

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Project description:BackgroundWe have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC).Materials and methodsBaseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy).ResultsFollowing re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values.ConclusionsCardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.

Project description:BackgroundWe aimed to characterize the outcomes of sleeve resection after neoadjuvant chemoimmunotherapy for the treatment of non-small cell lung cancer (NSCLC), including perioperative and oncologic outcomes, and to identify any impact of operative approach on resultant findings.MethodsWe identified patients with NSCLC who underwent sleeve resection after ≥2 cycles of neoadjuvant chemoimmunotherapy between May 2019 and April 2021 and retrospectively reviewed clinical records. Perioperative data were collected and compared between video-assisted thoracoscopic surgery (VATS) (n=8) and thoracotomy (n=15) groups. Immunohistochemistry (IHC) scores were compared between tumors with and without major pathological response (MPR).ResultsTwenty-three patients met inclusion criteria, with clinical stages as follows: IB, 2 (8.7%); IIIA, 14 (60.9%); and IIIB, 7 (30.4%). Treatment-related adverse events (TRAE) were recorded in 17 patients (73.9%), including anemia and neutropenia, with no patients exhibiting serious TRAE. Radiological evaluation revealed 5 (21.7%) patients with complete response (CR), 14 (60.9%) with partial response (PR), and 4 (17.4%) with stable disease (SD). Complete resection was accomplished for all patients. One VATS procedure was converted to thoracotomy due to extensive pleural adhesions. There were no significant differences in intraoperative blood loss (87.5±51.8 vs. 193.9±145.3 mL), operative time (198.8±79.7 vs. 225.5±55.0 min), number of lymph node examined (16.9±6.6 vs. 18.2±6.5), and hospital stay (5.5±2.8 vs. 9.2±11.2 days) between the VATS and thoracotomy groups (all P>0.05). Postoperative complications occurred in 3 patients, and 1 patient died of bronchopleural fistula (BPF) in the thoracotomy group. Complete pathological response (CPR) and MPR were achieved in seven (30.4%) and 13 (56.5%) patients, respectively. Both preoperative histopathology (P=0.024) and radiological response (P=0.002) were significantly associated with MPR. In postoperative specimens with MPR, the IHC scores of cluster of differentiation (CD)4, CD8, and CD20 were modestly higher, while programmed cell death receptor 1 (PD-1), lymphocyte-activation gene 3 (LAG3) and T cell immunoglobulin and ITIM domain (TIGIT) were lower compared with non-MPR specimens, albeit insignificantly.ConclusionsSleeve resection after neoadjuvant chemoimmunotherapy was feasible in patients with locally advanced NSCLC. Perioperative outcomes were comparable between the VATS and thoracotomy groups.

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PACIFIC: shifting tides in the treatment of locally advanced non-small cell lung cancer.

Publications

PACIFIC: shifting tides in the treatment of locally advanced non-small cell lung cancer.

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