Sarcoma in patients with Lynch syndrome and response to immunotherapy.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant genetic predisposition to multiple malignancies and is characterized by deficient DNA mismatch repair. Increased incidence of sarcomas is not formally ascribed to LS; however, increasing evidence suggests a preponderance of these malignancies in affected families. Sarcomas typically possess a low tumor mutational burden and incite a poor immune infiltrate, thereby rendering them poorly responsive to immunotherapy. METHODS: We searched the University of California, Los Angeles (UCLA) sarcoma program database for patients with a diagnosis of sarcoma and LS from 2016 to 2023. Three such patients were identified and all three were treated with PD1 blockade. RESULTS: We present three cases of LS-associated sarcomas (two soft tissue sarcoma and one osteosarcoma) with increased tumor mutational burdens. These patients were each treated with an anti-PD1 antibody and experienced a response far superior to that reported for non-LS-associated sarcomas. CONCLUSIONS: Increased mutational burden and immune infiltrate are observed for sarcomas associated with LS. Although unselected patients with sarcoma have demonstrated poor response rates to immunotherapy, our findings suggest that patients with Lynch-associated sarcomas are more likely to respond to treatment with anti-PD1. These patients should be given consideration for immunotherapy.

Cancer-Associated B Cells in Sarcoma.

Despite being one of the first types of cancers studied that hinted at a major role of the immune system in pro- and anti-tumor biology, little is known about the immune microenvironment in sarcoma. Few types of sarcoma have shown major responses to immunotherapy, and its rarity and heterogeneity makes it challenging to study. With limited systemic treatment options, further understanding of the underlying mechanisms in sarcoma immunity may prove crucial in advancing sarcoma care. While great strides have been made in the field of immunotherapy over the last few decades, most of these efforts have focused on harnessing the T cell response, with little attention on the role B cells may play in the tumor microenvironment. A growing body of evidence suggests that B cells have both pro- and anti-tumoral effects in a large variety of cancers, and in the age of bioinformatics and multi-omic analysis, the complexity of the humoral response is just being appreciated. This review explores what is currently known about the role of B cells in sarcoma, including understanding the various B cell populations associated with sarcoma, the organization of intra-tumoral B cells in tertiary lymphoid structures, recent trials in immunotherapy in sarcoma, intra-tumoral immunoglobulin, the pro-tumor effects of B cells, and exciting future areas for research.

Reduction of opioid use after orthopedic surgery: a scoping review.

BACKGROUND: The opioid epidemic is one of the biggest public health crises of our time, and overprescribing of opioids after surgery has the potential to lead to long-term use. The purpose of this review was to identify and summarize the available evidence on interventions aimed at reducing opioid use after orthopedic surgery. METHODS: We searched CENTRAL, Embase and Medline from inception until August 2019 for studies comparing interventions aimed at reducing opioid use after orthopedic surgery to a control group. We recorded demographic data and data on intervention success, and recorded or calculated percent opioid reduction compared to control. RESULTS: We included 141 studies (20 963 patients) in the review, of which 113 (80.1%) were randomized controlled trials (RCTs), 6 (4.3%) were prospective cohort studies, 16 (11.4%) were retrospective cohort studies, 5 (3.6%) were case reports, and 1 (0.7%) was a case series. The majority of studies (95 [67.4%]) had a follow-up duration of 2 days or less. Interventions included the use of local anesthetics and/or nerve blocks (42 studies [29.8%]), nonsteroidal anti-inflammatory drugs (31 [22.0%]), neuropathic pain medications (9 [6.4%]) and multimodal analgesic combinations (25 [17.7%]. In 127 studies (90.1%), a significant decrease in postoperative opioid consumption compared to the control intervention was reported; the median opioid reduction in these studies was 39.7% (range 5%-100%). Despite these reductions in opioid use, the effect on pain scores and on incidence of adverse effects was inconsistent. CONCLUSION: There is a large body of evidence from randomized trials showing the promise of a variety of interventions for reducing opioid use after orthopedic surgery. Rigorously designed RCTs are needed to determine the ideal interventions or combination of interventions for reducing opioid use, for the good of patients, medicine and society.

The Prevalence and Outcomes of Unexpected Positive Intraoperative Cultures in Presumed Aseptic Revision Knee Arthroplasty.

BACKGROUND: The prevalence and outcomes of unexpected positive intraoperative cultures (UPC) in presumed aseptic revision total knee arthroplasty (TKA) are unclear. The purpose of this study was to determine the prevalence of UPC and infection-free implant survival in this patient population. Secondly, we aimed to compare the infection-free implant survival between cohorts based on number of UPCs and antibiotic treatment. METHODS: We reviewed our institutional database from 2006 to 2019 for all TKA revisions (n = 1795) to identify all presumed aseptic TKA revisions with intraoperative culture(s). After exclusions, 775 revisions were eligible and those with UPC were included in the Kaplan-Meier analysis to determine infection-free implant survival for the cohorts. RESULTS: The prevalence of UPC was 9.8%. The 2- and 5-year infection-free survival was 97.4% and 95.3%, respectively. The 5-year infection-free survival from the same microorganism as the UPC was 98.7%. Infection-free survival was similar for the 1 versus ≥2 UPC cohorts (P = .416), however was poorer for the cohort treated with antibiotics (P = .021). Only one of 3 subsequent PJI-related implant failures was caused by the same microorganism (polymicrobial) as the UPC. There were no subsequent infections in patients with a single UPC not treated with antibiotics. CONCLUSIONS: The prevalence of UPC was 9.8% and the infection-free implant survival is excellent. Infection-free survivorship from PJI caused by the same UPC microorganism is outstanding. Comparisons between cohorts must be interpreted with caution due to study limitations. A single UPC in patents without other signs of infection does not require antibiotic treatment. LEVEL OF EVIDENCE: IV.

Administration of Adenosine Triphosphate Provides Additional Value Over Programmed Electrophysiologic Study in Confirmation of Successful Ablation of Atrioventricular Accessory Pathways.

Objectives: To study the benefit of adenosine triphosphate (ATP) in evaluating ablation endpoints of accessory pathways (AP) and subsequent long-term prognosis. Methods: We reviewed consecutive patients with supraventricular tachycardias due to APs that underwent radiofrequency catheter ablation (RFCA) from January 2016 to September 2018 in our center. The patients were divided into two groups: the ATP group (who had passed both the ATP test and PES after ablation as the endpoint) and the non-ATP group (who had passed PES only after ablation as the endpoint). We reviewed the patients' intra-cardiac electrograms and analyzed their long-term outcomes. Results: In total, 1,343 patients underwent successful RFCA. There were 215 patients in the ATP group with one lost to follow-up. There were 1,128 patients in the non-ATP group with 39 lost to follow-up. Twenty-three patients in the ATP group demonstrated additional electrophysiological entities due to ATP administration, including reappearance of the ablated APs in 16 patients, discovery of PES-undetected APs in 5, induction of atrial fibrillation in 5, premature atrial contractions in 1, and premature ventricular contractions in another. During the 7 to 39 months (average 24.4 ± 9.5 months) follow-up, the recurrence rate was 8.41% (18/214) in the ATP group and 6.80% (74/1,084) in the non-ATP group. In subjects with recurrence, 14 patients (14/18 = 77.8%) in the ATP group and 50 patients (50/74 = 67.6%) in the non-ATP group accepted redo ablations. Among the ATP-group, all the 14 redo APs were the old ones as before. Among the non-ATP-group, redo ablations confirmed that 39 APs were the old ones, while 20 APs were newly detected ones which had been missed previously. The difference in recurrent AP locations confirmed by redo procedures between the two groups was significant (p = 0.008). In the non-ATP group, 20 (40%) of redo cases were proven to have multiple APs, while 33 (3.3%) cases who did not suffer from recurrence had multiple APs. Existences of multiple APs in recurred cases were significantly higher than that in non-recurred ones in the non-ATP group (p < 0.001), while there was no such difference in the ATP group (p = 0.114). Conclusions: The existence of multiple APs was more common in recurrent cases if ATP was not used for confirmation of ablation endpoints. ATP probably has additional value over PES alone by detecting weak AP conductions. ATP can evoke atrial and ventricular arrhythmias.

Prevalence and Outcomes of Unexpected Positive Intraoperative Cultures in Presumed Aseptic Revision Hip Arthroplasty.

BACKGROUND: The prevalence and outcomes of unexpected positive cultures (UPCs) of specimens taken during presumed aseptic revision total hip arthroplasty (THA) are unclear. The purpose of this study was to determine the prevalence of UPC and infection-free implant survival in this patient population. Secondary aims included identifying factors associated with subsequent infection-related failure in patients with UPC. METHODS: We reviewed all THA revisions (n = 2,288) performed at our institution from 2006 to 2019. Presumed aseptic revision THAs with intraoperative culture(s) were eligible (n = 1,196), and those with UPC were included in a Kaplan-Meier analysis to determine the infection-free implant survival and in Cox regression analysis to identify factors associated with infection-related failure. RESULTS: UPC(s) were documented for 9.2% (110) of 1,196 aseptic THA revisions. The 2- and 5-year infection-free implant survival in the entire UPC cohort was 93.1% (95% confidence interval [CI] = 90.5% to 95.7%) and 86.8% (95% CI = 82.9% to 90.7%), respectively. The 2- and 5-year infection-free survival with failure due to infection with the same microorganism as identified in the UPC as the end point was 95.8% (95% CI = 93.7% to 97.9%) and 94.3% (95% CI = 91.7% to 96.9%), respectively. Subsequent infection-related failures caused by the same microorganism as identified in the UPC were more likely to occur after revisions with ≥2 UPCs than after those with 1 UPC (p = 0.024). Revision due to adverse metal reaction was a risk factor for subsequent infection-related failure (hazard ratio [HR] = 14.49, 95% CI = 2.69 to 78.04). Patients with a single UPC who were not treated with antibiotics had no subsequent periprosthetic joint infections (PJIs) caused by the same microorganism as identified in the UPC. CONCLUSIONS: The prevalence of UPC was 9.2%, and the infection-free implant survival in patients with UPC is encouraging. Implant survival free of PJI caused by the same microorganism as identified in the UPC was excellent. Aseptic revision for adverse metal reaction was a risk factor for subsequent PJI in patients with UPC. No patient with a single UPC who was not treated with antibiotics developed PJI caused by the UPC-identified microorganism, suggesting that in the absence of other signs of infection a single UPC does not warrant antibiotic treatment. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Esophageal contraction during cryoablation: A possible protective mechanism.

BACKGROUND: Contraction of the esophagus was observed during cryoablation for paroxysmal atrial fibrillation (PAF). The purpose of this study is to investigate the mechanism of esophageal contraction and the correlation between the contraction and esophageal thermal lesions. METHODS: This prospective study enrolled 64 patients with PAF undergoing second-generation cryoballoon (CB2) ablation for pulmonary vein isolation (PVI). During PVI for the left inferior pulmonary vein, contrast esophagography was performed before and during cryoablation. The sample population was divided into two groups: A (31 patients) and B (33 patients). Group A consisted of patients in whom the distal half of the CB was in proximity to the esophagus, while for group B the esophagus was away from the distal half of the CB. Esophageal contraction was recorded as a variation in the width of the esophageal lumen during PVI. Postablation esophageal endoscopy was done on all patients. RESULTS: The reduction in the width of the esophageal lumen in group A was greater than in group B during freezing (40.12 ± 23.24% vs 8.14 ± 10.35%, P < .001). Following endoscopy, no apparent esophageal lesion was detected in all patients. CONCLUSION: The extent of esophageal contraction is correlated with the positioning of the esophagus at the distal half of the CB. The findings of this study indicate that esophageal contraction during freezing may be a self-protective mechanism.

Treatment of atypical pacemaker-mediated tachycardia with ablation of the retrograde atrioventricular nodal pathway.

A 25-year-old runner received a single-lead, VDD pacemaker after ablation of AV nodal reentrant tachycardia complicated by intermittent AV block. The rate-adaptive AV delay algorithm (RAAV), which shortens the sensed AV interval (SAV) at faster atrial rates, was programmed to provide a physiologic SAV with exercise. She developed repetitive, atypical, long-RP pacemaker-mediated tachycardia (PMT) because the RAAV shortened the antegrade SAV and retrograde conduction occurred over the slow AV nodal pathway. PMT was refractory to usual programming solutions. Using high-density electroanatomic mapping, we were able to ablate the retrograde limb of PMT without further damaging AV conduction.

The influence of cryoballoon manipulation on luminal esophageal temperature during ablation for atrial fibrillation.

BACKGROUND: Esophageal injury is related to a reduction in luminal esophageal temperature (LET) in second-generation cryoballoon (CB) ablation; however, methods to prevent these reductions in temperature have not been well characterized. METHODS: Esophageal temperature was continuously monitored using a LET probe in patients undergoing pulmonary vein (PV) isolation using the second-generation CB. A rotational maneuver of the CB was performed if the initial ablation resulted in a decrease of more than 4℃ in LET. The refrigerant injector near the distal CB pole was used as a fluoroscopic marker to measure the nearest distance between the CB and the LET probe. RESULTS: A total of 52 consecutive patients were enrolled in this study. The rotation was applied in 19 patients and 20 PVs (seven left superior pulmonary veins [LSPVs], seven left inferior PVs [LIPVs], and six right inferior PVs [RIPVs]) with a reduction in LET of more than 4℃ during freezing. The nadir temperature of CB applications was similar before and after CB rotation in all PVs. There was significant difference in the minimum LET before and after rotation during freezing in LSPVs (28.4 ± 3.7 vs 32.4 ± 2.3℃, P = .02), LIPVs (28.4 ± 1.4 vs 32.6 ± 2.7, P = .01) and RIPVs (26.1 ± 4.3 vs 34.0 ± 1.3℃, P = .002). The differences in mean balloon to LET distance were measured for all veins before and after rotation; LSPV (right anterior oblique [RAO], 11.0 ± 1.7 vs 13.8 ± 4.5 mm, P = .05); LIPV (RAO, 10.7 ± 4.3 vs 14.6 ± 6.1 mm, P = .03); RIPV (LAO, 11.8 ± 5.5 vs 14.2 ± 5.7 mm, P = .01). CONCLUSIONS: CB rotational maneuvers during ablation can prevent significant reduction in LET and may prevent esophageal injury during the procedure.

Evaluation of Electrophysiological Mechanisms of Post-Surgical Atrial Tachycardias Using an Automated Ultra-High-Density Mapping System.

OBJECTIVES: This study aimed to evaluate the electrophysiological mechanisms of post-surgical atrial tachycardias (ATs) during mapping with an automated high-resolution mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts). BACKGROUND: Mapping and ablation of post-operative ATs following previous open-heart surgery is often challenging because the potential mechanisms remain incompletely understood. METHODS: Fifty-one consecutive patients underwent mapping and ablation of post-surgical ATs. RESULTS: A total of 64 ATs were identified, and the mechanism was macro re-entry in 58 of 63 (92.1%) ATs, focal in 4 ATs, localized micro re-entry in 1 AT, and undetermined in 1 AT. Of 11 patients who underwent surgical repair of congenital heart disease, 6 (54.5%) had peri-tricuspid re-entrant AT, 5 had either right atrial (RA) free-wall incisional ATs or figure-8 re-entrant ATs, with an isthmus between the tricuspid annulus and the RA free-wall incision or between the incisions, and none had left atrial (LA) or focal ATs. In 32 patients with valve replacement and 8 who underwent valvuloplasty, peri-tricuspid ATs were observed in 14 (43.4%) and 6 (75%) patients, RA free wall or septal incisions-related ATs were seen in 7 and 2 patients, and LA macro re-entrant ATs were observed in 12 patients and 1 patient, respectively. A macro pseudo re-entry pattern was identified in 8 of 51 patients (15.7%). All these activations could be easily excluded by manually moving the window of interest, except in 2 cases with a figure-8 re-entrant configuration. CONCLUSIONS: RA macro re-entrant ATs predominate, irrespective of the types of initial surgical procedures, but LA ATs occur more frequently in patients with valve replacement. Pseudo re-entry atrial activation is common and easily recognized by adjusting the mapping window.

Prolonged Sinus Pauses upon Termination of Paroxysmal Atrial Fibrillation: Abnormal Right Atrial Electrophysiologic and Electroanatomic Findings.

The efficacy of pulmonary vein antral isolation for patients with prolonged sinus pauses (PSP) on termination of atrial fibrillation has been reported. We studied the right atrial (RA) electrophysiologic and electroanatomic characteristics in such patients. Forty patients underwent electroanatomic mapping of the RA: 13 had PSP (group A), 13 had no PSP (group B), and 14 had paroxysmal supraventricular tachycardia (control group C). Group A had longer P-wave durations in lead II than did groups B and C (115.5 ± 15.4 vs 99.5 ± 10.9 vs 96.5 ± 10.4 ms; P=0.001), and RA activation times (106.8 ± 13.8 vs 99 ± 8.7 vs 94.5 ± 9.1 s; P=0.02). Group A's PP intervals were longer during adenosine triphosphate testing before ablation (4.6 ± 2.3 vs 1.7 ± 0.6 vs 1.5 ± 1 s; P <0.001) and after ablation (4.7 ± 2.5 vs 2.2 ± 1.4 vs 1.6 ± 0.8 s; P <0.001), and group A had more complex electrograms (11.4% ± 5.4% vs 9.3% ± 1.6% vs 5.8% ± 1.6%; P <0.001). Compared with group C, group A had significantly longer corrected sinus node recovery times at a 400-ms pacing cycle length after ablation, larger RA volumes (100.1 ± 23.1 vs 83 ± 22.1 mL; P=0.04), and lower conduction velocities in the high posterior (0.87 ± 0.13 vs 1.02 ± 0.21 mm/ms; P=0.02) and high lateral RA (0.89 ± 0.2 vs 1.1 ± 0.35 mm/ms; P=0.04). We found that patients with PSP upon termination of atrial fibrillation have RA electrophysiologic and electroanatomic abnormalities that warrant post-ablation monitoring.

A new electrophysiologic observation in patients with idiopathic left ventricular tachycardia.

BACKGROUND: In patients with idiopathic left ventricular tachycardia (ILVT), the arrhythmogenic substrate is poorly understood. OBJECTIVE: The purpose of this study was to elucidate the ILVT characteristics and outcome of radiofrequency catheter ablation in patients with ILVT. METHODS: Twenty-four patients with ILVT and 15 patients with left accessory pathways (control) underwent high-density mapping of the left His-Purkinje system during sinus rhythm (SR) using 3-dimensional electroanatomic mapping. RESULTS: Fragmented antegrade Purkinje potential (FAP) was represented at the left ventricular septum slightly inferoposterior to the left posterior fascicle (LPF) in 23 patients with ILVT. In control subjects, no FAPs could be recorded at the same region, FAPs were identified at the proximal portion of the LPF (4 patients) and at the distal LPF (1 patient). The finding of any FAPs in ILVT patients was significantly higher than that in control patients (23/24 vs 5/15, P < .01). Radiofrequency ablation at the area of FAP resulted in successful ablation in 23 patients with ILVT. No ILVT recurred during follow-up of 16.3 ± 7.2 months. CONCLUSION: In patients with ILVT, FAP located at the left ventricular septum slightly inferoposterior to the LPF is a novel finding using 3-dimensional electroanatomic mapping. The FAP may represent an arrhythmogenic substrate in ILVT and may be used for guiding successful ablation.

Iron deposition following chronic myocardial infarction as a substrate for cardiac electrical anomalies: initial findings in a canine model.

PURPOSE: Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. METHODS: Two groups of dogs (ex-vivo (n = 12) and in-vivo (n = 10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity ([Formula: see text]) and conductivity ([Formula: see text]). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n = 5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs). RESULTS: Compared to IRON- sections, IRON+ sections had higher[Formula: see text], but no difference in[Formula: see text]. A linear relationship was found between iron content and [Formula: see text] (p<0.001), but not [Formula: see text] (p = 0.34). Among two groups of animals (Iron (<1.5%) and Iron (>1.5%)) with similar scar volumes (7.28% ± 1.02% (Iron (<1.5%)) vs 8.35% ± 2.98% (Iron (>1.5%)), p = 0.51) but markedly different iron volumes (1.12% ± 0.64% (Iron (<1.5%)) vs 2.47% ± 0.64% (Iron (>1.5%)), p = 0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. CONCLUSION: The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may evolve as an arrhythmogenic substrate in the post MI period.

Biological pacemaker created by percutaneous gene delivery via venous catheters in a porcine model of complete heart block.

BACKGROUND: Pacemaker-dependent patients with device infection require temporary pacing while the infection is treated. External transthoracic pacing is painful and variably effective, while temporary pacing leads are susceptible to superinfection. OBJECTIVE: To create a biological pacemaker delivered via venous catheters in a porcine model of complete heart block, providing a temporary alternative/adjunct to external pacing devices without additional indwelling hardware. METHODS: Complete atrioventricular (AV) nodal block was induced in pigs by radiofrequency ablation after the implantation of a single-chamber electronic pacemaker to maintain a ventricular backup rate of 50 beats/min. An adenoviral vector cocktail (K(AAA) + H2), expressing dominant-negative inward rectifier potassium channel (Kir2.1AAA) and hyperpolarization-activated cation channel (HCN2) genes, was injected into the AV junctional region via a NOGA Myostar catheter advanced through the femoral vein. RESULTS: Animals injected with K(AAA) + H2 maintained a physiologically relevant ventricular rate of 93.5 ± 7 beats/min (n = 4) compared with control animals (average rate, 59.4 ± 4 beats/min; n = 6 at day 7 postinjection; P <.05). Backup electronic pacemaker utilization decreased by almost 4-fold in the K(AAA) + H2 group compared with the control (P <.05), an effect maintained for the entire 14-day window. In contrast to the efficacy of gene delivery into the AV junctional region, open-chest, direct injection of K(AAA) + H2 (or its individual vectors) into the ventricular myocardium failed to elicit significant pacemaker activity. CONCLUSIONS: The right-sided delivery of K(AAA) + H2 to the AV junctional region provided physiologically relevant biological pacing over a 14-day period. Our approach may provide temporary, bridge-to-device pacing for the effective clearance of infection prior to the reimplantation of a definitive electronic pacemaker.

Long-term survival in patients with synchronous, solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery.

PURPOSE: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). PATIENTS AND METHODS: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. RESULTS: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS >or=90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). CONCLUSIONS: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.

Stereotatic radiosurgery of 468 brain metastases < or =2 cm: implications for SRS dose and whole brain radiation therapy.

PURPOSE: The national standard stereostatic radiosurgery (SRS) dose for brain metastases < or =2 cm is 24 Gy as established by the Radiation Therapy Oncology Group study 90-05, in which planned whole brain radiotherapy (WBRT) was not used. On the basis of our institutional experience, the goal of this study was to determine the optimal SRS dose and influence of WBRT on local tumor control among 468 < or =2-cm metastases. METHODS AND MATERIALS: Between October 1992 and May 2001, 468 newly diagnosed or recurrent < or =2-cm brain metastases, among 160 patients, were treated with SRS (dose range, 7-30 Gy; median, 20). A total of 240 metastases received planned WBRT (range, 6.75-50.4 Gy; median, 40.5) vs. 228 metastases that did not. The variables tested by multivariate analysis for their potential effect on tumor control included histologic type, site of metastasis, primary diagnosis, tumor volume, SRS dose, newly diagnosed vs. recurrent metastasis, and planned WBRT vs. no planned WBRT. RESULTS: Follow-up ranged from 1 to 82 months (median 7). On multivariate analysis, the addition of WBRT was the most significant predictor of local tumor control. Overall, patients who received WBRT had superior local tumor control rates (97% vs. 87% in those who did not receive WBRT; p = 0.0001). Patients receiving WBRT and SRS > or =20 Gy achieved local control rates of 99% compared with 91% control rates when treated with WBRT and SRS <20 Gy (p = 0.0029). Increasing the SRS dose to >20 Gy resulted in no improvement in local tumor control and a higher rate of Grade 3 and 4 neurotoxicity, approaching statistical significance (5.9% vs. 1.9%, p = 0.078). CONCLUSION: First, optimal control of brain metastasis < or =2 cm was seen with 20-Gy SRS combined with planned WBRT. Second, SRS doses >20 Gy resulted in no obvious improvement in local control and appeared to be associated with a greater rate of complications.