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Salvage Therapy for Locoregional Recurrence After Stereotactic Ablative Radiotherapy for Early-Stage NSCLC.

ABSTRACT: Although isolated local (LRs) and regional recurrences (RRs) constitute a minority of post-stereotactic ablative radiotherapy (SABR) relapses, their management is becoming increasingly important as the use of SABR continues to expand. However, few evidence-based strategies are available to guide treatment of these potentially curable recurrences. On behalf of the Advanced Radiation Technology Committee of the International Association for the Study of Lung Cancer, this article was written to address management of recurrent disease. Topics discussed include diagnosis and workup, including the roles of volumetric and functional imaging as well as histopathologic methods; clinical outcomes after salvage therapy; patterns of recurrence after salvage therapy; and management options. Our main conclusions are that survival for patients with adequately salvaged LRs is similar to that for patients after primary SABR without recurrence, and survival for those with salvaged RRs (regardless of nodal burden or location) is similar to that of patients with de novo stage III disease. Although more than half of patients who undergo salvage do not develop a second relapse, the predominant pattern of second failure is distant, especially for RRs. Management requires rigorous multidisciplinary coordination. Isolated LRs can be managed with resection and nodal dissection, repeat SABR, thermal ablation, or systemic therapies. RRs can be treated with combined chemoradiotherapy, radiation or chemotherapy alone, or supportive services. Finally, regular and structured follow-up is recommended after post-SABR salvage therapy.

SUBMITTER: Brooks ED

PROVIDER: S-EPMC7058490 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Salvage Therapy for Locoregional Recurrence After Stereotactic Ablative Radiotherapy for Early-Stage NSCLC.

Brooks Eric D ED Verma Vivek V Senan Suresh S De Baere Thierry T Lu Shun S Brunelli Alessandro A Chang Joe Y JY

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20191109 2

Although isolated local (LRs) and regional recurrences (RRs) constitute a minority of post-stereotactic ablative radiotherapy (SABR) relapses, their management is becoming increasingly important as the use of SABR continues to expand. However, few evidence-based strategies are available to guide treatment of these potentially curable recurrences. On behalf of the Advanced Radiation Technology Committee of the International Association for the Study of Lung Cancer, this article was written to add ...[more]

PMID: 31712134

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Project description:ImportanceStereotactic ablative radiotherapy (SABR) is first-line treatment for patients with early-stage non-small cell lung cancer (NSCLC) who cannot undergo surgery. However, up to 1 in 6 such patients will develop isolated local recurrence (iLR) or isolated regional recurrence (iRR). Little is known about outcomes when disease recurs after SABR, or about optimal management strategies for such recurrences.ObjectiveTo characterize long-term outcomes for patients with iLR or iRR after SABR for early-stage NSCLC with the aim of informing treatment decision making for these patients with potentially curable disease.Design, setting, and participantsIn this cohort study, a retrospective review was conducted of 912 patients prospectively enrolled in an institutional database at a tertiary cancer center from January 1, 2004, through December 31, 2014.Main outcomes and measuresOverall survival, progression-free survival, recurrence patterns, demographics, salvage techniques, patterns of salvage failure, and toxic effects.ResultsOf the 912 patients in the study (456 women and 456 men; median age, 72 years [range, 46-91 years]), 756 (82.9%) had T1 tumors at initial diagnosis; 502 tumors (55.0%) were adenocarcinomas and 309 tumors (33.9%) were squamous cell carcinomas. Of 912 patients with early-stage I to II NSCLC who received definitive SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions), 102 developed isolated recurrence (49 with iLR and 53 with iRR), and 658 had no recurrence. Median times to recurrence after SABR were 14.5 months (range, 1.5-60.8 months) for iLR and 9.0 months (range, 1.9-70.7 months) for iRR; 39 of 49 patients (79.6%) with iLR and 48 of 53 patients (90.6%) with iRR underwent salvage with reirradiation, surgery, thermal ablation, or chemotherapy. Median follow-up times for patients with iLR or iRR were 57.2 months (interquartile range, 37.7-87.6 months) from initial SABR and 38.5 months (interquartile range, 19.9-69.3 months) from recurrence. Rates of overall survival at 5 years from initial SABR were no different between patients with iLR and salvage treatment (57.9%) and patients with no recurrence (54.9%; hazard ratio, 0.89; 95% CI, 0.56-1.43; P = .65) but were lower for patients with iRR and salvage treatment (31.1%; hazard ratio, 1.43; 95% CI, 1.00-2.34; P = .049). Patients receiving salvage treatment had longer overall survival than patients who did not (median, 37 vs 7 months after recurrence; hazard ratio, 0.40; 95% CI, 0.09-0.66; P = .006). Twenty-four of 87 patients (27.6%) who received salvage treatment for iLR or iRR subsequently developed distant metastases. No patient experienced grade 5 toxic effects after salvage treatment.Conclusions and relevanceLife expectancy after salvage treatment for iLR was similar to that for patients without recurrence, but survival after salvage treatment for iRR was similar to that of patients with stage III NSCLC. Patients who received salvage treatment had significantly improved survival. Because salvage treatment for iLR or iRR was based on a consistent multidisciplinary approach, this may help in clinical decision making.

Project description:ObjectivesOur goal was to evaluate stereotactic ablative radiotherapy (SABR) as a salvage option for isolated recurrence of NSCLC in the lung parenchyma after definitive treatment of stage I to III disease.MethodsPatients who had histologically confirmed, positron emission tomography-staged, isolated NSCLC recurring locally or metastasis in the lung parenchyma (≤3 cm, suitable for SABR) after previous definitive treatment were prospectively enrolled in this trial and treated with volumetric, image-guided SABR to 50 Gy in four fractions. Patients were then followed with computed tomography or positron emission tomography/computed tomography. Primary end points included the pattern of failure after salvage SABR, overall survival (OS), and progression-free survival (PFS).ResultsFifty-nine patients with recurrent disease were treated with salvage SABR. The median age was 70 years (range 45-86 years), and the median follow-up time after salvage SABR was 58.3 months. Re-recurrence after salvage SABR developed in 19 patients (32%). Measuring from the date of salvage SABR, the estimated 5-year rates of local, regional, and distant failure were 5.2%, 10.3%, and 22.4%, respectively; the estimated PFS was 46.2% at 3 years and 41.1% at 5 years; and the OS rates were 63.5% at 3 years and 56.5% at 5 years. A high post-SABR neutrophil-to-lymphocyte ratio was found to predict poor survival. Grade 3 treatment-related adverse events developed in three patients (5%). No patient had a grade 4 or 5 event.ConclusionOur study showed that salvage SABR provides excellent 5-year OS, local control, and PFS rates with minimal toxicity for patients with isolated NSCLC recurrence in the lung parenchyma. These results are striking and comparable to historically reported outcomes of patients with primary early-stage NSCLC treated with definitive SABR. SABR appears to be a very effective and safe salvage option for patients with isolated lung parenchyma recurrent disease after definitive treatment and should be considered along with surgery as a potential first-line option for patients with local lung parenchymal recurrent disease.

Project description:PurposeTo explore whether prostate motion mitigation using the rectal distension-mediated technique is safe and effective in stereotactic ablative radiation therapy (SABR) salvage treatment of intraprostatic cancer recurrences following initial radiotherapy for primary prostate cancer.Materials and methodsBetween July 2013 and December 2020, 30 patients received salvage SABR for 68Ga- PSMA-11 PET/CT-detected intra-prostatic relapses. Median time from primary RT to salvage reirradiation was 70.2 (IQR, 51.3-116.0) months. Median PSA at retreatment was 3.6 ng/mL (IQR, 1.9-6.2). Rectal distension-mediated SABR was achieved with a 150-cm3 air-inflated endorectal balloon and a Foley catheter loaded with 3 beacon transponders was used for urethra visualization and on-line tracking. MRI-based planning employed a 2-mm expansion around the planned target volume (PTV), reduced to 0-mm at the interface with critical organs at risk (OARs). Volumetric Modulated Arc Therapy (VMAT) permitted a 20% dose reduction of the urethra. VMAT simultaneous integrated boost (SIB) of the dominant intraprostatic lesion was deployed when indicated. Median SABR dose was 35 Gy (7 Gy per fraction over 5 consecutive days; range 35-40 Gy). Toxicity assessment used CTCAE v.4 criteria.ResultsMedian follow-up was 44 months (IQR, 18-60). The actuarial 3- and 4-year biochemical relapse free survival was 53.4% and 47.5%, respectively. Intraprostatic post-salvage relapse by PSMA PET/CT was 53.3%. Acute grade 2 and 3 genitourinary (GU) toxicities were 20% and 0%, respectively. There were no instances of acute grade ≥2 rectal (GI) toxicity. Late grade 2 and 3 GU toxicities occurred in 13.3% and 0% of patients, respectively. There were no instances of grade ≥2 late rectal toxicity. Patient-reported QOL measures showed an acute transient deterioration in the urinary domain 1 month after treatment but returned to baseline values at 3 months. The median IPSS scores rose over baseline (≥5 points in 53% of patients) between month 6 and 12 post-treatment as a result of urinary symptoms flare, eventually receding at 18 months. The bowel domain metrics had no appreciable changes over time.ConclusionPursuit of local control in intraprostatic failures is feasible and can be achieved with an acceptably low toxicity profile associated with effective OAR sparing.

Dataset Information

Salvage Therapy for Locoregional Recurrence After Stereotactic Ablative Radiotherapy for Early-Stage NSCLC.

Publications

Salvage Therapy for Locoregional Recurrence After Stereotactic Ablative Radiotherapy for Early-Stage NSCLC.

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