Cervical cancer: a new era.

Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer.

Postoperative urinary retention by void trial methodology following radical hysterectomy for cervical cancer.

OBJECTIVES: Radical hysterectomy is the standard of care for management of early-stage cervical cancer and is associated with postoperative urinary retention. No clear consensus exists regarding optimal voiding trial methodology for mitigating postoperative urinary retention. Our objective was to evaluate the association between type of postoperative voiding trial and risk of urinary retention after radical hysterectomy for cervical cancer. METHODS: We conducted a retrospective analysis of patients undergoing radical hysterectomy for apparent early-stage cervical cancer (FIGO 2018 Stage IA2-IB2) between January 2014 and February 2023. We compared incidence of urinary retention and perioperative outcomes based on method of postoperative voiding trial (timed, autofill, or backfill). Multivariate logistic regression was used to determine association of type of void trial with absence of urinary retention within 30 days postoperatively. RESULTS: Of the 115 patients identified, 48 (41.8%) patients completed a timed void trial, 40 (34.7%) an autofill void trial, and 27 (23.5%) a backfill void trial. 44.3% of patients developed postoperative urinary retention with no differences based on void trial (p = 0.17). Urinary retention was more likely to resolve by 7 (p = 0.012) and 30 days (p = 0.01) for patients undergoing backfill voiding trials, compared to other trials. In multivariate models, backfill void trial was associated with absence of 30-day urinary retention, compared to other trials (aOR 15.1; 95% C.I. 1.5-154.9). CONCLUSIONS: Rates of urinary retention following radical hysterectomy do not differ based on postoperative void trial methodology. A backfill void trial following radical hysterectomy may lead to increased rates of resolution of postoperative urinary retention.

Peripartum Uterine Clostridial Myonecrosis: A Report of Two Fatal Cases.

INTRODUCTION: Uterine clostridial myonecrosis is a rare infection associated with a high mortality rate. This report presents 2 cases of maternal mortality resulting from peripartum clostridial myonecrosis of the uterus. CASE PRESENTATION: Case 1 is a 30-year-old woman (nullipara) who presented in labor at term with an intra-amniotic infection and fetal demise. She rapidly developed septic shock, and cesarean hysterectomy was performed for a suspected necrotizing uterine infection later identified to be Clostridium septicum. Case 2 is an adolescent who presented in septic shock following first trimester medication abortion and died during emergent exploratory laparotomy; cultures grew Clostridium sordellii. Both patients expired within 18 hours of hospital admission. DISCUSSION: Given the rapidly progressive course of clostridial infections, maintaining a high index of suspicion is imperative for ensuring timely diagnosis and effective treatment. Prompt recognition of clinical features associated with clostridial myonecrosis - abdominal pain, tachycardia, leukocytosis and hyponatremia - is essential in preventing mortality. The utilization of point-of-care ultrasound may expedite the diagnosis of uterine myonecrosis. When uterine myonecrosis is suspected, immediate initiation of penicillin-based antibiotics, alongside clindamycin, and aggressive surgical intervention including hysterectomy are essential for ensuring survival. Although the decision to perform a hysterectomy can be challenging, especially in cases involving child-bearing-aged patients, it is a vital step to avert a fatal outcome. CONCLUSIONS: By presenting these cases, we aim to raise awareness of this uncommon, but highly lethal infection to expedite diagnosis and treatment to improve patient outcomes.

Incidence of postoperative venous thromboembolism in patients with vulvar carcinoma undergoing vulvectomy with or without lymphadenectomy.

OBJECTIVES: The incidence of venous thromboembolism (VTE) following radical surgery for vulvar carcinoma remains poorly characterized, and recommendations for postoperative chemoprophylaxis are varied. Our objective was to assess the incidence of postoperative VTE in patients undergoing surgery for vulvar carcinoma and to determine if VTE incidence differs by radical vulvectomy with or without lymph node assessment. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients with a diagnosis of vulvar cancer undergoing radical vulvectomy with or without lymph node assessment from 2012 to 2020. Clinical characteristics and 30-day incidence of VTE as well as other postoperative outcomes were abstracted. Variables were compared using Chi-square test and Fischer's exact test, as well as Kruskal-Wallis and Wilcoxon rank sum tests where appropriate. RESULTS: A total of 1672 patients underwent radical vulvectomy for vulvar carcinoma. 11 patients (0.7%) experienced postoperative VTE within 30 days of surgery. The incidence of VTE was similar when radical vulvectomy was performed alone or with lymph node dissection by any method (p = 0.116). Longer operative times (p = 0.033) and greater postoperative length of stay (p = 0.001) were associated with increased risk of postoperative VTE. CONCLUSIONS: The incidence of postoperative VTE is low in patients undergoing radical vulvar surgery in this national cohort. Inguinofemoral lymph node dissection by any method does not appear to be a risk factor for VTE when compared to radical vulvectomy alone. Further research is needed to determine if extended VTE prophylaxis is beneficial in this population.

Postpartum Opportunistic Salpingectomy Compared With Bilateral Tubal Ligation After Vaginal Delivery for Ovarian Cancer Risk Reduction: A Cost-Effectiveness Analysis.

OBJECTIVE: To compare the cost effectiveness of opportunistic salpingectomy and bilateral tubal ligation for sterilization immediately after vaginal delivery. METHODS: A cost-effectiveness analytic decision model was used to compare opportunistic salpingectomy with bilateral tubal ligation during vaginal delivery admission. Probability and cost inputs were derived from local data and available literature. Salpingectomy was assumed to be performed with a handheld bipolar energy device. The primary outcome was the incremental cost-effectiveness ratio (ICER) in 2019 U.S. dollars per quality-adjusted life-year (QALY) at a cost-effectiveness threshold of $100,000/QALY. Sensitivity analyses were performed to determine the proportion of simulations in which salpingectomy would be cost effective. RESULTS: Opportunistic salpingectomy was more cost effective than bilateral tubal ligation with an ICER of $26,150/QALY. In 10,000 patients desiring sterilization after vaginal delivery, opportunistic salpingectomy would result in 25 fewer ovarian cancer cases, 19 fewer ovarian cancer deaths, and 116 fewer unintended pregnancies than bilateral tubal ligation. In sensitivity analysis, salpingectomy was cost effective in 89.8% of simulations and cost saving in 13% of simulations. CONCLUSION: In patients undergoing sterilization immediately after vaginal deliveries, opportunistic salpingectomy is more cost effective and may be more cost saving than bilateral tubal ligation for reducing ovarian cancer risk.

Fluorescein Mapping in Vulvar Paget Disease.

BACKGROUND: Vulvar Paget disease often requires extensive and, in some cases, multiple resections to treat. A fluorescein-mapping procedure followed by a staged vulvectomy may be an effective technique to tailor resection and identify clinically occult lesions. TECHNIQUE: We describe a two-step procedure; first, intravenous fluorescein sodium is injected, and the vulva is illuminated with a Wood's lamp. Representative biopsies are obtained and correlated on final pathology with the extent of disease to develop a final plan for excision. Second, using fluorescein to identify the confirmed areas of disease, the appropriate excisional procedure is performed once mapping biopsy pathology is known. EXPERIENCE: We describe our experience with eight patients with vulvar Paget disease undergoing fluorescein mapping biopsies and staged vulvectomy. Using intravenous fluorescein sodium, all patients were found to have Paget disease beyond the visible margins of their gross lesions. No patients experienced a recurrence of Paget disease within a median follow-up time of 32 months, comparable with other directed methods of surgical resection. CONCLUSION: We report a technique for the injection of fluorescein sodium for the visualization of vulvar Paget disease capable of providing accurate surgical margins and identification of occult satellite lesions with a high degree of safety and a favorable cost profile. This staged approach to vulvectomy could offer improved accuracy of resection for vulvar Paget disease with few drawbacks.

When we open and close: Postoperative outcomes after aborted primary cytoreduction for ovarian cancer.

Objective: Little data exists to adequately counsel patients on the postsurgical morbidity and outcomes of an aborted primary debulking (AD) for advance stage epithelial ovarian cancer. Our objectives were to examine the 30-day morbidity of AD, percentage of patients who subsequently undergo neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICS), residual disease at ICS, and predictors for complications after AD. Methods: This was a single-institution retrospective analysis of patients who underwent AD for ovarian cancer from 01/2008 to 12/2020 using ICD-10 diagnoses and procedure codes. Patient demographics, perioperative metrics, and residual disease at ICS were collected. Thirty-day postoperative complications were graded by the Common Terminology Criteria for Adverse Events. Fisher's exact tests compared categorical and Wilcoxon rank-sum tests compared continuous variables. Logistic regression provided unadjusted odds ratios to identify predictors for post-AD complications. Results: Forty-eight patients underwent AD, and 43 were included for analysis. All had at least stage IIIC high grade serous ovarian cancer. All patients subsequently underwent ICS, with 21 (48.8%) achieving no residual macroscopic disease and 21 (48.8%) to ≤ 1 cm of macroscopic disease. After AD, 16 (37.2%) experienced at least one G ≥ 3 event within the first 30 days. The most common complication was gastrointestinal complications. Preoperative albumin was the only significant predictor for G ≥ 3 complication after AD. Conclusions: Approximately one-third of patients will experience at least one G ≥ 3 complications after AD. Complications may be anticipated by low preoperative albumin. Patients can be counseled that, after AD, proceeding to subsequent NACT and ICS and achieving optimal debulking is common.

Racial and ethnic enrollment disparities in clinical trials of poly(ADP-ribose) polymerase inhibitors for gynecologic cancers.

OBJECTIVES: Disparities persist in the enrollment of racial/ethnic groups in clinical trials for ovarian cancers. We sought to analyze the enrollment rates of patients by race/ethnicity in phase II/III clinical trials involving poly(ADP-ribose) polymerase (PARP) inhibitors for ovarian cancers and compare these to the racial/ethnic prevalence of ovarian cancers in the United States. METHODS: This study was a retrospective review of clinical trials registered with ClinicalTrials.gov. Studies included evaluated PARP inhibitors for the treatment of ovarian, fallopian tube, and primary peritoneal cancers. Enrollment rates for clinical trials were stratified by race/ethnicity and type of cancer. Enrollment fractions (EFs) were calculated using prevalence data from the Surveillance, Epidemiology, and End Results Program. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare racial/ethnic group enrollment rates to Non-Hispanic (NH) White enrollment rates. RESULTS: Forty-eight trials were identified, 15 of which met inclusion criteria. The EFs for included trials, were 1.5% for NH-White, 0.47% for NH-Black, 0.33% for Hispanic, and 2.38% for Asian/Pacific Islander. Patients who identified as NH-Black and Hispanic were significantly underrepresented compared to those who identified as NH-White (OR 0.23, 95% CI [0.18-0.29] and OR 0.3, 95% CI [0.25-0.38] respectively, p < 0.001). CONCLUSIONS: NH-Black and Hispanic patients are significantly underrepresented in clinical trials evaluating PARP inhibitors for ovarian cancers compared to NH-White cohorts. Phase II/III trials assessing PARP inhibitors for ovarian cancers do not accurately represent the populations diagnosed with these malignancies. Enrollment strategies are needed to increase diversity in PARP inhibitor clinical trials for women's cancers.

Postoperative venous thromboembolism in gynecologic oncology patients undergoing minimally invasive surgery: Does modality matter?

OBJECTIVES: Minimally invasive surgery (MIS) is increasingly utilized for gynecologic cancers. While incidence of venous thromboembolism (VTE) after MIS is low, some guidelines recommend extended chemoprophylaxis for these patients undergoing MIS. Our objectives were to determine incidence of postoperative VTE in patients undergoing MIS, evaluate differences in the incidence by MIS modality and assess the need for extended chemoprophylaxis. METHODS: We conducted a retrospective cohort study including all patients undergoing MIS (robot-assisted, multi-port laparoscopy, single-port laparoscopy) for gynecologic cancers between January 2014 and December 2018 at our institution. Demographic and perioperative variables were collected. Patients <18 years, with benign pathology, or on preoperative anticoagulation were excluded. Chi-square, Fisher's exact test, and one-way ANOVA were performed to determine risk factors related to VTE occurrence. RESULTS: We identified 806 patients who underwent MIS with median age 61. Most had Stage I disease (81.5%) and uterine cancer (81.5%). Five VTE events occurred within 90 days following surgery (0.6%). Incidence of 90-day VTE did not differ between MIS modalities (p = 0.6). Patients with longer OR times (p = 0.004) were more likely to experience VTE. Age, smoking status, BMI, type of cancer and stage were not significant risk factors for VTE. CONCLUSIONS: The incidence of postoperative VTE in patients with gynecologic cancers undergoing MIS is low and does not appear to differ by MIS modality. Given the very low incidence of postoperative VTE, extended chemoprophylaxis is unlikely to benefit patients with gynecologic malignancies undergoing MIS procedures.

Postpartum Salpingectomy Compared With Standard Tubal Ligation After Vaginal Delivery.

OBJECTIVE: To compare operative outcomes of postpartum salpingectomy and tubal ligation after vaginal delivery. METHODS: This retrospective cohort study identified patients who underwent tubal sterilization between January 1, 2009, and December 31, 2019, at a large academic hospital, using the electronic medical record. All patients who delivered vaginally and underwent tubal sterilization during their delivery admissions were included. The primary outcome was total operative time. Secondary outcomes included estimated blood loss, perioperative complications, and readmission within 6 weeks postpartum. Patients who underwent bilateral tubal ligation were compared with those who underwent bilateral salpingectomy using Pearson's χ2 test, Fisher exact, and Student's t test. RESULTS: A total of 317 eligible patients were identified. One hundred and six (94%) salpingectomies were completed using a bipolar electrocautery device. Operative time was 3 minutes shorter in the salpingectomy group, 30 minutes (interquartile range 24-38) compared with 33.5 (26-42) minutes, P=.032. Patients who underwent salpingectomy were more likely to have estimated blood loss of 5 mL or less (our institutional shorthand for minimal blood loss) than women who underwent bilateral tubal ligation (78 [69%] vs 112 [55%], P=.015). There were no significant differences in perioperative complications between the groups. CONCLUSION: When using electrocautery, bilateral salpingectomy can be completed in the immediate postpartum period after vaginal delivery with equivalent operative times to bilateral tubal ligation.

Clinical Outcomes After Lung Stereotactic Body Radiation Therapy in Patients With or Without a Prior Lung Resection.

OBJECTIVES: Tumor control (TC), toxicity and survival, following stereotactic body radiation therapy (SBRT) were compared between patients with and without a prior lung resection (PLR). MATERIALS AND METHODS: The study is comprised of 130 patients with 141 peripheral tumors treated with SBRT at our institution from 2009 to 2013. Primary TC and lobar control (LC) were defined per RTOG 0236. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Survival/TC and toxicity were compared between patients with and without PLR using the Kaplan-Meier method and cumulative incidence, respectively. Fine and Gray regression was used for univariable/multivariable analysis for radiation pneumonitis (RP). RESULTS: Of the 130 patients with median age 70 years (range, 42 to 93 y), 50 had undergone PLR (median time between PLR and SBRT: 33 mo; range, 1 to 206), including pneumonectomy (12%), lobectomy (46%), wedge resection (42%). With a median follow-up of 21 months in survivors, the PLR group had better TC (1-y 100% vs. 93%; P<0.01) and increased grade ≥2 (RP; 1-y 12% vs. 1%; P<0.01). OS was not significantly different between the 2 groups (1-y 91% vs. 85%; P=0.24). On univariable/multivariable analyses, biologically effective dose was associated with TC (hazard ratios, 0.97; 95% confidence interval, 0.94-0.999; P=0.04). Chemotherapy use was associated with grade ≥2 RP for all patients (hazard ratios, 14.92; 95% confidence interval, 5.68-39.21; P<0.0001) in multivariable analysis. PLR was not associated with increased RP in multivariable analysis. CONCLUSIONS: Patients with PLR who receive lung SBRT for lung tumors have high local control and relatively low toxicity. SBRT is an excellent option to treat second lung tumors or pulmonary metastases in patients with PLR.

The impact of using an intraoperative goal directed fluid therapy protocol on clinical outcomes in patients undergoing total pancreatectomy and islet cell autotransplantation.

BACKGROUND: Patients undergoing total pancreatectomy and islet cell autotransplant (TPIAT) for treatment of pancreatitis are at risk for complications of over and under resuscitation. We hypothesized that using a goal directed fluid therapy (GDFT) protocol might impact clinical outcomes. MATERIALS AND METHODS: A consecutive series of adult patients undergoing TPIAT were managed intraoperatively using either standard fluid therapy (SFT, n = 44) or GDFT (n = 23) as part of a pilot study between January 2013 and May 2015. Patient characteristics, intraoperative, and postoperative data were recorded prospectively, then retrospectively analyzed for differences between the groups. RESULTS: The GDFT group had lower total fluid resuscitation (3,240 cc vs 5,173 cc, p < 0.0001) and transfusion requirements (1.0 cc/kg vs 3.3 cc/kg, p = 0.050) compared to the SFT group. The pre to postop nadir hemoglobin change was significantly less for GDFT (4.2 vs 5.1 gm/dl, p = 0.021) despite less transfusion. CONCLUSIONS: Compared to SFT, using an intraoperative GDFT protocol in TPIAT patients was associated with significantly decreased intraoperative fluid resuscitation, blood transfusion and less postoperative dilutional anemia, without any difference in complications of underresuscitation. This pilot study suggests that GDFT is likely safe and further investigation is warranted.

Long-Term Glycemic Control in Adult Patients Undergoing Remote vs. Local Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant. RESULTS: Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group. CONCLUSIONS: At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Inter-scan and inter-observer tumour volume delineation variability on cone beam computed tomography in patients treated with stereotactic body radiation therapy for early-stage non-small cell lung cancer.

INTRODUCTION: Quantification of volume changes on cone beam computed tomography (CBCT) during lung stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) may provide a useful radiological marker for radiation response and for adaptive treatment planning. This study quantifies inter-scan and inter-observer variability in tumour volume delineation on CBCT. METHODS: Three clinicians independently contoured the primary gross tumour volume (GTV) manually on CBCTs taken immediately before SBRT treatment (pre) and after the same SBRT treatment (post) for 19 NSCLC patients. Relative volume differences (RVD) were calculated between the pre- and post-CBCTs for a given treatment and between any two of three observers for a given CBCT. Coefficient of variation (CV) was used to quantitatively measure and compare the extent of variability. RESULTS: Inter-observer variability had a significantly higher CV of 0.15 ± 0.13 compared to inter-scan CV of 0.03 ± 0.04 with P < 0.0001. The greatest variability was observed with tumours (<2 cm in diameter) versus larger tumours with 95% limit of agreement (LOA) (Mean ± Standard Deviation) of 1.90% ± 19.55% vs. -0.97% ± 12.26% for inter-scan RVD and 29.99% ± 73.84% vs. 9.37% ± 29.95% for inter-observer RVD respectively. CONCLUSIONS: Inter-observer variability was greater than inter-scan variability for tumour volume delineation on CBCT with greatest variability for small tumours (<2 cm in diameter). LOA for inter-scan variability (~12%) helps defines a threshold for clinically meaningful tumour volume change during SBRT treatment for tumours with diameter greater than 2 cm, with larger thresholds needed for smaller tumours.

Key clinical beam parameters for nanoparticle-mediated radiation dose amplification.

As nanoparticle solutions move towards human clinical trials in radiation therapy, the influence of key clinical beam parameters on therapeutic efficacy must be considered. In this study, we have investigated the clinical radiation therapy delivery variables that may significantly affect nanoparticle-mediated radiation dose amplification. We found a benefit for situations which increased the proportion of low energy photons in the incident beam. Most notably, "unflattened" photon beams from a clinical linear accelerator results in improved outcomes relative to conventional "flat" beams. This is measured by significant DNA damage, tumor growth suppression, and overall improvement in survival in a pancreatic tumor model. These results, obtained in a clinical setting, clearly demonstrate the influence and importance of radiation therapy parameters that will impact clinical radiation dose amplification with nanoparticles.

Evaluation of initial setup accuracy and intrafraction motion for spine stereotactic body radiation therapy using stereotactic body frames.

PURPOSE: The purposes of this study were (1) to evaluate the initial setup accuracy and intrafraction motion for spine stereotactic body radiation therapy (SBRT) using stereotactic body frames (SBFs) and (2) to validate an in-house-developed SBF using a commercial SBF as a benchmark. METHODS AND MATERIALS: Thirty-two spine SBRT patients (34 sites, 118 fractions) were immobilized with the Elekta and in-house (BHS) SBFs. All patients were set up with the Brainlab ExacTrac system, which includes infrared and stereoscopic kilovoltage x-ray-based positioning. Patients were initially positioned in the frame with the use of skin tattoos and then shifted to the treatment isocenter based on infrared markers affixed to the frame with known geometry relative to the isocenter. ExacTrac kV imaging was acquired, and automatic 6D (6 degrees of freedom) bony fusion was performed. The resulting translations and rotations gave the initial setup accuracy. These translations and rotations were corrected for by use of a robotic couch, and verification imaging was acquired that yielded residual setup error. The imaging/fusion process was repeated multiple times during treatment to provide intrafraction motion data. RESULTS: The BHS SBF had greater initial setup errors (mean±SD): -3.9±5.5mm (0.2±0.9°), -1.6±6.0mm (0.5±1.4°), and 0.0±5.3mm (0.8±1.0°), respectively, in the vertical (VRT), longitudinal (LNG), and lateral (LAT) directions. The corresponding values were 0.6±2.7mm (0.2±0.6°), 0.9±5.3mm (-0.2±0.9°), and -0.9±3.0mm (0.3±0.9°) for the Elekta SBF. The residual setup errors were essentially the same for both frames and were -0.1±0.4mm (0.1±0.5°), -0.2±0.4mm (0.0±0.4°), and 0.0±0.4mm (0.0±0.4°), respectively, in VRT, LNG, and LAT. The intrafraction shifts in VRT, LNG, and LAT were 0.0±0.4mm (0.0±0.3°), 0.0±0.5mm (0.0±0.4°), and 0.0±0.4mm (0.0±0.3°), with no significant difference observed between the 2 frames. CONCLUSIONS: These results showed that the combination of the ExacTrac system with either SBF was highly effective in achieving both setup accuracy and intrafraction stability, which were on par with that of mask-based cranial radiosurgery.

Salvage whole brain radiotherapy or stereotactic radiosurgery after initial stereotactic radiosurgery for 1-4 brain metastases.

Patients with limited brain metastases are often candidates for stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT). Among patients who receive SRS, the likelihood and timing of salvage WBRT or SRS remains unclear. We examined rates of salvage WBRT or SRS among 180 patients with 1-4 newly diagnosed brain metastases who received index SRS from 2008-2013. Competing risks multivariable analysis was used to examine factors associated with time to WBRT. Patients had non-small cell lung (53 %), melanoma (23 %), breast (10 %), renal (6 %), or other (8 %) cancers. Median age was 62 years. Patients received index SRS to 1 (60 %), 2 (21 %), 3 (13 %), or 4 (7 %) brain metastases. Median survival after SRS was 9.7 months (range, 0.3-67.6 months). No further brain-directed radiotherapy was delivered after index SRS in 55 % of patients. Twenty-seven percent of patients ever received salvage WBRT, and 30 % ever received salvage SRS; 12 % of patients received both salvage WBRT and salvage SRS. Median time to salvage WBRT or salvage SRS were 5.6 and 6.1 months, respectively. Age ≤60 years (adjusted hazard ratio [AHR] = 2.80; 95 % CI 1.05-7.51; P = 0.04) and controlled/absent extracranial disease (AHR = 6.76; 95 % CI 1.60-28.7; P = 0.01) were associated with shorter time to salvage WBRT. Isolated brain progression caused death in only 11 % of decedents. In summary, most patients with 1-4 brain metastases receiving SRS never require salvage WBRT or SRS, and the remainder do not require salvage treatment for a median of 6 months.

Generation of fluoroscopic 3D images with a respiratory motion model based on an external surrogate signal.

Respiratory motion during radiotherapy can cause uncertainties in definition of the target volume and in estimation of the dose delivered to the target and healthy tissue. In this paper, we generate volumetric images of the internal patient anatomy during treatment using only the motion of a surrogate signal. Pre-treatment four-dimensional CT imaging is used to create a patient-specific model correlating internal respiratory motion with the trajectory of an external surrogate placed on the chest. The performance of this model is assessed with digital and physical phantoms reproducing measured irregular patient breathing patterns. Ten patient breathing patterns are incorporated in a digital phantom. For each patient breathing pattern, the model is used to generate images over the course of thirty seconds. The tumor position predicted by the model is compared to ground truth information from the digital phantom. Over the ten patient breathing patterns, the average absolute error in the tumor centroid position predicted by the motion model is 1.4 mm. The corresponding error for one patient breathing pattern implemented in an anthropomorphic physical phantom was 0.6 mm. The global voxel intensity error was used to compare the full image to the ground truth and demonstrates good agreement between predicted and true images. The model also generates accurate predictions for breathing patterns with irregular phases or amplitudes.

Local control after fractionated stereotactic radiation therapy for brain metastases.

Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastases, but concerns over potential toxicity limit applications for larger lesions or those in eloquent areas. Fractionated stereotactic radiation therapy (SRT) is often substituted for SRS in these cases. We retrospectively analyzed the efficacy and toxicity outcomes of patients who received SRT at our institution. Seventy patients with brain metastases treated with SRT from 2006-2012 were analyzed. The rates of local and distant intracranial progression, overall survival, acute toxicity, and radionecrosis were determined. The SRT regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4-6.4 cm). Median survival after SRT was 10.7 months. Median time to local progression was 17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year. Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most common symptom being mild headache. Symptomatic radiation-induced treatment change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.